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Do Antidepressants Increase Risk of Adult Suicide?

According to the FDA, there has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) classified as having major depressive disorder and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a very slight reduction with antidepressants compared to placebo in adults aged 65 and older.

This may sound somewhat encouraging for those who are thinking of taking antidepressants and are over 24-years old if they are willing to put aside concerns about the many other negative side effects associated with taking this class of drugs. However, interpreting these findings is highly problematic for a number of reasons. For example, these results were based on short-term studies, typically lasting just a few weeks, while many people used the drugs for years. Many drugs that were viewed as relatively safe when the short-term evidence became available later turned out to have serious negative effects when the long-term effects started to come in.

Other concerns have to do with the fact that the current available studies are almost always carried out by the drug companies that have a massive interest in proving that the drugs are safe. With the largest lobbyist group in Washington, DC (see HERE), even those working for the FDA may be incentivized to underrepresent the number of suicidal incidents and suicides. Here’s an analysis by  who looked closely at this issue:

“In a meta-analysis of the placebo-controlled trials from 2006, the FDA reported only five suicides in 52,960 patients on SSRIs (one per 10,000 patients)(3), but there were many more suicides in these trials(2). Five years earlier, in 2001, Thomas Laughren, who was responsible for the FDA’s meta-analysis, published a paper using FDA data where he reported 22 suicides in 22,062 patients randomised to antidepressants(4), which is 10 per 10,000, or 10 times as many as he reported in 2006. In Laughren’s 2001 paper, there were four times as many suicides on antidepressants as on placebo, which was statistically significant (P = 0.03, my calculation). However, Laughren did not tell his readers about this but wrote: “There is obviously no suggestion of an excess suicide risk in placebo-treated patients.” No, but there surely was in the drug-treated patients!”

In interpreting the safety of these types of drugs, there are many other types of concerns hidden in the data. For example, there is strong reason to think that the subjects in these published studies are not at all the typical people who take antidepressants. Usually when someone is depressed and is open to taking antidepressants to feel better, they go to a nearby physician and get a prescription for the actual drug. That’s not at all how the subjects in these studies go about it. They have to fill out more forms than usual, and they have to agree to be part of an experiment that has them being randomly assigned to taking either the real drug or a placebo.

Now think about that. If you are depressed and open to taking these types of drugs, why would you agree to not knowing if you are taking the real pill or the fake one? Here’s a possible clue. As it turns out, many, if not all, of the subjects who agree to this are already taking one or more psychiatric drugs, including antidepressants. They have to agree to stop taking the antidepressants that they were taking, which typically leads to very uncomfortable withdrawal reactions.

So, again, why would people who are already depressed agree to undergo such an ordeal. It seems to me that it is very possible that many of these subjects had come to feel that the drugs that they had been taking had not been helping them. Thus, they became willing to try being part of the experiment in the hope that they will be put on another experimental drug they have not tried yet and it might end up providing the relief they were seeking.

Now, add this to the picture. Those who agreed to being subjects were excluded if they had had any suicidal thoughts or attempts. So, keeping this in mind, it turns out that many in this group of subjects are those who were placed in the past on antidepressants and did not have suicidal issues when taking them. This leads one to conjecture that this is a group of people who are particularly less likely to have suicidal issues than most people when they use antidepressants. After all, many people who choose to go on antidepressants in the usual manner (going to a local doctor) do so because they have begun to have suicidal thoughts and feelings, and some may have made an attempt to end their life. These folks would be excluded from participating in the study. Thus, those who participate in these studies are a special group who tend to not have suicidal reactions before taking antidepressants and when taking antidepressants.

Given all of these problems, how can we get some additional relevant information about whether these drugs increase suicidal issues for adults? Well, here’s a recent published study that I think is worthwhile to consider.

Published October, 2016 in the Journal of the Royal Society of Medicine (see HERE), it looked at healthy volunteers with no history of mental illness who agreed to take antidepressants for several weeks. When the study began, none of them were taking any psychiatric drug. Therefore, if these healthy individuals suddenly began to experience suicidal issues when taking the drugs, it is far less likely to be blamed on either their mental illness condition or as a result of being on an antidepressant for some time and suddenly being asked to withdrawal from it just prior to when the study began. Here’s a summary from the study’s discussion section.

We found that antidepressants double the risk of suicidality and violence, and it is particularly interesting that the volunteers in the studies we reviewed were healthy adults with no signs of a mental disorder….

While it is now generally accepted that antidepressants increase the risk of suicide and violence in children and adolescents5,12 (although many psychiatrists still deny this10), most people believe that these drugs are not dangerous for adults. This is a potentially lethal misconception.7,10,15,24

As far as we know, our review is the first of the risk of suicide and violence in healthy volunteers….

In one of the two crossover trials we excluded because we did not have data on the first period separately, a healthy volunteer committed suicide, which was mentioned in both published articles.A14,A15 She had received duloxetine in increasing doses for 16 days, tapered off the maximum dose of 400 mg daily very quickly (in just four days according to the design of the study) and killed herself four days later while on placebo. The authors, several of whom were employees of Eli Lilly or owned stock in the company, judged her suicide ‘to be unrelated to study drug treatment’,A15 although it is well known that the suicide risk is high when an antidepressant is stopped abruptly.10,23 There was no more information about the suicide in the articles, and it was not included in the listing of adverse events we acquired from Eli Lilly, which only mentioned a woman who reported suicidal ideation twice while on placebo. As we do not know if this was the same patient, we asked Eli Lilly for access to anonymised data for the volunteer who committed suicide and the detailed person narrative, as we also wanted to know how it could be possible to state that the suicide was not related to duloxetine, but the company refused to give us the data….

Although only two of the 29 clinical study reports were eligible for our meta-analysis, e.g. as the studies needed to be double-blind, two researchers (AØB and PBD) read them all (2224 pages) and extracted data independently, as we wanted to explore possible selective reporting of harms in the published articles. Nineteen clinical study reports reported on the harms we investigated and nine of these were published, but less than half of the harms were reported in the articles (21 of 50 events on antidepressants and two of four events on placebo)….

There can be little doubt that we underestimated the harms of antidepressants. For 11 of our 13 trials, we only had access to the published article, and it well documented that the drug companies underreport seriously the harms of antidepressants related to suicide and violence, either by simply omitting them from the reports, by calling them something else or by committing scientific misconduct.25,7,10,27 In trials of duloxetine and sertraline, for example, only 33 of 45 cases of suicidal ideation, attempt or injury listed in a trial register were also mentioned in the published reports.2

Psychiatrists believe that the suicide risk with antidepressants is only increased till age 24, but this misconception builds on seriously flawed trial data that the FDA has published.12 Several meta-analysts have pointed out just how unreliable the trials are.5,10,28,29 A 2005 meta-analysis conducted by independent researchers of the published trials included 87,650 patients of all ages and found twice as many suicide attempts on drug than on placebo (odds ratio 2.28, 95% CI 1.14 to 4.55).28 They also found out that many suicide attempts must have been missing; some of the investigators responded that there were suicide attempts they had not reported in their trials, while others replied that they did not even look for them. Further, events occurring shortly after active treatment was stopped were not counted. Another 2005 meta-analysis conducted by independent researchers used UK drug regulator data and included 40,826 patients; they found a non-significant doubling in suicides or self-harm events when events occurring later than 24 hours after the randomised phase was over were included (relative risk 2.14, 95% confidence interval 0.96 to 4.75, our calculation).29 These researchers also noted that the companies had underreported the suicide risk in their trials, and they found that non-fatal self-harm and suicidality were seriously underreported compared to the reported suicides.

Even the FDA’s 2006 meta-analysis of 100,000 patients in 372 placebo-controlled trials12,30 is seriously flawed. Based on trials that were included in FDA’s analysis, one of us has estimated that there are likely to have been 15 times more suicides on antidepressant drugs than reported by the FDA.10 Two important reasons for the underreporting of suicides are that the FDA trusted the data the companies sent to them and that they only included events up to 24 hours after the randomised phase was over.10

Well, this is just one study that discusses the issue of suicide risks for adults choosing to take antidepressants. I chose to present it because it is the most recent study on this topic, and it seemed to me to present some additional information not usually available in the US literature.

Until next time, may you find healthy ways to deal with the many challenging experiences life has to offer.

 

Depression As Illness: A Case Study

About the Author

Jeffrey Rubin grew up in Brooklyn, received his PhD from the University of Minnesota and has taught conflict resolution there as well as at a psychiatric clinic, a correctional facility and a number of public schools. He has published articles on anger and conflict resolution and has authored three novels.

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