A wide variety of antidepressant drugs are available for the treatment of major depression. On average, these drugs have been found to offer limited improvements to patients’ symptoms over the short-term. Deciphering how these drugs elicit their effects has been a challenge, making it difficult to develop more targeted pharmaceutical approaches – ones which may better address the diverse mechanisms causing or contributing to a patient’s condition. Consequently, it can be difficult for clinicians to prescribe or recommend an antidepressant likely to be of benefit to a specific patient. As such, it is crucial to have up-to-date information on the antidepressant drugs currently available, to allow clinicians to make informed decisions concerning the treatment of major depression in their patients.
Comparing the safety and efficacy of 21 antidepressants
In a recent review published in The Lancet, researchers compared the safety and efficacy of 21 antidepressants. The study obtained data from clinical trials involving adult patients diagnosed with major depressive disorder. The researchers assessed efficacy with respect to the number of patients who experienced a reduction in depression symptoms of 50% or greater, also known as the response rate, the severity of depression by the end of the trial, the proportion whose depression symptoms subsided (remission), and the proportion which withdrew due to adverse events. They assessed tolerability with respect to the number of patients who withdrew from a trial. The time frame was between zero and eight weeks of treatment. For trials that did not record data at the eight-week mark, the nearest time point was used.
The antidepressants were more effective than the placebo
The researchers reviewed data from 522 studies, conducted between 1979 and 2016. Of the 116,477 patients included in these studies, 87,052 had been randomly assigned to receive one or more of the 21 antidepressant drugs and 29,425 had been randomly assigned to the placebo. Of the 21 antidepressants studied, all were more effective than the placebo. The lowest overall response rate was with reboxetine, 1.37 times that of the placebos, and the highest was with amitriptyline, 2.13 times that of the placebo.
Agomelatine and fluoxetine were the most tolerable of the drugs studied, having 16% and 12% fewer withdrawals than the placebos. In contrast, clomipramine patients withdrew from trials 30% more than placebo patients. Comparing the 21 antidepressant against one another, escitalopram, mirtazapine, paroxetine, agomelatine, and sertraline were found to be more effective and tolerable than average. Reboxetine, trazodone, and fluvoxamine, on the other hand, were found to be generally ineffective and poorly tolerated by patients.
The findings suggest the antidepressant drugs escitalopram, mirtazapine, paroxetine, agomelatine, and sertraline may be of most appropriate for the general treatment population. Of note, fluoxetine, which is one of the few antidepressants effective in children and adolescents, was found to have moderate efficacy and tolerability among the studies examined.
Future research into fluoxetine may provide some insight into the mechanistic differences between major depression in juveniles and adults and how best to treat the condition at different stages of life. As the authors note, the quality of the studies they examined varied. As such, the efficacy of antidepressants for which few high-qualities were conducted, such as amitriptyline, bupropion, and venlafaxine, may be underestimated.
Written by Raishard Haynes, MBS
Reference: Ciprian, A. et al. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. The Lancet. http://dx.doi.org/10.1016/ S0140-6736(17)32802-7