Warning -- Antidepressants may trigger suicide attempts in adults with major depression

New Delhi: The use of antidepressants significantly triggers suicide attempts in adults with major depression, finds a recent study published in the journal Psychotherapy and Psychosomatics. The risk is 2.5 times greater than those who received a placebo.

According to the study, 1 in every 200 people who receive antidepressant treatment attempt suicide owing to the effects of the drug.

The study led by Michael P. Hengartner, a senior research fellow at the Zurich University of Applied Sciences, and Martin Plöderl, a senior researcher at Paracelsus Medical University, Salzburg, examined whether the use of newer-generation antidepressants, relative to placebo, bear an increased risk of (attempted) suicide when the analysis is based on the number of patients instead of patient exposure years (PEY). The newer generation antidepressants include SSRI, SNRI and atypical serotonergic-noradrenergic antidepressants like mirtazapine.

For the purpose, the researchers examined the records submitted to the US drug regulator FDA between 1987 and 2013 regarding all suicides and suicide attempts recorded in the safety summaries of all antidepressant trials for marketing authorisation of new antidepressant drugs for the treatment of adult major depression.

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Key findings of the study include:

• In these randomised controlled clinical trials, the rate of suicide was about 3 times higher in those taking antidepressants compared to placebo, and the rate of non-fatal suicide attempts and suicides combined was about 2.5 times higher in those taking antidepressant compared to placebo.


• The absolute risk increase in the rate of both fatal and non-fatal suicide attempts for antidepressants vs placebo to be about 0.5%, which is statistically a highly significant effect.


• Attempted suicide mostly occurs shortly after treatment initiation and not during continuation or maintenance phases.

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While this study does not attempt to identify the precise cause, other studies have suggested that rare adverse drug reactions such as akathisia or extreme agitation, as well as severe withdrawal reactions upon stopping the drug, may increase the suicide risk.

An earlier analysis of this data did not reveal the increased risk because the method used was incorrect. Previously, calculations were based on ‘person exposure years’ (PEY) rather than the number of patients receiving treatment. PEY is not the correct method here (especially when treatment duration with drug and placebo differ) because it assumes that the hazards (i.e. the suicide risk) remain constant over time, whereas the evidence shows that the highest suicide risk occurs in the first four weeks after the start of treatment, as well as shortly after the drug has been stopped. For this reason, both the FDA and MHRA require that the number of patients receiving treatment should be used for these calculations rather than PEY.

Other opinion leaders and some patients have argued that antidepressants reduce the overall suicide risk, due to their mood-altering effects. However recent studies across various countries show that, on average, increases in antidepressant prescriptions over time correlate with slightly increased suicide rates. These studies note however that this association does not imply causation.

Commenting on the findings, Dr Hengartner says, ’Our study signals a rare but serious risk that needs to be brought to the attention of healthcare practitioners, particularly when starting or stopping antidepressants. We suggest that this risk should be taken into account when doctors discuss the harms and benefits of SSRI and other newer-generation antidepressants with adult patients. It is also important that people should not stop antidepressants suddenly, and that any reduction should be discussed first with the prescriber.

To read the study follow the link https://doi.org/10.1159/000501215