1 Boring Old Man

The Hidden Harm of Antidepressants

An in-depth analysis of clinical trials reveals widespread underreporting of negative side effects, including suicide attempts and aggressive behavior

Scientific American

By Diana Kwon

February 3, 2016

Antidepressants are some of the most commonly prescribed medications out there. More than one out of 10 Americans over age 12 — roughly 11 percent — take these drugs, according to a 2011 report by the National Center for Health Statistics. And yet, recent reports have revealed that important data about the safety of these drugs — especially their risks for children and adolescents — has been withheld from the medical community and the public.

In the latest and most comprehensive analysis, published last week in BMJ [the British Medical Journal], a group of researchers at the Nordic Cochrane Center in Copenhagen showed that pharmaceutical companies were not presenting the full extent of serious harm in clinical study reports, which are detailed documents sent to regulatory authorities such as the U.S. Food and Drug Administration and the European Medicines Agency [EMA] when applying for approval of a new drug. The researchers examined documents from 70 double-blind, placebo-controlled trials of two common types of antidepressants — selective serotonin reuptake inhibitors [SSRI] and serotonin and norepinephrine reuptake inhibitors [SNRI] — and found that the occurrence of suicidal thoughts and aggressive behavior doubled in children and adolescents who used these medications.

This paper comes on the heels of disturbing charges about conflicts of interest in reports on antidepressant trials. Last September a study published in the Journal of Clinical Epidemiology revealed that a third of meta-analyses of antidepressant studies were written by pharma employees and that these were 22 times less likely than other meta-studies to include negative statements about the drug. That same month another research group reported that after reanalyzing the data from Study 329, a 2001 clinical trial of Paxil funded by GlaxoSmithKline, they uncovered exaggerated efficacy and undisclosed harm to adolescents.

Because of the selective reporting of negative outcomes in journal articles, the researchers in the most recent BMJ study turned to clinical trial reports, which include more detailed information about the trials. They discovered that some of most the useful information was in individual patient listings buried in the appendices. For example, they uncovered suicide attempts that were passed off as “emotional liability” or “worsening depression” in the report itself. This information, however, was only available for 32 out of the 70 trials. “We found that a lot of the appendices were often only available upon request to the authorities, and the authorities had never requested them,” says Tarang Sharma, a PhD student at Cochrane and lead author of the study. “I’m actually kind of scared about how bad the actual situation would be if we had the complete data”…

I was a late comer to what this Scientific American article is about, in my later sixties, retired from a psychotherapy practice that had been more out of the mainstream than I knew at the time. In retirement, I had started volunteering in some general clinics and was struck with a couple of things. First, the patients were almost universally taking a lot of medications in odd combinations unfamiliar to me. But even more striking, they came with expectations from the medications that were well beyond any possibilities I knew. To borrow a book title, I felt like a stranger in a strange land. About that time, I read in the New York Times that the chairman of the department I had been affiliated with for over thirty years was under investigation for unreported income from pharmaceutical companies [Top Psychiatrist Didn’t Report Drug Makers’ Pay]. And somewhere in there, I had prescribed an SSRI to a 17 year old young man who became confused, agitated, and suicidal within days – all thankfully clearing as fast as they came when the medication was discontinued. At the time, I didn’t know that could happen.

I’m surprised at how much the disillusionment I felt affected me. I had experienced my share of such things before, but this one was different. Reading back over the blogs I’ve written since then, I’ve bounced from place to place in how I understood [or didn’t understand] it all. I was lucky. I had a strong hard science background from a former career and could look into the science involved. And I’ve met a number of like minded people along the way who brought a wealth of experience and wisdom my way – helping me answer questions I didn’t even know were there to be asked. But there were two concrete experiences that helped me with my own uncomfortable disillusionment. The first was going to the Allen Jones TMAP Trial in Austin in January 2012 where I watched any number of regular people caught up in some little piece of the drama without allowing themselves to see the whole picture. The second was being involved in the research for one of those articles up there and seeing the details – another example of people neither stepping back far enough to see the big picture nor getting close enough to see what they were involved in. In both instances the main problems were at the top, and had to do with unnecessary secrecy.

Medical advances have often been accompanied by high hopes and enthusiasm [illusion] followed by the more accurate reality that comes with clinical experience [dis·illusionment]. This sequence has been eroded at both ends. The Clinical Trials that are meant to be a simplistic starting place have been jury-rigged and given an undeserved enduring authority. Meanwhile, academic medical departments and journals have not only become engaged in the hype, but have also failed in their traditional role as watchdogs and skeptics. In the process, the appropriate disillusionment that comes with clinical experience with medications is being replaced with a disillusionment with medicine itself – an unacceptable trade-off.