Antidepressants have carried a black box warning for years related to new or worsening suicidal behavior in children and young adults. A possible link, however, between SSRIs and other types of violent behavior has been more difficult to identify with studies finding inconsistent results. A recent large Swedish study, recently published in the journal PLOS One, now jumps into the debate.
The study used a somewhat novel approach in employing a “within subject” design by comparing individuals between periods someone was and was not taking a medication. Records between
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2006 and 2009 from a large national registry were used for this study and over 850,000 individuals were identified who were prescribed an SSRI medication (subjects who likely only took the medication very briefly were excluded). Another national registry was also used to identify individuals convicted of violent crimes, although other types of crimes were also investigated as a secondary outcome. The authors also tried to quantify the cumulative SSRI dose and divided subjects into groups of low, moderate, and high.
A total of 10.8% of the sample had been prescribed an SSRI with citalopram and sertraline being the most common. The main finding of the study, and the one that received the most press, was that for both males and females between the ages of 15 and 24 only, there was a statistically significant increase in the rate of violent crime during the period someone was taking the medication compared to the intervals that they weren’t. The “hazard ratio” for the 15-24 age group was 1.4 which roughly translates into a 40% increased likelihood. Described in the original study but not well reported by many press articles, however, was the important fact that this risk was increased only among youth with low SSRI doses and not those with moderate or high overall SSRI exposure. Some significant associations were also found between SSRI use and some non-violent crimes as well as non-fatal accidents. Regarding other types of antidepressants, a link was also found between violent crime and the antidepressant venlafaxine while, interestingly, the antidepressant mirtazapine was found to be related to a reduced risk of violent crime.
Sorting out what all of this means is challenging. While it might be easy to jump to the conclusion that SSRIs cause violent behavior (and many have), the data can’t really support that claim. In fact, the authors state in their discussion that one possibility is almost the opposite, namely that the finding of the link with violent crime only among those taking subtherapeutic doses suggests that undertreatment may be the mechanism behind this link. That said, if antidepressants really worked wonders for young people, we should see that therapeutic SSRI usage was associated with a reduced risk of violent behavior, which it wasn’t. These kinds of finer points have unfortunately been missing in much of the media coverage of this study.
While the within-subjects design is a clever way to reduce some potential confounding factors, it is important to remember also that the study is not randomized. Therefore, another complicating issue is that individuals were probably more likely to be prescribed medications during times when they were feeling more depressed, anxious, and angry to start with, and thus at higher risk of acting violently. Another fact to keep in mind is that while a 40% increase in violent crime sounds scary, the absolute numbers remain low. When taking SSRI medications, the conviction rate of violent crimes was 1.0% rate compared to 0.6% without medications.
It is certainly true that young people may become quite agitated when given SSRI antidepressants and it can be a tough call for clinicians to be able to distinguish between because a medication problem (requiring a drop or discontinuation of medication) and a worsening of the primary condition (which might prompt the opposite response).
In the end, we need to be cautious when using SSRIs, like any class of prescription medication, and be open to the possibility that sometimes the medication is the problem and not the solution. At the same time, it would be a shame if this study raises unnecessary panic that possibly could end up making the situation worse.
Molero Y, et al. Selective Serotonin Reuptake Inhibitors and Violent Crime: A Cohort Study. PLOS One. Sept 2015, epub ahead of print.