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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)

  • David Banner

    Hmmmmm....Many patients we see would disagree with this. They appreciate the better quality sleep and improved mood. Purely placebo? Perhaps, but that’s not my experience. Naturally some develop side effects, so they stop, and we try to avoid long term use due to weight gain. What are the alternatives? Addictive hypnotics and benzos ? Far more problematic TCAs? Barely existent secondary care referral? (who if they see them will ask you to prescribe mirtazapine then discharge them). Other placebos? I appreciate that the researchers are not tasked with finding alternatives, but in the GP surgery we need realistic options, otherwise co-prescribing will continue.

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  • You often use Mirtazipine for the sleep side effects.That is instead of using more addictive pams etc what do they want us to do instead.

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  • The combination of mirtazapine with venlafaxine (AKA California Rocket Fuel) has become a popular combination in first world countries but the evidence its better than monotherapy is lacking. If we really gave two sh#ts about practising proper evidence-based medicine, and got over our own hang-ups regarding "drugzzz" it would be appropriate to consider other treatment modalities such as ECT,transcranial magnetic stimulation and then agents like ketamine before cruddy medicine like antidepressant polypharmacy. We should also be backing investigative work into agents such as psilocybin and LSD sessions coupled with psychotherapy- but we have to have a word with ourselves first and put our preconceived notions aside.

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  • The drug to use to help with sleep is low dose trazodone. It’s brilliant as an adjunct. Better than mirtazapine as it is less weight gaining and fewer side effects at low dose.
    Mirtazapine in combo with SNRI should really be left to secondary care if used as a treatment for treatment resistant depression. Outside of what should be expected of primary care in my opinion. By this point the person needs a thorough look at to see if something else is going on ( eg bipolar misdiagnosed) ; non adherence; other comorbidities etc

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  • Vinci Ho

    I do feel uncomfortable about a lot of those ‘evidences’ where the size of population was relatively small and follow-up period was short.
    Apart from keeping the index of suspicion of a differential diagnosis, I believe depression is a condition associated with multiple perpectuating factors. A scoring system to grade the severity at the time of diagnosis is helpful but the definition of ‘treatment resistance’ using same scoring system could be parochial as quality of life and social circumstances were changing as well . Biological depression is presumably more difficult than reactive depression.
    All in all , we do not seem to have an united view of how to approach and manage this , in my view , heterogeneous condition.

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  • usually the diagnosis is wrong and we are treating PD etc with pharma. and wonder why it not work.

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  • In an area where we have virtually no psychiatry services,where the wait for iapts can be upwards of 4 months,that is rural deprived and under GPd and under funded we do not have many options compared to comparatively affluent and better funded urban areas.We are stuck with the drugs cause there is nothing else.After all did Mrs May not say mental health is our priority!

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  • Bornjovial

    NICE has accepted that Mirtazapine and SSRI combination in its previous guidelines as one of the few exceptions where 2 antidepressants are used together.
    Obviously we need to consider the study effects.
    We need to note that SSRI`s themselves have very high placebo effect (in excess of 50%) and we still use them, so I hope the study had enough numbers to be statistically significant

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  • I agree watchdoc

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  • Mirtazapine low dose at night is very helpful for sleep, it is mostly used for this as opposed to benzos for example. I have been using this for patients for years and find it very good as is trazodone, but it is horses for courses. I think there was a study with low dose nortriptyline at night with low dose SSRI, not done in UK, though I do not use this. Several studies [ Rush et al ] have shown benefits from low does combinations with different groups.

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