Antidepressants and suicide in young people

The recent article "Evaluating medicines: let's use all the evidence' was a timely reminder of the potential limitations of relying solely on randomised clinical trials (RCTs) in making decisions about the use of medications.

Nowhere is this more applicable than in the contentious area of antidepressants, particularly the selective serotonin reuptake inhibitors (SSRIs), and potential suicide risk in children and adolescents. There have been sporadic case reports of an association between antidepressants and suicidal behaviour; the efficacy of antidepressants in young people has been questioned; and meta-analyses of RCTs of antidepressants have demonstrated a weak association with suicidal behaviour, although not with suicide.

Although the RCT is the recognised “gold standard”, certain questions cannot be answered by such trials. With regard to suicide, this is partly because of the ethical dilemma of offering placebo to people who may be suicidal, but, even more so, is the impossibility of mounting a sufficiently powered study because of the low base rate of suicide. For example, it has been calculated that, if one were to use the RCTs of antidepressants which have been published, then it would have been necessary to have recruited about 1.9 million subjects to detect a 20% decrease in suicide. It is also pertinent that, in the RCTs which have led to concerns, suicidal behaviours had not been the specific focus of research, but were spontaneously reported events, and it could be argued that an overdose of active medication would be more likely to evoke reporting than an overdose of placebo.

Because of limitations in the interpretation of RCTs, it has been observed that real-life clinical monitoring may be the only way in which clinicians and drug regulators can make reasoned decisions about some treatments. Indeed, with regard to antidepressants and suicide in young people, there have been a number of recent naturalistic observations published, and it is important to incorporate them into clinical decision making.

Ludwig and Marcotte analysed SSRI use and suicide data from 27 countries, and found a strong association between an increase in antidepressant prescribing and a reduction of suicide in people older than 15 years, although the data were not conclusive for people aged 10–15 years. However, there have been studies from four countries which can inform us further about suicide and antidepressants in the young.

Jick et al analysed data from the United Kingdom General Practice Research Database (GPRD), which contains more than 35 million patient-years of information. They found a similar risk of suicide when commencing one of either two tricyclic antidepressants or two SSRI antidepressants, and a decreasing risk with time. An accompanying editorial noted that the analysis simply demonstrated that antidepressants were being “prescribed for the right indication, and that they do not immediately eliminate suicide risk. That we knew”. It is important to note that Jick et al extended their analysis to examine adolescent suicide, and found no suicides in those aged 10–19 years who were on one or other of the study drugs. However, they reported that there were 15 people in that age group in the GPRD who had died by suicide, and none had received an antidepressant drug. One might, perhaps provocatively, ask why the media did not criticise practitioners for not using antidepressants in those people.