Janus Christian Jakobsen, MD, PhD, of The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Denmark, and colleagues reviewed evidence for the efficacy of antidepressants compared with placebo in patients with MDD. They carried out searches for the terms “depression” and ‘antidepressants” in the Cochrane Library, BMJ Best Practice, and PubMed, targeting reviews from 1990 to June 2019.
Many of the studies reviewed showed significant effects for antidepressants on depressive symptoms. However, the investigators noted that effect sizes have questionable value to most patients based on UK National Institute for Health and Care Excellence criteria for clinical significance developed from the Hamilton Depression Rating Scale. In addition, available evidence is limited by a high or unclear risk for bias. In particular, industry involvement in research may bias studies toward positive results and exclusion criteria in randomized clinical trials may skew data.
The researchers raised the issue of potential harms caused by antidepressants, including sleep disturbances, suicide, sexual dysfunction, as well as withdrawal symptoms, which may cause patients to continue treatment. Furthermore, according to the study, most trials assess short-term effects, whereas more than 60% of people in the United States on antidepressants have taken them for more than 2 years.
Future large randomized clinical trials with long-term follow-up and a low risk of bias are critical to determining the efficacy and safety of antidepressants in MDD.
The investigators wrote, “Evidence indicates that a reduction in depressive symptoms may not be the single most important outcome to patients, but rather factors such as the ability to participate in everyday activities and return to work.” They concluded that antidepressants should not be used routinely in adults with MDD until further evidence shows that the benefits outweigh the harms.
Jakobsen JC, Gluud C, Kirsch I. Should antidepressants be used for major depressive Disorder? BMJ Evid Based Med. 2019. doi:10.1136/bmjebm-2019-111238