New Findings on Polypharmacy in Depression

Peter M. Yellowlees, MBBS, MD


March 11, 2019

This transcript has been edited for clarity.

This is the Medscape Psychiatry Minute. I'm Dr Peter Yellowlees.

In routine clinical practice, antidepressants are increasingly being combined. However, there are few clinical trials investigating the effectiveness of this practice.

Now, a team from Bristol Medical School in England has investigated the effectiveness of combining mirtazapine with a serotonin-noradrenaline reuptake inhibitor (SNRI) or a selective serotonin reuptake inhibitor (SSRI) antidepressant for treatment-resistant depression in primary care.[1]

A total of 480 patients were recruited from 106 general practices in the UK who scored 14 or more on the Beck depression inventory. Overall, 241 patients were randomized to mirtazapine and 239 to placebo, both given in addition to usual SSRI or SNRI treatment, with follow-up and primary analysis at 12 weeks.

The researchers did not find evidence of a clinically important benefit for mirtazapine in addition to an SSRI or an SNRI over placebo. They concluded that this remains an area of important unmet need where evidence of effective treatment options is limited.

What is the take-home message from this study? First, there are inevitably some methodologic concerns about the dosages of the drugs involved (30 mg mirtazapine, and unknown for SNRI/SSRI), which in specialist psychiatric practice are often higher.

In my own practice, I commonly combine the sedating mirtazapine (given at night) with one of the stimulating SSRIs (bupropion) or stimulating SNRIs (venlafaxine), given in the morning, and in higher doses than in this study.

Like many colleagues, I have found this combination effective in many instances, but there is little formal clinical trial practice to support this approach, and that is what we need. Although this is a negative trial, it is welcome and will hopefully serve as a good example of the real-world trials we so badly need.

Thank you for listening to this Medscape Psychiatry Minute. Do continue to enjoy your practice.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.