07/11/17

Blind Spots with Antipsychotics, Part 1

Carrie Fisher was flying back to her home in Los Angeles on December 23, 2016 when she went into cardiac arrest. She was removed from the plane and later died in the hospital. Her daughter, Billie Lourd, said: ““She was loved by the world and she will be missed profoundly.” She was a well-known actress, writer and humorist. She wrote six books, some of which described her life, loves and adventures, which included drug addiction and bipolar disorder. A series of articles lamented that she was taken too soon, but there wasn’t anything said about a possible connection between her sudden cardiac death (SCD) and the medication she took for her bipolar disorder.

Fisher was a vocal mental health advocate and talked freely about her bipolar disorder and over the years. An article contained the following statements made by Fisher about her mental health and use of medication. In an interview with Diane Sawyer in December of 2000, she said: “I am mentally ill. I can say that. I am not ashamed of that. I survived that, I’m still surviving it, but bring it on. Better me than you.” At a February 2001 rally in Indianapolis for increased state funding for mental health and addiction treatment, she said: “Without medication I would not be able to function in this world. Medication has made me a good mother, a good friend, a good daughter.”

Writing for Mad in America, Corinna West raised the question of whether Fisher’s too soon passing was related to her use of psych meds. West referred to an article in the European Heart Journal by Honkola et al. that concluded: “The use of psychotropic drugs, especially combined use of antipsychotic and antidepressant drugs, is strongly associated with an increased risk of SCD at the time of an acute coronary event.” Variety reported Carrie Fisher was taking Prozac (an antidepressant), Abilify (an antipsychotic) and Lamictal (a mood stabilizer).

This study confirms that combining antidepressants and old school [first generation] antipsychotics causes an 18-fold increase in death during a cardiac event. Combining antidepressants with any antipsychotic causes an over 5-fold increase in relative risk of death during a cardiac incident.

To put this into some context, West noted: “Vioxx was pulled from the market for a 2-fold increase in relative risk factor of strokes and heart attacks.” It may have led to the death of 50,000 to 70,000 people while it was on the market. She then did some speculative calculations and suggested psych meds may contribute to 74,191 additional heart attacks annually and 33,386 deaths from SCD per year.

She also noted how people with serious mental illness have a 25-year lower life expectancy than others and a significantly greater risk of myocardial infarction. The NASMHPD “Morbidity and Mortality Report” said that it has been known for several years that people with serious mental illness die younger than the general population. “In fact, persons with serous mental illness (SMI) are now dying 25 years earlier than the general population.” The report also said people with SMI also suffer from a greater percentage of modifiable risk factors associated with cardiovascular disease, such as obesity, smoking, diabetes, hypertension and dyslipidema (high cholesterol). Corrine West noted the data from the “Morbidity and Mortality Report” showed that psychiatric drugs increased 4 of the top 5 normal risk factors for cardiac disease. Smoking was included as a risk factor because many individuals using psych meds find the nicotine helps relieve some of the numbness caused by the meds. See the following chart from the report.

There is increasing evidence of multiple adverse effects from the long-term use of antipsychotics in addition to the risk of SCD. Murray et al. concluded there was a lack of evidence for the long-term effectiveness of prophylactic (maintenance) antipsychotic use; and a growing concern with the cumulative effects of antipsychotics on physical health and brain structure. “There is enough evidence concerning the adverse effects of antipsychotics on physical health to compel psychiatrists to act.”

Murray et al. said long-tem maintenance treatment with antipsychotics was “based on hope rather than evidence.” They pointed to two serious methodological problems. First, studies claiming that antipsychotic maintenance treatment substantially reduced the risk of relapse were often limited to two years of follow-up. Second, the studies compared schizophrenic patients continuing on antipsychotics with those who stopped taking antipsychotics, not individuals who never used the drugs. So the withdrawal effect from antipsychotics in the discontinuation group influenced the higher relapse rates, making it a confounding variable to the supposed positive results with antipsychotic maintenance treatment.

The Murray et al. researchers did think there was no clear link between antipsychotic-associated changes in brain structure and cognitive decline or functional impairment. However, studies like that of Ho et al. suggested antipsychotics can “have a subtle but measurable influence on brain tissue loss over time.” Ho et al. said there was also a problem with dopamine receptor supersensitivity in some antipsychotic users. This supersensitivity could be a factor in the decreased efficacy of antipsychotics with continued prescription; and it may contribute to relapse when an individuals stops using antipsychotics. “There is an urgent need for neurochemical imaging studies addressing the question of dopamine supersensitivity in patients.” In their conclusion, the researchers gave the following recommendations.

[The wise psychiatrist] will treat acute psychosis with the minimum necessary dose of antipsychotics, employing weight sparing antipsychotics wherever possible; dopamine partial agonists have this property and may also be less likely to induce dopamine supersensitivity. Following recovery, the psychiatrist should work with each patient to decrease the dose to the lowest level compatible with freedom from troublesome psychotic symptoms; in a minority of patients, this level will be zero.

You can read a summary review of the study by Justin Karter on Mad in America here.

Not all of the above-cited researchers agreed with the conclusions of each other. But collectively they pointed to evidence of a link between antipsychotics and adverse cardio vascular events, brain shrinkage, and dopamine supersensitivity. Murray et al. also suggested that studies of long-tem antipsychotic maintenance treatment unfairly stacked their results in favor of antipsychotic maintenance by using patients who were withdrawn/discontinued from using antipsychotics as their control group. So when the recent press release from Columbia Medical Center regarding Goff et al. concluded the benefits of antipsychotics outweigh the risks was disconcerting and confusing at first. The Goff et al. abstract asserted: “Little evidence was found to support a negative long-term effect of initial or maintenance antipsychotic treatment on outcomes, compared with withholding treatment.”

The press release acknowledged the above concerns that antipsychotic medications have been said to have toxic effects and negatively impact long-term outcomes. However it went on to say that if this view was not justified by data, it had the potential to “mislead some patients (and their families) to refuse or discontinue antipsychotic treatment.” Therefore a team of researchers led by Jeffrey Lieberman, the Lawrence C. Kolb Professor and Chairman of Psychiatry at Columbia University College of Physicians and Surgeon, undertook “a comprehensive examination of clinical and basic research studies that examined the effects of antipsychotic drug treatment on the clinical outcomes of patients and changes in brain structure.” Lieberman was liberally quoted in the Columbia press release with regard to their findings supporting how the benefits of antipsychotics outweigh the risks. He said:

The evidence from randomized clinical trials and neuroimaging studies overwhelmingly suggests that the majority of patients with schizophrenia benefit from antipsychotic treatment, both in the initial presentation of the disease and for longer-term maintenance to prevent relapse. . . . Anyone who doubts this conclusion should talk with people whose symptoms have been relieved by treatment and literally given back their lives.

Lieberman went on to suggest that only a very small number of individuals recover from an initial psychotic episode without the use of antipsychotic maintenance treatment. “Consequentially, withholding treatment could be detrimental for most patients with schizophrenia.” He acknowledged where rodent studies suggested antipsychotics can sensitize dopamine receptors, but “there is no evidence that antipsychotic treatment increases the risk of relapse.” Further, although antipsychotic medications can increase the risk of metabolic syndrome, which is linked to heart disease, diabetes and stroke, their study did not include a risk benefit analysis of this concern.

Wait a minute. Why didn’t their study include a risk benefit analysis for metabolic syndrome? It seems to be one of the most reliably documented adverse effects, as noted above. Could it be that the intended message of the research—namely how strong evidence supports the benefits of antipsychotic medications—would not have been as clearly communicated if the risk benefit analysis concluded there was a substantial risk of metabolic syndrome? By the way, according to the Mayo Clinic,

Metabolic syndrome is a cluster of conditions — increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels — that occur together, increasing your risk of heart disease, stroke and diabetes. Having just one of these conditions doesn’t mean you have metabolic syndrome. However, any of these conditions increase your risk of serious disease. Having more than one of these might increase your risk even more. If you have metabolic syndrome or any of its components, aggressive lifestyle changes can delay or even prevent the development of serious health problems.

Dr. Lieberman has been a vocal advocate of modern psychiatry and equally critical of those who question many of its claims, as with those documented here. My previous encounters with his presentation of evidence and data, like his discussion of the conclusions of Goff et al. above, have led me to be skeptical of his conclusions without further investigation. I believe his fervent desire to defend modern psychiatry and current psychiatric methods has distorted how he interprets and presents conflicting evidence. He seems to have a blind spot when assessing and interpreting evidence counter to his position. The above question about the failure to include a risk benefit analysis of metabolic syndrome is one illustration of what I mean.

So what do others have to say with regard to the Goff et al. study? We’ll look at some of those critiques in Part 2 of this article.

06/30/17

Rooting for the Underdog

In July of 2010, a 57-year-old partner at the law firm Reed Smith jumped in front of a subway train in Chicago and died. His widow, Wendy Dolin, sued the pharmaceutical companies GlaxoSmithKline (who originally manufactured Paxil) and Mylan (the drug company who manufactured paroxetine, the generic version that Stewart Dolin took), charging that the drug caused akathisia, which led to his suicide. GSK attorneys dismissed the testimony of the plaintiff’s expert witness as “junk science,” which argued for a link between the drug and suicide. However it seems the jury disagreed, since on April 20^th, 2017 they awarded a $3 million verdict for the plaintiff.

Mylan was released from the suit by the trial judge, who ruled they had no control over the drug’s label. GSK continues to maintain the company wasn’t responsible since it hadn’t manufactured the drug taken by Dolin. A Chicago Tribune article quoted Wendy Dolin as saying the ruling was “a great day for consumers.” The trial was not just about the money for her. It was about awareness to a health issue. But this isn’t the end. “Officials from the pharmaceutical company said the verdict was disappointing and that they plan to appeal.” GSK continues to assert they weren’t responsible because they didn’t manufacture the drug taken by Dolin.

Writing for Mad in America, attorney and activist Jim Gottstein noted the legal significance of the case, as it established GSK did not inform the FDA or doctors that Paxil could cause people to commit suicide—a conclusion GSK continues to deny. A second legal hurdle overcome by the ruling is a Catch-22 dilemma since SSRIs, like Paxil, are now usually prescribed as generics. “The generic drug manufacturer [Mylan} isn’t liable because it was prohibited from giving any additional information and the original manufacturer [GSK] isn’t liable because it didn’t sell the drug.” You can read Jim Gottstein’s article for an explanation of how these legal hurdles were overcome.

Bob Fiddaman interviewed Wendy Dolin after the verdict and she described some disturbing tactics used by GSK attorneys. She said depositions that should have been a few hours long became eight hours, “in an attempt to wear people down.” She said GSK asked the same question over and over again, hoping to confuse or manipulate people. She alleged they also called her friends, trying to get them to say something negative about her relationship with her deceased husband.

As a therapist, as a mother and a compassionate human being, I am aware there was no purpose to have done such. I have talked to therapists, physicians and pharmaceutical lawyers and all agree there was nothing gained by this other than to show me that GSK would stop at nothing to intimidate me.

During the trial it came to light that 22 individuals had died in Paxil clinical trials, 20 by suicide; two other deaths were suspected to be suicide. “All 22 victims were taking Paxil at the time, and 80% of these patients were over the age of 30.” GSK tried to argue their “illness” caused their deaths and not Paxil. Wendy Dolin said the lawsuit showed that “akathisia is a real, legitimate adverse drug reaction.” The public needs to be aware of its signs and symptoms.

Wendy said she knew even before they went to trial, that GSK would appeal the ruling if they lost. She thought there was a GSK lawyer in the courtroom during the trial gathering information for the appeal process. She said it had been suggested this case could go all the way to the Supreme Court, because GSK is afraid of the legal ramifications of a guilty verdict. The process could take 5-7 years. She said: “Clearly this case has never been about money. For me, it has always been about awareness, highlighting akathisia and ultimately changing the black box warning to include all ages.”

Writing for STAT News, Ed Silverman suggested the new head of the FDA, Scott Gottlieb, should require a stronger warning label for Paxil. “For the past decade, Paxil’s label has not carried any information indicating the drug poses a statistically significant risk of suicidal behavior for anyone over 25.” Yet there is scientific evidence of such a risk. See Table 16 in the linked “Exhibit 40” document of his article (I assume it’s from the Dolin trial). Silverman said: “For public health reasons, the FDA should pursue a warning.” A former FDA commissioner was quoted as saying it was hard for him to understand why the warning of increased suicidal risk was not in the label.

But sucidality is not just a risk with Paxil (paroxetine). A meta-analysis done by Peter Gotzsche of the Cochrane Collaboration concluded that antidepressants doubled the risk of suicidality and aggression in children and adolescents. Gotzsche and his team of researchers reviewed the clinical study reports for duloxetine (Cymbalta), fluoxetine (Prozac and Sarafem), paroxetine (Paxil), sertraline (Zoloft), and venlafaxine (Effexor). Estimates of harm could not be accurately done because the quality of the clinical study reports varied drastically, limiting their ability to detect the harms. The true risk for serious harms was uncertain, they said, as the low incidence of these events and the poor design and reporting of the trials made it difficult to get accurate estimates.

A main limitation of our review was that the quality of the clinical study reports differed vastly and ranged from summary reports to full reports with appendices, which limited our ability to detect the harms. Our study also showed that the standard risk of bias assessment tool was insufficient when harms from antidepressants were being assessed in clinical study reports. Most of the trials excluded patients with suicidal risk and so our numbers of suicidality might be underestimates compared with what we would expect in clinical practice.

In April of 2016, the CDC released data indicating the suicide rate in the U.S. increased by 24% from 1999 to 2014. Overall, the age-adjusted suicide rate increased from 10.5 per 100,000 in 1999, to 13.0 per 100,000 in 2014. The rates increased for both males and females and for all ages from 10 to 74. The age-adjusted rates for males (20.7 per 100,000 population), was over three times that of females (5.8 per 100,000). Males preferred firearms as a method (55.4%), while poisoning was the most frequent method for females (34.1%). However, this was a lower percentage for both sexes than in 1999. See the following figure from the CDC Report noting suicide deaths by method and sex for 1999 and 2014.

This reverses a trend from 1985 to 2000, where the U.S. suicide rate was dropping. See the following chart taken from an NPR report on the same data. The president-elect of the American Psychiatric Association (APA), Maria Oquendo, said she thought the late 1980s drop was probably due to the fact that new antidepressants (SSRIs) were more effective and had fewer side effects.

Karter noted how Oquendo and Christine Moutier (from the American Foundation for Suicide Prevention) both saw the addition of black box warnings of the potential for suicide in teenagers and young adults as contributing the rise in suicide rates. Moutier was more direct, stating the progress in depression treatment in the 80s and the 90s “was undone in recent years because of concerns that antidepressants could increase suicide risk.” Oquendo thought the increase of suicide deaths in younger populations was potentially due to the understandable reluctance of physicians to prescribe antidepressants to these individuals, “even when they’re aware the individual is suffering from depression.” She added how research showed the benefits outweigh the risks of prescribing antidepressants to children and adolescents.

But Justin Karter indicated this suggestion, that the warning labels led to a decreased number of antidepressant prescriptions for teenagers and adults, was inaccurate. Although several media outlets reported the increase in the suicide rate, they didn’t report the corresponding increase of Americans taking antidepressants, a rate that has nearly doubled.

There was a report published in the British Medical Journal in June of 2014 that indicated black box warnings on SSRIs had a paradoxical effect, with an increase in suicide attempts among youths. Mad in America cited 12 critics of the study and noted its multiple flaws. The unwarranted conclusion, namely lead to increasing the prescription of antidepressants to teenagers and youths, had the potential to do considerable harm. Mad in America concluded that it should never have been published. Among the problems with the study were the following:

The researchers’ stated conclusion, which was that a decrease in antidepressant prescribing in youth following the black box warning led to an increase in suicide attempts, isn’t supported by their own data. (1) There was not a significant decrease in SSRI prescriptions to teenagers and young adults following the black box warning. (2) Psychotropic drug poisonings are not a good proxy for suicide attempts. (3) This coding category actually tells of poisonings due to the use of psychiatric drugs, as opposed to their non-use. (4) Finally, there was no significant increase in the number of poisonings.

Additionally, Kantor et al., in “Trends in Prescription Drug Use Among Adults in the US” reported data from the National Health and Nutrition Examination Survey (NHANES) indicated that the use of antidepressants increased from 6.8% to 13% between 1999 and 2012. Yet, as Justin Karter reported, “The American Psychiatric Association guidelines continue to suggest medications as the preferred treatment for moderate to severe depression.”

If you’re still not convinced, take some time to read through a series of scientific articles submitted by Peter Breggin in his affidavit for another Paxil-related suicide trial. The topics covered included exhibits of Paxil causing suicidal behavior as well as SSRIs and SSRI withdrawal causing suicidality. There is another section on Dr. Breggin’s website that is an “Antidepressant Drug Resource & Information Center” with even more relevant articles.

Given the above discussion on antidepressants, the recent court ruling in Illinois awarding $3 million to Wendy Dolin has the potential to lead to an unknown number of future lawsuits, if it is upheld upon appeal. This could end up costing the pharmaceutical companies that brought now off patent SSRIs and SNRIs to market untold millions and possibly billions of dollars in further awards. So you can bet that GlaxoSmithKline has plenty of pharma companies (and their legal representatives) rooting for GSK to overturn the ruling in the Dolin case. Me, I’m rooting for the underdog here—the 13% of Americans who are taking antidepressant medications without clearly knowing the potential they have to make their depression and its consequences worse.

08/23/16

Clinical Trial Sleight-of-Hand

7501727 - a rabbit in a hat and a magic wand against white background

In 2005 a researcher named John Ioannidis published a seminal paper on publication bias in medical research, “Why Most Published Research Findings are False.” When Julia Belluz interviewed Ioannidis for Vox ten years later, she reported that as much as 30% of the most influential medical research papers turn out to be wrong or exaggerated. She said an estimated $200 billion, the equivalent of 85% of the global spending on research, is wasted on poorly designed and redundant studies. Ioannidis indicated that preclinical research on drug targets received a lot of attention since then. “There are papers showing that, if you look at a large number of these studies, only about 10 to 25 percent of them could be reproduced by other investigators.”

Ioannidis noted even with randomized control trials, there is empirical evidence indicating only a modest percentage can be replicated. Among those trails that are published, about half of the initial outcomes of the study are actually reported. In the published trials, 50% or more of the results are inappropriately interpreted, or given a spin that favors the sponsor of the research. “If you multiply these levels of loss or distortion, even for randomized trials, it’s only a modest fraction of the evidence that is going to be credible.”

One of the changes that Ioannidis’s 2005 paper seemed to produce was the introduction of mandatory clinical trial registration guidelines by the International Committee of Medical Journal Editors (ICMJE). Member journals were supposed to require prospective registration of trials before patient enrollment as a condition of publication. The purpose is that registering clinical trial ahead of time publically describes the methodology that should be followed during the trial. If the published report of the trial afterwards differed from its clinical trial registration, you have evidence that the researchers massaged or spun their research data when it didn’t meet the originally proposed outcome measures. In other words, they didn’t play by the rules they said ahead of time they were going to do in their research if they didn’t “win.”

Julia Rucklidge and two others looked at whether five psychiatric journals (American Journal of Psychiatry, Archives of General Psychiatry/JAMA Psychiatry, Biological Psychiatry, Journal of the American Academy of Child and Adolescent Psychiatry, and the Journal of Clinical Psychiatry) were indeed actually following the guidelines that said they would follow. They found that less than 15% of psychiatry trials were prospectively registered with no changes in their primary outcome measures (POMs). Most trials were either not prospectively registered, had either their POMs or timeframes changed sometime after registration, or they had their participant numbers changed.

In an article for Mad in America, Rucklidge said they submitted their research for review and publication in various journals, including two of the five they investigated. Six medical or psychiatric journals rejected it—they refused to publish Rucklidge et al.’s findings. PLoS One, a peer-reviewed open access journal did accept and publish their findings. She said while the researchers in their study could have changed their outcome measures or failed to preregister their trials for benign reasons, “History suggests that when left unchecked, researchers have been known to change their data.”

For example, an initial clinical trial for an antidepressant could be projected to last for 24 weeks. The 24-week time frame would be one of the initial primary outcome measures—will the antidepressant be more effective than a placebo after 24 weeks. After gathering all the data, the researchers find that the antidepressant was not more effective than placebo at 24 weeks. But let’s say it was more effective than placebo at 18 weeks. What gets reported is the results after 18 weeks; the 24 week original timeframe may disappear altogether when the research results are published.

People glorify their positive results and minimize or neglect reporting on negative results. . . . At worst, our findings mean that the trials published over the last decade cannot be fully trusted. And given that health decisions and funding are based on these published findings, we should be very concerned.

Looking ahead, Rucklidge had several suggestions for improving the situation with clinical trials.

1) Member journals of the ICMJE should have a dedicated person checking trial registries, trials should simply not be published if they haven’t been prospectively registered as determined by the ICMJE or the journals should state clearly and transparently reasons why studies might be published without adhering to ICMJE guidelines.2) If authors do change POMs or participant numbers or retrospectively register their trials, the reasons should be clearly outlined in the methods section of the publication.3) To further improve transparency, authors could upload the full clinical trial protocol, including all amendments, to the registry website and provide the raw data from a clinical trial in a format accessible to the research community.4) Greater effort needs to be made to ensure authors are aware of the importance of prospectively registering trials, by improving guidelines for submission (3) and when applying for ethical approval.5) Finally, reviewers should not make decisions about the acceptability of a study for publication based on whether the findings are positive or negative as this may be implicitly encouraging authors to be selective in reporting results.

Rucklidge also mentioned another study by Mathieu, Chan and Ravaud that looked at whether clinical trial registrations were actually looked at by peer-reviewers. The Mathieu et al. survey found that only one-third of the peer reviewers looked at registered trial information and then reported any discrepancies to journal editors. “When discrepancies were identified, most respondents (88.8%) mentioned them in their review comments, and 19.8% advised editors not to accept the manuscript.” The respondents who did not look at the trial registry information said that main reasons they failed to do so was because of the difficulty or inconvenience in accessing the registry record.

One suggested improvement by Mathieu, Chan and Ravaud was for journals to provide peer reviewers with the clinical trial registration number and a direct Web link to the registry record; or provide the registered information with the manuscript to be reviewed.

The actions of researchers who fail to accurately and completely register their clinical trials, alter POMs, change participant numbers, or make other adjustments to their research methodology and analysis without clearly noting the changes is akin to the sleight-of-hand practiced by illusionists. And sometimes the effect is radical enough to make an ineffective drug trial seem to a new miracle cure.

05/31/16

To Be or Not to Be Bipolar

On The Oprah Winfrey Show in October 2007, Sinéad O’Connor disclosed that she had been diagnosed with bipolar disorder in 2003. The website, “Famous Bipolar People,” said Sinéad had suffered from depression and had thoughts of suicide since the age of 23. She also experienced voices urging her to harm herself. The voices got so loud, she said, she took herself to hospital. She was put on antidepressants, which helped. “These all confirmed that she had bipolar disorder.” Then a few years ago, she went public with an announcement that she had been misdiagnosed with bipolar disorder for eight years.

During her interview with Oprah, she said she didn’t think she was born with bipolar disorder. She thought her illness was caused by a number of outside pressures. “I believe it was created as a result of the violence I experienced.” She was scared to take the medication at first. But she realized that she had nothing to lose, so she tried them. “It was brilliant because I felt this huge hole. And when I took the meds, within half an hour, it was literally like I felt concrete coming in to fill the hole.” She said she thought she had died and then was ‘born again’ as a result of taking the meds.

But after spending eight years on the medications, she realized her depression was still there. Additionally, “some of the same problems she’d had before being medicated were persisting.” And she received complaints about her weight from people in the music business. By the way, weight gain is one of the side effects from antipsychotic medication. When she mentioned her weight problem to her doctors, they suggested taking her off of the bipolar meds as a remedy.

Writing for About Health, Angel Rouse said O’Connor was alarmed with the casualness of the suggestion and aware that simply stopping meds could be dangerous. So she sought outside opinions, eventually getting three additional ones. Their conclusion was that she was not bipolar. Rather, she actually suffered from PTSD. She revealed that when she cancelled her tour in 2012, she had tried to stop taking her medication cold turkey. Ironically, as a result of that attempt, she struggled with bipolar problems of mania and depression for nearly a year. Interviewed for the Irish Mirror, she said:

The illness was in fact what happens when you don’t go about coming off these meds properly. I’m delighted to be able to say that after ten years of poisoning myself with these drugs and having to live with the extremely difficult side-effects of them I can shortly begin the very, very slow indeed, process of getting them out of my system and my life and getting my life back.

Sinéad O’Connor is not a unique case. The NAMI (National Alliance on Mental Illness) website claims that 2.6% or 6.1 million American adults have a bipolar disorder. NAMI referenced this “mental health fact” on data they took from the National Institute of Mental Health (NIMH), which in turn cited this article by Kessler et al. from JAMA Psychiatry on the prevalence, severity and comorbidity of DSM-IV disorders. See Table 1 in the article for the reported percentage. But if Sinéad O’Connor could be misdiagnosed as having a bipolar disorder and mistakenly placed on potentially harmful medications that are seen as necessary to stabilize and control the bipolar ‘illness,’ how many others are similarly misdiagnosed? Regarding the medications she was on, O’Connor told the Irish Mirror:

They are extremely debilitating drugs. Tiring to the extreme. Ironically, extremely depressing. They can cause suicidal or self-harm type thinking. They can mess up your menstrual cycle very badly and cause you to be incapacitated for a week before. . . . [They] f**k up your liver, your kidneys, your eyes, your appetite, your entire way of thinking and generally your entire life.

Within his seminal book, Anatomy of an Epidemic, Robert Whitaker described “The Bipolar Boom” in chapter nine. He related a talk given by Fredrick Goodwin at the 2008 annual meeting of the American Psychiatric Association (APA). Goodwin said the illness has been altered since 1990. There was more rapid cycling; more mixed states; more lithium treatment failures than when he’d coauthored Manic-Depressive Illness. “The illness is not what Kraepelin described anymore, and the biggest factor, I think, is that most patients who have the illness get an antidepressant before they ever get exposed to a mood stabilizer.” Whitaker said not everyone speaking agreed that antidepressants had been disastrous for bipolar patients, but no one questioned Goodwin’s assessment that bipolar outcomes had noticeably worsened since 1990.

On his website, Whitaker noted that before 1955, bipolar illness had been a rare disorder. Only 12,750 people were hospitalized with the disorder that year. There were only about 2,400 “first admissions” that year in the country’s mental hospitals. Outcomes were fairly optimistic. Seventy-five percent of these first-admissions were projected to recover within 12 months. And only 15% of first-time admissions were expected to become chronically ill. And at least 70% were projected to return to work and have active social lives.

Today, bipolar illness is said to affect one in every 40 adults in the United States. A rare disorder has become a very common diagnosis. There are several reasons for this. First, many drugs–both illicit and legal–can stir manic episodes, and thus usage of those drugs leads many to a bipolar diagnosis. Second, the diagnostic boundaries of bipolar illness have been greatly broadened.

Allen Frances is a psychiatrist and the author of Saving Normal. He was also the chair for the DSM-IV, which expanded the criteria in diagnosing bipolar diagnosis by adding the bipolar II category. In Saving Normal, he described a dilemma when the APA was revising bipolar diagnosis for the fourth edition of the DSM. Patients with “hypomania,” less-than-full-manic episodes, didn’t fit neatly into the unipolar or bipolar depression categories. The bipolar II category was seen as a compromise that would lessen the dangers of classifying them as having unipolar depression and treating them with antidepressant medication that could trigger a manic episode.

We knew that bipolar II would expand the bipolar category somewhat into unipolar territory, but we did not think that it would double. Undoubtedly, our decision resulted in more accurate diagnosis and safer treatment for many previously missed truly bipolar patients. But like all fads, it overshot and had led to unnecessary medication for many unipolar patients who have been misdiagnosed as bipolar on very flimsy grounds and are now receiving unnecessary mood stabilizing drugs.

Whether you agree with Frances’ assessment that adding bipolar II resulted in more accurate diagnosis and safer treatment for many, don’t miss that he also said it led to misdiagnosis and unnecessary medication. If you follow this link, also given above, to Robert Whitaker’s website, Mad in America, you will find a series of journal articles describing how substance abuse can be related to developing bipolar disorder; the effects of antidepressant use on bipolar disorder and how these drugs can worsen long-term bipolar outcomes; and the deterioration of bipolar outcomes in the modern era.

For a postscript, I want to return to note one last piece of information on Sinéad O’Connor. While she has cast off her diagnosis of bipolar disorder, it isn’t finished with her. Many websites, like that of “Famous Bipolar People” mentioned above, still list her as one of their own. There was a concluding note in the “About Health” article on Sinéad O’Connor that said: “In spite of her having stated clearly on several occasions that she does not have bipolar disorder, O’Connor continues to be included at many sites that compile lists of famous bipolar people.”

Famous Bipolar People, if Sinéad had said it’s over between the two of you, accept it and move on. There are plenty of more fish in the sea. You still have Kay Redfield Jamison. She’s written two books that touch on bipolar disorder, An Unquiet Mind and Touched with Fire. And both have been made into movies. The movie, Touched with Fire, is a fictional love story about two people with bipolar disorder who meet in a psychiatric hospital and fall in love. The trailer has a slight Romeo and Juliet feel to it; two young lovers who family and friends try to keep apart. So there will be plenty of new discussions about who is and who isn’t bipolar related to the movie. Just let go of Sinéad; let her go and move on.

03/29/16

Tip of the ADHD Iceberg

Stimulant medications prescribed to children with ADHD are known to cause hallucinations and psychotic symptoms. The risk of these adverse events was widely thought to be minimal, but a recent study published in the journal Pediatrics suggests that is not the case. MacKenzie et al. reported that psychotic symptoms were found in 62.5% of youth who had taken stimulants versus 27.4% of individuals who had never taken stimulants. The researchers said this association was still significant even after potential confounding variables were controlled.

Mad in America noted in “ADHD Drugs Linked to Psychotic Symptoms in Children” that clinical trials used to test the safety and efficacy of stimulant medications such as Adderall, Ritalin and Vyvanse estimate that only 1-2% of children on stimulants have such a reaction. MacKenzie et al. suggested these underestimates were partly because researchers often rely upon participants to self-report these symptoms, which leads to significant underreporting. Among the children diagnosed with ADHD in the study, 11 of 17 (65%) treated with stimulants experienced psychotic symptoms, while only 4 (25%) of the 16 who were not treated with stimulants had such symptoms.

The children included in the MacKenzie et al. study had at least one parent with a diagnosis of major depression, bipolar disorder or schizophrenia. However, “the association between stimulants and psychotic symptoms remained consistent after the researchers controlled for other risk factors, age, gender, and parent diagnosis.” The researchers were also able to confirm that the occurrence of the symptoms coincided with the time when the children were actively taking stimulant medications. They concluded:

We report an association between the use of stimulant medication and psychotic symptoms in children and adolescents at familial risk of mental illness. The association of current use of stimulants with current psychotic symptoms and the close temporal relationship between stimulant use and psychotic symptoms in youth who started and stopped stimulants indicated a potential causal relationship. The findings suggest that psychotic symptoms may be relatively common adverse effects of stimulants in youths with a family history of major psychiatric disorders.

In “Psychotic Symptoms in Children on Stimulants,” Dr. Lydia Furman, an Associate Editor for Pediatrics, said the study put a microscope on the subpopulation of children with an ADHD diagnosis, whose risk of psychotic symptoms is substantially higher. She added that the study was just the tip of the iceberg with regard to ADHD diagnosis, stimulant treatment and the risk in adulthood of psychotic disorders or episodes. She cited a study by Moran et al. that demonstrated how adult individuals with psychotic disorders, who were exposed to stimulants in their youth, had a significantly earlier age of onset of psychosis than those who were unexposed.

But Furman seems more interested in seeing ADHD diagnosis as an increased risk factor for adult diagnosis of psychotic disorders, rather than looking at the evidence of how stimulant medications seem to trigger or increase the risk of psychotic symptoms. She commented that an additional body of evidence suggests that ADHD diagnosis in childhood is associated with an increased risk of adult diagnosis of psychotic disorders, and then referenced two studies: Rho et al. and Dalsgaard et al. It wasn’t clear to me from the abstracts that stimulant medication as a confounding variable was controlled for in either study.

Given that the MacKenzie study found the symptoms of psychosis occurred during the active use of stimulant medication, and that the association remained even after the researchers controlled for risk factors including parental diagnosis, it seems the more significant results were that using stimulant medication may trigger hallucination and psychotic symptoms more frequently than has been previously reported.

Cherland and Fitzpatrick reported in a 1999 study, “Psychotic Side Effects of Psychostimulants,” that 6% of children developed psychotic side effects from methylphenidate (Ritalin). They also indicated their findings likely were an underestimate in the prevalence. Significantly, the symptoms stopped as son as the medication was discontinued. No psychotic symptoms were reported among children diagnosed with ADHD who did not receive medication.

Dr. Peter Breggin also reported the danger of ADHD medications triggering symptoms of psychosis in his article for International Journal of Risk & Safety in Medicine. He noted how several studies have compared stimulant-induced psychoses to the symptoms of schizophrenia. Methylphenidate has even been used to experimentally produce or worsen psychotic symptoms in adults diagnosed with schizophrenia. He commented that psychoactive drugs would tend to produce psychosis at a higher rate in children than in adults.

In his “Simple Truths About Psychiatry” series of videos on YouTube (Simple Truth 7 and Simple Truth 8), Dr. Breggin said stimulant drugs don’t fix or cure anything. They actually cause biochemical imbalances in the brain that make children docile, and take away their spontaneity. This adverse effect is then interpreted as a positive effect. I agree with Breggin that these drugs should never be given to children. Ultimately, he asserted that children who are raised on stimulant drugs will never know who they really are. “Since you’re messing up several neurotransmitters in the brain, you’re going to be causing life-long changes in the child’s brain.”

An NIH-funded study by Collins and Clearly found there has been a 43% overall increase in the diagnosis of ADHD since 2003. Among children between the ages of 10 and 14 the increase was 47%, and 52% among adolescents aged 15-17. There were increasing trends for all racial/ethnic groups, most notably among Hispanics, where the increase in ADHD diagnosis was 83% from 2003 to 2011. Dr. Clearly hedged his bet, saying that the reported increase could be a true increase in ADHD or it could be the result of a tendency to over-diagnose the condition. “Additional studies must be done to identify the underlying cause of the increase.”

In the meantime, his advice was for parents to “talk to your doctor.” That is often pharma-speak for “get a prescription.” We may be just beginning to see the tip of the iceberg of consequences from ADHD medications.

03/8/16

Chemical Straightjackets for Children

In a five-minute video, “Stop the Psych Drugging of Children—Now!, Dr. Peter Breggin made some alarming statements about the consequences of several decades of giving children psychiatric drugs. He said we have parents who believe their children are incorrigible. And we have children who grow up thinking they are defective and need psychiatric drugs. Many of the children who started out with a mere ADHD diagnosis when they were younger are growing up to be “career mental patients, taking multiple psychiatric drugs.” In an article he published in the journal Children & Society, Breggin reviewed in more detail many of the concerns he just touched on in his video. Here, I want to look at the growing problem of using antipsychotics with children.

Mad in America reported that a study published in JAMA Psychiatry indicated that the majority of children, adolescents and young adults who are prescribed antipsychotic medications have not been diagnosed with a mental disorder. “Most of the younger children (60.0%), older children (56.7%), adolescents (62.0%), and young adults (67.1%) treated with antipsychotics had no outpatient or inpatient claim that included a mental disorder diagnosis.” Among the children who do have a diagnosis for a mental disorder, many of them are being prescribed antipsychotics off label.

In other words, while antipsychotics are only approved to treat children diagnosed with schizophrenia and bipolar disorder, children with diagnoses like ADHD are being given these powerful drugs to “treat” their behavior problems. In addition, very few of the children receiving antipsychotics also receive psychotherapeutic care. Mark Olfson, the lead author of the study said:

Relatively few of these young people are receiving psychotherapy. We may need to put greater effort into increasing access to psychosocial interventions that can treat symptoms and behaviors that are currently being addressed with antipsychotic medications.

In the same issue of JAMA Psychiatry in which the Olfson et al. article was published, Drs. Carroll and Blader acknowledged in “Antipsychotic Use in Youth Without Psychosis” that the use of antipsychotic medications has been increasing since the mid-1990s. They added this pattern was most pronounced in the U.S. They affirmed evidence suggests that second-generation antipsychotic use was chiefly with children with aggression and behavioral problems, ADHD, and disruptive behavior disorders. “Although antipsychotics are clearly effective for aggressive behaviors … other interventions with lower adverse effect burdens, when implemented adequately, can avert the need for antipsychotic treatment.”

Reporting for the StarTribune, Gail Rosenblum noted that in 2014 20,000 prescriptions for antipsychotic medications were written for children 2 and younger. According to IMS Health, a healthcare data company, that was a 50% increase over the year before. Turn to the article to see a photo of a child playing with Lego-like blocks branded with “Risperdal” at a pediatrician’s office.

IMS found that at least 10,000 children, ages 2 and 3, were prescribed medications such as Adderall to treat attention deficit hyperactivity disorder (ADHD). The protocol falls outside of American Academy of Pediatrics guidelines. Children younger than age 2 received prescriptions for risperidone (commonly known as Risperdal), quetiapine (Seroquel) and the antidepressant Prozac.

In his Children & Society article, Dr. Breggin noted where the so-called second-generation antipsychotics cause the same adverse effects as the older antipsychotics. These adverse effects include: “lobotomy-like indifference and apathy, Parkinsonian symptoms, akathisia, dystonia, tardive dyskinesia, neuroleptic malignant syndrome, gynecomastia [enlarged breasts in men] and other sexual dysfunctions.” Tardive dyskinesia (TD), a movement disorder caused by antipsychotic drugs, is a major threat to children, according to Breggin. TD can effect any muscle functions that are wholly or partially under voluntary control. That includes the face, eyes, tongue, jaw, neck, back, abdomen, and more. Here are two videos of what TD looks like in a child. The first is a girl after she stopped taking her medications, presumably because of the TD. The second one is of another young girl trying to fall asleep.

Even ‘mild’ cases of eye blinking or grimacing can humiliate, stigmatize and isolate a child. More severe cases disable children with painful spasms in the neck and shoulders, abnormal posture and gait, or constant agitated body movements.

Additional concerns with the newer antipsychotics include a potential predisposition to heart disease and early death; weight gain and obesity; elevated blood sugar and diabetes; elevated blood lipids and atherosclerosis, and high blood pressure.

The New York Times published an article by Alan Schwartz, that looked at the growing practice of giving antipsychotics to children under the age of 2. His introductory case illustration was a boy who was first prescribed the antipsychotic Risperdal when he was 18 months of age. His mother indicated that she was never told of the potential risks to her son with Risperdal. “It was just ‘Take this, no big deal,’ like they were Tic Tacs,” said Genesis Rios. The prescribing doctor declined to be interviewed by the NYT.

Cases like that of Andrew Rios, in which children age 2 or younger are prescribed psychiatric medications to address alarmingly violent or withdrawn behavior, are rising rapidly, data shows. Many doctors worry that these drugs, designed for adults and only warily accepted for certain school-age youngsters, are being used to treat children still in cribs despite no published research into their effectiveness and potential health risks for children so young.

Schwartz reported that almost 20,000 prescriptions for antipsychotics such as risperidone (Risperdal) were written for children 2 years old and younger in 2014. This was a 50% jump from the year before. As a side note, prescriptions for the antidepressant fluoxetine (Prozac) rose 23 percent in one year for the same age group. A dozen experts in child psychiatry had never heard of children younger than 3 getting such medication and had difficulty explaining a reason for it. Dr. Martin Drell, a former president of the American Academy of Child and Adolescent Psychiatry said he was “hard pressed to figure out what the rationale would be.” Dr. Ed Tronick, a professor of developmental and brain sciences at the University of Massachusetts said:

I think you simply cannot make anything close to a diagnosis of these types of disorders in children of that age. . . . There’s this very narrow range of what people think the prototype child should look like. Deviations from that lead them to seek out interventions like these. I think it’s just nuts.

The American Academy of Pediatrics and the American Academy of Child and Adolescent Psychiatry have not taken a stand for or against the practice. They have no guidelines or position statements on the use of antidepressant or antipsychotics with children younger than 3. One possible factor in their silence is there are no formal trials in infants and toddlers with these medications. Dr. Mary Gleason a pediatrician and child psychiatrist at Tulane University School of Medicine said children with ages measured in months have brains whose neurological development was occurring at too rapid of a rate—and in still unknown ways—to risk using medications that could profoundly influence that growth. “There are no studies … and I’m not pushing for them,” said Dr. Gleason.

In an article for Psychiatric Services, psychiatrists at Dartmouth expressed concern about the increasing numbers of children being prescribed antipsychotic medications. In an article summarizing the concerns of the authors, Mad in America quoted them as saying:

The crux of the issue is this: Children in the United States have increasingly been prescribed antipsychotic medications despite potentially serious short- and long-term side effects. . . . Yet other efficacious and safer interventions are available. . . . We should be concerned about overuse of antipsychotics for many reasons. Children are inherently vulnerable because their brains and bodies are still developing and may be permanently altered by powerful medications. . . . Their disruptive behaviors are often related to disruptive parenting and stressful environments, which deserve primary attention. Adults may be motivated by the desire to achieve short-term control of behavior rather than to enhance children’s long-term growth and development.

Daviss et al. recommended five changes to reduce the use of antipsychotics in children. First, there is a need for preventive care that addresses socioenvironmental problems. Second, mental health professionals need to become more aware of the dangers of using antipsychotics in children as well as the availability of evidence-based therapies and interventions. Third, clinical guidelines need to be developed along with steps to ensure compliance with those guidelines. Fourth, there should be shared decision making when treating children with these medications. “Clinicians, patients, and parents all need better information on antipsychotics and should all be involved in deciding on appropriate treatment methods.” And fifth, education programs regarding these concerns are needed to reach the agencies and counselors who take care of and support vulnerable children.

Dr. Gleason commented that people are trying to do the best they can with the tools available to them. “There’s a sense of desperation with families of children who are suffering, and the tool that most providers have is the prescription pad.” These children and families deserve better than a choice between trying to cope with the behaviors they see their child struggle with, and using a chemical straitjacket with the potential of long-term cognitive and physiological harm.

02/26/16

Hollow Man Syndrome

On 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.

11/18/15

The Cycle of Antidepressant-Induced Helplessness

© Everett Collection, Inc. | dreamstime.com

Lawyers for GlaxoSmithKline (GSK) recently referred to evidence presented by a well-respected expert, Dr. Joseph Glenmullen, as “junk science.” He was irrational enough to testify that there was a connection between suicidality (the likelihood of an individual completing suicide) and suicide attempts. The case is one where the widow of a lawyer sued GSK because her husband committed suicide shortly after taking a generic version of the antidepressant. “Since there is no way Dr. Glenmullen can establish causation based on suicide data, he relies instead on data on ‘suicidality’ and suicide attempts, which are not appropriate surrogates for reaching conclusions about suicide.”

The above was taken from a brief news report on Mad in America, “Paxil Manufacturer Calls Evidence of Suicide Risk ‘Junk Science.’” The article said GSK has routinely overstated the drug’s efficacy. A widely cited 2001 study funded by GSK known as “Study 329” was recently reanalyzed and these results then published in the British Medical Journal. The reanalysis showed that the original claim by Study 329 that Paxil (paroxetine) was safe and effective for adolescents was wrong. The September 16, 2015 BMJ press release also noted where GKS had been fined $3 billion ($1 billion criminal, $2 billion civil) for fraudulently promoting paroxetine, among other violations.

Using previously confidential documents, researchers reanalyzed the original data from Study 329 and found that paroxetine was not more effective than placebo in treating major depression in adolescents. They concluded: “paroxetine was ineffective and unsafe in this study.” And yet for fourteen years Study 329 has been cited as demonstrating the safety and efficacy of paroxetine to treat adolescent depression. The BMJ Editor-in-Chief said the publication of the reanalyzed data “set the record straight” while it also “shows the extent to which drug regulation is failing us.”

All antidepressant medications are required to include a warning similar to what follows, which was taken from the Medication Guide for Paxil:

PAXIL and other antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, or young adults within the first few months of treatment or when the dose is changed.

Psychiatrist Peter Breggin noted in “The Proven Dangers of Antidepressants” that the FDA warning cautioning about the risks of newer antidepressants (Prozac, Zoloft, Paxil, Luvox, Celexa, and Lexapro, as well as Wellbutrin, Effexor, Serzone, and Remeron) followed a public hearing with dozens of family members and victims testifying about suicide and violence committed by individuals taking these medications.

While stopping short of concluding the antidepressants definitely cause suicide, the FDA warned that they might do so in a small percentage of children and adults. In the debate over drug-induced suicide, little attention has been given to the FDA’s additional warning that certain behaviors are “known to be associated with these drugs,” including “anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia (severe restlessness), hypomania, and mania.

Breggin was himself an expert witness in a 2012 court case that awarded $1.5 million medical malpractice verdict to a family of a man who committed suicide. He testified how antidepressants such as Paxil and Effexor could increase suicide risk in adults.

After reviewing extensive records and interviewing Mr. Mazella’s wife Janice, I concluded that Dr. Beals was negligent in reportedly prescribing Paxil for 10 years without seeing the patient, in failing to warn the patient and his wife about the serious risks associated with Paxil, in his doubling the Paxil dose and adding Zyprexa by telephone, and then in abandoning the patient during his decline. I also concluded that a hospital psychiatrist was negligent in not recognizing that Mr. Mazella was suffering from adverse drug effects and in discharging him without proper follow up two weeks before his death.

In his discussion on “The Proven Dangers of Antidepressants” linked above, Breggin also commented how there has been little attention to the additional FDA warning that additional behaviors are known to be associated with antidepressants, including “anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia (severe restlessness), hypomania, and mania.” He noted how he has repeatedly documented how the stimulation and activation profile of antidepressants can lead to out-of-control behavior, including violence.

In his article, “Antidepressant-Induced Mania,” psychologist Philip Hickey described how circular reasoning about activation from antidepressants becomes evidence of “an underlying latent bipolar disorder.” He indicated that psychiatry retrospectively applies their explanation as follows: “Before the individual showed any signs of mania, he must have had bipolar disorder because he became manic at a later date.” The hypothesis cannot be verified because the occurrence of a manic or hypomanic episode is the primary criterion for the bipolar diagnosis.

Yet there has been recent evidence that manic/hypomanic episodes can be caused by the use of antidepressant medications. Hickey reviewed a Psychiatric Times article written by Ross Baldessarini that reported on a meta-analysis that he and his colleagues did on antidepressant-associated mood-switching. Bipolar disorder is often seen as beginning with at least one episode of major depression, followed by an episode of mania or hypomania. This ‘switching’ of mood may occur during treatment with an antidepressant or other mood-elevating agent. And it is especially common among juveniles and young adults using an antidepressant for a mood disorder (depression or anxiety) or a stimulant for attention. “Such pathological shifts of mood and behavior may represent adverse drug actions or a manifestation of undiagnosed bipolar disorder.”

Hickey noted that Baldessarini et al. found that manic or hypomanic episodes were 5.6 times more common per year for individuals diagnosed with major depression who were taking antidepressants and others with the same diagnosis who were not taking them. After citing several quotations from the Baldessarini et al. study and the Psychiatric Times article, Hickey said: “What the authors are pointing out here is that antidepressants are clearly implicated in the ‘excess’ incidents of mania/hypomania, and they have even raised the question of a direct causal link.”

Baldessarini even suggested that when antidepressant-related manic episodes occur, the continued use of antidepressants might contribute to recurrent manic episodes. Although it is widely assumed that mood-stabilizing drugs are highly effective in preventing antidepressant-associated mood switching, it is not conclusively proven to be true. “Moreover, there is very limited evidence that prolonged antidepressant treatment provides substantial protection against recurrences of bipolar depression and that it might contribute to emotional instability or rapid cycling.”

When you add the research of Irving Kirsch, who has shown that antidepressants have little or no therapeutic effect at all (See “Do No Harm with Antidepressants”), we are left with a class of drugs that are no more effective than the placebos used in their clinical trials. As we saw here, they could also activate what they are taken to prevent or stabilize—depressive symptoms such as suicidality. Moreover, their use could also lead to mania or hypomania and thus elevate the initial diagnosis of major depression to the more serious one of bipolar disorder. And the icing on the cake is that if antidepressants are continued, they may contribute to further emotional instability or rapid cycling. This is a cycle of what Peter Breggin called iatrogenic helplessness generated by antidepressants. Here is his description in Brain-Disabling Treatments in Psychiatry:

The concept of iatrogenic helplessness and denial includes the patient’s and the doctor’s mutual denial of the damaging impact of the treatment as well as their mutual denial of the damaging impact of the patient’s underlying psychological and situational problems. Overall, iatrogenic helplessness and denial accounts for the frequency with which psychiatry has been able utilize brain-damaging technologies, such as electro-shock and psychosurgery, as well as toxic medications.

Iatrogenic refers to something induced inadvertently by a physician, medical treatment or diagnostic procedures. Breggin has been challenging the iatrogenic nature of psychiatric treatment for essentially his entire professional career as a psychiatrist. In 1983 he wrote in The Iatrogenics Handbook that iatrogenic denial involved the infliction of brain damage and dysfunction upon the patient to encourage them to deny both the existence of his problems and the iatrogenic brain damage. “I developed the brain-disabling hypothesis which states that all the major psychiatric treatments disable the normal brain rendering the individual more helpless and hence easier to manage or to ignore.”

11/11/15

Trick or Trick

A grocery store pharmacy in Quebec Canada was giving out psychiatric drugs for Halloween treats this year. A mother accidentally dropped divalproex (Depakote) and quetiapine (Seroquel) pills that she had picked up for her son. Other customers picked up the pills, which were wrapped in a blister packet, and placed them on the counter next to a candy basket. Somehow the pills were mixed in with the candy. “Seven of the pills ended up in the hands and bags of trick-or-treating children.”

A Constable said that an employee mixed the medications in with the candy by accident. But one mother said she immediately recognized the pills were drugs and took them away from her daughter who had “chewed and spat out the drugs distributed by mistake.” The “mistake” is puzzling, as the girl’s mother said: “It was a transparent bag, with the name of the person, the drug, the dosage, the pharmacist and the date and time the prescription was filled; October 31 at 8 a.m. in the morning,”

Police told parents that the pills weren’t dangerous, but that is just not true. The medication guide for quetiapine lists potential side effects as: the risk of suicidal thoughts or actions, depression, anxiety, panic attacks, irritability, anger or aggression, unusual changes in mood or behavior. The medication guide for divalproex lists similar potential side effects: the risk of suicidal thoughts or actions, depression, anxiety, agitation or restlessness, anxiety, irritability, anger or aggression, unusual changes in mood or behavior. And it can cause serious liver damage in children younger than 2 years old. Granted, these adverse effects would in all probability not occur if a child had wrongly ingested one pill, but the describing the pills as not dangerous was deceitful. Read more on this incident at The Fix or Vice.

Seroquel is an antipsychotic medication and Depakote is an anti-seizure medication that carries the label of “mood stabilizer” when used as a psychiatric medication. Antipsychotics are frequently combined with mood stabilizers in the treatment of bipolar disorder. A September 2105 study published in JAMA Psychiatry, “Treatment of Young People with Antipsychotic Medications in the United States,” examined at the prescription patterns among young people in the United States. The study looked at four age groups: younger children (1-6 years), older children (7-12 years), adolescents (13-18 years), and young adults (19-24 years).

The researchers found that most of the individuals treated with antipsychotics did not have a medical claim that included a mental disorder diagnosis. The percentages by age group were as follows: younger children (60.0%), older children (56.7%), adolescents (62.0%), and young adults (67.1%). When there was a diagnosis, the most common one was ADHD with younger children (52.5%), older children (60.1%) and adolescents (34.9%). Depression was the most commonly given diagnosis among young adults (34.5%).

Consistent with clinical diagnoses suggesting that antipsychotics are primarily used to manage impulsive or aggressive behaviors in children associated with ADHD, the highest rate of antipsychotic treatment was in adolescent boys, approximately half of whom also filled prescriptions for stimulants. Young adults treated with antipsychotics were more frequently diagnosed as having depression, bipolar disorder, and anxiety disorder than ADHD.

A National Institute of Mental Health (NIMH) press release on the study, quoted a co-author, Michael Schoenbaum, as saying antipsychotics should be prescribed with care. “They can adversely affect both physical and neurological function and some of their adverse effects can persist even after the medication is stopped.” He added what was particularly important about the study’s findings was that 1.5% of boys aged 10-18 are on antipsychotics. This rate was abruptly cut in half as adolescents become young adults.

In the current study, the combination of peak use of antipsychotics in adolescent boys and the diagnoses associated with prescriptions (often ADHD) suggest that these medications are being used to treat developmentally limited impulsivity and aggression rather than psychosis.

Mad in America quoted Dr. Christopher Correll, the medical director of the New York State Office of Mental Health, who noted that the powerful and almost immediate problems with antipsychotics can include weight gain and high glucose levels (a possible precursor of diabetes). “Prescribing antipsychotics seems predominantly aimed at aggressive and impulsive behaviors, especially in males, where the disruption in school and home insists on action and remediating symptoms.”

The study commented how the above noted decrease in prescribed antipsychotics after adolescence may be due to the normal maturation of neurobiological systems in late adolescence and early adulthood. “This normal maturation of neurobiological systems may underlie the decrease in antipsychotic treatment prevalence during late adolescence among youth who do not have enduring cognitive impairments and long-term severe behavioral disorders.” High rates of coprescribing antipsychotics with other classes of drugs were observed across all age groups. Stimulants (probably for ADHD) were the most commonly prescribed psychotropic class during preadolescent years.

A likely outcome in these cases is that agitation from the ADHD stimulants contributes to an increase in aggression among preadolescents, which results in the prescription of an antipsychotic to address the aggression. Dr. Peter Breggin said: “The antipsychotic drugs are often given to children when their behavior and mental state deteriorates as a result of being given stimulants.” Follow the link here to a page on his website where he discusses the potential harm from the psychiatric diagnosing and drugging of children. The page includes links to several videos in his Simple Truth series on YouTube that address topics such as: the harmful effects and action of stimulant drugs; and the negative effects of diagnosing children with ADHD. There is also a link to one of his articles published in Children & Society that “presents a scientific and ethical overview of the harm done to children by stimulants and by antipsychotics.”

The drugging of children in America and increasingly throughout the world is a tragedy. Millions upon millions of children and youth will never know their full potential because they grew up with an intoxicated brain — their neurotransmitters forever deformed by being bathed in these drugs during their formative years. Additional millions will become career consumers of psychiatric drugs with a vastly reduced quality of life and shortened lives.

09/30/15

Psychiatry, Diagnose Thyself! Part 1

Wow. I can hardly believe he said the things he did. Dr. Jeffery Lieberman, a former president of the American Psychiatric Association and the Chairman of the Department of Psychiatry at the Columbia University College of Physicians and Surgeons, took umbrage at an op-ed article written in The New York Times on January 17, 2015 by Stanford anthropologist T.M. Luhrmann, “Redefining Mental Illness.” Luhrmann referred in her article to a report by the British Psychological Society, “Understanding Psychosis and Schizophrenia,” that suggested interpreting paranoid feelings and hearing voices as symptoms of mental illness was only one way of thinking about them. She indicated the report said antipsychotic medications were sometimes helpful, but “there is no evidence that it corrects an underlying biological abnormality.” It went on to warn about the risks of taking these medications over the long term.

In a Medscape video “What Does The New York Times Have Against Psychiatry?” Lieberman referred to the NYT publication of her article as “journalistic opportunism.” He chided the editors for thinking that “providing a platform for this would be useful.” With regard to Luhrmann, he cited the title of her books, whose subject areas dealt with religion and God, witches, and psychiatry. Yes, they were eclectic topics, but how does that then lead him to this comment:

The equating of psychiatry with these other topics suggests that she thinks of psychiatry not as a hard science but as something that is either a philosophical or religious discipline, has a supernatural or religious dimension, or is in the realm of the supernatural.

I’ve read two of her books, Of Two Minds and When God Talks Back, and for the life of me I cannot follow how he can make that connection. There was not association of psychiatry with witchcraft or religion on Luhrmann’s part in her NYT article; I can only conclude the association was somehow in Lieberman’s mind, not Luhrmann’s article.

But she did comment how there was plenty of scientific evidence for the report’s claims. She then had the audacity to mention that the National Institute of Mental Health (NIMH) announced in 2013 that it would no longer pursue diagnosis-driven research. Under a program called Research Domain Criteria (RDoC), all research would begin from a matrix of “functional dimensions, grouped into broad domains such as cognition and reward-related systems.” One example she gave from the RDoC site was how psychiatric researchers would no longer study people with anxiety. Rather they would study fear circuitry.

Lieberman went on to name some additional publications by Lurhmann, and said: “This hearkens back to the days when psychiatry had only fanciful theories about the mind and what caused mental illness in people.” Thankfully, he said we are well past that. Articles like Luhrmann’s, according to Lieberman, are a throwback to the days of ignorance and fear; and they spread stigma.

Why would The New York Times do this? It is very disturbing that we still live in an age when the stigma of mental illness and the lack of interest in trying to present medical science as it deserves and needs to be for an informed public, is still preyed upon by this kind of journalistic opportunism.

Then Lieberman was interviewed on CBC radio podcast, “The Sunday Edition” on April 26, 2015. He was there to promote his new book, Shrinks, a history of psychiatry for the general public. After playing an excerpt of an interview he did over a year ago with Robert Whitaker, the host asked Lieberman to comment on what Whitaker had said in the excerpt. Lieberman said: “What he says is preposterous. He’s a menace to society because he’s basically fomenting misinformation and misunderstanding about mental illness and the nature of treatment.”

But he wasn’t finished. Lieberman went on to say how Whitaker “ostensibly considers himself to have been a journalist.” Whitaker has won awards for his journalism and was even a finalist for a Pulitzer in Public Service. But Lieberman lamented: “God help the publication that employed him.” Lieberman also thought Whitaker’s comments that some unmedicated patients did better than medicated ones were absolutely wrong. If you did a randomized, controlled study of any of the various psychiatric illnesses, using whatever is state of the art in psychiatry, including medication, Lieberman said: “the outcomes will be extraordinarily superior in the treated group.”

This led to “A Challenge to Dr. Lieberman” by Whitaker on his website for Lieberman to provide a list of randomized studies that show how medicated patients have a much better long-term outcome than unmedicated patients. He noted how he had posted the abstracts of the studies he cited in his book, Anatomy of an Epidemic on his website, madinamerica.com. “So here is you chance to point to the studies I left out.”

1 Boring Old Man commented on this outburst by Dr. Lieberman and Whitaker’s reply, observing how Lieberman sees himself as the spokesman and champion for “Psychiatry.” His article also described the Lieberman rant against Lurhmann and also cited several articles written by Lieberman over the past few years with the same theme. I’d just finished reading Lieberman’s book and was struck in reading 1 Boring Old Man’s article by how it seemed Lieberman was casting himself in a role similar to the one he gave Robert Spitzer in Shrinks. Spitzer was portrayed there as an unlikely hero and a psychiatric revolutionary who, in effect, saved psychiatry from imploding during the 1970s. Psychiatry today seems to be in similar situation, with questions being raised about the current validity and reliability of DSM diagnosis, and the credibility of psychiatry itself.

So if Lieberman sees himself as a modern psychiatric hero, then Robert Whitaker would be a natural pick by Lieberman as an antipsychiatry foil, replacing David Rosenhan, who was a “foe” of psychiatry in the 1970s. In Shrinks, Lieberman discussed the controversies over the DSM-5, saying the APA hadn’t experienced that kind of public pressure since the early 1970s, “when the Rosenhan study, the homosexual controversy, and the antipsychiatry movement compelled the APA to move away from psychoanalysis and endorse a radically new paradigm for psychiatric diagnosis. See “A Censored Story of Psychiatry, Part 1, Part 2” and “The Quest for Psychiatric Dragons, Part 1, Part 2” for more on Spitzer, Rosenhan and these issues.

In his role as a “foe of psychiatry,” Whitaker has published three well-received books by both the general public and individuals within the mental health profession that are critical of the current state of psychiatry and mental healthcare. His most recent book, Psychiatry Under the Influence, was just released on April 23, 2015.

So we have these successive actions: Lurhmann’s article published in the NYT on January 17th. Three days later Lieberman recorded his Medscape response, which was published online on February 18, 2015. The release date for Lieberman’s book, Shrinks, was on March 10, 2015. Whitaker’s review of Shrinks appeared on his website, Mad in America on March 19th. The release date for Whitaker’s book, Psychiatry Under the Influence, was on April 23rd. Lieberman’s CBC interview was on April 26, 2015. Whitaker’s invitation to Lieberman was on April 26th as well.

I don’t think he’ll take Whitaker up on his challenge. He can’t. The science doesn’t support his position. Go to madinamerica.com and read through the abstracts mentioned above by Whitaker to confirm this. But why would one of the top psychiatrists of our time write and say such obvious drivel?

It’s all PR. In his review of Shrinks, Whitaker noted how Shrinks doesn’t tell a previously unknown tale. Rather, it “relates a story that the American Psychiatric Association has been telling the American public ever since it published DSM III in 1980.” Whitaker and Cosgrove noted in Psychiatry Under the Influence that by adopting a disease model and insisting psychiatric disorders were discrete illnesses in the 1970s, the APA simultaneously responded to its antipsychiatry critics and addressed its image problem by presenting itself to the public as a medical specialty. “Metaphorically speaking, psychiatry had donned a white coat.” Whitaker pointed out in his review how Lieberman wore a doctor’s white coat for a promotional video he did on YouTube, where he discusses his book. I noticed that he did the same thing for his Medscape video critique of Lurhmann and the NYT.

Whitaker said Shrinks provided a revealing self-portrait of psychiatry as an institution. Lieberman repeats the same story the APA has been telling the public since the publication of the DSM-III. “And it is this narrative, quite unmoored from science and history, that drives our societal understanding of mental disorders and how best to treat them.” He observed that Lieberman diagnosed the Freudians as extravagant, grandiose and having irrational faith in its world-changing powers. The same symptoms seemed to be present in Shrinks.

Faith Seeking Understanding

Charles Sigler, D.Phil.

Tag Archives: Mad in America