Mirtazapine for patients with depression in primary care

Depression is common and most depressed patients are treated by their general practitioner (GP). Antidepressants are very widely prescribed, but a substantial proportion of those who take them do not get better. There is very little evidence to guide GPs when this happens, and most are unsure what to do when their patients do not respond to the medication. Many patients remain in a depressed state for long periods of time, despite taking antidepressant treatment.

We have recently completed a trial studying the effects of cognitive behavioural therapy for this group of patients, but we are looking for other ways to help those whose depression does not respond to initial treatment, and we think that it might be useful to use combinations of antidepressant drugs. 

Most of the antidepressants prescribed in the UK as first line treatment are Selective Serotonin Reuptake Inhibitors (SSRIs) like Fluoxetine (Prozac). However, there is another well-established antidepressant called Mirtazapine, that works in a different way from SSRIs and the related noradrenaline reuptake inhibitors (SNRIs). There is a strong pharmacological rationale that the distinct chemistry of mirtazapine and reuptake inhibitors act in a synergistic way.

The design we want to use is a randomised clinical trial, comparing the addition of mirtazapine to a placebo for patients with depression who have had one or more trials of an antidepressant and have currently been on an SSRI or SNRI for at least 6 weeks and are still depressed. Participants who agree will be randomly allocated to receive either mirtazapine or a placebo that appears identical. Neither the patient, GP, or study investigator will know whether the patient is taking mirtazapine or placebo. They will continue to take their SSRI antidepressant and be treated by their GP in the usual way. After 12 weeks we will measure levels of depression in the participants and we will have a clearer idea about the effectiveness of this combination of antidepressants. However, we will continue to follow up all participants for a year. This will allow us to see if there are medium or longer-term benefits of this combination treatment.