October 12, 2016

expert reaction to antidepressants and risk of suicide and violence in healthy people

A review of published evidence on the effect of antidepressants on suicidal behaviour and violence in healthy people is published in Journal of the Royal Society of Medicine with the authors reporting ‘antidepressants double the occurrence of events in adult healthy volunteers that can lead to suicide and violence.’

Prof. Seena Fazel, Professor of Forensic Psychiatry and Wellcome Trust Senior Research Fellow, University of Oxford, said:

“There are a number of serious limitations with this review that mean that its conclusions are not justified. The most problematic is that it conflates a whole range of side effects – from ‘unusual thoughts’, ‘being jittery’ to ‘caffeine feeling’, to the more serious outcomes such as self-harm and violence. In fact, when you look at the data from included trials, none of them report the latter – all of the information is based on the first category of relatively minor side effects.

“Second, the review does not discuss the large body of high quality evidence from other research approaches that do not support their main conclusion, that antidepressants are harmful to adults. Contextualizing the evidence is important because this review is based on only 612 participants, and we need to look at the high quality research drawn from population studies that run into the hundreds of thousands of persons treated with antidepressants.

“Finally, the review makes the mistake of over-extending the implications of their limited findings. None of the included trials had a suicide or suicide-related event but the paper talks incorrectly of risks of suicide.”

Prof. Sir Simon Wessely, President of the Royal College of Psychiatrists and Professor of Psychological Medicine, King’s College London’s Institute of Psychiatry, Psychology & Neuroscience, said:

“This paper shows that antidepressants have side effects such as odd dreams, nervousness and shaking.  This is very familiar to most, if not all, clinicians. But importantly, no data presented in the paper supports extrapolating from these side-effects to self-harm and violence.

“The strongest conclusion one can draw from this data is to say that some symptoms such as agitation occur in depression itself and in response to antidepressants, and that sometimes these symptoms are also experienced by people who go on to commit acts of violence or self-harm.

“Overall, medications used in any branch of medicine that do good can also do harm. The same applies in psychiatry.

“Current evidence from large scale studies continues to show that for antidepressants the benefits outweigh the risks. If the evidence changes then so will our advice, but this study changes nothing.”

Dr David Christmas, Member of the Psychopharmacology Committee, Royal College of Psychiatrists and Consultant Psychiatrist in The Advanced Interventions Service, Dundee, said:

“Whilst Professor Gøtzsche has a range of well-established beliefs regarding the harms of antidepressants, the type of study reported here isn’t suitably constructed to answer the questions that they wanted to ask. Most of the trials reported varied in the type of drug used, the dose, duration and the mechanisms of reporting harms.

“Importantly, the study only identified emergent harms that are associated (directly or indirectly) with suicide and violence. It didn’t identify a higher rate of these outcomes from the studies they used. Using a meta-analysis of randomised-controlled trials to ask these questions introduces additional problems that haven’t been properly addressed by the methods used.

“Ultimately, whilst Professor Gøtzsche and colleagues believe that antidepressants cause increased suicide in all ages, this is an opinion that isn’t supported by this study. Further, the recognition of an increased risk of self-harm and suicide in younger people taking antidepressants is well-recognised and there is much evidence to suggest that the risk is reduced by antidepressants in older people with depression.

“The study does highlight, however, the importance of recording and reporting all adverse events from clinical studies, whether it’s a drug treatment or psychological treatment; and the close monitoring of all patients taking medication.”

Prof. Phil Cowen, Professor of Psychopharmacology, University of Oxford, said:

“The study shows clearly that antidepressants can cause adverse effects in healthy volunteers as they do in patients. This is to be expected and reinforces the case that antidepressants in clinical practice should be used with care, only when indicated and when treatments with fewer harms have not been helpful. However, the authors then go on to claim ‘that antidepressants double the risk of suicidality and violence’ in these healthy participants. However, when one examines the adverse effects reported in Table 3 of their paper there are no reports of violence or suicidal behaviour. What one sees are known adverse effects of serotonergic antidepressants such as anxiety, nervousness, tremor and abnormal dreams. These occur in about 15% of the drug-treated participants compared with about 10% of those receiving placebo.

“These side-effects are clinically significant, frequently distressing and an important topic for discussion between patient and clinician. However, the notion that they are necessarily indicative of violence and suicide seems to me rather like arguing that transient annoyance with a colleague is much the same thing as attempted murder.”

Prof. Guy Goodwin, Past President of the European College of Neuropsychopharmacology (ECNP) and Professor of Psychiatry, University of Oxford, said:

“This manuscript claims to show that antidepressants double the risk of suicide and violence, but it does not. The methodology is fatally flawed and leads to conclusions that are highly misleading.

“The data are taken from studies in which healthy volunteers were randomised to receive either a SSRI or a placebo. The authors then solemnly recorded the number of people that had nervousness, anxiety, tremor, bad dreams and agitation events. The researchers counted these instances as ‘harms that can lead to suicide or violence’ when in fact there appear to have been no specific suicidal events at all. I think it is absurd to describe these nervousness and agitation as events potentially leading to suicide or violence. If ‘nervousness, anxiety, tremor, bad dreams and agitation events’ are risk factors for suicide or violence, then probably the majority of people in the UK would be at risk of suicide or violence, which obviously isn’t so. Even giving placebo to healthy volunteers produced a 10% rate of such events. It is absurd to describe them as events leading potentially to suicide or violence.

“I was Principal Investigator on one of the larger studies that was cited. At no point during our study was there any suggestion of suicidality among our volunteers whose mood was regularly and explicitly rated. However, by changing what is deemed to be a risk of suicidality, the methodology used by these authors makes our study looks like it supports their conclusions. The suggestion that their review shows a doubling of risk of suicide and violence is simply science fiction.”

‘Precursors to suicidality and violence on antidepressants: systematic review of trials in adult healthy volunteers’ by Bielefeldt et al. published in Journal of the Royal Society of Medicine on Wednesday 12th October. 

Declared interests

Prof. Fazel: “No grants from any pharma, but on one occasion I did receive a speaker’s fee from Janssen (who make an antipsychotic) that I donated to charity.

Prof. Cowen: “In the last three years I have been a member of an advisory board for Lundbeck.”

Prof. Goodwin: “Principal Investigator on one of reviewed studies (funded by Servier, but data from a non-Servier drug); I have advised Lundbeck, Servier on the development of antidepressant drugs and GSK, Lilly, MSD and Pfizer on matters relating to drug development for bipolar disorder.”

All others: No declarations received