Effects of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) on suicidality, violence and quality of life

PhD dissertation looks beyond published literature to investigate the harms of depression medication

MSc Tarang Sharma defended her PhD dissertation on 23 April 2018.  She studied the effects of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) on suicidality, violence and quality of life based on clinical study reports.

Why study the effects of depression pills in clinical study reports?
Clinical study reports (CSRs) are detailed summaries of trial results prepared by the drug industry for submissions to regulatory authorities in order to obtain marketing authorization. Published trial reports of depression pills are notoriously known for gross dissemination bias and therefore the true effects of the pills are yet to be determined. Tarang and her co-workers studied almost 70,000 pages of CSRs describing 73 placebo-controlled trials obtained from European drug regulators.

What were the most important results?
Suicidality and aggression more than doubled in children and adolescents that were on SSRIs or SNRIs compared to those on placebo. Often, details of serious harms were only available in individual patient listings or patients’ narratives. We showed for the first time that more patients on SSRIs or SNRIs dropped out from the trials when compared to patients on placebo despite the fact that some patients in the placebo group must have been harmed because of withdrawal symptoms from stopping earlier drugs. Quality of life outcomes were almost never reported on in journal publications and the results were sometimes completely omitted from the CSRs or only very limited, partial information was available.

Conclusions
Due to problems with selective reporting, even within CSRs, raw data from clinical drug trials should be preferred when conducting systematic reviews, with CSRs being the next-best option. As SSRIs and SNRIs can have very serious detrimental effects on children and adolescents, far more than previously noted, their use in young people should be reconsidered. In fact, even when considering all ages, placebo seems to be a better pill than an antidepressant drug because the patients weigh the benefits against the harms when they decide whether to stay in a trial or to drop out.


Funding: Laura and John Arnold Foundation, and the Nordic Cochrane Centre.


Read the full PhD thesis.

Principal supervisor: Peter C. Gøtzsche
Primary co-supervisor: David Healy
External assessor: Jørn Wetterslev

Examiners:
John Brodersen (chair)
Gustav Nilsonne
Matteo Bruschettini