Adults who start treatment with antidepressants for depression are 2.5 times more likely to attempt suicide when compared to placebo, according to new research published today in the journal Psychotherapy and Psychosomatics.
The study found that approximately 1 in every 200 people who start treatment will attempt suicide due to the pharmacologic effects of the drug. This number is significant given around 7.4 million people were prescribed antidepressants in England alone last year, and given international estimates which suggest around 1 in 20 suicide attempts will end in death.
The study, ‘Newer-generation antidepressants and suicide risk in randomized controlled trials: A re-analysis of the FDA database’, reanalyses the safety summaries submitted to the FDA (the US drug regulator) for new generation antidepressants (SSRI, SNRI and atypical serotonergic-noradrenergic antidepressants like mirtazapine). The study was led by Dr Michael P. Hengartner, a senior research fellow at the Zurich University of Applied Sciences and member of the Council for Evidence-based Psychiatry (CEP), and Dr Martin Plöderl, senior researcher at Paracelsus Medical University, Salzburg.
Hengartner and Plöderl examined all suicides and suicide attempts recorded in the safety summaries of all antidepressant trials submitted to the US drug regulator FDA between 1987 and 2013 for marketing authorisation of new antidepressant drugs for the treatment of adult major depression. 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.
Based on this, the study estimates 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. 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.
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. ’
Dr James Davies, co-founder of CEP, says, ‘It is known that antidepressants increase the risk of suicide among young people and adolescents, and for this reason their use is restricted among these patient groups. However this research indicates that suicide risks also occur for some adults. This new evidence should now be reviewed by regulators, reflected in clinical guidelines and brought up in conversations between doctors and their patients.’
The study can be viewed (open access) at the following link: https://www.karger.com/Article/Pdf/501215