When the idea that selective serotonin re-uptake inhibitors (SSRIs) might make people feel suicidal first started to be discussed by people like David Healy, I admit I was sceptical. It didn’t seem to me the drugs had much effect at all, and I couldn’t understand how a chemical substance could produce a specific thought. Since that time, however, the evidence has accumulated, and moreover, it is clear that the suicidal thoughts and behaviours usually occur in the context of a state of intense tension and agitation that the drugs seem to precipitate in some individuals, especially the young. It seems this state can be so unpleasant as to make people impulsively harm themselves, and some evidence suggests it may lead to aggressive behaviour as well.
Because these effects did not show up in randomised controlled trials, however, they were dismissed and few efforts were made to study them properly. Then some large meta-analyses, which combined results from different trials, started to find an association between the use of modern antidepressants and suicidal thoughts and actions, especially in children.
The latest large meta-analysis, conducted by a group of researchers from the Nordic Cochrane centre in Denmark, confirms the association between suicidality and SSRI use in children, and also finds evidence of an association with aggression in this age group. This is the first meta-analysis to report an association between SSRI use and aggression, and confirms other evidence described by David Healy and colleagues in 2006.
In my commentary on the study, I highlight how the analysis also points to why such findings have taken such a long time to be confirmed. The analysis used data gleaned from Clinical Study Reports prepared by drug companies for the purposes of regulatory approval. Looking in the appendices of these reports revealed many incidences of suicidal behaviour that were not recorded as adverse events in the Results section of the reports, and were presumably not reported in published articles either.
I have been asked whether I think this is evidence of a conspiracy by drug companies to suppress evidence of the dangers of their products. It may be, but it is also evidence of a more systemic failing. The advice from leading psychiatrists is to not take too much notice and to carry on prescribing. With a few exceptions, psychopharmacology researchers have shown no interest in studying the way these drugs alter normal mental functions and emotions. We know very little therefore about the state of agitation that SSRIs can induce, how often it happens, in what circumstances and what sort of thoughts and behaviours it can give rise to.
Why the reluctance to investigate this matter properly? Financial conflicts of interest is one answer, of course. Other factors include psychiatrists’ professional insecurity, and doctors’ perceived need to have something to offer the people who queue up daily in the hope of a remedy for their distress. I hope the publicity this latest study has received will spur the research community into action, and make doctors think more carefully about reaching for the prescription pad.