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GPs 'should stop co-prescribing mirtazapine and SSRIs for depression'

Prescribing mirtazapine with SSRIs or SNRIs for treatment-resistant depression is no more effective than placebo, a study has suggested.

Researchers said that GPs should stop the ‘growing practice’ of adding mirtazapine to SSRIs or SNRIs, as it is may cause more adverse effects.

The study looked at just under 500 patients from UK general practices who had been taking an SSRI or SNRI for depression but remained symptomatic after six weeks.

Around half of the patients were assigned to receive mirtazapine in addition to their SSRI or SNRI and half were assigned to receive a placebo.

At 12 weeks’ follow up, all patients had reduced levels of depression, measured using the Beck Depression Inventory score, with the mirtazapine group scoring 18.0 and the placebo group scoring 19.7, down from an initial score of 31.5 and 30.6 respectively.

The difference in scores was not statistically significant however, and the researchers described mirtazapine as ‘unlikely’ to have clinical benefit. They found that the differences became even smaller at 24 and 52 weeks’ follow up.

They noted that more patients who were taking mirtazapine reported more non-serious adverse effects than those were taking the placebo, with 46 patients who reported adverse effects stopping mirtazapine at 12 weeks, compared to nine stopping the placebo.

The researchers said in the paper: ‘These findings challenge the growing practice of the addition of mirtazapine to SSRI or SNRI in this group of patients

'The lack of clear evidence of benefit in our study, combined with the increased burden of adverse effects in the mirtazapine group, means that we cannot recommend this combination as a routine strategy in primary care for those who remain depressed after adequate treatment with SSRI or SNRI antidepressants.’

BMJ 2018; available online 31 October

Readers' comments (14)

  • particularly to David Banner, but also the study authors: they have omitted mention of one 'side effect' that does not result in ceasing medication early with Mirtazapine - it is addictive and additively so to Quetiapine and Z-drugs/gabapentapams.
    TCAs are choice if sedation is needed!
    Ans if Mrs May agrees we should prioritise mental health care, then refer them all for more appropriate therapies rather than drugs, and secondary care can use waiting list statistics to bid for some of her special funding!
    Mirtazapine is horrible - first do no harm.

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  • Edoardo Cervoni

    My professional experience is in keeping with the observations described in this study. Heterogeneous pooling is a very well known challenge to any clinical research, particularly when all the variables at play are unclear, but I think this was an important publication.
    In fact, many of us did read it.

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  • amitriptyline 10mg is also useful as a non addictive hypnotic that can be used for many years without any loss of effect.
    Even in leafy sussex we have trouble accessing timely and helpful secondary care psychiatry so its mainly done by the first line GPs and usually highly efficient and successful.

    It annoys the heck out of me that we are expected to follow the evidence base of 'their' choice but if we quote evidence that sunday appointments are a waste of resources this is disallowed.
    Could Pulse run a hypocrisy of the month section?

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  • I do think that GPs should have secondary care experience as part of their training. Some GPs come with their predudices about psychiatry and psychiatrists as drug pushers. If you get the diagnosis of depression and anxiety right appropriate drug use is life saving and changing. So much utter tosh about antidepressants being ‘addictive’ it’s shameful

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