Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis
Published February 8, 2017:
” We have clearly shown that SSRI significantly increase the risks of both serious and several non-serious adverse events. The observed harmful effects seem to outweigh the potential small beneficial clinical effects of SSRI, if they exist.“
Conclusions
SSRIs versus placebo seem to have statistically significant effects on depressive symptoms, but the clinical significance of these effects seems questionable and all trials were at high risk of bias. Furthermore, SSRIs versus placebo significantly increase the risk of both serious and non-serious adverse events. Our results show that the harmful effects of SSRIs versus placebo for major depressive disorder seem to outweigh any potentially small beneficial effects.
Brief Overview of the Study
Highlights of the study bolded and with added emphasis:
Background
The evidence on selective serotonin reuptake inhibitors (SSRIs) for major depressive disorder is unclear.
Methods
Our objective was to conduct a systematic review assessing the effects of SSRIs versus placebo, ‘active’ placebo, or no intervention in adult participants with major depressive disorder. We searched for eligible randomised clinical trials in The Cochrane Library’s CENTRAL, PubMed, EMBASE, PsycLIT, PsycINFO, Science Citation Index Expanded, clinical trial registers of Europe and USA, websites of pharmaceutical companies, the U.S. Food and Drug Administration (FDA), and the European Medicines Agency until January 2016. All data were extracted by at least two independent investigators. We used Cochrane systematic review methodology, Trial Sequential Analysis, and calculation of Bayes factor. An eight-step procedure was followed to assess if thresholds for statistical and clinical significance were crossed. Primary outcomes were reduction of depressive symptoms, remission, and adverse events. Secondary outcomes were suicides, suicide attempts, suicide ideation, and quality of life.
Results
A total of 131 randomised placebo-controlled trials enrolling a total of 27,422 participants were included. None of the trials used ‘active’ placebo or no intervention as control intervention. All trials had high risk of bias. … SSRIs significantly increased the risks of serious adverse events…. This corresponds to 31/1000 SSRI participants will experience a serious adverse event compared with 22/1000 control participants. SSRIs also significantly increased the number of non-serious adverse events. There were almost no data on suicidal behaviour, quality of life, and long-term effects.
Conclusions
SSRIs might have statistically significant effects on depressive symptoms, but all trials were at high risk of bias and the clinical significance seems questionable. SSRIs significantly increase the risk of both serious and non-serious adverse events. The potential small beneficial effects seem to be outweighed by harmful effects.
Link to full study: http://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-016-1173-2
As Patents Expire Truth Begins to Surface
As I pointed out first in the 1994 issue of my text on antidepressants, “Prozac: Panacea or Pandora?,” the truth about the adverse effects of medications generally do not surface until the expiration of patents on these drugs – the time that the income on these drugs drastically drops as the majority of drugs in a group of drugs begins to go generic. Are we finally beginning to see that after years of warning of these deadly side effects? If so it is time to really begin warning about the deadly effects of withdrawal done too rapidly. We could be facing a nightmare of people wanting to withdraw from these drugs when most doctors know so very little about safe withdrawal from antidepressants.
PLEASE let people know to wean extremely gradually down off these drugs! For two decades the warning above has been at the top of our website warning of abrupt or rapid withdrawal. The body and brain need time to readjust after so many chemical changes!
Keep in mind the case of Traci Johnson, the young healthy volunteer (no depression), who took the antidepressant Cymbalta for 20 days and then after a withdrawal period of only four days hung herself in the laboratory for Eli Lilly, the manufacturer. After that tragedy and subsequent wrongful death suit Eli Lilly changed their time period for withdrawal in their clinical trials by double! So after 20 days on they began taking 8 days to wean off – almost the exact amount of time we have found over the years is a safe period of time to withdraw without serious reactions is about half the amount of time on the drug.
