Imagine it’s your birthday. You’re expecting a phone call from a close friend, but it never comes. You called them on their birthday, so why didn’t they call you? Do they not care enough to remember your birthday? You feel hurt. Where did this feeling of hurt come from? It wasn’t the lack of a phone call that caused the hurt. It was the thoughts about the lack of a phone call that hurt. What if, instead of taking the missing phone call personally, you had thought: Thoughts play a powerful role in determining how people feel and how they act. If someone thinks positively about something, they’ll probably feel positively about it. Conversely, if they think negatively about something—whether or not that thought is supported by evidence—they will feel negatively. Cognitive restructuring is the therapeutic process of identifying and challenging negative and irrational thoughts, such as those described in the birthday example. These sort of thoughts are called cognitive distortions. Although everyone has some cognitive distortions, having too many is closely linked to mental illnesses such as depression and anxiety. Cognitive behavioral therapy (CBT), and several other approaches to psychotherapy, make heavy use of cognitive restructuring. Each of these therapies leverages the powerful link between thoughts, feelings, and behaviors to treat mental illness. The thought-feeling-behavior link is a big topic in itself, and beyond the scope of this guide. If you want to learn more, check out our CBT Psychoeducation guide and worksheet. Remember, cognitive restructuring refers to the process of challenging thoughts—it isn’t a single technique. There are many techniques that fall under the umbrella of cognitive restructuring, which we will describe (alongside several therapy tools) throughout this guide. Identifying Negative Thoughts / Cognitive Distortions Cognitive restructuring starts with the identification of irrational negative thoughts (cognitive distortions). This is trickier than it sounds. Cognitive distortions can happen so quickly that they come and go before we’ve noticed them. They’re more like a reflex than an intentional behavior. Below, we’ll discuss how to help your clients identify their cognitive distortions. Step 1: Psychoeducation Before jumping into the “doing” part of cognitive restructuring, it’s important for clients to understand what cognitive distortions are, and how powerful they are in influencing one’s mood. Start with psychoeducation about the cognitive model and cognitive distortions, using plenty of examples. Step 2: Increase Awareness of Thoughts After building a general understanding of the cognitive model, your clients will learn to identify their own cognitive distortions. This takes practice. It’s not natural, during a fit of rage, to stop and wonder: “What thoughts led me to this moment?” To hone in on the most important cognitive distortions, start by looking for negative emotions. When are symptoms of depression, anger, or anxiety at their worst? If your client has difficulty identifying their emotions, focus on behaviors. What behaviors do they want to change? What triggers those behaviors? Think of these situations like alarms, alerting you that cognitive distortions are nearby. This discussion is intended to improve your client’s awareness of situations where cognitive distortions are impacting their mood and behavior. The more specific triggers or situations they can identify, the easier it will be to recognize them in the moment. With the completion of step 2, your client has laid the foundation for a core tool of cognitive restructuring: thought records. Step 3: Thought Records A thought record (also called a thought log) is a tool for recording experiences, along with the thoughts, feelings, and behaviors that accompany them. This exercise will help your clients become aware of cognitive distortions that previously went unnoticed, and unquestioned. With practice, they will learn to identify cognitive distortions in the moment, and immediately challenge them. Each row of a thought record represents a unique situation. The headings for each column will differ slightly between thought records, but generally they include “situation”, “thoughts”, “feelings”, “consequences”, and sometimes, “alternate thought”. Ideally, each row is filled in shortly after a situation ends. Sometimes, the mere awareness of a cognitive distortion will be enough to eliminate it. Other cognitive distortions are more deeply ingrained, and require extra work. This is where cognitive restructuring techniques, which make up the rest of this guide, will come in handy. Cognitive Restructuring Techniques When looking at other people’s cognitive distortions, they seem easy to dispute. No matter how much your friend believes that they’re the “worst person ever”, you know that to be untrue. But when it comes to a person’s own cognitive distortions, they can be much more difficult to overcome. That’s why they persist. We believe in our own cognitive distortions, no matter how inaccurate they may be. For these difficult cognitive distortions, we have several techniques to help tear them down. These techniques should be used again and again, whenever cognitive distortions are identified. With enough repetition, the cognitive distortions will be extinguished and replaced with new, balanced thoughts. Here are the techniques. Socratic Questioning Socrates was a Greek philosopher who emphasized the importance of questioning as a way to explore complex ideas and uncover assumptions. This philosophy has been adopted as a way to challenge cognitive distortions. Once a cognitive distortion has been identified, this technique is simple. The cognitive distortion will be assessed by asking a series of questions. Therapists can set an example by asking these questions of their clients, but ultimately, the client should learn to question their own thoughts. Decatastrophizing Oftentimes, cognitive distortions are just an exaggerated view of reality. Before a first date, a person might find themselves overwhelmed with anxiety, thinking of all the things that might go wrong. Maybe their date won’t like how they look, or maybe they’ll make a fool of themselves. With the decatastrophizing technique, we ask very simple questions: “What if?” or “What’s the worst that could happen?” This sequence of questioning helps to reduce the irrational level of anxiety associated with cognitive distortions. It highlights the fact that even the worst-case scenario is manageable. Putting Thoughts on Trial In this exercise, your client will act as a defense attorney, a prosecutor, and a judge. First, your client will act as a defense attorney by defending their negative thought. Ask them to make an argument for why the thought is true. Remember to stick to verifiable facts. Interpretation, guesses, and opinions aren’t allowed! Next, ask your client to act as the prosecutor. Now they will present evidence against the negative thought. Just like in the previous step, require that they stick to facts, while excluding opinions. Finally, ask your client to act as the judge. They will review the evidence, and deliver a verdict. The verdict should come in the form of a rational thought. If you would like to continue learning about cognitive behavioral therapy, cognitive distortions, and cognitive restructuring. Related Article: Cognitive Distortions Cognitive Benefit of Highly Touted MIND Diet Questioned Cognitive Distortions - CBT

The drug’s developers respond to the FDA’s decision to deny approval and consider future directions for this indication. Information about the US Food & Drug Administration (FDA)’s Complete Response Letter (CRL) for Zurzuvae’s (zuranolone’s) New Drug Application (NDA) for treating major depressive disorder (MDD) may provide some clarity about next steps for the agent. The FDA announced in August that (zuranolone) was approved as a treatment for postpartum depression (PPD) in adults, but not approved for its other proposed indication of MDD.1 Reports note that the FDA cited concerns about safety due to the drug’s adverse effects, a lack of evidence of the drug’s effectiveness, and the need for more studies in order to support approval for the MDD indication.2,3 “The FDA approved zuranolone for the indication of PPD but did not approve it for the second indication of unipolar major depression in women and men,” John J. Miller, MD, told Psychiatric Times®. “…Sage [Therapeutics] and Biogen, collaborators in the zuranolone development project, will need to review the reasons why the FDA denied approval for unipolar major depression in women and men, and determine how to proceed.”1 Miller is Editor in Chief of Psychiatric Times; medical director at Brain Health; a staff psychiatrist at Seacoast Mental Health Center; and a consulting psychiatrist at Exeter Hospital and Insight Meditation Society. In response to the decision, Sage and Biogen have been reviewing the FDA’s feedback in detail in order to determine next steps.3 Sage has also announced that it is cutting around 40% of its workforce following reports that its shares had dropped almost 54% by August 7.4 “In regard to the CRL for MDD, we are highly disappointed for patients, particularly amid the current mental health crisis and millions of people with MDD struggling to find symptom relief,” said Barry Greene, chief executive officer at Sage, in a press release. “We remain committed to our mission to deliver life-changing brain health medicines.”2 Some specific issues in the MDD research cited by the FDA include a patient who was unresponsive to stimuli for 50 minutes following administration of a high dose of zuranolone, and a small number of patients who reported having suicidal thoughts after either starting or stopping zuranolone treatment. It has also been reported that a couple of patients had seizures. 3,4 In the CRL, however, the FDA stated that other factors, such as comorbid conditions and consumption of another drug that lists seizures as a possible adverse effect, may have been the actual cause(s) of the seizures in these patients.5 There have also been positive findings about zuranolone for the treatment of MDD throughout the road to approval. When the rolling NDA submission for zuranolone was completed in December 2022, data from the LANDSCAPE and NEST development programs showed that zuranolone demonstrated rapid and sustained improvement of depressive symptoms, largely good tolerability, and a consistent safety profile.6 Representatives from Sage and other entities have also offered differing views about the MDD research and the FDA’s conclusions. According to Matthew Henson, spokesman for Sage, the patients referenced above had received a double-sized dose of zuranolone.4 And Brian Abrahams, analyst for RBC Capital Markets, has been quoted as saying that the FDA’s conclusions about the overall safety profile of zuranolone “does not appear completely aligned with Sage’s historical interpretations.”3 In addition to determining next steps for MDD, Sage has announced that it is currently focusing on PPD, which it plans to launch in the fourth quarter of 2023. Zuranolone for the treatment of PPD is expected to be commercially available in fourth-quarter 2023 and to potentially draw $240 million in eventual sales.2,4 Related Article: Phase 3 Clinical Program Announced for Monotherapy Treatment for MDD

What can be done to restore balance in healthcare delivery KEY POINTS Mental health care tends to bring in less money than other areas of medicine. Private healthcare organizations are increasingly cutting back on delivering mental health care. There are specific steps that can be taken to reverse the outsourcing of mental health care to the public. Outsourcing of Mental Healthcare Who should be delivering healthcare? Private companies? The government? The debate over what works best will go on for years. As it continues, what clearly isn’t working is this strange hybrid situation we current have in which some aspects of healthcare are predominantly within the private world (including “not for profit” organizations that operate very much like private entities) while others are much more likely administered by federal, state, and local governments. Which type of healthcare goes one way or the other is fairly predictable, and is primarily driven by, big shocker, money. Certain areas of healthcare are simply more profitable than others. Surgery, imaging and radiology, cardiac care – these things tend to bring in dollars so it is no surprise that private healthcare providers build lots of capacity and offer plenty of access for these services. Primary care, not so much, but since primary care clinicians are the ones who often refer patients to these more profitable areas they tend to be tolerated and kept close within the organizational structure. What type of care is at the bottom of the heap? That would be mental health, which tends to be time-intensive, less procedure-based, and disproportionately needed by people with fewer financial resources. If times get tough, then, it can be very tempting to drop the less profitable areas of your business while holding on to the more profitable ones, and this is exactly what has been happening when it comes to large private hospitals and clinics and mental health care. And who is expected to pick up the slack for providing critical areas of care that tend to make less money? That would be you - in the form of state or county clinics that are funded and run by taxpayers. This form of public subsidy that permits private healthcare organizations to retain more profitable sectors of medicine while offloading the less profitable ones to the public has been going on for decades in mental health. In many areas around the county, things have now reached crisis levels, as anyone who has recently needed outpatient or inpatient mental health treatment (and who isn’t wealthy enough to pay out of pocket for it) can well attest. Hospital psychiatry units are closing fast, almost as fast as elective surgery centers are opening up. And while these private healthcare organizations may save money in the short-term, the long-term effect may be to convince more and more people that the whole private healthcare thing is fundamentally flawed and needs to be taken over (all of it) by the government. Short of that, however, there are some things that can help bring this system into better balance. Major healthcare providers are typically subject to regulation, often by state government. These regulatory bodies might consider using this power. Sure, big hospital, you can open up that shiny new vascular surgery center, but you have to keep your inpatient psychiatry unit going as well. Insurance providers, starting with federal and state ones like Medicare and Medicaid, could adjust their payment rates to bring mental health care closer to parity with physical health. Just imagine what might happen if a 3-hour autism evaluation (a complicated and potentially life changing assessment) was compensated anywhere near the rate of a 3-hour procedure or medical test. If this happened, I guarantee you that parents would no longer be waiting a year or more to get their child evaluated. We can continue to move away from traditional “fee for service” models, that provide financial incentives to do as many expensive tests and procedures as possible, to models that pay healthcare organizations a fixed amount of money per individual per month. These “capitated” models tilt the financial incentive the other way, rewarding organizations to keep people healthy. Given the research showing that mental health is a foundation for all health, the value of good mental health care, both preventively and for those already struggling, becomes hard to ignore. In summary, the ability of big private healthcare organizations to simply “opt out” of providing critically needed mental healthcare cannot continue and needs to be actively confronted. It is not the responsibility of the public taxpayer to balance the budgets of big corporations through the outsourcing of mental healthcare to publicly run clinics and hospitals. About Dr. Vilash Reddy a child, adolescent, and adult psychiatrist who is a blend of therapy with modern medicines and/or alternative remedies. He also have a holistic approach to each one of my patients, which can be a fusion of medicine and/or therapy and/or alternative supplements/remedies. And he customize and educate you throughout the process.

The investigators also concluded that depression screening alone may not be sufficient to effectively identify suicide risk. October 5 is National Depression Screening Day. A recent study that compared the effectiveness of suicide screening and several types of depression screenings supported the efficacy of the 9-item Patient Health Questionnaire (PHQ-9) in comparison to other screening tools. However, the study investigators also concluded that depression screening alone may not be sufficient to effectively identify suicide risk. The study, conducted by researchers at the Ohio State University Wexner Medical Center and Wesleyan University, compared the effectiveness of suicide risk screening and depression screening alone among primary care patients. The study included 2744 patients between the ages of 18 and 89 years from 6 primary care clinics who completed several depression screenings—including the self-administered PHQ-9 and the 2-item Patient Health Questionnaire (PHQ-2)—and the suicidal ideation (SI) screening, which focused on “thoughts of killing yourself” within the past week, within the past month, and during one’s entire lifespan.1 Of these patients, 65.4% who screened positive for SI also screened positive for depression on the PHQ-9. The PHQ-9 also accurately identified more patients who had attempted suicide in the past 3 months than lifetime SI—however, lifetime SI accurately identified more patients who had attempted suicide within the past 6 and 12 months. “Our findings indicated depression screening with the PHQ-9 outperformed suicide risk screening under most conditions,” the investigators wrote, ultimately concluding that depression screening alone was not sufficient to identify all patients at risk for suicide.1 “Our results also suggest that supplementing the PHQ-9 with additional SI screening items did not meaningfully improve the identification of primary care patients who attempted suicide, particularly in the near term,” the investigators wrote. “On the contrary, our results suggest the possibility that additional SI screening—particularly screening that focuses on current or recent SI—may have the unintended effect of negatively influencing clinical decision-making.” The study has important implications for suicide prevention efforts. Suicide is a leading cause of death in the United States. According to the Centers for Disease Control and Prevention (CDC), suicide rates have been increasing in recent years, with adults aged 35 to 64 years accounting for nearly half of all suicides in the United States; with adults aged 75 years and older committing suicide at a rate of 20.3 per 100,000 suicides; and with suicide rates for children and young adults aged 10 to 24 years increasing by more than 50% between 2000 and 2021.2 “Our results indicate that depression screening was superior to suicide risk screening under most conditions for the specific purpose of identifying patients who would subsequently attempt suicide, with the PHQ-9 performing the best and screening for ‘thoughts of killing yourself’ within the past week or past month performing the worst,” the investigators concluded. “Use of the PHQ-9 instead of the PHQ-2 could markedly improve the identification of at-risk patients in primary care, particularly those who are most likely to attempt suicide in the short term.” Related Article: Suicide Prevention

“Over 32 weeks of follow-up, the percentage of patients with remission, the percentage of patients with a treatment response, and the change in the MADRS score from baseline favored esketamine nasal spray.” A long-term clinical trial comparing esketamine CIII nasal spray with quetiapine extended release found that esketamine had greater success with inducing remission in participants with treatment-resistant major depressive disorder (MDD). The clinical trial—a randomized, open-label, active-controlled, rater-blinded, phase 3b study called ESCAPE-TRD—aimed to evaluate the efficacy of flexibly dosed esketamine nasal spray (Johnson & Johnson’s Spravato) in comparison with the efficacy of quetiapine extended release, both when combined with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI), in patients with treatment-resistant MDD.1 The primary end point of the study was remission, which the investigators defined as a score of 10 or lower on the Montgomery-Åsberg Depression Rating Scale (MADRS) at week 8, and the key secondary end point of the study was for participants not to relapse through week 32 after achieving remission at week 8.2 The investigators assigned 336 participants to the esketamine group and 340 participants to the quetiapine group. Upon analysis at week 8, they noted that more participants in the esketamine group had achieved remission when compared with participants in the quetiapine group (91 of 336 participants [27.1%] vs 60 of 340 participants [17.6%]; P=0.003).2 They also noted that 73 of the 336 (21.7%) participants in the esketamine group experienced no relapse through week 32 after remission at week 8, compared with 48 of 340 (14.1%) participants in the quetiapine group.2 Overall, the participants treated with esketamine nasal spray were 1.54 times as likely to reach remission at week 8 than the participants treated with quetiapine extended release.3 “Over 32 weeks of follow-up, the percentage of patients with remission, the percentage of patients with a treatment response, and the change in the MADRS score from baseline favored esketamine nasal spray,” the investigators wrote. “The adverse events were consistent with the established safety profiles of the trial treatments.”2' Treatment-emergent adverse events were observed in 92% of participants treated with esketamine nasal spray and in 78% of participants treated with quetiapine extended release, and 4.2% of participants treated with esketamine nasal spray and 11% of patients treated with quetiapine extended release discontinued medication due to 1 or more adverse event(s).3 The results from ESCAPE-TRD were announced by Spravato (esketamine) developer Johnson & Johnson and published in The New England Journal of Medicine.4 The study published in The New England Journal of Medicine describes the full data gathered in ESCAPE-TRD for the first time.3 “This large head-to-head trial gives physicians important data to consider in the management of treatment-resistant depression by comparing the short- and long-term effectiveness of Spravato to an oral antipsychotic,” said Reina Benabou, MD, PhD, vice president of medical affairs, neuroscience, at Janssen Scientific Affairs, LLC, in a press release. “Spravato offers patients an additional important option. It is critical that those living with this difficult-to-treat condition have choices to consider for their personal treatment plans, in discussion with their health care providers.”3 Related Article: Study Compares Work Productivity Loss, Cost Savings in Esketamine Nasal Spray vs Quetiapine Extended-Release for TRD

Is psilocybin a viable treatment for MDD? Researchers performed a phase 2, double blind trial of single-dose psilocybin in patients with treatment resistant depression. Psilocybin is a hallucinogenic chemical in certain mushrooms known as magic mushrooms. Eating mushrooms that contain psilocybin can have a variety of effects, ranging from euphoria to hallucinations. CASE VIGNETTE “Mr Mora” is a 39-year-old African American male with a history of recurrent, severe major depressive disorder (MDD) without psychosis. The onset of his depression was in early adolescence. Mr Mora previously failed trials of sertraline, bupropion, venlafaxine, nortriptyline, lithium, aripiprazole, and perphenazine. He also sees a psychotherapist for monthly cognitive-behavioral therapy. His current regimen includes fluoxetine 80 mg daily and amphetamine-dextroamphetamine extended-release 20 mg daily, to which he has had a partial response. At his most recent outpatient clinic visit, Mr Mora asks whether he is a candidate for treatment with adjunctive psychedelics, and specifically asks about psilocybin. As his psychiatrist, how would you respond? Treatment-resistant depression (TRD) has been defined as failure of 2 different courses of treatment. Patients with TRD have greater duration of illness, illness severity, disability, physical illness, suicide risk, and economic costs than patients with treatment-responsive depression. Psilocybin has demonstrated antidepressant properties in patients with MDD and TRD.1-3 The Current Study Goodwin and colleagues4 conducted a phase 2 double-blind, dose-finding, parallel group, randomized controlled trial. The study sponsor, COMPASS Pathfinder, designed and funded the trial and provided a proprietary pharmaceutical-grade synthetic form of psilocybin (COMP360). An independent contract research organization (MedAvante-ProPhase) was responsible for assessment of participants using the Montgomery-Åsberg Rating Scale (MADRS), performed by trained, blinded, remote raters, as well as the statistical analyses. The sponsor performed data interpretation and post-hoc statistical analyses and paid for professional writing assistance for the first draft of the manuscript. The authors recruited adults aged 18 years or older with TRD, defined as a depressive episode without psychotic features, with failure to respond to an adequate dose and duration (≥ 8 weeks) of 2 to 4 pharmacological treatments for the current episode. The trial was conducted at 22 sites in Europe and North America between March 2019 and September 2021. Eligible participants completed a 3- to 6-week run-in period, during which antidepressants and medications affecting the central nervous system (CNS) were tapered and discontinued at least 2 weeks before the baseline visit. During this period, the participants met at least 3 times with a study therapist. Patients were randomized 1:1:1 to a single dose of psilocybin 25 mg, 10 mg, or 1 mg (control). The administration session lasted 6 to 8 hours and was accompanied by a lead therapist. Blood pressure was continuously monitored. Participants wore eyeshades and headphones with a specifically designed music playlist. The trial followed participants for 12 weeks after treatment, including 2 post-treatment integration sessions. The primary efficacy endpoint was the change in MADRS from baseline (day -1) to week 3 in the 25 mg- and 10 mg-dose groups compared to the 1-mg dose. Secondary endpoints were the proportion of responders (≥ 50% improvement in MADRS total score) and remitters (MADRS total score ≤ 10) at week 3, and sustained response (week 3 response maintained through week 12). Safety assessments included evaluation of adverse events, the Columbia Suicide Severity Rating Scale, vitals signs, clinical laboratory tests, and electrocardiogram (ECG). The authors calculated that a sample of 216 participants (72/group) would have 90% power to detect a 6-point difference in the mean change in the MADRS total score from baseline to week 3. Efficacy analyses were performed in the modified intention-to-treat analysis set. The primary efficacy endpoint (change in MADRS total score) was evaluated using mixed model for repeated measures analysis. Response and remission were analyzed using generalized linear mixed models, and sustained response was analyzed using binary logistic regression. A total of 428 participants were screened, and 233 were randomized and received psilocybin treatment (79 25-mg, 75 10-mg, 79 1-mg). The mean participant age was 40 years, 52% of participants were female, and 92% were white. Two-thirds of participants were receiving antidepressant treatment, and mean MADRS scores were 32 to 33 at baseline. The least-squares mean change from baseline to week 3 in the MADRS total score was -12.0 in the 25-mg group, -7.9 in the 10-mg group, and -5.4 in the 1-mg group. This change was statistically significant for the 25- versus 1-mg, but not the 10- versus 1-mg groups. The incidence of response was 37% in the 25-mg group, 19% in the 10-mg group, and 18% in the 1-mg group, corresponding to a 2.9-fold increased odds of response in the 25- versus 1-mg groups. The incidence of remission was 29% in the 25-mg group, 9% in the 10-mg group, and 8% in the 1-mg group, corresponding to a 4.8-fold increased odds of response in the 25- versus 1-mg groups. The incidence of sustained remission was 20% in the 25-mg group, 5% in the 10-mg group, and 10% in the 1-mg group, which was not statistically significant between groups. Adverse events occurred in 84% in the 25-mg group, 75% in the 10-mg group, and 72% in the 1-mg group, which was not statistically significant between groups. The most frequent adverse events on the day of administration were headache, nausea, dizziness, and fatigue. Serious adverse events from day 2 to week 3 in the 25- and 10-mg groups included suicidal ideation (n=4), non-suicidal self-injurious behaviors (n=3), and hospitalization for depression (n=1). There were no serious adverse events in the 1-mg group during this period. There were no clinically significant changes in vital signs, clinical laboratory tests, or ECG. Study Conclusions The authors concluded that the trial showed the feasibility of psilocybin monotherapy for up to 12 weeks in patients with TRD. The change from baseline to week 3 in MADRS total score was significantly better with 25-mg, but not 10-mg, versus the 1-mg dose. Reported adverse effects included headache, nausea, dizziness, and fatigue, as well as numerically higher suicidal ideation and self-injurious behavior in the 25- and 10-mg groups. Study limitations include the lack of an active comparator, the lack of an ethnically diverse participant sample, and the exclusion of participants at clinically significant risk for suicide. The intensity of the acute subjective effects of 25- and 10-mg psilocybin may have reduced the effective of trial blinding, although the ability of participants to guess their dose assignment was not assessed. The Bottom Line A single dose of 25 mg versus 1 mg psilocybin significantly reduced depression scores over 3 weeks in patients with TRD. Larger and longer trials, including comparisons with existing treatments, are required to determine the efficacy and safety of psilocybin in this patient population. Dr Miller is a professor in the Department of Psychiatry and Health Behavior at Augusta University in Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric Times®. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute. Related Articles: Single Psilocybin Dose Again Shows Major Depression Benefit Psilocybin Reduces Symptoms, Disability in Major Depression Psilocybin Plus SSRIs for Treatment-Resistant Major Depression

The judge ordered me to undergo a psychiatric evaluation. I’d only been an attorney for just under five years and now a judge was ordering me to be tested. The legal brouhaha I’d managed to get myself in isn’t important, but the reason the judge ordered the psych eval is: I had had the temerity to challenge the local legal establishment by refusing to submit to what it wanted me to do. Looking back, I think I presented the judge with a severe case of cognitive dissonance, which he felt he could most easily solve if a psychiatrist declared me to be mentally ill. To the judge’s dismay, the evaluation came back with a finding of sanity along with an observation that some might see as a backhanded compliment: “Mr. Winward appears to be particularly well-suited to the practice of law.” I ultimately resolved that legal problem, but only because I hired an excellent attorney to represent me. As the order for undergoing a psych evaluation suggested, I wasn’t being a very good advocate for myself. My attorney, however, was effective. He knew the system, knew the available psychiatrists, and used that knowledge to get me, his client, the most favorable result. After this experience, I went on to practice law for another 30+ years, but with even more certainty that the old saying “Every man who is his own lawyer, has a fool for a client” is well-grounded in reality. Effective advocacy for a cause can’t come from the person who is caught in the system’s crosshairs. After over a decade of helping my wife with both drug withdrawal and recovery from their damaging effects, I’ve had to learn to adapt and apply ideas of effective advocacy to help her more successfully navigate the medical system, a journey that remains ongoing. For those who are currently helping loved ones through prescribed harm, I hope these insights will be useful. For those who are suffering from drug injury, finding someone who can advocate for or with you can be helpful. This is such a difficult process and no one should have to do it alone. I also understand that too many do face the system alone, and while not ideal, the following strategies will still provide insight into how to better navigate the medical system. Effective advocates need to be present to advocate. I don’t know if I can point to the exact time I became a constant presence at J.A.’s doctor appointments. I know that since she was diagnosed with drug-induced akathisia in 2016, I have attended almost every doctor appointment with her. It’s only been in the last year that I have not gone with her to every appointment, but these are with doctors we know and trust. Otherwise, the HIPAA release form is signed and I’m party to all of the appointments. Mental health diagnoses are only obtained through patient self-reporting. No blood or other diagnostic tests show a DSM diagnosis and time with the medical professional is limited. Unlike an attorney, an advocate in the psychiatric realm is a key witness for the patient and his or her experience. A third-party observer of behavior and symptoms carries a weight that the doctor cannot easily ignore. Having a third-party witness diminishes a doctor’s ability to pick and choose between the patient’s self-reported symptoms in making a treatment decision. Determining relevant information is always an important part of any doctor visit. For example, I have taken J.A. to the emergency room only twice over the years for problems caused by psychiatric medications. In 2011, I took her to the hospital because I didn’t know what to do. We had only been married three years and were both still operating under the mistaken assumption that she had bipolar disorder. Based on experiences I would have later, the doctor in the ER that day was phenomenal. He quickly figured out that J.A.’s symptoms were caused by stopping the SNRI, Pristiq, cold turkey after a prescription ran out and wasn’t refilled. I’m grateful that this ER doctor was so competent and understanding. In part, it was my good experience with him that created a baseline of expectations for what should be appropriate ER protocol and behavior. The second time I took J.A. to the emergency room was when she was experiencing horrific withdrawal symptoms from the atypical antipsychotic Latuda. This ER visit was a completely different experience than our visit in 2011. In hindsight, we had tapered from the drug too quickly, and the withdrawal effects had become unmanageable. Tardive dystonia froze the sternocleidomastoid muscles in her neck and she wore Icy Hot patches night and day across the back of her neck to try to moderate the pain. No amount of stretching, relaxation, or therapy would release the muscles. Her neck was so frozen she couldn’t drive a car because it required her whole body to move just to turn her head. Oromandibular dystonia caused her mouth to pop open uncontrollably and her limbs were dyskinetic. The akathisia was so bad, I had to take almost three months off of work just to be home with her to keep her safe. We had an appointment scheduled with a neurologist, but it was months away. Finally, when things had gotten so bad we were at a loss, both her psychiatrist and neuropsychologist told us to go to the emergency room. I handled a lot of the intake, explaining that J.A. was suffering from medication withdrawal. I also explained that her two treating physicians had recommended we go to the ER in order to get more rapid access to a neurologist. The ER doctor was at a loss and in my recollection, she was at least sympathetic as to why we were there. Finally, they called the on-call neurologist, who seemed unhappy that she had been summoned. Her approach and exam of J.A. was curt, perfunctory, and dismissive. As the ER visit started spiraling out of control, some of the steps we had taken prior to the visit paid off. Effective advocacy avoids irrelevant information. An important part of advocacy is also to remember the goal associated with the treatment you are seeking and not bring up irrelevant information that could be harmful. J.A. and I both knew by 2017 that the ER was a dangerous place for anything deemed “psychiatric,” so it was a conscious decision before ever leaving for the hospital that neither of us would talk about the most pressing concern: the daily suicidality that the withdrawal had created. J.A.’s previous struggle with drug-induced suicidality had blossomed into a full-blown offensive once she’d completely withdrawn. Prior to going to the ER, we specifically made the decision not to address the suicidality. We were at the hospital only to address the debilitating physical symptoms of withdrawal. This was a decision we made only after a lot of difficult experiences and a very concerted effort with therapists and doctors to put systems in place in our own lives that were protective. It’s vital to take the suicidality created by these drugs seriously. I also understand that there may be times when an ER visit is the only option. The message I want to convey is to stick to the information that is relevant in the moment to avoid any additional unnecessary, even more harmful medical interventions. Back in the ER as I watched the perfunctory neurological assessment, I knew that dystonia, dyskinesia, and akathisia weren’t typical neurological problems. I also knew a basic neurological exam would not show much of anything. The neurologist quickly made a diagnosis of “conversion disorder.” Sometimes when you are advocating for a client in court, things go epically wrong and as an advocate, you have to scramble to make the best of a bad situation. When the neurologist said “conversion disorder” I knew I was in a comparable situation. We had only gone to the ER out of desperation, and doctors we’d trusted had sent us there, but our trust in the medical system was already severely damaged. All this had culminated in the neurologist saying in medical-speak, right to my wife’s face, “It’s all in your head.” I knew then I needed to start advocating, not for medical treatment, but for the days, weeks, and months ahead. In that moment, my advocacy shifted from trying to get medical help to mitigating medical ignorance by letting J.A. know she wasn’t alone. With the suicidality element pressing in the back of my mind, I knew the matter had suddenly become one of life and death. “What?” I blurted out as soon as I heard ‘conversion disorder.’ “Can’t you feel her neck? I’ve lifted weights my entire life and I’ve never been able to get my neck muscles that hard and rigid and her neck has been like that for almost three months.” The neurologist shrugged and said in a diffident tone, “Stiff neck.” At that point I kind of lost it, but this was partly on purpose and strategic. “You’ve got to be kidding me!” I said. “I’m an attorney. I’m not a medical doctor, but I’ve been living with the impact of these drugs every day and have seen the changes. How is it that I know more about this than you do? You’re not helping and you clearly don’t know what to do. Maybe you should learn more about this so you can do your job.” I stopped my tirade short of security being called, but it was important to let J.A. know in a very public way that I wasn’t buying anything this doctor was saying. This had been a point of conflict with us prior to the ER visit. Even though I was attending doctor appointments with her, I would often be more deferential to the doctors than J.A. would have liked. From my vantage point, my deference was strategic. While it might have felt justified or even righteous to just rage at everyone in the medical community, that wouldn’t have accomplished what we ultimately wanted, which was to find the best treatment options available to us. Instead, I tried to pick my battles while focusing on our end goals. It took some time and patience to clarify with J.A. that my deference and silence did not mean I was in agreement with her doctors. I can’t stress how important it was for us to communicate with each other and get on the same page about this different approach. We found emotion-focused therapy (EFT) for couples very helpful in navigating the emotional swings that come with this process. When fighting the medical establishment, the last thing you or your injured loved one need is to be fighting each other. Her doctor’s office was about 35 minutes away, and so before every appointment, we began using the travel time to establish our objectives and focus our joint efforts on meeting those objectives, which made for significantly better appointments. It also improved our ability to communicate at home, giving us shared, foundational goals that we could revisit during the more challenging times. After my outburst at the ER, the only option they could offer was a Valium prescription, which we turned down. We returned home emotionally beat up and feeling abandoned by the medical community. The one consolation my outburst netted us was a contrite call from Patient Services to evaluate our “negative emergency room experience.” The sad truth is that if the outburst had come from J.A., it’s unlikely we would have received that call. If your loved one has suffered from psychiatric drug harm, they are going to feel that emotional pummeling every single day. It isn’t fair and it isn’t right, but you must keep the focus on what can be done and what can be controlled. I can’t overstate how difficult this is for everyone. Effective advocacy requires advocating within the system and learning that system. My biggest learning curve over the past fifteen years has been understanding the psychiatric medical system. In the beginning, I wasn’t overly familiar with the medications, the side effects, the troubling history, the schisms, disputes, and power struggles. I went in pretty much blind. The main thing I had going for me was my own experience working in my capacity as a professional. Doctors and lawyers carry a certain social gravitas with their positions, so I was at least familiar with interacting with the general public on the other side of the professional divide. I brought this awareness to my interactions with J.A.’s doctors. The fields of law and medicine are broad in scope and depth. No single person can hope to understand all of the information. The first few years of my legal practice I spent doing a more general practice. The breadth and variation of the cases often made me feel out of my depth, leaving a nagging sense that there might be something I was missing. As a result, I specialized in consumer bankruptcy law and the surprising areas of the law gradually became less frequent. Because of this, my comfort in my area of expertise greatly increased as uncertainty dwindled through repetition and experience, but whenever I approached the fringes of my expertise, uncertainty immediately returned. Uncertainty is not something that professionals enjoy, because any esteem that comes from the societal position also comes, rightfully, with the demand for expertise. When you are interacting with medical professionals, remember that they are first human beings whose occupation and client/patient expectations demand a high level of certainty and competence. Doctors have a dual objective: first, to be authoritative and knowledgeable, and second, to provide help and assistance to the patient. If you or your loved one introduce uncertainty into your interactions with a medical provider, you are attacking both of the physician’s primary objectives, which can compromise your goals. The role of the doctor is closest to the role of a judge in the law. The doctor has the ultimate authority over which medications and treatments are appropriate. One of the hardest things for most attorneys to do is treat judges as human beings. On a theoretical level, we expect the judge to be impartial and clear-headed, looking only at the law, but they are human. Studies have shown that sentences are more favorable after a good lunch, but the human aspect can also make the judge’s decisions feel suspect. Advocacy always feels fraught when you cannot control the outcome and every judge rules differently. Each physician will also be different, ranging from those who are more open-minded to those who have the “Please Don’t Confuse Your Google Search With My Medical Degree” mug on their desks. In the law, we say, “know your judge.” The same rule applies here: If you are interacting with medical professionals, know your Doc. In order to know your doctor, though, it will require a little bit of research and googling, not on your loved one’s condition, but on the doctor and the medications that are being prescribed. I wasn’t around when J.A. was first prescribed psychiatric drugs, nor were the information sources I’m going to reference, but if I had been there with the information that is available now and knowing what we know now, it is unlikely she would have ever taken the medication in the first place. Why do I say this? Let’s walk through it. First, I would have gone to Open Payments Data website and checked out the doctor’s name. I would have found out that the doctor she was seeing was on the speaking circuit for the makers of Celexa, Lexapro, Vyvanse, Abilify, and Latuda. As a speaker for these pharmaceutical companies, he made just over $900,000 from 2015 to 2021 as a part-time gig. If it hadn’t been for the pandemic, his side income from pharmaceutical companies would have easily topped a million dollars in just six years. You can also get older data at Pro Publica’s Dollar for Docs. I prefer the older data, because it spelled out which drugs the doctor was actually promoting. The new data requires a little more digging. If you find out your doctor is being paid by the pharmaceutical companies, find a new doctor. It is easier than changing a judge in a legal case and you can’t go into the healing process with a biased doctor. For example, our new doctor, in the same timeframe, left managed health care to practice independently, and from 2015 to 2021, took a grand total of $12.16 from pharmaceutical companies. Just remember, whether you like it or not, the doctor is the ultimate decision maker on prescribed medications, so it is important to know your doctor from the outset. If they are on a pharmaceutical payroll while in private practice, their obligations to their patients will be compromised, even if the doctor is unaware of it, because that’s how implicit bias works. Another problem you will have in advocating for your loved one with a psychiatrist is the psychiatric system itself. Psychiatry is a medical specialty, but it is a medical specialty with a sordid past (and present). No longer providing therapy in most places, the sole role of the psychiatrist has narrowed to being a psychiatric-prescription dispenser. If you take that away from them, you are taking away the raison d’être for the doctor’s entire medical practice. Yet, effective advocates know we cannot say any of this to most psychiatrists, even good ones we trust. I’m approaching advocacy from the aspect of obtaining medical help in withdrawing from psychiatric medications, but the same principles apply to considering any new medications and even maintaining a current pharmaceutical regimen. Once you are as familiar as you can be with the doctor’s inherent biases, you can maneuver the visits toward the desired end goal. For example, because J.A. was tapering a specific drug, we requested a switch from time-release capsules to chewable tablets, which allowed us to cut the pills and manage the drops more gradually. J.A. and I have had the good fortune to work with doctors who listen to us, yet I temper that statement with the knowledge that we keep each doctor within a designated sphere and don’t look to any one doctor or specialty as a cure-all. Effective advocacy requires proper choice of venue. As I said earlier, professionals abhor uncertainty. The medical profession is drawn up into specialties, but for medication withdrawal, our experience has been that you need a holistic approach. Attempting a holistic approach when dealing with a specialist carries with it some inherent uncertainty for everyone involved. Unfortunately, the injuries that come from psychiatric drugs don’t just impact mental functioning, they impact system-wide physiological functions as well. Over the years, besides meeting with psychiatrists, we’ve employed pain specialists, endocrinologists, general practitioners, audiologists, ME/CFS specialists, emergency room doctors, neurologists, a functional neurological rehab doctor, cognitive behavioral therapists, emotion focused therapists, neuropsychologists, physical therapists, nurse practitioners, and others that I’ve probably forgotten. Each has played a role in recovery, some positive, some neutral, and some negative. As we progress through the withdrawal journey, we tailor our presentation of what we feel we need, along with our progress, to each doctor according to his or her specialty. Psychiatric medications can wreak system-wide havoc on the body, but the endocrinologist doesn’t need to hear about that, she just needs to test thyroid function. The difficulty is in crafting a holistic approach from a fractionalized medical system. Focus on where you are, the doctor-venue that you find yourself in, and stick to the narrow range of what that doctor can do. Effective advocacy requires education, experimentation, and patience. In order to be an effective advocate, you have to know what is happening when you go into the doctor’s office. You have to know what the drugs do and what the side effects are. Don’t rely on the doctor to educate you. Read the medication labeling. Most psychotropic drugs come with massive documentation. Develop a relationship with your pharmacist. Pharmacists are extremely helpful in looking at drug effects and interactions with other medications. Read Robert Whitaker’s books, Mad in America and Anatomy of an Epidemic. Learn the drug types. In hindsight, I wish I’d known that I needed to learn all of these things sooner, but as soon as I was able to report negative drug effects to J.A.’s doctors, the approach to healing made a significant, positive shift. The education process to make it through psychiatric drug withdrawal remains ongoing. I read or listen to any book I can get my hands on that I think might help, even peripherally, and I’ve been doing that for years now. Right now I am reading A Straight Talking Introduction to Psychiatric Drugs: The Truth About How They Work and How to Come Off Them by Joanna Moncrieff and I wish I’d stumbled onto this book years sooner. This book distills in clear prose the foundational things you need to know about what each psychiatric drug does, as well as what someone is faced with when going through psychiatric drug withdrawal. I was wildly eclectic in searching for answers. Some things I came across spurred us to try things that completely failed. In J.A.’s earlier article, she compares drug harm to a van crashing and each passenger’s injuries being varied. This is why experimentation is so critical. Some things worked, some didn’t. Some approaches worked for a while and then stopped working. Some things we’ve come back to again and again. When something works, run with it, but remember, nothing is going to be as simple as just taking a pill. If your experience is anything like ours, the prescription cocktail J.A. found herself on was a direct result of doctors experimenting on dosages and medication types. Getting off the drugs is no different, only the withdrawal process ends up being experimentation in the other direction with a lot less support from the medical community. Effective advocacy requires developing lasting relationships. In my legal practice, knowing how opposing counsel will react and the strengths and deficits of our respective positions makes advocating for a positive result for a client much more likely. It also opens up negotiations for situations that can be mutually beneficial. It isn’t as glitzy as winning a court argument, but in general it is much more effective in almost all cases. Advocacy for family members within the realm of psychiatric medication harm is always more of a negotiation than a direct attack. Bundling up all of your evidence and printing out reams of paper explaining the research on drug harm or withdrawal effects to make a grand presentation to the doctor and win your family member’s case won’t work. First, you need to develop a relationship with your doctor and that only comes with time. It may also require switching doctors if there is no way to truly communicate or if they are unsupportive of your main objectives. The doctor needs to learn to trust you and your family member. Once that trust has been established, then options begin to open up that you can explore with the physician, but gaining trust is always the first important step, keeping in mind that trust is a two-way relationship. So, when a family member has been harmed by medications, helping them recreate trust is an important role of the advocate. The creation of trust between doctor and patient, the advocate and the patient, and the advocate and the doctor is necessary to achieve the desired goals and a better outcome for your loved one. Effective advocacy is a daily practice in an infinite game. When a case goes to court, the judge enters a ruling and there are clear winners and losers. A courtroom decision is an example of a finite game, a game in which there is a bounded conclusion. Advocating for a spouse or loved one with medical professionals rarely, if ever, has such a clear-cut conclusion. I found James P. Carse’s view of infinite games helpful in dealing with the shifting ground of the medical system. There is no standard set of rules and what rules are there can be subject to constant shifts and changes, but the objective is the same—relief, recovery, and better health for our loved ones. We must use all our wits and the experience at our disposal to keep events progressing in a way that makes healing more likely. The important aspect of the infinite game is to keep playing, even when there are setbacks. Advocacy is not just about medical professionals, though. You must also advocate with family members who don’t understand or who are not empathetic to what is happening. You must advocate with friends, neighbors, and employers. Intriguingly, probably the most important focus of your advocacy is letting your loved one know you support them. I strive constantly to listen and understand J.A.’s experiences. When we reach an understanding about what is happening and what can be done, my advocacy on her behalf improves. It is a daily practice, sometimes hourly, to remind ourselves of how far we’ve come, what works and what doesn’t, and what steps we can take to win the current day. Daily practice, perseverance, and focus is the only way to address and accomplish such a large task. Effective advocacy requires a working knowledge of drug harm and a keen focus on the battle at hand. The word “advocate” comes from the Latin advocare and it means to “add” a “voice.” My job as an advocate is to add a voice to J.A.’s suffering. The added voice is most effective when the speaker knows the true causes of the suffering. The voice must be raised, not just for the personal, but also for the broader systemic cry for compassionate and humane treatment with informed consent that more effectively avoids the dangers of psychotropic drugs. In this way advocacy is a two-track process. The physician’s office isn’t the place to launch a full-scale attack on psychiatry or demand systemic change. The main focus should be getting your family member the care they need. At times, J.A. and I have both struggled to keep our focus on the two different battles, but you can’t engage in battle when you are too wounded to fight. In large part, that is why it has taken us close to five years to begin writing about these experiences. Yet, the efforts of everyone here at Mad in America continue to be “added voices” we value as we continue to forge our path. Finally, the larger cause remains important for anyone adding their voice. As J.A. and I have both found, the larger cause allows us to transcend personal suffering to bring more power and strength to the collective voice of advocacy surrounding drug harm. It’s a voice we all must learn to use with and for our loved ones so they know they are not alone. Effective advocacy is vital to creating the optimal healing environment for everyone impacted by these drugs. *** Mad in America hosts blogs by a diverse group of writers. These posts are designed to serve as a public forum for a discussion—broadly speaking—of psychiatry and its treatments. The opinions expressed are the writers’ own. *** Mad in America has made some changes to the commenting process. You no longer need to login or create an account on our site to comment. The only information needed is your name, email and comment text. Comments made with an account prior to this change will remain visible on the site.

I wiped away tears and stared down at a deep gash in my arm as I typed. What I wrote would eventually become a blog post about my struggles with postpartum psychosis and suicidality. Even though I was in immense pain, I was hopeful that somehow my words might make someone else feel less alone. At least one in seven new parents develop postpartum depression and nearly 80% will suffer some form of depressive episode immediately following the birth of their child. Yet we continue to perpetuate the myth that new parenthood is universally the happiest time imaginable. For me, new parenthood was anything but. I nearly died. It was one of the hardest times of my life, and just when I was seeing light at the end of the tunnel, CPS came knocking at my door. In the saddest of ironies, the person who read my blog seven years ago and was responsible for Child Protective Services being called on me is currently writing publicly about the loss of her husband to suicide. She is telling the world that ultimately, it is a suicidal person’s responsibility to save themselves and that “personal accountability” is paramount for preventing suicide. She is a mental healthcare professional. She is also my sister-in-law. She caused tremendous harm to me and my family and is now causing further damage to anyone who is suicidal that might come across her writing. This is because what she is saying about her husband’s death is that it could have been prevented if only he had tried harder. Not only is this victim-blaming, but by leveraging her position as a mental health professional, she is perpetuating what has been dubbed “suicidism.” Alexandre Baril coined the term “suicidism” to describe the unique discrimination and marginalization suicidal people face. Suicidism intersects with ableism and sanism in important ways, insofar as most suicidal people are deemed “mentally unwell,” despite research indicating that while mental illness is a major risk factor, other precipitating causes, such as Adverse Childhood Experiences, psychological abuse, and marginalization play equally important roles. Suicidal persons are often criminalized as well. Saying someone “committed” suicide, for example, implies they perpetrated a crime, but against whom? Thieves victimize others but those who die by suicide are victims, not criminals. Thus, suicidologists have argued this terminology should not be used. Another important movement in suicide research is “postvention.” Rather than focusing on prevention strategies, many of which Baril rightly notes are suicidist, we need to pay more attention to how we frame suicide after it’s happened. Postmortem speculations about what led a person to suicide tend to pathologize victims. The person was “out of their mind” or must have been mentally unwell to do such a thing. As many advocates have argued, this is harmful, because it assumes no person could rationally contemplate dying: no “sane” person chooses to die, their “mental illness” did that to them. These sorts of statements subtly imply a suicidal person is a patient rather than an agent, and thus is incapable of authorship over their actions. But perhaps the most harmful ‘help’ offered is insisting that suicidal people reach out and “save themselves” without also recognizing how unsafe it can be to do so. Often, when people reach out — by calling a hotline or confiding in someone — they are punished. Suicidologists have warned against the commonly touted ‘solutions’, such as the 988 hotline, and have noted the likelihood of police intervention when contacting these services. Imagine calling a hotline hoping it would save your life, only to find yourself involuntarily hospitalized and drugged. Or worse, the police show up, and if you happen to be in crisis while also not being white, your chances of being shot dead are alarmingly high. For those who are hospitalized against their consent, their chances of dying by suicide after being released actually increase. In short, many intervention strategies are violence disguised as help. The irony in my case is that I did reach out. I blogged and shared that blog with a close-knit group of supposedly trustworthy family and friends. During my pregnancy, I knew I would need significant support to remain mentally healthy, so I proactively put those supports in place. I was doing everything right, according to my sister-in-law’s recent recommendations, namely, “recognizing my vulnerabilities” and holding myself accountable for my well-being. I told the truth: that I wanted to die. Rather than reach back toward me to help, she set off a chain of events that resulted in CPS knocking on my door. My family was terrorized by this for nearly two months until it was finally settled that I posed no risk to my child. To this day, I have panic attacks and nightmares, and when the doorbell rings, I often shriek in fear or drop my coffee all over the floor. This is textbook post-traumatic stress. My suicidality did not begin with my first pregnancy. I can remember planning to kill myself at age 16 and taking active steps to do so. I’ve also struggled with anorexia most of my life, which I later learned is the most lethal mental illness. Nevertheless, I’ve always managed to find coping mechanisms that keep me alive and in a mostly healthy relationship with food. I do triathlons and open water marathons and generally focus on goals I can see myself fulfilling in the future. But it’s not an exaggeration to say that most of my life is spent finding ways not to think about killing myself. This battle with suicidality reared its ugly head after the birth of my first child. The birth was incredibly long and traumatic, 60 hours in total, and ended in an emergency C-section, which I had desperately tried to avoid. I knew being sliced open would only exacerbate my body issues. Then there was the sleep deprivation. Three days of labor that resulted in a thankfully incredibly healthy new baby boy, did not result in much-needed sleep, as any new parent will know. A few weeks after his birth, I found myself hallucinating, having intrusive thoughts, and cutting myself. Even when I had a chance to sleep, I didn’t. I would sit in the dark in the living room alone, while my baby slept in the bedroom with my partner. I would sit there with a drink in hand, rocking back and forth, trying everything I could to shake it: the thought that I would be better off dead. One night like this, I penned a letter to my child and began making my plans. My partner found me early the next morning at my computer, with blood on my arm from a deep wound I’d inflicted. He encouraged me very strongly to go see someone. Suffice it to say, I’m a hard sell when it comes to entrusting my mental well-being with mental health professionals. Mostly, it’s the lack of scientific rigor in psychology that makes me skeptical, but this is not the essay for that discussion. There are plenty of books and articles out there that delve into all that. I’ve always been ambivalent about assuming any labels, primarily because I’ve received so many. Depending on the doctor, it can range from OCD, to generalized anxiety disorder, to bipolar, and I have even been diagnosed by one therapist as autistic. A psychologist once told me to pick a diagnosis so she could properly code for insurance. In short, I have a healthy dose of skepticism regarding the mental healthcare profession. Nevertheless, I begrudgingly went to see a psychiatrist and even more begrudgingly took the meds she prescribed. Immediately, I was able to sleep. My hypervigilance abated. With help, I eventually weaned myself off the SSRI I was taking, and looking back, I am glad I did. Research consistently links SSRIs with all sorts of complications, not least of which is a risk for suicide. I say all this with the very important caveat: if these drugs help you, by all means, take them. I did. I am pretty sure I would not have survived without them. There is no one-size-fits-all model for mental health and there certainly is not a consensus about the effectiveness of most psychotropic drugs. So there I was, feeling like myself again, looking at my beautiful child. I had just successfully taken a trip with him to a friend’s wedding. My partner and I were amazed to find that our nine-week-old slept through the night for the first time, in a hotel, seven hours from our home. We didn’t question it. We slept. Glorious, back-to-back hours of sleep. We danced at the reception. The pictures are some of my favorite images of our family. Our son was dressed in a little conductor outfit since the wedding was in an old train station. We were all so happy. Life finally seemed like it was worth living again. I was reminiscing about this great weekend while nursing him upstairs in the bedroom and that’s when I heard the doorbell ring. A few minutes later, my partner was in the doorway telling me I had to get down there. What followed was a nightmare that I am forced to relive whenever it chooses to push itself to the forefront of my thoughts. If CPS has never invaded your life, you are fortunate. Apparently all suicidal people are doing illegal drugs, because I was forced to pee in a cup, in my own bathroom, in front of the caseworkers. They told me they had 45 days to substantiate or drop the charges against me. After they riffled through my belongings and demanded to see how much milk I had pumped for my baby, I asked them who called. They told me that information is confidential, but they said it was because of a blog. I knew someone very close to me had filed the report. As expected, the allegations were unsubstantiated. But DCFS took the full 45 days to officially close the case, even though all they had to do was call my psychiatrist and it would have been settled. I was at a conference two days before their deadline, chairing a session, and my phone was buzzing incessantly. I had to leave the room to take the call because I knew it was them. They were trying to get a hold of my psychiatrist, on a Friday afternoon, and wanted me to help. I was flabbergasted. “So you are telling me you are just now trying to interview her?” I asked, exasperatedly. We requested a copy of the report once the case was closed and we were appalled by the sheer incompetence of the Arkansas DCFS. The colleagues I had suggested as references were all listed on the report as having been interviewed. Their responses sounded bizarre to me, so I called each of them and found out that they were never actually interviewed. The report also listed an interview with someone else, a person neither my partner nor I knew, and she claimed she was worried about her “friend’s” blog. It turns out she was a social worker employed in the same office as my partner’s sister. This is how we found out that my sister-in-law had a hand in causing the terror of CPS invading our lives. There isn’t really a word to convey how angry we were. I made vague comments on social media about being betrayed by family and how enraged I was, but never mentioned anyone by name. I needed an outlet for my feelings. Rather than try to understand this, my partner’s family began a smear campaign against me. His mom jumped in to tell me I was unfairly judging their “loving” family. This is the same woman who, weeks prior, had written an angry post directed at whoever did this: “Just let me get my hands on you. Nothing meaner than an angry grandma. You had no grounds or sensibility. Shame on you — hope it comes right back at you!” When she found out it was her daughter, however, I became the enemy. She even had the gall to tell me that “CPS only investigates the most serious cases,” which is patently false — CPS investigates every call they receive — but also, this contradicted her earlier claim that there were no grounds for the call in the first place. I could write a novella about the gaslighting and moving of goalposts that transpired in an attempt to frame me as the unhinged bitch who deserved what happened to her, but there is no point. I will forever be the scapegoat in the story they tell themselves in an attempt to avoid the truth. But I know truth. And I have receipts. Today, I realize my anger was a perfectly normal reaction to completely abnormal and abusive treatment, but back then, I saw my partner suffering, and it broke my heart. His sister did apologize, but her story about how my blog landed in the hands of that social worker never sat well with us, and today, seeing what she writes, her apology seems as hollow as the platitudes she invokes. Nevertheless, I genuinely wanted to allow my children to have relationships with aunts and uncles and cousins. I am an adoptee, and the product of a closed adoption, so I was involuntarily estranged from my own genetic family for most of my life. It is not a situation I would inflict on anyone, unless it was the only way to ensure their safety. Thus, I tried to bury it, for my partner and my children. But dust swept under a rug doesn’t magically disappear. It’s just hidden temporarily. It’s now been eight months since my sister-in-law’s husband died by suicide. When I learned it happened, my heart broke, for her, for her kids, but most of all, for him. A fellow suicidal person who did not survive. It is a tragedy and I would like to think it was preventable, but I cannot say this with confidence. I know that when I was at the height of my postpartum crisis, I was not delusional or irrational. Hopeless, yes, but my mind was clear and I had a well-reasoned path to end my pain. I did not want to be rescued or saved. I wanted to stop hurting. I have no idea what my brother-in-law was feeling in those moments, days, or weeks leading up to his death. But I know he died alone, with no one holding his hand, with no proper goodbyes, and likely believing his family would be better off without him. My sister-in-law states that if her husband had taken early steps to prevent his own spiraling into despair, then maybe he would never have reached such a helpless state. This is victim-blaming. For one, he was on medication, so he was trying to do something about his mental health, but also, it’s not entirely clear that depression is what caused this. Their marriage was acrimonious, and by her own admission, they were headed for divorce. I don’t want to speculate beyond what I know to be true, but it’s not wild conjecture to assume that there were discussions of custody and other anxiety-inducing and depressing conversations. To say it was “his” depression that caused this overlooks the material conditions that might have contributed to his desire to die. I also cannot help but think about how he knew what happened to me when I reached out. He saw what his wife, a clinical psychologist, did when I told the truth about wanting to die. It’s not unreasonable to think he might not have felt safe reaching out. Nevertheless, she touts her credentials in the wake of his death, stating false or outdated claims, such as that “the majority of people who die by suicide never ever communicate their intentions.” In reality, many suicidal people communicate their intent before dying, with some studies suggesting as many as 68% of victims do so. Moreover, we have to consider that communicating intent can take many forms, and hence, many researchers note that there are likely far more cries for help than their studies indicate. Regardless, this misinformation she is sharing, coupled with her insistence that there is no way she could have seen this coming, is troubling, and frankly, harmful. Causing harm and refusing to be held accountable for it seems to be a theme in my partner’s immediate family. When I was at my lowest, not one of them checked in on me to see if I was managing okay. Knowing I had tried to kill myself, none of them said “I’m so glad you are still here, because you matter.” It’s easy to tell a dead person they mattered. Humans are great at writing eulogies. But we are shit at making people feel like they matter while they are alive. I’m not saying I think my brother-in-law was made to feel like he didn’t matter, but to leave that unexplored as a possibility is to do a disservice to him as a human being. He deserved to be heard. He still does. To publicly proclaim that suicidal persons are responsible for their own rescue is to completely disregard what real despair feels like. Perhaps this is why, as Baril and others argue, it’s time we stop centering non-suicidal persons in discussions of suicidality. If you have never known what it’s like to want to die and to actively seek that out in earnest, then maybe you don’t have much insight into what a person in that state ought to be doing. Maybe, if folks quit talking about experiences they have never lived, others who are actually living those things would have space to share their stories, without shame, and without the interventions of policing systems. Perhaps, ironically, lives could be saved if we started truly hearing the ones who say they don’t want to be saved. I didn’t want to be saved. I believed it was better to save my family from me. Whenever I’ve struggled with thoughts of ending my life, the ideas running through my mind are not “help!” or “I wish someone would save me from myself!” It’s mostly relief, knowing that if I go, my children will not have to suffer because of my incompetence as a mom. Where on earth would I get that idea, you ask? It didn’t just spring forth from a deep well within me, I assure you. The world is fucking rough, and it’s especially rough on new moms, as I began this essay discussing. Today, as I write, it is hard to imagine looking at my children and thinking they’d be better off without me, but I vividly remember having those feelings in the moment. And guess what? Struggling with thoughts of suicide doesn’t make you selfish, or delusional, or a bad parent. Ironically, the last lines of the letter I wrote to my son seven years ago read: “I love you so much and want nothing but your happiness. Finally, I found a reason to be unselfish. Thank you for that. I love you, my little Bigfoot. Be kind. Be thoughtful. Be happy.” I am not sorry I blogged about being suicidal. I am sorry that those who should have supported me most chose instead to turn their backs on me and allow me and my family to suffer even more at the hands of the family-policing industrial complex. I am sorry they continue to perpetuate suicidist marginalization by speaking for a victim of suicide without his consent and by washing over the damage they have done and continue to do. Suicidal people exist, and yet we do not. This is because, in the minds of non-suicidal people, we are either dead, or we are one of them. Suicide has either claimed us, or we are “cured,” the thought of dying never again entering our mad minds. But we are here. We live in underground networks of secrecy, because we don’t want to be found out, lest we be subjected to suicidist violence. However, we must be heard. It is time to stop rendering living suicidal people voiceless, and to center them in discussions of what it’s like to experience suicidality. Proximity to it does not count, either. Much like adoption, unless you are adopted, you simply do not understand what it’s like to be adopted. Suicide rates have not declined over the last decade. In fact, they are on the rise among various demographics. All the different approaches to prevention, from the biological and social models, to the social justice approach, suffer from a common problem: silencing suicidal people. Thus, suicidism prevails. Suicide prevention regimes are steeped in it because people who have no lived experience with suicidality talk over those of us who do. I hope, for my brother-in-law’s sake, and for all others out there, both living and deceased, who have experienced suicidality, that the mic gets passed one day soon. You deserve to speak. But more importantly, you deserve to be listened to with care. *** Mad in America hosts blogs by a diverse group of writers. These posts are designed to serve as a public forum for a discussion—broadly speaking—of psychiatry and its treatments. The opinions expressed are the writers’ own. *** Mad in America has made some changes to the commenting process. You no longer need to login or create an account on our site to comment. The only information needed is your name, email and comment text. Comments made with an account prior to this change will remain visible on the site. Related Article: Suicide Prevention Suicide Prevention Must Expand Beyond Crisis Intervention

In a new study in JAMA Psychiatry, researchers found that children born to mothers who used SSRIs during pregnancy had reduced brain volume in multiple areas. Most brain volume reductions were still there at the follow-up when the kids were 15 years old. The researchers write that the affected areas of the brain are theorized to be involved in emotion regulation. “The results of this cohort study suggest that prenatal SSRI exposure may be associated with altered developmental trajectories of brain regions involved in emotional regulation in offspring,” the researchers write. The researchers were led by Dogukan Koc at Erasmus University Rotterdam, the Netherlands. This was part of Generation R, a population-based study in Rotterdam. The study included 3,198 mothers with a delivery date between April 1, 2002, and January 31, 2006, and the children were followed with three brain scans over time, the last of which occurred when they were 15. To account for factors such as the effect of underlying maternal depression and when, specifically, the mothers used antidepressants, the researchers split the cohort into five groups. There were 41 with SSRI use during pregnancy, 77 who only used SSRIs before pregnancy, 257 who did not use SSRIs but had depressive symptoms during pregnancy, 74 who had depressive symptoms only after giving birth, and 2,749 controls who had neither depressive symptoms nor SSRI use. According to the researchers, there was a “persistent association between prenatal SSRI exposure and less cortical volumes across the 10-year follow-up period, including in the superior frontal cortex, medial orbitofrontal cortex, parahippocampal gyrus, rostral anterior cingulate cortex, and posterior cingulate.” They add, “Prenatal SSRI exposure was consistently associated with lower volume, ranging from 5% to 10% in the frontal, cingulate, and temporal cortex across ages.” So, could this be explained by the mother’s depression? No, write the researchers. For mothers who were depressed but did not take SSRIs, the children were almost no different from the healthy controls. Prenatal depression was associated with a smaller volume in one area, the rostral anterior cingulate gyrus. Similarly, postnatal depression was associated with a smaller volume in one area, the fusiform gyrus. Those differences in one area each should be compared to the large, brain-wide reduction in volume in numerous areas experienced by kids whose mothers took SSRIs. Moreover, even in the fusiform gyrus, kids whose mothers took SSRIs had larger reductions in volume than kids whose mothers had depression but didn’t take SSRIs. The good news is that some of these brain volume reductions appeared to have a catch-up effect: for instance, amygdala volumes had increased by age 15, so kids who were exposed to SSRIs were not any different from controls. Unfortunately, many of the brain volume differences didn’t catch up. Moreover, it’s unclear what effect these volume differences throughout all of childhood would have on a kid’s development, even if it catches up by their late teenage years. Previous Research Studies have consistently found antidepressant use in pregnancy to be associated with myriad risks to neonatal health, including neonatal withdrawal syndrome, preterm birth, congenital disabilities, developmental problems, cardiopulmonary problems, and even death. In one study, researchers found a sixfold increase in neonatal withdrawal syndrome when mothers took antidepressants. In another study, researchers found that 30% of babies born to mothers who used antidepressants experienced neonatal withdrawal syndrome. None of the babies whose mothers did not use antidepressants had this complication. And yet another study found that over half (56%) of babies exposed to SSRIs had this problem. Researchers have argued that antidepressants should be discontinued in pregnancy because of this risk, which includes symptoms of hypoglycemia, tremors, hypotonia, hypertonia, tachycardia, rapid breathing, and respiratory distress in babies born to mothers who use antidepressants. Studies have also accounted for preexisting factors like depression severity by comparing women who continued using antidepressants during pregnancy with women who had the same indication and did use antidepressants initially—but stopped after becoming pregnant. That study found that those who continued to use antidepressants increased the risk of neonatal health complications in their newborns, including preterm birth, low birth weight, and hospitalizations. Other research has found that antidepressant use during pregnancy alters brain development in the fetus. These findings have appeared in top journals, too: A study in JAMA Psychiatry found that antidepressant use during pregnancy increased the risk of infants with speech disorders, while a study in the American Journal of Psychiatry found that antidepressant use during pregnancy increased the risk of impaired neurological functioning in infants. Related Article: Psilocybin Plus SSRIs for Treatment-Resistant Major Depression

When the STAR*D study was launched more than two decades ago, the NIMH investigators promised that the results would be rapidly disseminated and used to guide clinical care. This was the “largest and longest study ever done to evaluate depression treatment,” the NIMH noted, and most important, it would be conducted in “real-world” patients. Various studies had found that 60% to 90% of real-world patients couldn’t participate in industry trials of antidepressants because of exclusionary criteria. The STAR*D investigators wrote: “Given the dearth of controlled data [in real-world patient groups], results should have substantial public health and scientific significance, since they are obtained in representative participant groups/settings, using clinical management tools that can easily be applied in daily practice.” In 2006, they published three accounts of STAR*D results, and the NIMH, in its November press release, trumpeted the good news. “Over the course of all four levels, almost 70 percent of those who didn’t withdraw from the study became symptom-free,” the NIMH informed the public. Here is a graphic from a subsequent published review, titled “What Does STAR*D Teach Us”, that charts that path to wellness: This became the finding that the media highlighted. The largest and longest study of antidepressants in real-world patients had found that the drugs worked. In the STAR*D study, The New Yorker reported in 2010, there was a “sixty-seven-percent effectiveness rate for antidepressant medication, far better than the rate achieved by a placebo.” That happened to be the same year that psychologist Ed Pigott and colleagues published their deconstruction of the STAR*D trial. Pigott had filed a Freedom of Information Act request to obtain the STAR*D protocol and other key documents, and once he and his collaborators had the protocol, they were able to identify the various ways the NIMH investigators had deviated from the protocol to inflate the remission rate. They published patient data that showed if the protocol had been followed, the cumulative remission would have been 38%. The STAR*D investigators had also failed to report the stay-well rate at the end of one year, but Pigott and colleagues found that outcome hidden in a confusing graphic that the STAR*D investigators had published. Only 3% of the 4041 patients who entered the trial had remitted and then stayed well and in the trial to its end. The protocol violations and publication of a fabricated “principal outcome”—the 67% cumulative remission rate—are evidence of scientific misconduct that rises to the level of fraud. Yet, as Pigott and colleagues have published their papers deconstructing the study, the NIMH investigators have never uttered a peep in protest. They have remained silent, and this was the case when Pigott and colleagues, in August of this year, published their latest paper in BMJ Open. In it, they analyzed patient-level data from the trial and detailed, once again, the protocol violations used to inflate the results. As BMJ Open wrote in the Rapid Responses section of the online article, “we invited the authors of the STAR*D study to provide a response to this article, but they declined.” In fact, the one time a STAR*D investigator was prompted to respond, he confirmed that the 3% stay-well rate that Pigott and colleagues had published was accurate. While major newspapers have steadfastly ignored Pigott’s findings, after Pigott and colleagues published their 2010 article, Medscape Medical News turned to STAR*D investigator Maurizio Fava for a comment. Could this 3% figure be right? “I think their analysis is reasonable and not incompatible with what we had reported,” Fava said. That was 13 years ago. The protocol violations, which are understood to be a form of scientific misconduct, had been revealed. The inflation of remission rates and the hiding of the astoundingly low stay-well rate had been revealed. In 2011, Mad in America published two blogs by Ed Pigott detailing the scientific misconduct and put documents online that provided proof of that misconduct. In 2015, Lisa Cosgrove and I—relying on Pigott’s published work and the documents he had made available—published a detailed account of the scientific misconduct in our book Psychiatry Under the Influence. The fraud was out there for all to see. Pigott and colleagues subsequently obtained patient-level data through the “Restoring Invisible and Abandoned Trials” initiative (RIAT), and their analysis has confirmed the accuracy of their earlier sleuthing, when they used the protocol to deconstruct the published data. Thus, the documentation of the scientific misconduct by Pigott and colleagues has gone through two stages, the first enabled by their examination of the protocol and other trial-planning documents, and the second by their analysis of patient-level data. Yet, there has been no public acknowledgement by the American Psychiatric Association (APA) of this scientific misconduct. There has been no call by the APA—or academic psychiatrists in the United States—to retract the studies that reported the inflated remission rates. There has been no censure of the STAR*D investigators for their scientific misconduct. Instead, they have, for the most part, retained their status as leaders in the field. Thus, given the documented record of scientific misconduct, in the largest and most important trial of antidepressants ever conducted, there is only one conclusion to draw: In American psychiatry, scientific misconduct is an accepted practice. This presents a challenge to the American citizenry. If psychiatry will not police its own research, then it is up to the public to make the fraud known, and to demand that the paper published in the American Journal of Psychiatry, which told of a 67% cumulative remission rate, be withdrawn. As STAR*D was designed to guide clinical care, it is of great public health importance that this be done. An Intent to Deceive The World Association of Medical Editors lists seven categories of scientific misconduct. Two in particular apply to this case: “Falsification of data, ranging from fabrication to deceptive selective reporting of findings and omission of conflicting data, or willful suppression and/or distortion of data.” “Violation of general research practices” which include “deceptive statistical or analytical manipulations, or improper reporting of results.” The essential element in scientific misconduct is this: it does not result from honest mistakes, but rather is born from an “intent to deceive.” In this instance, once Pigott and colleagues identified the deviations from the protocol present in the STAR*D reports, the STAR*D investigators’ “intent to deceive” was evident. By putting the protocol and other key documents up on Mad in America, Pigott made it possible for the scientific community to see for themselves the deception. Their recent RIAT publication makes it possible to put together a precise numerical accounting of how the STAR*D investigators’ research misconduct, which unfolded step by step as they published three articles in 2006, served to inflate the reported remission rate. This MIA Report lays out that chronology of deceit. Indeed, readers might think of this MIA Report as a presentation to a jury. Does the evidence show that the STAR*D’s summary finding of a 67% cumulative remission rate was a fabrication, with this research misconduct born from a desire to preserve societal belief in the effectiveness of antidepressants? The Study Protocol According to the STAR*D protocol, patients enrolled into the study would need to be at least “moderately depressed,” with a score of 14 or higher on the Hamilton Depression Rating Scale (also known as HAM-D). They would be treated with citalopram (Celexa) at their baseline visit, and then, during the next 12 weeks, they would have five clinical visits. At each one, a coordinator would assess their symptoms using a tool known as the Quick Inventory of Depressive Symptomatology (QIDS-C). As this study was meant to mimic real-world care, physicians would use the QIDS data to help determine whether the citalopram dosage should be altered, and whether to prescribe other “non-study” medications, such as drugs for sleep, anxiety, or for the side effects caused by citalopram. At each clinic visit, patients would also self-report their symptoms using this same measuring stick (QIDS-SR). The QIDS instrument had been developed by the STAR*D investigators, and they wanted to see whether the self-rated scores were consistent with the QIDS scores assessed by clinicians. At the end of the treatment period, independent “Research Outcome Assessors” (ROAs) would assess the patients’ symptoms using both the HAM-D17 and the “Inventory of Depressive Symptomatology” scale (IDS-C30). The primary outcome was remission of symptoms, which was defined as a HAM-D score ≤7. The protocol explicitly stated: “The research evaluation of effectiveness will rest on the HAM-D obtained, not by the clinician or clinical research coordinator, but by telephone interviews with the ROAs.” And: “Research outcomes assessments are distinguished from assessments conducted at clinic visits. The latter are designed to collect information that guides clinicians in the implementation of the treatment protocol. Research outcomes are not collected at the clinic.” During this exit assessment, patients would also self-report their outcomes via an “interactive voice recording” system (IVR) using the QIDS questionnaire. This would be done “to determine how this method performed compared to the above two gold standards.” The protocol further stated: “Comparing the IDS-C30 collected by the ROA and the QIDS16, collected by IVR, allows us to determine the degree to which a briefer symptom rating obtained by IVR can be substituted for a clinician rating. If this briefer rating can substitute for a clinician rating, the dissemination and implementation of STAR*D findings is made easier. Thus, the inclusion of QIDS16 by IVR is aimed at methodological improvements.” After the first 12-week trial with citalopram, patients who hadn’t remitted were encouraged to enter a second “treatment step,” which would involve either switching to another antidepressant or adding another antidepressant to citalopram. Patients who failed to remit during this second step of treatment could then move on to a third “treatment step” (where they would be offered a new treatment mix), and those who failed to remit in step 3 would then get one final chance to remit. In each instance, the HAM-D, administered by a Research Outcome Assessor, would be used to determine whether a patient’s depression had remitted. At the end of the four steps, the STAR*D investigators would publish the cumulative remission rate, which they predicted would be 74%. Patients who remitted at the end of any of the four steps were urged to participate in a year-long maintenance study to assess rates of relapse and recurrence for those maintained on antidepressants. The existing literature, the protocol stated, suggested that a “worst case” scenario was that 30% of remitted patients maintained on antidepressants “experience a depressive breakthrough within five years.” Yet, it was possible that real-world relapse rates might be higher. “How common are relapses during continued antidepressant treatment in ‘real-world’ clinical practice?” the STAR*D investigators asked. “How long [are remitted patients] able to stay well?” In sum, the protocol stated: Patients had to have a HAM-D score of 14 or higher to be eligible for the trial. The primary outcome would be an HAM-D assessment of symptoms administered by a Research Outcome Assessor at the end of the treatment period. Remission was defined as a HAM-D score of 7 or less. The secondary outcome would be an IDS-C30 assessment of symptoms administered by a Research Outcomes Assessor at the end of the treatment period. The QIDS-C would be administered at clinic visits to guide treatment decisions, such as increasing drug dosages. Patients would also self report their symptoms on the QIDS scale (QIDS-SR) to see if their scores matched up with the clinicians’ numbers. The two QIDS evaluations during clinic visits would not be used to assess study outcomes. The QIDS-SR administered by IVR at the end of treatment was for the purpose of seeing whether using this automated questionnaire, which took only six minutes, could replace clinician-administered scales to guide clinical care once STAR*D findings were published. It was not to be used to assess study outcomes. Relapse and stay-well rates would be published at the end of the one-year follow-up. While the protocol was silent on how drop-outs would be counted, a 2004 article by the STAR*D investigators on the study’s “rationale and design” stated that patients with missing HAM-D scores at the end of each treatment step were “assumed not to have had a remission.” Thus, the STAR*D documents were clear: those who dropped out during a treatment step without returning for an exit HAM-D assessment would be counted as non-remitters. The Published Results Step 1 outcomes Trivedi, et al. “Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: Implications for clinical practice.” Am J of Psychiatry 163 (2006): 28-40. In January of 2006, the STAR*D investigators reported results from the first stage of treatment. Although 4,041 patients had been enrolled in the study, there were only 2,876 “evaluable” patients. The non-evaluable group (N=1,165) was composed of 607 patients who had a baseline HAM-D score of less than 14 and thus weren’t eligible for the study; 324 patients who had never been given a baseline HAM-D score; and 234 who failed to return after their initial baseline visit. Seven hundred ninety patients remitted during stage one, with their HAM-D scores dropping to 7 or less. The STAR*D investigators reported a HAM-D remission rate of 28% (790/2,876). At first glance, this appeared to be a careful reporting of outcomes. However, there were two elements discordant with the protocol. As Trivedi and colleagues noted in their “statistical analysis” section, patients were designated as “not achieving remission” when their exit HAM-D score was missing. In addition, they noted that “intolerance was defined a priori as either leaving treatment before 4 weeks or leaving at or after 4 weeks with intolerance as the identified reason.” Thus, by both of these standards, the 234 patients who had failed to return after their baseline visit, when they were first prescribed Celexa, should have been counted as treatment failures rather than as non-evaluable patients. They were “intolerant “of the drug and had left the trial without an exit HAM-D score. If the STAR*D investigators had adhered to this element of their study plan, the number of evaluable patients would have been 3,110, which would have lowered the reported remission rate to 25% (790/3,110). The second discordant element in this first publication tells more clearly of an “intent to deceive.” In their summary of results, they wrote: “Remission was defined as an exit score of ≤7 on the 17-item Hamilton Depression Rating Scale (HAM-D) (primary outcome) or a score of ≤5 on the 16-item Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR) (secondary outcome).” They were now presenting QIDS-SR as a secondary outcome measure, even though the protocol explicitly stated that the secondary outcome measure would be an IDS-C30 score administered by a Research Outcome Assessor. Moreover, they were now reporting remission using the QIDS-SR score at the patient’s “last treatment visit,” even though the protocol explicitly stated that “research outcomes are not collected at the clinic.” This switch to a QIDS-SR score from the clinic made it possible to count those who had no exit HAM-D score as remitters if their last in-clinic QIDS-SR score was five or less. This deviation from the protocol added 153 to their remitted count, such that on the QIDS-SR scale, 33% were said to achieve remission (943/2,876). The STAR*D investigators even published a graphic of remission rates with the QIDS-SR, setting the stage for it to be presented, when the cumulative remission rate was announced, as the primary method for assessing effectiveness outcomes. Step 2 outcomes Rush, et al. “Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression.” NEJM 354 (2006): 1231-42. Also: Trivedi, et al. “Medication augmentation after the failure of SSRIs for depression.” NEJM 354 (2006): 1243-1252. Two months later, the STAR*D investigators published two articles detailing remission rates for those who had failed to remit on citalopram and had entered the second treatment step (N=1,439). One publication told of patients who had been withdrawn from citalopram and then randomized to either bupropion, sertraline, or venlafaxine. There were 729 patients so treated in step 2, and the remission rate was 21% on the HAM-D scale and 26% on the QIDS-SR scale. The investigators concluded that “after unsuccessful treatment, approximately one in four patients had a remission of symptoms after switching to another antidepressant.” That conclusion presented the QIDS-SR as the preferred scale for assessing remission. The second publication told of remission rates for 565 patients treated with citalopram augmented by either bupropion or buspirone. The remission rate was 30% using HAM-D, and 36% using QIDS-SR. The investigators concluded that these two remission rates “were not significantly different,” yet another comment designed to legitimize reporting remission rates with QIDS. There were two other deviations from the protocol in these reports on step 2 outcomes, although neither was easily discovered by reading the articles. The first was that the 931 patients cited as being “unevaluable” in the step 1 report, either because they had a baseline HRSD score less than 14 (607 patients) or no baseline score at all (324), were now being included in calculations of remitted patients. This could be seen in a graphic in Rush’s article, which stated that of the 4,041 enrolled into the trial, by the start of second step 1,127 had dropped out, 1,475 had moved into the one-year follow-up, and 1,439 had entered step 2. The 931 patients were now simply flowing into one of those three categories. Here is the flow chart from the Rush paper that shows this fact: The re-characterization of the 931 patients as evaluable patients could be expected, of course, to markedly inflate cumulative remission rates. Not only were 607 not depressed enough to enter the study, but Pigott and colleagues, with their access to patient-level data, determined that 99 in this group had baseline HAM-D scores below 8. They met criteria for remission before they had been given their first dose of citalopram. The second deviation was that patients who, at a clinic visit, scored as remitted on the QIDS-SR and sustained that remission for “at least 2 weeks,” could now be counted as having remitted and “move to follow-up.” Depressive symptoms are known to wax and wane, and with this new laxer standard, patients were being given multiple chances to be counted as “remitted” during any treatment step, and doing so using a self-report scale that they had filled out many times. Final report on outcomes Rush, et al. “Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report.” Am J Psychiatry 163 (2006): 1905-1917. In November 2006, the STAR*D investigators provided a comprehensive report on outcomes from both the acute and maintenance phases of the study. The protocol deviations, and thus the intent to deceive, are on full display in this paper. Acute outcomes Their reported remission rate of 67% relied on three deviations from the protocol, and a fourth “theoretical” calculation that transformed 606 drop-outs into imaginary remitters. However, the patient numbers involved in the protocol deviations can seem confusing for this reason: in the summary paper, the count of evaluable patients has once again changed. The step 1 report told of 2,876 evaluable patients. The step 2 report added the 931 patients without a qualifying baseline HAM-D score back into the mix, which seemingly produced a total of 3,807 evaluable patients. But the final summary paper tells of 3,671 evaluable patients. So where did this drop of 136 in the number of evaluable patients come from? In the step 1 report, the Star*D investigator stated there were 234 patients, out of the entering group of 4,041 patients, who didn’t return for a second visit and thus weren’t included in the evaluable group. In this summary paper, the STAR*D authors state there are 370 in this group. They provide no explanation for why this “did not return” number increased by 136 patients. (See footnote at end of this report for two possibilities.) As for the 3,671 evaluable patients, the paper states that this group is composed of the 2,876 evaluable patients listed in the step 1 report, plus participants whose baseline HAM-D score was less than 14. The STAR*D authors do not explain why they are including patients who were not depressed enough to meet inclusion criteria in their count of evaluable patients. Nor do they state, in this summary report, how many are in this group. They also don’t mention their inclusion of patients who lacked a baseline HAM-D score. As such, what is evident in this paper is that numbers are once again being jiggled. However, if the reader does the arithmetic, it becomes apparent that the count of 3,671 evaluable patients consists of the 2,876 patients deemed evaluable in the step 1 report, plus 795 patients who lacked a qualifying HAM-D score (out of 931 initially stated to be in this group). What the STAR*D authors did in this final report—for reasons unknown—is remove 136 from the group of 931 who lacked a qualifying HAM-D score and added them to the “didn’t show up for a second clinic visit” group. While the patient count numbers have changed, it is still possible to provide a precise count, based on the new numbers in the final summary report, of how all three protocol deviations served the purpose of inflating the remission rate, and did so in one of two ways: either increasing the number of remitted patients, or decreasing the number of evaluable patients. Categorizing early dropouts as non-evaluable patients The step 1 report listed 234 participants who had baselines scores of 14 or higher who didn’t return for a “post baseline” visit. As noted above, the protocol called for these patients to be chalked up as treatment failures. In their summary report, the STAR*D investigators added 136 to this count of non-evaluable patients, a change that further lowers the denominator in their calculation of a cumulative remission rate (remitters/evaluable patients). 2. Including ineligible patients in their count of remitted patients The step 1 report excluded 931 patients whose baseline HAM-D scores were either less than 14 (607 patients) or were missing (324 patients). The final summary report includes 795 participants who lacked a qualifying HAM-D score, and as will be seen below, this group of 795 patients, who didn’t meet inclusion criteria, added 570 to the tally of remitted patients. 3. Switching Outcome Measures The STAR*D investigators did not report HAM-D remission rates. Instead, they only reported remission rates based on QIDS-SR scores obtained during clinic visits. They justified doing so by declaring that “QIDS-SR and HRSD17 outcomes are highly related,” and that QIDS-SR “paper and pencil scores” collected at clinic visits were “virtually interchangeable” with scores “obtained from the interactive voice response system.” The protocol, of course, had stated: that the HAM-D was to be the primary measure of remission outcomes that QIDS was not to be used for this purpose that symptom assessments made during clinic visits were not to be used for research purposes The justification that the STAR*D investigators gave for reporting only QIDS-SR scores suggested there was an equivalency between HAM-D and QIDS, when, in fact, the use of QIDS-SR regularly produced higher remission rates. The statement presented a false equivalency to readers. With these protocol deviations fueling their calculations, the STAR*D investigators reported the following remission rates for each of the four treatment steps. Thus, the cumulative remission rate at the end of four steps was said to be 51% (1,854/3,671). In their recent reanalysis, Pigott and colleagues reported what the remission rates would have been if the protocol had been followed. First, the evaluable group should have been 3,110 patients (4,041 minus the 931 patients who didn’t have a baseline HAM-D score, or didn’t have a HAM-D score of 14 or higher). Second, HAM-D scores should have been used to define remission. Here is the data: Thus, if the protocol had been followed, the cumulative remission rated at the end of four steps would have been 35% (1,089/3,110). The protocol deviations added 765 remitters to the “got well” camp. Pigott’s 2023 report also makes it possible to identify the precise number of added remissions that came from including the 931 ineligible patients in their reports, and from switching to QIDs as the primary outcome measure. Even after these machinations, the STAR*D investigators still needed a boost if they were going to get close to their predicted get-well rate of 74%. To do so, they imagined that if the drop-outs had stayed in the study through all four steps of the study and remitted at the same rate as those who did stay to the end, then another 606 patients would have remitted. And voila, this produced a remission rate of 67% (2,460/3,671). This theoretical calculation, as absurd as it was from a research standpoint, also violated the protocol. Those who dropped out without an exit HAM-D score less than 8 were deemed to be non-remitters. This theoretical calculation transformed 606 treatment failures into treatment successes. Here is the final tally of how the STAR*D investigators’ research misconduct transformed a 35% remission rate into one nearly double that: That is the account of research misconduct that took place in the acute phase of the STAR*D study. The abstract of the summary report told of an “overall cumulative remission rate,” without mentioning the theoretical element. As can be seen in this screenshot, the fabrication was presented as a bottom-line result: This, in turn, became the fake number peddled to the public. For instance: The NIMH touted this number in a press release. The New Yorker, famed for its fact-checking, pointed to the 67% remission rate as evidence of the real-world effectiveness of antidepressants. Many subsequent articles in the research literature told of this outcome. A 2013 editorial in the American Journal of Psychiatry stated that in the STAR*D trial, “after four optimised, well-delivered treatments, approximately 70% of patients achieve remission.” A graphic depicted this stay-well rate: More recently, after an article by Moncrieff and colleagues debunked, yet again, the chemical imbalance theory of depression, several major newspapers, including The New York Times, trotted out the 67% figure to reassure the public that they needn’t worry, antidepressants worked, and worked well. One-year outcomes There were 1,518 who entered the follow-up trial in remission. The protocol called for regular clinical visits during the year, during which their symptoms would be evaluated using QIDS-SR. Clinicians would use these self-report scores to guide their clincal care: they could change medication dosages, prescribe other medications, and recommend psychotherapy to help the patients stay well. Every three months their symptoms would be evaluated using the HAM-D. Relapse was defined as a HAM-D score of 14 or higher. This was the larger question posed by STAR*D: What percentage of depressed patients treated with antidepressants remitted and stayed well? Yet, in the discussion section of their final report, the STAR*D investigators devoted only two short paragraphs to the one-year results. They did not report relapse rates, but rather simply wrote that “relapse rates were higher for those who entered follow-up after more treatment steps.” Table five in the report provided the relapse rate statistics: 33.5% for the step 1 remitters, 47.4% for step 2, 42.9% for step 3, and 50% for step 4. At least at first glance, this suggested that perhaps 60% of the 1,518 patients had stayed well during the one-year maintenance study. However, missing from the discussion and the relapse table was any mention of dropouts. How many had stayed in the trial to the one-year end? There was a second graphic that appeared to provide information regarding “relapse rates” over the 12-month period. But without an explanation for the data in the graphic, it was impossible to decipher its meaning. Here it is: Once Pigott launched his sleuthing efforts, he was able to figure it out. The numbers in the top part of the graphic told of how many remitted patients remained well and in the trial at three months, six months, nine months and one year. In other words, the top part of this graphic provided a running account of relapses plus dropouts. This is where the drop-outs lay hidden. Before Pigott published his finding, he checked with the STAR*D biostatistician, Stephen Wisniewski, to make sure he was reading the graphic right. Wisniewski replied: “Two things can happen during the course of follow-up that can impact on the size of the sample being analyzed. One is the event, in this case, relapse, occurring. The other is drop out. So the N’s over time represent that size of the population that is remaining in the sample (that is, has not dropped out or relapsed at an earlier time).” Here, then, was the one-year result that the STAR*D investigators declined to make clear. Of the 1,518 remitted patients who entered the follow-up, only 108 patients remained well and in the trial at the end of 12 months. The other 1,410 patients either relapsed (439) or dropped out (971). Pigott and colleagues, when they published their 2010 deconstruction of the STAR*D study, summed up the one-year results in this way: Of 4,041 patients who entered the study, only 108 remitted and then stayed well and in the study to its one-year end. That was a documented get-well and stay-well rate of 3%. Improper Reporting of One-Year Results The World Association of Medical Editors lists “improper reporting of results” as research misconduct. The hiding of the dismal long-term results fits into that definition of misconduct. In the protocol, the STAR*D researchers stated they would determine the stay-well rate at the end of one year. However, they didn’t discuss this figure in their published report of the one-year outcomes, and to MIA’s knowledge, none of the STAR*D investigators has subsequently written about it. The 3% number isn’t to be found in psychiatric textbooks, and again, to the best of MIA’s knowledge, no major U.S. newspaper has ever published this result. The only acknowledgement by a STAR*D investigator of this dismal outcome came when Medscape News asked Maurizio Fava about Pigott’s finding, and he acknowledged that it wasn’t “incompatible” with what they had reported. As such, the STAR*D investigators have mostly kept it hidden from the public and their own profession, and it likely would never have surfaced had it not been for Ed Pigott’s obsession with fleshing out the true results from the “largest and longest trial of antidepressants ever conducted.” Indeed, in 2009, NIMH director Thomas Insel stated that “at the end of 12 months, with up to four treatment steps, roughly 70% of participants were in remission.” He was now informing the public that 70% of the 4,041 patients who entered the study got well and stayed well, a statement that exemplifies the grand scale of the STAR*D fraud. Seventy percent versus a reality of 3%—those are the bottom-line numbers for the public to remember when it judges whether, in the reporting of outcomes in the STAR*D study, there is evidence of an “intent to deceive.” Institutional Corruption In Psychiatry Under the Influence, Lisa Cosgrove and I wrote about the STAR*D trial as a notable example of “institutional corruption.” There were two “economies of influence” driving this corruption: psychiatry’s guild interests, and the extensive financial ties that the STAR*D investigators had to pharmaceutical companies. The American Psychiatric Association, which is best understood as a trade association that promotes the financial and professional interests of its members, has long touted antidepressants as an effective and safe treatment. After Prozac was brought to market in 1988, the APA, together with the makers of antidepressants, informed the public that major depression was a brain disease, and that the drugs fixed a chemical imbalance in the brain. The prescribing of these drugs took off in the 1990s, and has continued to climb ever since, such that today more than one in eight American adults takes an antidepressant every day. The STAR*D results, if they had been accurately reported, would have derailed that societal belief. If the public had been told that in this NIMH study, which had been conducted in real-world patients, only 35% remitted, even after four treatment steps, and that only 3% remitted and were still well at the end of one year, then prescribing of these drugs—and societal demand for these drugs—surely would have plummeted. The STAR*D investigators, through their protocol deviations and their imagined remissions in patients that had dropped out, plus their hiding of the one-year results, turned the study into a story of the efficacy of these drugs. They were, in a business sense, protecting one of their primary “products.” In addition, through their research misconduct, they were protecting the public image of their profession. The 67% remission rate told of skillful psychiatrists who, by trying various combinations of antidepressants and other drugs, eventually helped two-thirds of all patients become “symptom free.” The remitted patients were apparently completely well. Even though STAR*D was funded by the NIMH, the corrupting influence of pharmaceutical money was still present in this study. The STAR*D investigators had numerous financial ties to the manufacturers of antidepressants. Here is a graphic that Lisa Cosgrove and I published in Psychiatry Under the Influence, which counted the number of such ties the various investigators had to pharmaceutical companies. In total, the 12 STAR*D investigators had 151 ties to pharmaceutical companies. Eight of the 12 had ties to Forest, the manufacturer of citalopram. The drug companies that sold antidepressants, of course, would not have been pleased if their key opinion leaders published results from a NIMH trial that told of real-world outcomes so much worse than outcomes from industry-funded trials of their drugs. The real-world efficacy that emerged in the STAR*D trial belied the advertisements that told of highly effective drugs that could make depression miraculously lift. Thus, the poisoned fruit of institutional corruption: newspapers still today point to the 67% remission rate as evidence of the efficacy of antidepressants, while most of the public—and prescribers of these drugs—remain unaware of the true results. The Harm Done The articles published by Pigott and colleagues since 2010 have provided a record of the scientific misconduct of the STAR*D investigators. This MIA Report simply presents a chronology of the fraud, and, relying on their work, a numerical accounting of how each element of research misconduct boosted remission rates. The purpose of this MIA Report is to make clear the “intent to deceive” that was present in the STAR*D investigators’ deviations from the protocol, their publication of a fraudulent cumulative remission rate, and their hiding of the one-year outcome that told of a failure of this paradigm of care. This research misconduct has done extraordinary harm to the American public, and, it can be argued, to the global public. As this was the study designed to assess outcomes in real-world patients and guide future clinical care, if the outcomes had been honestly reported, consistent with accepted scientific standards, the public would have had reason to question the effectiveness of antidepressants and thus, at the very least, been cautious about their use. But the fraud created a soundbite—a 67% remission rate in real-world patients—that provided reason for the public to believe in their effectiveness, and a soundbite for media to trot out when new questions were raised about this class of drugs. This, of course, is fraud that violates informed consent principles in medicine. The NIMH and the STAR*D investigators, with their promotion of a false remission rate, were committing an act that, if a doctor knowingly misled his or her patient in this way, would constitute medical battery. This cataloging of harm done extends to those who prescribe antidepressants. Primary care physicians, psychiatrists, and others in the mental health field who want to do right by their patients have been misled about their effectiveness in real-world patients by this fraud. The harm also extends to psychiatry’s reputation with the public. The STAR*D scandal, as it becomes known, fuels the public criticism of psychiatry that the field so resents. Yes, and this may seem counterintuitive, there is now an opportunity for psychiatry to grasp. The American Psychiatric Association, and the international community of psychiatrists, could take a great step forward in regaining public trust if they spoke out about the STAR*D fraud and requested a retraction of the published articles. Doing so would be an action that told of a profession’s commitment, as it moves forward, to uphold research standards, and to provide the public with an honest accounting of the “evidence base” for psychiatric drugs. However, failing to do so will only deepen justified criticism of the field. It will be a continuance of the past 15 years, when psychiatry has shown, through its inaction, that research misconduct in this domain of medicine—misconduct that rises to the level of scientific fraud—is acceptable practice, even though it may do great harm. A Public Petition to Retract the STAR*D Summary Article As we believe this is a matter of great importance to public health, Mad in America has put up a petition on change.org urging the American Journal of Psychiatry to retract the November 2006 summary article of the STAR*D results. A 2011 article on the subject of retraction in a medical journal noted the following: Articles may be retracted when their findings are no longer considered trustworthy due to scientific misconduct or error, they plagiarize previously published work, or they are found to violate ethical guidelines. . . Although retractions are relatively rare, the retraction process is essential for correcting the literature and maintaining trust in the scientific process. In this case, the facts are clear: the 67% remission rate published in the American Journal of Psychiatry in November 2006 can no longer be “considered trustworthy due to scientific misconduct,” and that retraction of the article “is essential for correcting the literature and maintaining trust in the scientific process.” The article also noted that “there is no statute of limitation on retractions.” Moreover, the World Association of Medical Editors, in its “Professional Code of Conduct,” specifically states that “editors should correct or retract publications as needed to ensure the integrity of the scientific record and pursue any allegations of misconduct relating to the research, the reviewer, or editor until the matter is resolved.” And here is one final fact that makes the case for retraction. The NIMH’s November 2006 press release, which announced that “almost 70% of those who did not withdraw from the study became symptom free,” contains evidence that the NIMH itself, or at least its press office, was duped by its own investigators. Either that, or the NIMH silently countenanced the fraud. First, it notes that of the 4,041 who entered the trial, “1,165 were excluded because they either did not meet the study requirements of having “at least moderate” depression (based on a rating scale used in the study) or they chose not to participate.” Thus, it stated, there were 2,871 “evaluable patients.” The NIMH press office either didn’t know that 931 patients who lacked a HAM-D baseline score that met eligibility criteria had been added back into the mix of remitted patients, or else it deliberately hid this fact from the public. Second, the press release stated that the purpose of the QIDS-SR assessments during clinic visits was to inform ongoing care: “Patients were asked to self-rate their symptoms. The study demonstrated that most depressed patients can quickly and easily self-rate their symptoms and estimate their side effect burden in a very short time. Their doctors can rely on these self-rated tools for accurate and useful information to make informed judgments about treatment.” This, of course, was consistent with the protocol, that QIDs would be used for this purpose, but instead was the instrument that the STAR*D investigators used to report remission rates in their summary paper. Here is Ed Pigott’s opinion on the call for retraction: “I started investigating STAR*D in 2006 and with colleagues have published six articles documenting significant scientific errors in the conduct and reporting of outcomes in the STAR*D trial. STAR*D’s summary article should clearly be retracted. This is perhaps best seen by the fact that its own authors lack the courage to defend it. By rights and the norms of ethical research practice, STAR*D authors should either defend their work and point out the errors in our reanalysis or issue corrections in the American Journal of Psychiatry and New England Journal of Medicine where they published their 7 main articles. What they can’t defend must be retracted.” Our hope is that information about this Mad in America petition will circulate widely on social media, producing a public call for retraction that will grow too loud for the American Journal of Psychiatry to ignore. Indeed, the publication of the RIAT re-analysis of the STAR*D results in a prestigious medical journal presents a Rubicon moment for American psychiatry: either it retracts the paper that told of a fabricated outcome, or it admits to itself, and to the public, that scientific misconduct and misleading the public about research findings is accepted behavior in this field of medicine. —– Footnote: There are two possible explanations for the increase in the number of the 4,041 participants who were said to have failed to return for a second visit (from 234 in the step 1 report to 370 in the final summary). One possibility is that 136 of the 931 patients said to lack a qualifying HAM-D score never returned for a second visit, and thus in the summary report, they were added to this “didn’t return” group and removed from the 931 group, leaving 795 participants who lacked a qualifying HAM-D score included in the count of evaluable patients. A second possibility can be found in the patient flow chart published in the step 1 report. Here it is: You can see here that there were 4,177 who consented to being in the study. Then 136 were deemed to be ineligible for some reason, and thus weren’t included in the count of 4,041 patients who entered the study. However, the 136 ineligible patients in the 4,177 count would have had a first screening visit, and once they were told they were ineligible, would not have returned for a second clinic visit. So the possibility here is that the STAR*D authors took this group of 136 ineligible patients, who never entered the study, and added them into the “did not return” group in order to further decrease the denominator in their final remission count. Thus, there are two possibilities. The first tells of an extraordinary numerical coincidence. There were 136 patients who were declared ineligible before the study began, and a second, different group of 136 patients who lacked a qualifying HAM-D score, yet were allowed to enter the study but failed to return for a second clinic visit. The second possibility tells of falsification of data, a particularly egregious form of research misconduct.

Depression and anxiety were not associated with outcomes for most cancer types, including breast cancer, prostate cancer, and alcohol-related cancer, according to findings from a large, individual participant data meta-analysis. An exception was for lung and smoking-related cancers, but key covariates appeared to explain the relationship between depression, anxiety, and these cancer types, the investigators reported. The findings challenge a common theory that depression and anxiety increase cancer risk and should "change current thinking," they argue. "Our results may come as a relief to many patients with cancer who believe their diagnosis is attributed to previous anxiety or depression," first author Lonneke A. van Tuijl, PhD, of the University of Groningen and Utrecht University, the Netherlands, noted in a press release. Analyses included data from up to nearly 320,000 individuals from the 18 prospective cohorts included in the international Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. The cohorts are from studies conducted in the Netherlands, United Kingdom, Norway, and Canada, and included 25,803 patients with cancer. During follow-up of up to 26 years and more than 3.2 million person-years, depression and anxiety symptoms and diagnoses showed no association with overall breast, prostate, colorectal, and alcohol-related cancers (hazard ratios, 0.98-1.05). For the specific cancer types, the investigators "found no evidence for an association between depression or anxiety and the incidence of colorectal cancer (HRs, 0.88-1.13), prostate cancer (HRs, 0.97-1.17), or alcohol-related cancers (HRs, 0.97-1.06)." "For breast cancer, all pooled HRs were consistently negative but mean pooled HRs were close to 1 (HRs, 0.92-0.98) and the upper limit of the 95% confidence intervals all exceeded 1 (with the exception of anxiety symptoms)," they noted. An increase in risk observed between depression and anxiety symptoms and diagnoses and lung cancer (HRs, 1.12-1.60) and smoking-related cancers (HRs, 1.06-1.60), in minimally adjusted models, was substantially attenuated after adjusting for known risk factors such as smoking, alcohol use, and body mass index (HRs, 1.04-1.08), the investigators reported. "Depression and anxiety have long been hypothesized to increase the risk for cancer. It is thought that the increased cancer risk can occur via several pathways, including health behaviors, or by influencing mutation, viral oncogenes, cell proliferation, or DNA repair," the authors explained, noting that "[c]onclusions drawn in meta-analyses vary greatly, with some supporting an association between depression, anxiety, and cancer incidence and others finding no or a negligible association." The current findings "may help health professionals to alleviate feelings of guilt and self-blame in patients with cancer who attribute their diagnosis to previous depression or anxiety," they said, noting that the findings "also underscore the importance of addressing tobacco smoking and other unhealthy behaviors – including those that may develop as a result of anxiety or depression." "However, further research is needed to understand exactly how depression, anxiety, health behaviors, and lung cancer are related," said Dr. Tuijl.

PSYCHIATRIC VIEWS ON THE DAILY NEWS “An ounce of prevention is worth a pound of cure.” -Benjamin Franklin Next week is National Suicide Prevention Week, with World Suicide Prevention Day beginning the week on Sunday. The goal is to reduce the likelihood of suicide because it is irreversible and usually leaves loved ones with much anguish and guilt. Over 20 years, from around 2000-2020, the suicide rate dropped significantly globally, but increased significantly in the United States. There was a record high in 2022. In particular, the rate has been increasing in teenage girls, while physicians seem to top the list of professions at risk. Guns are increasingly used as the lethal method. Fortunately, there is some emerging good news as far as addressing suicidality earlier and better. In society, there is the new 988 suicide helpline. Though the public still needs to learn about it, it has proven useful for not only suicidal concerns, but other mental health needs. As exemplified at Yale, there is some change for the better for suicidal students. After a suicide in 2021, Yale activists ended up suing the school and achieved a recent settlement that provides more support and care instead of the suicidal student being sent away and not easily welcomed back in.1 Adequate mental health services in schools seems to lower suicide risk. We do need to consider how to reduce the causes of the increase in suicides and attempts. The pandemic and other risk factors include job loss, social isolation, loneliness, financial stress, and discrimination. However, suicide and other self-destructive tendencies usually begin in individuals long before any public expression or call for help. The basic point is that most everybody on occasion will have suicidal or other self-destruction thoughts or actions. Take myself. Although I have never had a suicidal thought or even casually or exasperatingly said “I wished I was dead,” I was quite self-destructive as a youth, leading me to be named Most Accident Prone for my high school graduation. That ended when I met and dated my wife of 55 years early in college at the University of Michigan. Interpret that as you will. (If you read my column on Tuesday, you will know she is a natural therapist.) Having an overly critical inner voice is at the root of much self-destructive behavior, thinking of such internal criticisms as “you are stupid” or “you are not attractive.” This inner negativity usually comes from parents who berate their children, and sometimes teachers do, too. Children also naturally blame themselves for parental problems. This inner criticism often escalates with being discriminated against, big losses, chronic physical pain, major life changes, housing problems, addiction, postpartum depression, and the antidepressant and antipsychotic medication side effect of akathisia. When psychological and/or physical pain combines with hopelessness, as can happen with many psychiatric disorders, suicide risk becomes especially high. That can happen with severe and unrelenting suffering, and result in a request for what is sometimes called physician-assisted suicide. As usual, successful treatment of psychiatric disorders will lessen suicide risk. The main protective factor for suicide is connectivity. Most important is having someone to talk to who is trusted, including family, friends, and therapists. The challenge is being able to ask loved ones for verification of negative thoughts, even if that temporarily makes you feel ashamed for even doing so publicly. When cutting off suicidality fails, sometimes paradoxically the person or patient seems better, but for no clear and convincing reason. That may mean they are relieved because they decided on suicide, putting them at the highest risk. Both clinicians and social connections should not be fooled by that. My gratitude today is for only having one patient who died by suicide, way back at the start of my residency training. Dr Moffic is an award-winning psychiatrist who has specialized in the cultural and ethical aspects of psychiatry. A prolific writer and speaker, he received the one-time designation of Hero of Public Psychiatry from the Assembly of the American Psychiatric Association in 2002. He is an advocate for mental health issues related to climate instability, burnout, Islamophobia, and anti-Semitism for a better world. He serves on the Editorial Board of Psychiatric Times. Related Article: Look at the staggering affect of 988 -- Suicide & Crisis Lifeline Implementation Suicide Prevention Must Expand Beyond Crisis Intervention Providing Hope During National Suicide Prevention Month