Combination-drug treatment of depression may pose more harm than help to those unresponsive to single SSRI treatment

By Mohamad Hamze

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) are commonly prescribed for the treatment of depression, but an increasing number of clinically depressed patients fail to respond to single antidepressant regiments. Thus, physicians have come to supplement SSRI/SNRI treatment in these patients with atypical antidepressants like mirtazapine.

Earlier this month, a study funded by the United Kingdom’s National Institute for Health Research was published in the British Medical Journal and sought to explore if this combination had a significant effect on depression severity in patients who did not respond to single-medication SSRI/SNRI regiments after six weeks. The double-blind trial studied how 480 adults with treatment-resistant depression responded to combination- versus single-drug treatments. While around four out of ten patients showed a 50% improvement in depression severity after 12 weeks of treatment, the study did not find a clinically significant difference between the group treated with mirtazapine and the group treated with placebo at this or any later time points.

This study’s results imply that psychiatrists and general practitioners should limit the use of combination-drug treatments in patients whose depression does not respond to single treatments on the basis of both cost and patient wellness. Instead, clinicians are urged to consider non-pharmacological alternatives like cognitive behavioral therapy (CBT) which, according to study co-author Dr. David Kessler, “has been shown to be effective in this group of patients” where combination-drug therapy has been poorly tolerated.

University of Bristol. (2018, November 1). Drug combination for treatment resistant depression no more effective than single. ScienceDaily. Retrieved November 12, 2018 from