Tag: Joanna Moncrieff

04/21/20

Pros and Cons of Antipsychotics

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Antipsychotic treatment is often associated with weight gain and metabolic syndrome, a cluster of symptoms that increases the risk of heart disease, stroke and diabetes, independent of other adverse effects like sexual dysfunction, drowsiness, dizziness, restlessness, and others. In The Lancet, Pillinger et al compared and ranked 18 antipsychotics on the basis of their metabolic side-effects. They found that antipsychotics varied widely in their effects on body weight, BMI, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and glucose concentrations. Olanzapine (Zyprexa) and clozapine (Clozaril) were ranked the worst for metabolic-related adverse effects, while ironically being identified as among the most effective antipsychotic drugs. Aripiprazole (Abilify, Aristada), brexpiprazole (Rexulti), cariprazine (Vraylar), lurasidone (Latuda), and ziprasidone (Geodon) were the most benign profiles.

In the same issue of The Lancet, Yoav Domany and Mark Weiser compared the results of this study with a network meta-analysis on the efficacy and adverse effects of antipsychotics. Clozapine was the most efficacious in reducing overall symptoms and amisulpride (Solian) was the most efficacious in reducing positive symptoms. “One would hope that data on efficacy and adverse events could be taken together with the detailed information on metabolic adverse events from this study to consider a personalized medicine approach in treating patients with schizophrenia.”

This approach could be part of a shared decision-making process, based on a discussion with the patient weighing the benefits and disadvantages of each treatment option. Such an approach is hampered by the fact that clozapine and olanzapine, which consistently come out among the best in terms of efficacy, are also consistently associated with the highest rates of metabolic adverse effects, hindering such a process at this stage.

One limitation of the Pillinger et al study was the studies in its meta-analysis were quite short, in the range of 2-13 weeks. The authors noted how randomized controlled trials are generally short and recommended that future studies should “examine antipsychotic-induced metabolic dysregulation in patients receiving long-term maintenance therapy.” Further, lifestyle and treatment factors (physical comorbidity, alcohol use, smoking, diet, exercise, and co-prescription of psychiatric—eg, mood stabilisers—or physical health medications—eg, statins or anti-glycaemic drugs) may have influenced metabolic outcomes. “Treatment guidelines should be updated to reflect differences in metabolic risk, but the choice of the treatment intervention should be made on an individual patient basis, considering the clinical circumstances and preferences of patients, carers, and clinicians.”

Standard treatment guidelines are that antipsychotic medications should continue indefinitely after someone has experienced more than one psychotic episode. But according to Sandra Steingard, there is less agreement treatment guidelines after a single psychotic episode.  “Current guidelines recommend drug treatment for two to five years, the idea being that if a person remains well during that time, it might then be safe to stop the drug.” She said most psychiatrists assumed that by reducing risk of relapse you would improve long-term outcomes. But that assumption may not be correct. Not only are there risks of weight gain and tardive dyskinesia, antipsychotics seem to impair functional outcome. Robert Whitaker reported that Martin Harrow and Thomas Jobe did a long-term study of 200 psychotic patients. Patients who were off medication had better cognitive functioning and lower levels of anxiety than medicated patients. Patients on medication were more likely to be psychotic at follow-up. “Eighty-six percent of the medication-compliant patients were psychotic at the 4.5-year follow-up, compared to 21% of those who had stayed off antipsychotics. This dramatic difference remained throughout the study.” See the following chart.

Harrow also found that once patients who went off medication were stable, they were likely to remain stable for extended time periods. None of the stable, off-med patients stable at the 7.5-year follow-up relapsed in the next 7.5 years. Seventy to 90% of the unmedicated patients were working more than half time, compared to roughly 25% of the medicated patients. Those with milder disorders who continued taking medications had worse outcomes than schizophrenia patients who were off their medications.

Harrow discovered that patients off medication regularly recovered from their psychotic symptoms over time (2-year to 4.5-year outcomes), and that once this happened, they had very low relapse rates. At the same time, a majority of the patients on medication regularly remained psychotic, and even those who did recover often relapsed. Harrow’s results provide a clear picture of how antipsychotics worsen psychotic symptoms over the long term.

Schizophrenia monotherapy treatment is not always effective, and some individuals receive additional interventions, such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) and psychological therapies. Ortiz-Orendain and others conducted a Cochrane review that compared antipsychotic monotherapy and combined treatment. The authors found low-quality evidence that combined antipsychotics improved the clinical response. The study indicated that more people who received combination therapy showed an improvement in symptoms. But there were no clear differences with other outcomes, such as relapse, hospitalization, adverse events, discontinuing treatment or leaving the study early. In her review of the Ortiz-Orendain et al study for The Mental Elf, Elena Marcus said it was a well conducted systematic review. However,

One of the main limitations of this review lies in the quality of included studies, with outcomes rated as low or very low quality which really questions our confidence in the reported estimates. There was a particularly high or unclear risk of reporting bias and attrition bias across studies and as authors included quasi-randomised trials there was a risk of selection bias in ~70% of studies. Whilst five studies were clearly quasi-randomised, for 39 studies there was not enough information to judge whether sequence generation was truly random, so the risk of bias here was unclear rather than high.

Users of antipsychotic medications also describe a distinctive experience, characterized by sedation, cognitive impairment, emotional blunting and reduced motivation. These are in addition to the various physical effects, including weight gain, sexual dysfunction and neurological consequences. Thompson et al described a synthesis of qualitative data about mental and behavioral changes associated with taking antipsychotics, and how these interact with symptoms of psychosis and people’s sense of self and agency. They found that neuroleptics interfered with people’s ability to carry out basic activities. But they also reduced the intensity of intrusive psychotic experiences and other symptoms, such as anxiety and insomnia.

Anything that changes our mental faculties is likely to impact on our sense of ourselves, and this is a common experience in relation to mood or experience-modifying agents. In the studies we reviewed, some participants felt neuroleptic-induced effects deprived them of important aspects of their personality; their drives, imagination or humour, for example. Others felt that by reducing the symptoms of psychosis, the drugs were able to restore them to a state in which they felt ‘themselves’ again. Similarly, some people were content to view themselves as having a disease requiring ongoing treatment, while others felt that taking neuroleptic medication symbolised a tainted identity. Schizophrenia or psychosis can disrupt people’s sense of self, and studies of personal recovery have described the importance of reconstructing a sense of self in a way that is distinct from symptom improvement. Therefore, although neuroleptics may effectively suppress symptoms, their effects can nevertheless be experienced as detrimental to sense of self and identity, with important implications for social functioning and achievement of life goals.

John Read and Ann Sacia of the University of East London surveyed 650 individual’s experiences with antipsychotics. Two-thirds (66.9%) of the participants said their experiences with antipsychotic drugs was more negative than positive, with 34.9% stating their experiences were extremely negative. Nearly a quarter (22.1%) of the participants said their experiences were more positive than negative, with 5.7% saying their experiences were extremely positive. The authors said at the point of prescription clinicians should provide a full range of information about antipsychotics, including potential benefits and harms, difficulties withdrawing, and information on alternative treatments, such as psychological therapies.

Implied in the above critique of antipsychotics is the view that psychiatric drugs are psychoactive substances in the same way alcohol or heroin are psychoactive substances. This is what Joanna Moncrieff refers to as the ‘drug-centered’ model of drug action. Conversely, the opening study by Pillinger et al seems to view antipsychotics according to a ‘disease-centered’ model of drug action. Moncreiff said the disease-centered model is borrowed from medicine and presents drugs through the prism of disease, disorder or the symptoms the drugs are thought to treat. The significant effects (or efficacy) are the ones the drugs exert on the diseased or abnormal nervous system. Any others are of secondary interest and referred to as above as side effects or adverse effects.

In contrast, the ‘drug-centred’ model suggests that far from correcting an abnormal state, as the disease model suggests, psychiatric drugs induce an abnormal or altered state. Psychiatric drugs are psychoactive substances, like alcohol and heroin. Psychoactive substances modify the way the brain functions and by doing so produce alterations in thinking, feeling and behaviour. Psychoactive drugs exert their effects in anyone who takes them regardless of whether or not they have a mental condition. Different psychoactive substances produce different effects, however. The drug-centred model suggests that the psychoactive effects produced by some drugs can be useful therapeutically in some situations. They don’t do this in the way the disease-centred model suggests by normalising brain function. They do it by creating an abnormal or altered brain state that suppresses or replaces the manifestations of mental and behavioural problems.

The above discussion suggests individuals being treated with antipsychotics should weigh the risks and benefits of the medication prescribed to them. They need to gather information on their medication, its potential side effects and then monitor how they respond to the drug. This is consistent with what Joanna Moncrieff called the drug-centered model of drug action. The Harrow study also indicated that the use of antipsychotics may not be the best long-term treatment protocol for schizophrenia. If you are using or considering the use of antipsychotics, weigh the pros and cons.

02/25/20

Rethinking and Transforming Psychiatry

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“We believe that a fundamental rethinking of psychiatric knowledge creation and training is in order.” This statement was made in a commentary published in the New England Medical Journal, “Medicine and the Mind—The Consequences of Psychiatry’s Identity Crisis.” The authors are two prominent Harvard researchers in psychiatry, Caleb Gardner and Arthur Kleinman, so their words cannot be dismissed as ‘anti-psychiatry.’ They went on to say biologic psychiatry has so far failed to produce a comprehensive theoretical model for any major psychiatric disorder. However, they think it would be “too great a loss,” to diminish its role drastically as suggested by Anne Harrington. Rather than contracting to an exclusive focus on biologic structure, “the field needs to expand if we are to meet the needs of real people.”

I have mixed feelings about their proposal. Their critique of biological psychiatry, the acknowledgment of over prescribing psychiatric medication, the abandonment of its social, interpersonal, and psychodynamic foundations are concerns I share. But they balked at Anne Harrington’s proposal in Mind Fixers to limit its scope to severe, mostly psychotic disorders. She said there is hardly any knowledgeable person who believes the so-called biological revolution of the 1980s made good on its therapeutic and scientific promises. “It is now increasingly clear to the general public that it overreached, overpromised, overdiagnosed, overmedicated, and compromised its principles.” If psychiatry needed to be rebuilt, as the authors said, won’t there have to be some dismantling first? Otherwise, there is a danger of building on an unstable, unreliable foundation.

Harrington pointed to how in 2013, just before the publication of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), Thomas Insel, who was then the director of NIMH, said the agency was re-orienting its research away from DSM categories; that is was critical to realize that “we cannot succeed if we use DSM categories as the ‘gold standard’” for diagnosis. He said it was like using the nature of chest pain or the quality of a fever to create a diagnostic system. Harrington said, “Put another way, there seemed to be little if any sound biology undergirding the psychiatric enterprise.”

In Psychology Today, Jonathan Shedler wrote, “A Psychiatric Diagnosis Is Not a Disease.” He said there was a circular logic to psychiatric diagnosis. “How do we know a patient has depression? Because they have the symptoms. Why are they having symptoms? Because they have depression.” He elaborated that psychiatric diagnoses were categorically different from medical diagnoses like atherosclerosis, myocarditis, or pneumonia, because they are descriptive rather than explanatory. “Medical diagnoses point to etiology—underlying biological causes.”

In an addendum, Shedler said he appreciated the lively discussion his article inspired. He was surprised by some of the comments, from individuals he assumed to be psychiatrists, who had impugned his credentials to discuss psychiatric diagnosis. But he took comfort in knowing that Allen Frances, MD, Chair of the DSM-IV Task Force, had the same view. Frances also said mental disorders were not diseases, but constructs. They were descriptive, rather than explanatory.

There was a study published in Psychiatry Research, “Heterogeneity in Psychiatric Diagnostic Classification,” that examined the heterogeneous nature of categories within the DSM-5, and its consequences for clinicians, clients and the diagnostic model itself. Heterogeneity was found in specific diagnostic criteria, including symptom comparators, duration of difficulties, indicators of severity, and the perspective used to assess difficulties. Each of the three researchers called for dismantling, not expanding DSM diagnosis.

The lead researcher of the study, Kate Allsopp, said for Medical Express: “Although diagnostic labels create the illusion of an explanation they are scientifically meaningless and can create stigma and prejudice.” Peter Kinderman, another author, said: “This study provides yet more evidence that the biomedical diagnostic approach in psychiatry is not fit for purpose.” He added the diagnostic system wrongly assumed that all distress resulted from disorder. John Read, who was the third author, said: “Perhaps it is time we stopped pretending that medical-sounding labels contribute anything to our understanding of the complex causes of human distress or of what kind of help we need when distressed.”

Psychiatric Times published an interview with Allen Frances for Conversations in Critical Psychiatry. Although he thought psychiatry was among the noblest of professions, “I fear that too many psychiatrists are now reduced to pill pushing, with far too little time to really know their patients well and to apply the rounded biopsychosocial model that is absolutely essential to good care.” He despaired that diagnostic inflation resulted in a too loose of a diagnostic system. “Diagnoses should be written in pencil, and under-diagnosis is almost always safer and more accurate than over-diagnosis.” With regard to epidemiological studies that tend to exaggerate rates of mental disorders, Frances said:

Never believe the extremely high rates of mental disorders routinely reported by epidemiological studies in psychiatry—usually labelling about 25% of the general population as mentally ill in the past year, about 50% lifetime. This entire literature has a systematic, but unacknowledged, methodological bias that inherently results in over-reporting. Because epidemiology requires such huge samples—in the tens of thousands—it is prohibitively expensive to conduct clinical interviews. Instead phone surveys are done by non-clinicians following a highly structured format that allows no clinical judgment whether the symptoms reported cause sufficient clinically significant distress and impairment to qualify as a mental disorder. Since there is no sharp boundary between normal distress and mental disorder, not assessing for clinical significance includes among those labelled mentally ill many who are merely distressed. The rates reported in studies are really only upper limits, not accurate approximations of true rates. They should be, but never are, reported as such.

His final word on DSM was: “DSM should be seen only as a tool helpful in guiding clinical judgment, not as a replacement for it.”

Returning to “Medicine and the Mind” by Gardner and Kleinman, psychiatrist Sandy Steingard said she shared their wish that research funding would be allocated to fields other than basic biologic research. But she was surprised they appeared to support buttressing psychiatry’s hold as leaders in research and program development. “I need some convincing that the problems we agree exist will be best addressed within my profession. In recent years, I have been most impressed by approaches to mental distress that emanate from outside of psychiatry.”

Finally, there was an article published in Public Understanding of Science that aimed to analyze the ‘critical reception’ of the DSM-5—how it has been received, discussed and criticized by different categories of people: “The Critical Reception of the DSM-5.” They noted two major themes surrounding the critical reception of the DSM-5, the pseudo-scientific nature of the manual and its normalizing power. Mental health professionals, especially psychiatrists, were more invested in the debate on the scientific nature of the DSM-5. There was a more eclectic variety of audiences in the debate over the normalizing power of the manual.

In the first debate (the scientific nature of the DSM), we found opposing argumentative positions regarding whether or not the manual is a scientific tool and questioning the type of science to which the manual adheres. In the second debate (the normalising power of the DSM), opinions were also polarised: while some argued that the manual was potentially socially harmful, some pointed out its lack of inherent agency and others mentioned its potential benefits. Although these debates have been noted in previous studies (Demazeux, 2015; Ecks, 2016), our research aims to deepen the understanding of such discussions.

They concluded the DSM was not simply a scientific manual. Rather, it is “a social laboratory where political, sociological, ethical and psychological issues are discussed and confronted.” In order to critically analyze the DSM, the authors said it was important to consider the claims that challenge the APA’s narrative of the DSM, namely its scientific and democratic nature. They said a range of arguments interacted and overlapped “in differing and opposing ways.” This was said to nuance the idea often presented academic publications that critiques of the DSM were mostly fixed, repeating the same themes and antagonistic positions.

The above issues were not being discussed in fringe, antipsychiatry forums. Rather, they appeared in well-received, medical and psychological arenas: The New England Medical Journal, Psychology Today, Psychiatry Research, Medical Express, Psychiatric Times, the National Institute of Mental Health. The people addressing them: Allen Frances, Thomas Insel, Caleb Gardner, Arthur Kleinman and others are or were key individuals within the mental health, psychiatric, diagnostic fields. The time is coming where just discussing the issues and concerns will not be enough; change will be necessary.

Psychiatry and diagnosis need to be reined in. They have extended their “reach” too far as it is, and scaling back is a necessary and essential step before any future recasting of the role of psychiatric treatment for mental “disorders.” Anne Harrington’s suggestion to limit its scope to severe, mostly psychotic disorders is a good first step. Dr. Joanna Moncrieff, a psychiatrist, seems to share this view. In “Rethinking Modals of Psychotropic Drug Action,” and “The Psychoactive Effects of Psychiatric Medication,”  she proposed a “drug centered model” of drug action, rather than the existing “disease centered model,” whose core assumption is that psychotropic drugs help correct “a biochemical abnormality that represents a biological substrate of a specific disease process.”

In The Myth of the Chemical Cure, Moncrieff acknowledged abandoning the disease-centered model would challenge “some of the most fundamental principles of modern psychiatry.” Yet she said it would also open the way “to a more honest practice” that requires its own specialist knowledge, and implements a more democratic treatment process:

Adopting a drug-centred model of drug action would require psychiatrists to become more informed about the effects of different psychoactive drugs, and become attuned to evaluating the subjective experiences of their patients in a more equal and reciprocal relationship. Where their function was to participate in mechanisms of social control this would be openly acknowledged and rigidly controlled rather than veiled, as currently, under the cloak of medicine.

In “The Psychoactive Effects of Psychiatric Medication,” she pointed out how re-orienting drug therapy towards a drug-centered model raised some questions about the validity and relevance of diagnostic systems like the DSM-5. The idea that psychiatric drugs exert “a disease- or disorder-specific action” has been one of the principal justifications for modern psychiatric classification. Using psychiatric drugs explicitly for their psychoactive effects would require a different understanding of the nature of psychiatric problems. It would break the link between diagnoses and treatment, “and enable a frank discussion about the purpose and ethics of the already frequent ‘off-label’ use of prescribed psychoactive medications, such as their use for behavioral control in children and the elderly.”

Gardner and Kleinman were not advocating going this far, but I think psychiatry needs a transformation. Long live the transformation!

01/8/19

Antidepressant Fall From Grace, Part 2

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In 1995 Irving Kirsch and Guy Sapirstein set out to assess the placebo effect in the treatment of depression. Like most people, Kirsch used to think that antidepressants worked—the active ingredient in the antidepressant helped people “cope with their psychological condition.”  They weren’t surprised to find a strong placebo effect in treating depression; that was their hypothesis and the reason to do the study. What did surprise them was how small the drug effect was—the difference between the response to the drug and the response to the placebo. “The placebo effect was twice as large as the drug effect.”

Along with Thomas Moore and others, Kirsch then did an analysis of data submitted to the FDA for approval of the six most widely prescribed antidepressants approved between 1987 and 1999: fluoxetine (Prozac), paroxetine (Paxil), sertaline (Zoloft), venafaxine (Effexor), nefadozone (Serzone) and citalopram (Celexa). The researchers found that 80% of the response to medication was duplicated in placebo control groups. The mean difference between drug and placebo was clinically negligible. You can read more about this study in Prevention & Treatment, “The Emperor’s New Drugs.”

When they published their findings, Kirsch sad he was pleasantly surprised by the consensus about their findings. “Some commentators argued that our analysis had actually overestimated the real effect of antidepressants.” One group of researchers said the minimal difference between antidepressant treatment and controls was a “dirty little secret” that had been known all along. “The companies that produce the drugs knew it, and so did the regulatory agencies that approve them for marketing. But most of the doctors who prescribe these medications did not know it, let alone their patients.”

According to Irving Kirsch, pharmaceutical companies have used several devices to present their products as better than they actually are. First they will withhold negative studies from publication. While publication bias effects all areas of research, it is acutely problematic with drug trials. “Most of the clinical trials evaluating new medications are sponsored financially by the companies that produce and stand to profit from them.”

The companies own the data that come out of the trials they sponsor, and they can choose how to present them to the public — or withhold them and not present them to the public at all. With widely prescribed medications, billions of dollars are at stake.

Positive studies may be published multiple times, a practice known as “salami slicing.” Often this is done in ways that makes it difficult for reviewers to recognize the studies were done on the same data. The authors may be different. References to the previous publication of the data are often missing. Sometimes there are minor differences in the date used between one publication and another. Sometimes positive data is cherry-picked from a clinical trial and published, giving the impression that the drug seemed more effective than it really was. For more information on this issue, see: The Emperor’s New Drugs: Exploding the Antidepressant Myth by Irving Kirsch.

Published in 2004, the STAR*D study (Sequenced Treatment Alternatives to Relieve Depression) was a multisite, multistep clinical trial of outpatients with nonpsychotic major depression. It was designed to be more representative of the real world use of antidepressants than typical clinical trials; and to show the effectiveness of antidepressants in the best of circumstances. STAR*D was funded by the NIMH at a cost of $35 million dollars and took six years to complete. It was hailed as the “largest antidepressant effectiveness trial ever conducted.” Robert Whitaker described it as follows:

The STAR*D trial was designed to test whether a multistep, flexible use of medications could produce remission in a high percentage of depressed outpatients. Those who didn’t get better with three months of initial treatment with an SSRI (citalopram) then entered a second stage of treatment, in which they were either put on a different antidepressant or given a second drug to augment an antidepressant. Those who failed to remit in step two could go on to a step three, and so on; in total, there were four treatment steps.

According to the NIMH, in level 1, about one-third of participants became symptom-free. In level 2, about 25% of participants became symptom-free. So a half of the participants in the STAR*D study became symptom-free after two treatment levels. “Over the course of all four treatment levels, almost 70 percent of those who did not withdraw from the study became symptom-free.” However, there was a progressive dropout rate: 21% withdrew after level 1; 30% after level 2; and 42% after level 3.

An overall analysis of the STAR*D results indicates that patients with difficult-to-treat depression can get well after trying several treatment strategies, but the odds of beating the depression diminish with every additional treatment strategy needed. In addition, those who become symptom-free have a better chance of remaining well than those who experience only symptom improvement. And those who need to undergo several treatment steps before they become symptom-free are more likely to relapse during the follow-up period. Those who required more treatment levels tended to have more severe depressive symptoms and more co-existing psychiatric and general medical problems at the beginning of the study than those who became well after just one treatment level.

The message communicated to doctors and the public was that STAR*D showed that antidepressants enabled 67% of depressed patients to recover. Robert Whitaker said an article in The New Yorker commented this “effectiveness rate” was “far better than the rate achieved by a placebo.” But this “cumulative” remission rate of 67% was in fact a theoretical rate that assumed those who dropped out of the study would have the same remission rates as those who remained. “They [also] included remission numbers for patients who weren’t depressed enough at baseline to meet study criteria, and thus weren’t eligible for analysis.” Irving Kirsch said the STAR*D symptom remission was temporary for most: “Approximately 93 percent of the patients who recovered relapsed or dropped out of the trial within a year.”

Recently, Kirsch and others acquired the STAR*D raw data through the MIMH and reanalyzed the HRSD (Hamilton Rating Scale for Depression) results. The HRSD was identified by the original as the primary outcome measure for STAR*D. “Yet the outcome that was presented in almost all the study papers was the QIDS (Quick Inventory of Depressive Symptomatology), a measure made up especially for the STAR-D study, with no prior or subsequent credentials.” The QIDS was devised as a way of tracking symptoms during the course of treatment NOT as an outcome measure. And the original study protocol stated it should not be used as an outcome measure.

Analysis of the HRSD data in STAR*D failed to reach the threshold required for a minimal improvement. “It is also below average placebo improvement in placebo-controlled trials of antidepressants.” The STAR*D results were about “half the magnitude of those obtained in standard comparative drug trials.” Commenting on STAR*D in his book, The Emperor’s New Drugs, Irving Krisch said:

This is a rather bleak picture of the effects of antidepressant treatment. In the best of circumstances—which is what the trial was designed to evaluate—only one out of three depressed patients showed a lasting recovery from depression, and since there was no evaluation of what the recovery rate might have been with placebo treatment, there was no way of knowing whether their recovery was actually due to the medication they had been given.

In her review of the Kirsch reanalysis of the STAR*D study, Joanna Moncrieff said STAR*D suggests that in real life situations, people who take antidepressants do not do very well. “In fact, given that for the vast majority of people depression is a naturally remitting condition, it is difficult to believe that people treated with antidepressants do any better than people who are offered no treatment at all.” She thought this might be the reason the results of the main outcome measure (the HRSD) remained unpublished for so long—and also an explanation for the substitution of the QIDS as an outcome measure. In the original STAR*D analysis:

Whether this was deliberate on the part of the original STAR-D authors or not, it was certainly not made explicit. There should surely be uproar about the withholding of information about one of the world’s most widely prescribed class of drugs. We must be grateful to Kirsch and his co-authors for finally putting this data in the public domain.

According to data gathered by the CDC, 10.7% of all U.S. adults in 2011-2014 reported using an antidepressant in the past 30 days. This is 5.9 times the reported usage for 1988-1994. Demographically, the percentages of U.S. adults who used antidepressants increased with age. The percentages of women using antidepressants were also consistently higher then men for all age groups. Yet their effectiveness in treating depression has been shown to be little better than a placebo. And given that they have a multitude of adverse effects—even the SSRIs—in most cases, no medication may be better than an antidepressant.

See “Dirty Little Secret” and “Do No Harm with Antidepressants” on this website for more information on the antidepressant research of Irving Kirsch. See “The Lancet Story on Antidepressants,” Part 1 and Part 2 for more on the ongoing debate over the effectiveness of antidepressants. See “Antidepressant Fall From Grace, Part 1” for a brief history of antidepressants.

04/20/18

The Lancet Story on Antidepressants, Part 2

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While introducing his review on The Mental Elf of a Lancet study by Cipriani et al., “Comparative efficacy and acceptability of 21 antidepressant drugs,” Andre Tomlin commented how it had been a rough few months where “anti-antidepressant voices” really hit the mainstream. Neuroskeptic thought the study was a nice piece or work, but had very little new information. He also thought the media hype over it was “frankly bananas.” In Part 1 of this article, I looked at the more positive responses to the Cipriani et al. study. Here we will look at the rest of the story from the “anti-antidepressant voices.”

Turn to Part 1 if you want to hear what The Mental Elf and Neuroskeptic had to say about the Cipriani et al. study first. Here we’ll look at the thoughts of Peter Gøtzsche, Joanna Moncrieff and the Council for Evidence-Based Psychiatry.

Tomlin seems to question Gøtzsche’s ‘evidence,’ that antidepressants actually kill people who take them. But turn to “In the Dark About Antidepressants” or “Psychiatry Needs a Revolution” for more on Gøtzsche’s ‘evidence’ on the harm from antidepressants before you dismiss his claims. Remember that Peter Gøtzsche is a careful medical researcher and the Director of the Nordic Cochrane Center. Along with 80 others, he helped start the Cochrane Collaboration in 1993, which is “a global independent network of researchers, professionals, patients, carers, and people interested in health.”

In “Rewarding the Companies that Cheated the Most in Antidepressant Trials, “ Dr. Gøtzsche’s opening comment was: “It is well known that we cannot trust the data the drug companies publish, and it seems that, in psychiatric drug trials, the manipulations with the data are particularly pronounced.” He described, with supporting citations, how half the deaths and suicides that occur in randomised drug trials are not published. When independent researchers have the opportunity to analyze trial data themselves, “the results are often markedly different to those the companies have published.” He then said:

Fraud and selective reporting are of course not limited to the most serious outcomes but also affect other trial outcomes. Several of the authors of a 2018 network meta-analysis in the Lancet are well aware that published trial reports of depression pills cannot be trusted. I therefore do not understand why they are authors on this paper.

He noted how most of the data analyzed by the Cipriani et al. study came from published trials reports, “which we know are seriously unreliable for depression trials.” Gøtzsche pointed out where one of the coauthors for the study had previously coauthored a study showing that “the effect of depression pills was 32% larger in published trials than in all trials in FDA’s possession.” In his opinion, the meta-analytic analysis of the Cipriani et al. study had no clinical value and was “so complicated that it is impossible to know what all this leads to. But we do know that statistical maneuvers cannot make unreliable trials reliable.”

In addition to the doubtful effect of antidepressants noted in the study (see Part 1), Gøtzsche thought ranking the drugs according to their effect and acceptability was a futile exercise. “My thought was that the authors had rewarded those companies that had cheated the most with their trials.” He said it was highly unlikely that some depression pills were both more effective and better tolerated than others.

One doesn’t need to be a clinical pharmacologist to know that this seems too good to be true. Drugs that are more effective than others (which is often a matter of giving them in higher, non-equipotent doses), will usually also be more poorly tolerated.

The reality is that despite serious flaws in depression drug trials, “the average effect is considerably below what is clinically relevant.” That was demonstrated in the Cipriani et al. study and has been shown in several other studies. Examples of the serious flaws noted by Gøtzsche included: “[a] lack of blinding because of the conspicuous adverse effects of the pills, cold turkey in the placebo group because people were already on depression pills before they were randomised, industry-funding, selective reporting and data massage.” He concluded the benefits to harm of depression pills meant that placebo was better than the drug.

Joanna Moncrieff was appalled at the almost universally uncritical coverage given to the Cipriani et al. study. In her article, “Challenging the new hype about antidepressants,” she noted where John Geddes, one of the study’s coauthors, said only one in six people with depression receive effective treatment; and he wanted to make that six out of six. By her calculations, if 9% of the UK population is already taking antidepressants, “and they only represent 1 in 6 of those who need them, then 54% of the population should be taking them. I make that another 27 million people!” Dr. Moncrieff went on and noted once again, that despite the hype, there was nothing groundbreaking in this latest meta-analysis. “It simply repeats the errors of previous analyses.”

The analysis consists of comparing ‘response’ rates between people on antidepressants and those on placebo. But ‘response’ is an artificial category that has been arbitrarily constructed out of the data actually collected, which consists of scores on depression rating scales, like the commonly used Hamilton rating Scale for Depression (HRSD). Analysing categories inflates differences (3). When the actual scores are compared, differences are trivial, amounting to around 2 points on the HRSD, which has a maximum score of 54. These differences are unlikely to be clinically relevant, as I have explained before. Research comparing HRSD scores with scores on a global rating of improvement suggest that such a difference would not even be noticed, and you would need a difference of at least 8 points to register ‘mild improvement’. [See her article for the noted citations and a link to her previous discussion on the HRSD]

Participants in a clinical trial can deduce whether or not they are in the experimental group with the antidepressant medication by recognizing the side effects with antidepressant medication “(e.g. nausea, dry mouth, drowsiness and emotional blunting) irrespective of whether or not they treat depression.” If that happens, these participants may then receive an amplified placebo effect by knowing they are taking an active drug rather than an inactive placebo. “This may explain why antidepressants that cause the most noticeable alterations, such as amitriptyline, appeared to be the most effective in the recent analysis.”

She also pointed out ‘real world’ studies showing the long-term effects of people treated with antidepressants. “The proportion of people who stick to recommended treatment, recover and don’t relapse within a year is staggeringly low (108 out of the 3110 people who enrolled in the STAR-D study and satisfied the inclusion criteria).”  Several studies have found that the outcomes for people treated with antidepressants “are worse than the outcomes of people with depression who are not treated with antidepressants.” Moncrieff said calling to increase the use of antidepressants, as Geddes did, will not address the problem of depression and will only “increase the harms these drugs produce.”

As the debate around the [media] coverage highlighted, many people feel they have been helped by antidepressants, and some are happy to consider themselves as having some sort of brain disease that antidepressants put right. These ideas can be reassuring. If people have had access to balanced information and decided this view suits them, then that is fine. But in order for people to make up their own minds about the value or otherwise of antidepressants and the understanding of depression that comes in their wake, they need to be aware that the story the doctor might have told them about the chemical imbalance in their brain and the pills that put it right, is not backed up by science [see her article for a link to this topic], and that the evidence these pills are more effective than dummy tablets is pretty slim.

The Council for Evidence-Based Psychiatry also pointed out “the new research proves nothing new.” Further, they cited where the Royal College of Psychiatrists (RCP) represented the Cipriani et al. study as “finally putting to bed the controversy on anti-depressants.”

This statement is irresponsible and unsubstantiated, as the study actually supports what has been known for a long time, that various drugs can, unsurprisingly, have an impact on our mood, thoughts and motivation, but also differences between placebo and antidepressants are so minor that they are clinically insignificant, hardly registering at all in a person’s actual experience.

Then on February 24th, the President of the Royal Collage of Psychiatry and the Chair of its Psychopharmacology Committee stated in a letter to The London Times that: “the vast majority of patients, any unpleasant symptoms experienced on discontinuing antidepressants have resolved within two weeks of stopping treatment.” This led to a “Formal Complaint to the UK Royal College of Psychiatrists” when Professor John Read and others wrote to the RCP disputing that claim. The formal complaint stated:

To mislead the public on this issue has grave consequences. People may be misled by the false statement into thinking that it is easy to withdraw and may therefore try to do so too quickly or without support from the prescriber, other professionals or loved ones. Other people, when weighing up the pros and cons of starting antidepressants may make their decision based partly on this wrong information. Of secondary concern is the fact that such irresponsible statements bring the College, the profession of Psychiatry (to which some of us belong), and – vicariously – all mental health professionals, into disrepute.

The complaint cited several research papers documenting how withdrawal effects from antidepressants “often last far longer than two weeks.” The cited research included a study done by the Royal Collage of Psychiatry (RCP) itself, “which found that withdrawal symptoms were experienced by the majority (63%), generally lasted for up to 6 weeks and that a quarter reported anxiety lasting more than 12 weeks. Within 48 hours of the misleading statement in The Times, the survey results were removed from the RCP website, as was a leaflet by the RCP on antidepressant withdrawal. You can listen to a podcast interview with Professor John Read here. There is a link to the RCP leaflet and The Times article there as well.

Stay tuned; this controversy isn’t over yet. In conclusion, to paraphrase Paul Harvey, “Now you know the rest of the Lancet story on antidepressants.”

07/21/17

Blind Spots with Antipsychotics, Part 2

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The American Journal of Psychiatry published an article by Goff et al. that addressed concerns that antipsychotic medications can adversely effect long-term outcomes of people with schizophrenia. Their conclusion was that there was little evidence to support “a negative long-term effect of initial or maintenance antipsychotic treatment on outcomes,” when compared to withholding medication treatment. Additionally, the researchers said while a subgroup of patients may benefit from “nonpharmacological treatment approaches,” they warned of the potential for an “incremental risk of relapse” and recommended the need for further research into the question. But did these researchers have a blind spot in how they evaluated their evidence?

In part one of this article, I reviewed some of the research evidence that supported concerns with long-term antipsychotic treatment. There was evidence supporting a link between long-term antipsychotic use and adverse cardiovascular events, brain shrinkage, and dopamine supersensitivity, as well as questions regarding the efficacy of antipsychotic maintenance treatment. There also seemed to be a disregard in Goff et al. of the evidence for the risk of metabolic syndrome with long-term antipsychotic use in their risk-benefit analysis of antipsychotic use. Yet health concerns from metabolic syndrome have been connected to the glaring difference in a shortened life expectancy, with persons suffering with serious mental illness dying 25 years earlier than the general population.

My previous encounters with Dr. Jeffrey Lieberman, who was the lead researcher for Goff et al., have led me to be cautious of his assertions without further investigation. I believe he has a serious blind spot when it comes to assessing and interpreting information counter to his position. See (“A Censored Story of Psychiatry, “Part 1, Part 2;  “Psychiatry, Diagnose Thyself!” Part 1, Part 2) for more on my concerns with Dr. Lieberman. So if there was a blind spot in Goff et al., what do other experts have to say about their conclusions?

Joanna Moncrieff wrote a response to Goff et al. on the Mad in America website, which can be accessed here. Moncrieff is a practicing psychiatrist, academic and author. She is one of the founding members and current co-chair person for the Critical Psychiatry Network, “a group of psychiatrists from around the world who are sceptical of the idea that mental disorders are simply brain diseases and of the dominance of the pharmaceutical industry.” She has written extensively on this issue, including a recent book on the troubling story of antipsychotic drugs entitled: The Bitterest Pill. You can read more about her thinking and her background on her website. She said she was shocked by how Goff et al. dismissed the concerns with long-term antipsychotic treatment and the evidence of brain impacts.

It is riddled with distortion, ignores the most pressing criticisms, and is shot through with the unexamined presumption that the multitude of problems currently labelled as schizophrenia or psychosis will one day be revealed to be due to a specific brain abnormality that is targeted by antipsychotics.

She doesn’t dispute the usefulness of antipsychotics for treating acute psychosis, what Goff et al. called initial antipsychotic treatment. Yet she noted where “decades of research into early intervention has not demonstrated that early antipsychotic treatment improves long-term outcomes.” She pointed out where Goff et al. stated the effectiveness of maintenance treatment has been well established, but then failed to acknowledge that randomised trials of maintenance treatment were typically maintenance treatment versus sudden withdrawal. “Thus they completely fail to address concerns that effects of withdrawal of long-term treatment inevitably confound such studies.”

The most worrying thing about the Goff et al. paper to Moncrieff was the minimization of the evidence that antipsychotics produce brain shrinkage. They claim that shrinkage of brain grey matter has been shown to be part of schizophrenia, claiming that brain differences were detected long before the introduction of antipsychotics. The paper they cited was a 1985 study by Bogerts and Schonfeldt-Bausch, which was a post mortem study done long after antipsychotics had been introduced.

The presence of differences between the brains of people with schizophrenia and controls does not establish that there is progression of brain volume loss, which is what has been clearly demonstrated in people and animals taking antipsychotics. There are no studies that show progressive brain changes in people diagnosed with schizophrenia or psychosis in the absence of antipsychotic treatment.

Dr. Moncrieff concluded her article by saying:

I still think antipsychotics can be useful, and that the benefits of treatment can sometimes outweigh the disadvantages, even in the long-term for some people. However, it does no one any service to pretend that they are innocuous substances that somehow magically transform (hypothetically) abnormal schizophrenic brains back to normal. Psychiatrists need to be fully aware of the detrimental effects of antipsychotics on the brain and body. They also need to acknowledge the way these drugs make life so miserable for many people, even for some who might have been even more distressed were they to be without them… Psychiatrists need to support people to evaluate the pros and cons of antipsychotic treatment for themselves and to keep doing this as they progress through different stages of their problems. To do this they need to be able to acknowledge the real nature of these drugs, and not sweep inconvenient truths under the carpet!

Miram Larsen-Barr also wrote a response to Goff et al. that appeared on Mad in America, which can be accessed here. She is a clinical psychologist with the University of Auckland, New Zealand. Larsen-Barr created and is the Service Director for Engage Aotearoa, an initiative that aims to make recovery information more easily accessible to the general public. She has “lived experience” of recovery from trauma, depression and suicidality. Her doctoral research explored experiences of taking, and attempting to stop, antipsychotic medication.

For her doctoral research she talked to 144 people who take or have taken antipsychotics. One-third thought antipsychotics had relieved their symptoms and given them back their lives—but another third said quite the opposite. She said the claim that the benefits of antipsychotic medications conclusively outweigh the adverse effects is just not true. It is true for some; entirely the opposite for others; and a mixed bag for the remaining individuals. You can access a copy of her thesis research here.

In my study, overall subjective experiences ranged on a continuum from “life-saver” to “hell” and every point between (Larsen-Barr, 2016). Around a third reported overall positive experiences such as “A major relief from the monsters […] for me they have saved my life” and “Helped me get through an unstable period of my life.” And around a third of the participants reported mixed experiences such as, “A short term help when needed then a burden” and “A double edged sword. They help me with my bad experiences but they also take away the wind in my sails.”Another third reported wholly negative experiences such as, “The worst experience of my life […] affected every aspect of my health and wellbeing.” The therapeutic benefits certainly did not outweigh the costs for those who described the overall experience of taking antipsychotics as “The ruin of my life” or said they were “Helpful to a point but […] robbed me of everything I value in myself as a person.”

Larsen-Barr reported that few people in her study reported being well-informed of the potential benefits and risks before antipsychotic treatment. While about one-third reported beneficial results, 79% overall did contemplate stopping their medication, with 73% making at least one attempt. She said her study suggested the desire to stop antipsychotic medications was not just because of negative experiences. These decisions were primarily based upon whether or not taking AMs helped the person to “function in daily life.”

A full third of her survey sample had discontinued medications at the time of the study, which was similar to the stable discontinuation rate found in Harrow’s long-term study. Larsen-Barr found half of 105 survey participants who attempted to stop remained AM-free for one year or more; some over five years ago. Her research showed “withdrawal often entails a lack of information, poor support, and a range of physical, emotional, cognitive, social and functional disruptions that can be difficult to cope with, and which may include exacerbation of symptoms to the point of relapse.” For more on the Harrow study and concerns with antipsychotics, see “The Case Against Antipsychotics” by Robert Whitaker and “Worse Results with Psych Meds” on this website.

In part 1 of this article there was a discussion of how Carrie Fisher’s sudden cardiac death may have been associated with her use of psychiatric medications. Yet the possibility of her medications being a contributing factor to her death seemed to be overlooked in many articles about her unexpected death. For example, writing for Scientific American, Tori Rodriguez raised the possibility that Fisher’s bipolar disorder played a role in her death. Not the medication used to treat her bipolar disorder, but the disorder itself.

“Did Carrie Fisher’s Bipolar Disorder Contribute to Her Death?” noted several possible connections to her bipolar disorder, but only made an oblique comment about how the medications may cause adverse effects like weight gain, diabetes higher triglycerides and even sudden cardiac death. Rodriguez noted how Fisher’s earlier substance abuse and struggles with her weight have been speculatively raised as contributing factors to her death. But she said one possibility that has been overlooked was the connection between bipolar disorder and cardiovascular disease and mortality. Individuals with bipolar disorder are twice as likely to develop or die from cardiovascular disease. The onset of cardiovascular disease occurs up to 17 years earlier in persons with bipolar disorder than in the general population. But as we’ve seen, that connection seems to be with the medications and not the disorder itself.

Rodriguez said Carrie Fisher “fit the bill” for several of the risk factors for sudden cardiac death at different points in her life. Then she said: ‘There is no definitive way to know whether her bipolar disorder or addiction history contributed to her death.” Yet there does seem to be a strong likelihood that not only did her use of antipsychotic medications help her be a better mother, friend and daughter, it may have contributed to her sudden cardiac death as well.

01/13/17

Iatrogenic Gun Violence

© StephanieFrey | stockfresh.comfresh eggs. Araucanas are also known as the Easter Chicken for the blue or greenish colored eggs they lay.

Whenever I read about horrific violence like the incident in the Fort Lauderdale airport, I wonder what role psychiatric medications played. I wonder if the violent behavior was iatrogenic—was it caused by psychiatric medications? This question will sound counter intuitive for many people. Surely the reverse is true. Psychiatric medication and proper diagnosis should have prevented it. Let’s see if it is.

Esteban Santiago was deployed to Iraq from April 2010 to February 2011 with the 130th Engineer Battalion, the 1013th Engineer Company of the Puerto Rico National Guard. After flying from Alaska to Fort Lauderdale Florida, he retrieved his baggage, which incidentally contained a semi-automatic handgun. Santiago had followed proper protocol, checking the weapon with TSA. He went into the men’s bathroom, loaded his weapon and opened fire in Terminal 2 of the airport, killing five people and wounding six others. A witness said he was just randomly shooting people, with no rhyme or reason to it.

Family members reported that he was a changed man when he returned from Iraq. His aunt said his mind was not right. At times he seemed normal, but other times he seemed lost. In Iraq, his unit cleared roads of improvised explosive devices and maintained bridges. Two people in his unit died while he was in Iraq. His aunt said: “He talked about all the destruction and the killing of children. He had visions all the time.” He had changed.

His brother Bryan confirmed that recently Esteban was hallucinating, but said he was receiving psychological treatment. Bryan said he believes the shooting rampage resulted from mental issues that surfaced after the Iraq tour. When Esteban’s tour ended, he was hospitalized for mental problems. Upon his release, he went to Puerto Rico where his father was ill and eventually died. While in Puerto Rico, he received mental health therapy. Esteban eventually moved to Alaska, where he joined the Alaska National Guard in November 2014. He was discharged in August of 2016.

Over the course of 2016, Santiago was repeatedly reported to Anchorage police for physical disturbances. In January of 2016 he was arrested and charged with assault and criminal mischief after an argument with his girlfriend. He allegedly yelled at her while she was in the bathroom and broke down the bathroom door. She told investigators that he tried to strangle her and struck her on the side of the head.

Santiago pleaded no contest to criminal mischief and assault charges. Under a deferred prosecution agreement, his charges would have been dismissed if he complied with the conditions. He was due back in court on March 28th, 2017 to assess his progress.

While living in Alaska, Esteban continued to receive psychological treatment, according to his brother. Although his girlfriend alerted the family to the situation in Alaska, Bryan said he did not know what mental health problem Esteban was being treated for; they never spoke about it by phone.

His son was born in September of 2016. In November of 2016, Esteban walked into an FBI office in Anchorage to report that his mind was being controlled by a U.S. intelligence agency. He told officials he had a firearm in his car, along with his newborn son. Santiago was checked into a mental health facility; his firearm was logged as evidence for safe keeping. The infant’s mother came for their child. FBI special agent Marlin Ritzman said:

During the interview, Mr. Santiago appeared agitated, incoherent and made disjointed statements. Although he stated he did not wish to harm anyone, as a result of his erratic behavior our agents contacted local authorities, who took custody of Mr. Santiago and transported him to the local medical facility for evaluation.

After conducting database reviews, interagency checks and interviews with his family members, the FBI closed its assessment of Santiago. Agents found no ties to terrorism during their investigation. A CNN senior law enforcement analyst and former FBI assistant director said Santiago hadn’t been adjudicated a felon and he hadn’t been adjudicated as mentally ill. So they couldn’t keep his weapon. The Walther 9-millimeter pistol was returned to him in the beginning of December. Authorities told CNN it was the pistol he used in the shooting incident in Fort Lauderdale.

Typically, Esteban was considered to be a calm young man who was never violent. Recently he began selling his possessions, including his car. Friends and associates noticed more erratic behavior. He bought a one-way ticket to Fort Lauderdale and packed his pistol and two magazines. His carryon bag with the pistol was his only luggage. He flew from Anchorage to Minneapolis to Fort Lauderdale. He retrieved his bag from the baggage claim area and went into a men’s room stall to load his pistol.

He shot the first people he saw, going up and down the carousels of the baggage claim, shooting through luggage to get at people that were hiding. He thinks he fired 15 bullets, aiming at his victim’s heads. A witness said Esteban showed no remorse. He didn’t say anything. “No emotion, no nothing. About as straight-faced as you get.” Afterwards, he just lay face down, spread eagle, waiting for the deputies to come and get him.

The above report was pieced together from information contained in the following reports by The New York Times here,  NJ.com here, CNN here, and NPR here.

There was no explicit mention of Santiago’s repeated involvement in “psychological treatment” involving psychiatric medications, but it highly probable he was taking psychiatric medication of some sort. The lack of any mention of his being prescribed medication may simply be due to confidentiality regulations. Or this silence could be due to the chicken-and-egg argument often applied to incidents involving violence and individuals with known psychiatric problems. Their mental illness, not the drugs to treat it, caused their horrific behavior.

Several psychiatrists have voiced concerns with psychiatry, its over reliance upon medication and denial of serious adverse effects from medication, like violence and suicide. Joanna Moncrieff said she’s sad her profession has not taken the harms drug treatments can do more seriously. She said it has a long history of ignoring the adverse effects of drugs, or attributing them to the underlying disease—of blaming the patient instead of the drug. “Too many psychiatrists have just accepted that drug treatments are good, and have not wanted to contemplate that actually these treatments could be harmful.”

First and foremost, she said, psychiatry needs to adopt a drug-centered model for understanding its drug treatments and what they do to people. Psychiatrists need more information, knowledge and training on what the drugs do—what effects they produce in people; “how they change the way that people think and feel and what sort of impact those changes have on people’s lives.” Watch two brief videos of her expressing her concerns here. You can read more about her “drug-centered model” here on this website: “A Drug is a Drug is a Drug.”

Peter Breggin has raised concerns with the association of violence and antidepressants since the early days of Prozac. In his 1991 book, Toxic Psychiatry, Dr. Breggin related newspaper and scientific reports pointing to an association between Prozac and “compulsive, self-destructive and murderous activities.” He said then he was personally familiar with several cases of compulsive suicidal or violent feelings that developed after taking Prozac. Over the years, his familiarity grew.

In “Psychiatry Has No Answer to Gun Massacres,” Breggin described how the Columbine High School shooter, Eric Harris had a “therapeutic” level of Luvox (fluvoxamine) in his body at the time of the murders.  He had a dose increase in his medication 2 ½ months before the assault and showed signs of drug toxicity five weeks before the event. James Holmes, the Aurora Colorado theater shooter, was in psychiatric treatment with the medical director of student health services, who was considered an expert on campus violence. She was concerned enough about Holmes to report him to the campus police and the campus threat assessment team a few weeks before the assault. When the assessment team suggested putting him on a 72-hour involuntary hold, she rejected the idea. “When Holmes quit school, the school washed its hands of all responsibility for him.”

In a 2010 journal article, “Antidepressant-Induced Suicide, Violence, and Mania: Risks for Military Personnel,” Dr. Breggin related how the adverse effects described in the 2009 edition of the Physicians’ Desk Reference for Zoloft (sertaline) resembled the most frequent psychiatric disorder associated with combat—PTSD—with its hyperalert overstimulated symptoms. He said identical or nearly identical warnings can be found in all antidepressant labels. “All these potentially dangerous symptoms are also commonly seen in PTSD in military personnel, posing the risk of worsening this common military disorder.”

Looking at the revised 2016 medication guide for Zoloft, we see that nothing much has changed with regard to adverse effect warnings. It said Zoloft and other antidepressant medications could increase suicidal thoughts or actions. Symptoms needing immediate attention included: acting aggressively or violent, feeling agitated, restless angry or irritable, an increase in activity or talking more than what is normal, acting on dangerous impulses, trouble sleeping, new or worse anxiety or panic attacks, trouble sleeping, other unusual changes in behavior or mood.

A condition known as “serotonin syndrome” has symptoms such as: agitation, hallucinations, coma and other changes in mental status. Symptoms of potential manic episodes included: greatly increased energy, racing thoughts, unusually grand ideas, severe trouble sleeping’s, reckless behavior, excessive happiness, talking more or faster.

Dr. Breggin concluded his article with the following cautions and recommendations. He said there was a strong possibility the increased suicide rates among active-duty soldiers were in part caused or made worse by the widespread prescription of antidepressant medication. Alone, they can cause a stimulant-like series of adverse effects. “These symptoms of activation can combine adversely with similar PTSD symptoms found so commonly in soldiers during and after combat.” He recommended the military study the relationship between psychiatric drug treatment and suicide as well as random or personal violence. He also suggested that antidepressants should be avoided in the treatment of military personnel.

Another emerging concern of an association between antidepressants and violence is in the research done by Yolande Lucire. She suggested that mutations in CYP450-encoding genes contributed to problems metabolizing psychiatric drugs, and thus were contributing factors in three cases of antidepressant-induced akathisia-induced homicide. The cytochrome P450 family of enzymes is responsible for metabolizing most of the drugs used in psychiatry. You can read her article here. You can also find another article: “Psych Drugs and Violence” on this web site. Within that article you will find a link to another article by Lucire on antidepressant-induced akathisia-related homicide and the CYP450 genes.

Hasn’t there been enough evidence associating suicide and violence with psychiatric medications, especially antidepressants, for open dialogue and more comprehensive scientific research into this public health issue? How many more Columbines, Auroras and Fort Lauderdales need to happen before we begin to address the association of psychiatric drugs and violence?

07/12/16

Common Sense with Lithium

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© Suljo | stockfresh.com

Lithium carbonate (not the element lithium) is used as a psychiatric medication primarily with bipolar disorder. It can be used with other psychiatric disorders such as major depression and schizophrenia, when first line medications are not effective. There are several advantages to lithium, particularly when it comes to cost. Available as a generic medication, a typical daily dose costs between 90 cents and $1.20. Major downsides are that therapeutic doses are just lower than toxic doses and there is the potential of direct damage to the kidneys and thyroid.

The website drugs.com said that since the toxic levels for lithium are so close to the therapeutic levels, patients and their families should watch for early symptoms, then discontinue the drug and inform the physician should they occur. Indications of lithium toxicity may include: diarrhea, vomiting, drowsiness, muscular weakness and lack of coordination. There are a host of other potential side effects that include: confusion, dry mouth, muscle twitching or trembling, vertigo, increased urination, memory problems and weight gain. These are only a few of the side effects found in 10% or more of the persons using lithium. See drugs.com or the Wikipedia listing for a more detailed discussion of lithium side effects.

In the late 1800s lithium was a popular ingredient in elixirs and tonics. It was even added to beer and other beverages. The theory was that it dissolved uric acid, so it could break up kidney stones and the uric acid crystals associated with gout. It was found to have no such effects. Lithium was eventually banned by the FDA in 1949 when it was found to cause cardiovascular problems.

Coincidentally, that same year an Australian physician named John Cade published a paper describing his treatment of 10 patients with mania with lithium. Cade had noticed that lithium made guinea pigs docile, so he thought it could have a therapeutic effect in manic patients. He announced dramatic effects in his paper and claimed they were specific to mania. What he failed to mention was that one patient died, two others had to discontinue lithium because of severe toxicity and one patient refused to take it. None of this was reported in his paper. Side effects were noted 41 times in the clinical records, but only 1 time in the published article. See The Myth of the Chemical Cure by Joanna Moncrieff for a more detailed description of lithium as a psychiatric treatment.

In Anatomy of an Epidemic, Robert Whitaker noted that psychiatrists in the U.S. had little interest in lithium until manic-depression was distinguished into unipolar and bipolar forms. Only a few placebo-controlled trials of lithium had ever been done up to that point. In 1985 UK researchers could only identify four with any merit. But within those studies, lithium was said to have a good response rate in 75% of the patients. This was much higher than the response rate in the placebo group.

A 1994 meta-analysis of nineteen studies by J.P. Baker of patients who were on lithium and had their lithium withdrawn showed that 53.7% of the patients relapsed, versus 37.5% of the lithium-maintained patients. This was seen as clear evidence that lithium prevented relapse. However, only 29% of patients who were gradually withdrawn from lithium relapsed. Note how this rate was better than those in the drug-maintained group.

Whitaker said this wasn’t very robust evidence of lithium’s benefit to patients, especially when you considered the additional studies raising concerns about lithium’s long-term effects. There was also a high rate of patients who stopped taking lithium—over 50%—because of how the drug dulled their minds and slowed their physical movements. In 1999 Baldessarini et al. found that almost half of all patients relapsed within five months of quitting lithium, while individuals who did not use lithium took nearly three years to reach that percentage of relapse. “The time between episodes following lithium withdrawal was seven times shorter than it was naturally.” Whitaker noted:

Although lithium is still in use today, it lost its place as a first-line therapy once “mood stabilizers” were brought to market in the late 1990s.

Now there has been a growing body of evidence that suggests lithium prevents suicide. In 2003 Baldessarini and others found that long-term lithium maintenance patients had lower suicide rates than individuals who did not. Cipriani et al. found lithium was an effective treatment for reducing the risk of suicide in people with mood disorders as well as bipolar disorder. Lewitzka et al. did a comprehensive review of more than 20 years of studies investigating the anti-suicide effect of lithium in patients with affective disorders. They also concluded lithium to be “an effective treatment for reducing the risk of suicide and suicide attempts in patients with affective disorders over the long-term course.”

Joanna Moncrieff reviewed several meta-analyses indicating the anti-suicide effects of lithium in The Myth of the Chemical Cure and said the studies included in these analyses had conflicting results. An article on her website, “Lithium and Suicide: What Does the Evidence Show?” said the proposed effect of decreased mortality rates was inexplicable since lithium was a toxic drug that made most people feel rather depressed. She wondered if the sedating effect of the lithium sapped people of the will to act. “A closer look at the evidence, however, suggests the idea [lithium reducing suicidality] is simply not justified.”

The first issue was that the evidence supporting this idea consisted of follow-up studies with individuals on long-term lithium, as with Copper et al. Moncrieff commented how these people are a particularly compliant group with medication. “People who follow their lithium regime religiously are, in general, not likely to be the people who are chaotic, impulsive, desperate and most likely to commit suicide.” One study, by Gonzalez-Pinto et al., showed that people who were highly compliant with their lithium were five times less likely than those who were ‘poorly compliant’ to commit suicide. A second issue was that given small margin of error between therapeutic and toxic doses of lithium, people with suicidality tendencies are less likely to be given lithium.

Another confounding issue is that people with medical conditions are less likely to be given lithium. Not only can lithium cause kidney and thyroid problems, but it interacts with many commonly prescribed drugs like diuretics, ACE inhibitors and NSAIDS like aspirin and ibuprofen. This can result in dangerously high lithium levels. So caution is used when starting lithium with someone who is physically sick or taking other medication. Moncrieff said better randomized controlled trials are needed.

She thought it curious that a meta-analysis by Cipriani et al. in 2013 did not include a single placebo-controlled trial where the suicide rate was zero, so she looked more closely at its methology. Moncrieff discovered that the authors excluded any trial whose treatment arm was uninformative, namely those whose suicide rates were zero. “This decision is totally unsound, however, as it reduces the denominator (the total number of participants) and thereby makes the events included appear more common than they actually were.” She speculated this was why some well-known studies were not included in the analysis of suicides. When the studies with no suicides were included, “the number of participants would have been much larger and the proportion of suicides in the placebo group much smaller.”

 So there is the evidence on lithium and suicide. The meta-analysis that has been accepted as demonstrating that lithium prevents suicide spuriously inflated the suicide rate on placebo by excluding studies in which no suicides occurred. The only double blind, prospective study designed to test whether lithium reduces suicide in people at high risk, ended up unblinding many of its participants, and in any case suicidal events were low in both groups.

The fact that studies of suicide prevention have been so difficult to recruit to, suggests patients may have more sense than researchers in this field!

02/26/16

Hollow Man Syndrome

25674445_sOn her blog Joanna Moncrieff reflected on a memory she has of a young woman she encountered as a medical student in the 1980s who was confused and frightened when first brought to the hospital. She thought she was being watched and manipulated by evil forces. She believed there was something implanted in her body. Put on an antipsychotic, she became increasingly quiet as the dose was increased. But she also became emotionless, expressionless and physically sluggish. To Joanna, the woman seemed “empty and lifeless compared to what she had been before, although she was less distressed.” This was seen as making her ‘better.’

That reminded me of a young man I knew briefly around the same time who had a psychotic episode, triggered by his heavy use of marijuana. At least, that was his theory. My impression of him after his release from the hospital, where he also began using an antipsychotic, was that his personality had withered; he’d become a hollow man. A few years ago, I met briefly with someone trying to reclaim their thinking ability after taking lithium for over fifteen years. They wanted to cut back on the levels of lithium they were taking. We began working on that plan, but they kept getting caught up in a cognitive eddy of fear that they were going to lose their salvation. Was that psychosis or impaired thinking from the medication?

Another time I was concerned that after a first time manic episode an adolescent would remain on a maintenance dose of an antipsychotic for the rest of his/her life.  Over time I convinced the family to transfer care to a psychiatrist willing to taper the teen off the antipsychotic. The person’s dose was initially halved and symptoms of mania emerged within ten to fourteen days of the initial taper. Was that a suppressed bipolar disorder emerging or was it a reaction to too steep an initial taper? The reaction was viewed by the family as a manifestation of the bipolar disorder that had been kept at bay by a low maintenance dose of the antipsychotic. They decided to stop counseling with me.

These and other experiences have led to the several articles I’ve written on the complications and dangers of antipsychotic medications. Reading the thoughts of psychiatrists like Joanna Moncrieff, Peter Breggin, and David Healy and others on Mad in America over the years had an effect as well. I appreciate the approach of Dr. Moncrieff, who said: “There are times when the use of antipsychotic drugs seems to produce just enough suppression that people can put aside their psychotic preoccupations, and re-establish a connection with the outside world.” Yet she can still see where “they produce an artificial state of neurological restriction,” like a chemical straightjacket.

In my view antipsychotic drugs can be useful in suppressing psychotic symptoms, and sometimes, when people are beset by these symptoms on a continual basis, life on long-term drug treatment, even with all its drawbacks, might be preferable to life without it. But most people who experience a psychotic breakdown recover. [Emphasis added] In this situation, antipsychotics are recommended not on the basis that they provide relief from severe symptoms, but because they are said to reduce the risk of relapse.

The Cochrane Collaboration published a review of antipsychotic maintenance treatment for schizophrenia in 2012. Their report was the first systematic review comparing the effects of all antipsychotic drugs to placebo for maintenance treatment. This is standard care after an acute phase of schizophrenia to prevent relapse. (And it seems, if a teenage manic episode is suspected of being a latent bipolar disorder) Not surprisingly, they found that antipsychotics were more efficacious than placebo in preventing relapse, especially at seven to 12 months. But they noted it was rare to find a study that did follow up longer than 12 months.

Randomised controlled trials (RCTs) since the 1950s have consistently shown that antipsychotic drugs effectively reduce relapses and need for hospitalisation. Conversely, they are, as a group, associated with a number of side effects such as movement disorders, weight gain and sedation.

Moncrieff pointed out two additional problems with these kinds of comparisons. First is the fact that they don’t compare people started on long-term medication treatment and people who were drug free in the placebo groups. Rather, the latter group consists of people who are withdrawn from long-term antipsychotics. Usually the taper or withdrawal occurs too quickly, precipitating discontinuation symptoms, like with the teen I described above. “The difference in relapse rates is almost certainly exaggerated in these studies, therefore, especially since relapse is often defined only in terms of a modest deterioration in general condition or symptoms.”

Another problem is there is typically little data in the studies on anything other than the so-called “relapse,” which is too loosely defined in most studies. So global functioning could be worse for people on continuous drug treatment than they would have been without it, even if they did experience a relapse. “Since the data has not been collected, we just don’t know.”

The first problem perpetuates a distorted message of how antipsychotic medications prevent relapse. The second problem means there is no information on whether someone might be better off if they didn’t use medication.

Moncrieff recently published an article in PLOS Medicine that called for a rethinking of antipsychotic maintenance: “Antipsychotic Maintenance Treatment: Time to Rethink?” Her summary points in the article were:

  • Existing studies of long-term antipsychotic treatment for people with schizophrenia and related conditions are too short and have ignored the impact of discontinuation-related adverse effects.
  • Recent evidence confirms that antipsychotics have a range of serious adverse effects, including reduction of brain volume.
  • The first really long-term follow-up of a randomised trial found that patients with first-episode psychosis who had been allocated to a gradual antipsychotic reduction and discontinuation programme had better functioning at seven-year follow-up than those allocated to maintenance treatment, with no increase in relapse.
  • Further studies with long-term follow-up and a range of outcomes should be conducted on alternatives to antipsychotic maintenance treatment for people with recurrent psychotic conditions.

She described a long-term randomized controlled trial (RCT) by Wunderlink et al. in the Netherlands (in this article as well as in her blog) that confirms how long-term antipsychotic use will impair a person’s ability to function. The study also showed that when you gradually reduce people’s antipsychotics in a supportive manner, they are better off in the long-term.

This study should fundamentally change the way antipsychotics are used. These are not innocuous drugs, and people should be given the opportunity to see if they can manage without them, both during an acute psychotic episode and after recovery from one. If psychiatrists had not forgotten the lessons of the past, and if they had been prepared to acknowledge what they saw the drugs doing with their own eyes, this would have come about long ago.

The studies used to justify current clinical practice don’t provide reliable data on the pros and cons of long-term antipsychotic therapy. More research is needed to evaluate the efficacy of a gradual and individualized approach to antipsychotic discontinuation. Assessment of outcomes in addition to relapse is needed. Moncrieff recommended that while we await the results of further long-term discontinuation studies, that we reconsider antipsychotic maintenance treatment as the default strategy for people with recurrent psychotic disorders.

In “Psychiatric Drug-Induced Chronic Brain Impairment,” Peter Breggin described how chronic brain impairment (CBI) from chronic exposure to psychiatric drugs produces effects similar to those from a traumatic brain injury. He drew a parallel of effects between electroshock treatment, closed head injuries from repeated concussions (like what was portrayed in the movie, Concussion), and long exposure to psychiatric drugs:

The brain and its associated mental processes respond in a very similar fashion to injuries from causes as diverse as electroshock treatment closed head injury from repeated sports-induced concussions or TBI in wartime, chronic abuse of alcohol and street drugs, long-term exposure to psychiatric polydrug treatment, and long-term exposure to particular classes of psychiatric drugs including stimulants, benzodiazepines, lithium and antipsychotic drugs.

He said that by recognizing CBI, clinicians can enhance their ability to identify individuals who need to be withdrawn from long-term psychiatric drug treatment. Most patients show signs of recovery from CBI early in the withdrawal process. “Many patients, especially children and teenagers, will experience complete recovery.” With others, recovery could take place gradually; sometimes over years. Even when recovery is incomplete, Breggin said most patients wish to remain on reduced medication or none at all.

The symptoms of this syndrome include (1) Cognitive deficits, often first noticed as short-term memory dysfunction and impaired new learning, and difficulty with attention and concentration; (2) Apathy, indifference or an overall loss of enjoyment and interest in life activities; (3) Affective dysregulation, including emotional lability, loss of empathy and increased irritability; (4) Anosognosia or a lack of self-awareness about these changes in mental function and behavior.

09/2/15

Do No Harm with Antidepressants

© Jrabelo | Dreamstime.com
© Jrabelo | Dreamstime.com

In April of 2006, I first read Irving Kirsch’s 2002 article, “The Emperor’s New Drugs.” In that article, Kirsch described how 80% of the response to antidepressant medications was duplicated in placebo control groups. Kirsch’s analysis was of the very same clinical data submitted to the FDA between 1987 and 1999 for the approval of 6 widely prescribed antidepressants. The allusion to Hans Christian Andersen’s tale, “The Emperor’s New Clothes” was fitting. Kirsch played the role of the little boy in Andersen’s tale to my understanding of how antidepressants work. He pointed to antidepressants and said: “But they have little or no therapeutic effect at all!”

Since 2006 I’ve become familiar with the work of several individuals questioning the received wisdom of psychotropic medications, including Joanna Moncrieff. Her book, The Myth of the Chemical Cure, had its own “aha!” moment in the development of my thinking on the clinical use of psychiatric medications. A search of  “Faith Seeking Understanding” by their names will pull up other articles where I have referenced them.

Not too long ago, I saw a link to a new article by Joanna Moncrieff and Irving Kirsch, “Empirically derived criteria cast doubt on the clinical significance of antidepressant-placebo differences.” I’ve read previous articles written by Moncrieff and Kirsch, “Efficacy of antidepressants in adults” and “Clinical trials and the response rate illusion.” But still looked forward to reading their latest. It seems to have hammered home the final nail in the coffin of the ineffectiveness of antidepressants for me.

In “The Emperor’s New Drugs,” Kirsch found that the drug/placebo difference was less than 2 points on the Hamilton-D (HAM-D) scale, a scale often used in studies for assessing the effects of antidepressants. Even then, Kirsch et al. were saying that: “the clinical significance of these differences is questionable.” The spin put on his conclusions was that this was only to hold true only for individuals with mild cases of depression. Moderate to severe depression should still have antidepressants as a first-line treatment.

However, in “Efficacy of antidepressants in adults,” Moncrieff and Kirsch pointed out that the studies included in “The Emperor’s New Drugs,” were mainly with patients suffering with severe to very severe depression. They cited additional studies questioning the efficacy of antidepressants and concluded: “Recent meta-analyses show selective serotonin reuptake inhibitors have no clinically meaningful advantage over placebo;” and that “Claims that antidepressants are more effective in more severe conditions have little evidence to support them.”

In their most recent article, Moncrieff and Kirsch tackled the issue of how antidepressants have been shown to be statistically superior to placebo. This statistical significance has been true from the time of Kirsch’s work on “The Emperor’s New Drugs, ” where the authors said that: “Although mean differences were small, most of them favored the active drug, and overall, the difference was statistically significant.” Moncrieff and Kirsch commented that a three-point difference on the HAM-D scale could not be detected by clinicians. Clinically relevant drug-placebo differences would have to be 7 points or greater on the HAM-D scale. “Currently, drug effects associated with antidepressants fall far short of these criteria.”

These conclusions were built upon the work of German psychiatrist Stefan Leucht and his colleagues. You can read a less technical discussion of the importance of this research in Dr. Moncrieff’s blog, here. She said that a reduction of 2 points on the 52 point HAM-D scale, while statistically significant, seemed to be an insignificant amount. “Leucht et al. provide some empirical evidence to support that hunch.”

Given that there was little if any difference in clinically relevant effects between one treatment and another, Moncrieff and Kirsch suggested that patients and healthcare providers should be aware that all treatments, including placebo, produce some positive effect on symptom scales, “while none outperforms a pill placebo to a meaningful degree.”

The small differences detected between antidepressants and placebo may represent drug-induced mental alterations (such as sedation or emotional blunting) or amplified placebo effects rather than specific ‘antidepressant’ effects. At a minimum, therefore, it is important to ascertain whether differences correlate with clinically detectable and meaningful levels of improvement.

So where does this discussion lead us? Treating depressive symptoms with antidepressants should not be a first option. “Given the choice, most depressed patients prefer psychotherapy over medication.” Moncrieff and Kirsch suggest that decisions about treatment should include patient preference, safety and cost. With regard to safety, antidepressants should be a last choice for treatment alternatives.

Their article referenced a study by Andrews et al., “Primum non nocere” (first, do no harm), which noted a series of harmful effects from SSRIs. Serotonin has wide reaching effects on adaptive processes throughout the body and could have many adverse health effects. They described how antidepressants effect the proper functioning of homeostatic mechanisms in the body.  Long-term use is associated with a loss of symptom reducing effectiveness with SSRIs. This suggests that the brain is pushing back against the effects of SSRIs and trying to regain the homeostasis present before the use of antidepressants began. “Because of the complex role that serotonin plays in shaping the brain, antidepressants could have complex effects on neuronal functioning.”

Additional negative side effects included attention problems, driving performance, falling and bone fractures in the elderly, gastrointestinal problems such as diarrhea, constipation and irritable bowel syndrome. SSRIs may increase the risk of abnormal bleeding. They can related to an increase risk of cardiovascular events. There is concern that SSRIs can effect neonatal development. One study suggested SSRI use during pregnancy, especially the first trimester, led to an increased risk of Autism Spectrum Disorders. Andrews et al. summarized their findings here:

We have reviewed a great deal of evidence of the effects of antidepressants on serotonergic processes throughout the body. Some of the effects are widely known, but they have been largely ignored in debates about the utility of antidepressants. Indeed, it is widely believed that antidepressant medications are both safe and effective; however, this belief was formed in the absence of adequate scientific verification. The weight of current evidence suggests that, in general, antidepressants are neither safe nor effective; they appear to do more harm than good.

08/26/15

The Elephant in the Room

© tiero | 123rf.com
© tiero | 123rf.com

In 2006, Joanna Moncrieff asked why it was so difficult to stop psychiatric drug treatment? Received wisdom had answered that the difficulty arises from the underlying illness manifesting itself as the therapeutic effects of the medication becomes weaker. This presumes that the medications have disease-specific actions; that there is a disease-centered model of psychotropic drug action. But what if it had nothing to do with the original problem? Moncrieff suggested that problems experienced after psychiatric drug withdrawal were often related to the withdrawal process rather than the underlying condition. “If this is the case, then the recurrent nature of psychiatric disorders may be partially attributable to the iatrogenic effects of psychiatric drugs.”

She reviewed several case study examples to illustrate this concern and then indicated there were two possible mechanisms for withdrawal related disorders from this evidence. First, there were pharmacodynamic adaptations that took place. Long-term use of drugs that suppresses particular neurotransmitters (like serotonin in SSRIs) seems to cause an increase in number or a supersensitivity of the relevant receptors. When the receptors are no longer influenced by the drug, there is an over-activation of the neurotransmitter system—a rebound effect.

This may result in the characteristic discontinuation syndromes, may cause rapid onset psychosis and may act a source of  ‘‘pharmacodynamic stress,’’ which increases vulnerability to relapse.

A psychological reaction to the medication withdrawal, either by others or the patient, can also trigger symptoms or increase the patient’s vulnerability to relapse. Moncrieff said: “In my experience, psychological reactions by patients, staff and carers are important determinants of the success or failure of drug discontinuation, a proposition that is open to empirical testing.”

Moncrieff seems to be suggesting two things here. First, the importance of recognizing that post withdrawal symptoms will occur when a drug is tapered or stopped. Second, the importance of a system of support to the person seeking to successfully taper or stop their medications. Both of these factors are well known to anyone attempting to establish and maintain abstinence from addictive substances.

Along with David Cohen, Jonna Moncrieff suggested that we rethink our models of psychotropic drug action in their 2005 article. They noted the predominant “disease-centered model” of drug action that presumed psychiatric medications worked by acting on a specific disease process. In contrast, they suggested a “drug-centered model” that focused on the physiological, behavioral and subjective effects of the drug. Here, the therapeutic value of a drug stemmed from the usefulness of its effects in clinical situations. There is no presumption that it corrects some biological abnormality.

Moncrieff has also presented the differences between the disease-centered and the drug-centered models of drug action in her book, The Myth of the Chemical Cure. Moncrieff and Cohen used the distinction in a 2006 article, “Do Antidepressants Cure or Create Abnormal Brain States?” Applying the disease-centered model to antidepressants, they said:

Modelled on paradigmatic situations in general medicine—such as the use of insulin in diabetes, antibiotics in infectious disease, chemotherapy in cancer—the disease-centred model suggests that antidepressants help restore normal functioning by acting on the neuropathology of depression or of depressive symptoms.

Instead they proposed the drug-centered model was a better explanation for the observed drug effects in psychiatric conditions. “Instead of relieving a hypothetical biochemical abnormality, drugs themselves cause abnormal states, which may coincidentally relieve psychiatric symptoms.” After completing their analysis, they suggested that the term “antidepressant” should be abandoned, as the drugs were not treating a specific disease state.

Our analysis indicates that there are no specific antidepressant drugs, that most of the short-term effects of antidepressants are shared by many other drugs, and that long-term drug treatment with antidepressants or any other drugs has not been shown to lead to long-term elevation of mood.

This then brings us to “the elephant in the room”: a frank discussion on “The Psychoactive Effects of Psychiatric Medication” by Moncrieff, Cohen and Porter. They said when viewing the influence of psychiatric medications through the disease-centered model of action, their psychoactive effects have been obscured. “Despite six decades of intensive research in neuropharmacology … there is a lack of evidence that psychiatric drugs have a disease-specific action independent of their demonstrable psychoactive effects.” Approaching psychotropics as drugs that produce immediate and delayed psychoactive effects, with tolerance and dependence suggests that a radical change of thinking is needed.

Lessons from the use and misuse of other psychoactive substances can help to enlighten us about the broad range of behavioral effects that different psychiatric medications are likely to exert, and how these effects might interact with the psychological, behavioral, and other problems we call mental disorders.

Individuals who are prescribed psychiatric medications in this manner should be treated as consumers, “rather than passive recipients of diagnosis-driven prescribing.” The subjective experience of the individual would guide the use of psychiatric medications in a “collaborative dialogue” with the prescriber—rather than changes in symptoms or clusters of symptoms. “Only when we appreciate the nature of psychiatric drugs as psychoactive substances can we start to accumulate the knowledge necessary to enable prescribers and consumers to use these drugs safely and effectively.”

I heartily agree that we need to promote a drug-centered model of psychiatric drug action. However, additional changes will need to be made. Otherwise, the consumer-driven marketing model—“Ask your doctor if “X” is right for you”—will continue largely unchanged. Direct to the consumer advertising by Pharma will have to stop. Changes in how pharmaceuticals are approved though the FDA will have to occur. Better methodologies need to be developed for the approval process.

Transparency in pharmaceutical research needs to become the norm. Closer scrutiny into the potential harm and negative side effects has to occur, including long-term negative side effects. The psychoactive effect of drugs and its potential as negative side effect in all pharmacological products has to be weighed equally with the potential therapeutic benefit.