Adding Mirtazapine to SSRI as good as placebo in resistant depression: BMJ

Bristol, UK: Patients whose depression does not respond to a single antidepressant are prescribed a combination of mirtazapine with an SSRI (selective serotonin reuptake inhibitor) or SNRI (serotonin-noradrenaline reuptake inhibitor) antidepressant by psychiatrists and GPs.

However, a large clinical trial published in the BMJ has found that adding mirtazapine to an SSRI or SNRI was no more effective than placebo in a treatment-resistant group of primary care patients with depression. The study, also found that patients taking mirtazapine in combination with another antidepressant had more adverse effects and were more likely to stop treatment than those who took an antidepressant and placebo.

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David Kessler, from the Centres for Academic Mental Health and Academic Primary Care at the University of Bristol, and colleagues conducted the study to investigate the effectiveness of combining mirtazapine with SNRI or SSRI antidepressants for treatment-resistant depression in primary care.

Depression is one of the top five contributors to the global burden of disease and by 2030 is predicted to be the leading cause of disability in high-income countries. People with depression are usually managed in primary care in the UK and antidepressants are often the first line of treatment. However, many patients do not respond to antidepressants.

The National Institute for Health and Care Excellence (NICE) advises GPs to reconsider treatment if there has been no response after 4-6 weeks of treatment. The practice of adding mirtazapine has grown as psychiatrists and GPs search for effective ways of treating those who don't respond to a single antidepressant. Previous small-scale studies had shown that this combination might be effective.

The study involved patients over 17 years who were being treated for depression in primary care and had been taking an SSRI or SNRI antidepressant for at least six weeks.

All 480 patients who took part continued to take their SSRI or SNRI and were randomly assigned to one of two groups: either additionally taking mirtazapine or a placebo. Neither the patients nor researchers knew to which group each patient had been assigned. They were followed up at 12, 24 and 52 weeks to see whether their depression had improved.

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Key Findings:

• They were still depressed using International Classification of Diseases (ICD-10) criteria.


• At 12 weeks just under 40% of patients had responded to treatment as measured by a halving of the severity of their depressive symptoms; there was a small difference in favor of the mirtazapine group but it was not clinically important and the study could not rule out the possibility of 'no effect'.


• Outcomes at the later time points showed even smaller differences between the groups with no evidence of worthwhile benefit over the longer term.

"Half of the patients in primary care who take antidepressants remain depressed despite sticking to their treatment, yet there is little evidence about how to treat those for whom the drugs don't work," said Dr. Kessler.

"Our study has found that there is unlikely to be a clinically important benefit for mirtazapine over placebo in addition to an SSRI or SNRI antidepressant in primary care patients with treatment-resistant depression and that the combination is not well tolerated. We recommend that GPs think very carefully before adding mirtazapine as the second antidepressant in this group of patients. This is particularly important when there are clear alternatives such as cognitive behavioral therapy, which has been shown to be effective in this group of patients."

For further reference follow the link: https://doi.org/10.1136/bmj.k4218