Two Large Studies Show Decline In Suicide Attempts With Antidepressant Treatment

Genetic Variations May Predispose Some Men To Suicidal Thoughts During Treatment For Depression

Genetic Variations May Predispose Some Men To Suicidal Thoughts During Treatment For Depression

Researchers at Harvard/Mass General have contributed some interesting data to the conversation about suicidality and antidepressant treatment. Roy Perlis and colleagues examined available DNA info on patients who had new onset suicidal thoughts after starting drug therapy, and found an interaction effect (sex x genetic variation) that suggested that the men with the genetic variation were at greater risk of suicidal thoughts. The article by Roy Perlis and colleagues appeared in the most recent issue of Archives of General Psychiatry. For a lay description of the study see this article in Medical News Today.

Because of the nature of the sample and the narrow scope of the findings, this study contributes most to the understanding about a possible link between suicidality and antidepressant use, about which I have posted before. But my main interest in it here relates to what new findings (especially those with a strong biomedical basis) mean to clinicians and how we think about risk assessment.

If replicated and expanded findings like these might lead to more targeted approaches to suicidality (and probably psychopharmacology for depression). However, for the clinician faced with an at-risk person in treatment, each new discovery will be merely one factor to synthesize into an overall, well-constructed risk formulation. It is doubtful we'll ever get to the point where a single data point (genetic or otherwise) will be strong enough to predict risk by itself. We'll always need good, old fashioned, clear-headed, complexity-embracing clinical judgment to discern risk. In fact, new findings related to risk (especially complex ones like those in the Perlis study) point out the importance of having a sturdy framework for thinking through risk assessment. A systematic framework allows the clinician to incorporate new findings into thinking and practice.

The need for a framework for thinking through risk may seem too obvious to mention. But consider what most training in suicide risk assessment consists of. Nearly every clinician I've spoken to (including myself) learned to assess suicide by asking a few basic questions about suicidal thinking, plan, intent, and ability to agree to stay safe. Most of us were not taught a "framework at all." We did not learn to assess for suicide risk the way we do other clinical issues--via systematic assessment and synthesis of multiple data points. In my opinion, that is why many clinicians I talk to feel so unsatisfied with the experience of working with people who voice suicidality.

All that to say...we're likely to see more genetic links with suicide risk. My goal is to be prepared to assimilate new findings within:

  • a compassionate and autonomy-respecting approach to gathering data (of all kinds) and intervening

  • a systematic way of thinking through multiple risk factors to arrive at a formulation

  • a coherent and predictable format for documenting and responding to risk

FDA ammends recommendation for antidepressant blackbox warning

In a previous post, I reflected on unintended consequencesof the FDA blackbox warning on antidepressants.   The FDA has proposed modification of the warning that (a) extends the age range of the warning to 24 and (b) includes explicit recognition that there is no data indicating danger for other ages, and that untreated depression presents its own risk.   The American Psychiatric Association has issued this press release(note: .pdf file)  applauding this second part of the new FDA proposal.

Unintended consequences of antidepressant black box warning?

An article by Charles Nemeroff and colleagues in the Archives of General Psychiatry this month reports reports on the "Impact of Publicity Concerning Pediatric Suicidality Data on Physician Practice Patterns in the United States." (If you don't have access to the journal, you can read a report on the article here.)   The authors show that antidepressant prescription rates for children and adolescents have declined and there has been a shift in proscriber patterns from "generalists" (PCPs) to "specialists" (generally psychiatrists) since the FDA placed a black box warning related to suicide risk.  The warning includes the following statement: "Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders."  You can read the entire warning in a .pdf here).

The study does not study who is not getting medication that might have in the past--just that fewer kids are getting the medicine.  Whether that is ultimately good or bad remains to be seen.

Kelly Posner, who headed the FDA/Columbia Reclassification study, spoke at our Department Grand Rounds last month and lead a seminar with a smaller group of us about the reclassification scheme.  (The reclassification project looked in detail at reported adverse events that started this controversy.)   She clearly thought the consequences of the warning would be mostly negative.   She shared her concern (which has been stated by others as well) that the unintended consequence of the black box warning will be fewer youth treated for depression and more deaths by suicide, as a result.  From what I have read, that remains an empirical question and one that will require careful interpretation of data before inferring causality. What is clear is that the black box warning was probably based more on political and emotional concerns than on science (see also Marshall, Posner, and Greenhill, 2006), and that the risk of untreated depression is probably greater than the risk of adverse events from treatment.

[mounting soapbox]  That said...when this discussion comes up I think it is important to add psychotherapy and counseling to the landscape.  Untreated depression can be deadly, but that doesn't mean the treatment has to be medication.  [coming down off soapbox]

What are the implications for risk assessment?   I'm still trying to understand that.  How I am guiding our clinicians at this point is this:   When conducting a risk assessment of an adolescent or young adult in the first weeks following initiation of antidepressants, we need to note that antidepressants have been recently started.  But rather than name this as a "risk factor" we would do better to note how the medication response will be monitored and indicate the risk-related symptoms that are being targeted by the medication.  That is, connect the medication to the risk factors it is designed to reduce, more than to the risk it might carry.


  1. Marshall, R. D., Posner, K., & Greenhill, L. (2006). Risk Perception Research and the Black Box Warning for SSRIs in Children. Journal of the American Academy of Child & Adolescent Psychiatry, 45(7), 765.

  2.  Nemeroff, C.B. et al. (2007. Impact of Publicity Concerning Pediatric Suicidality Data on Physician Practice Patterns in the United States.  Archives of General Psychiatry, 64:466-472.