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Background  Depression is the leading cause of disability worldwide, and is a major contributor to the overall global burden of disease. The number of prescriptions for antidepressants has risen dramatically in recent years yet up to 50% of patients who are treated for depression with antidepressants do not report feeling better as a result of treatment, and do not show the desired improvement on depression measures. We report a qualitative study embedded in a trial of second antidepressant for people who had not responded to one antidepressant, exploring the acceptability of a combination of antidepressants from the perspectives of both patients and practitioners, together with experiences of participating in a clinical trial.    Methods  A qualitative study embedded in a randomized controlled trial investigating the effectiveness and cost-effectiveness of combining mirtazapine with Serotonin-Noradrenaline Reuptake Inhibitor (SNRI) or Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants versus SNRI or SSRI therapy alone (the MIR trial). 59 interviews were conducted with people who declined to participate in the trial, people who completed the study and people who withdrew from the intervention, and 16 general practitioners.    Results  Across the data-sets, four main themes were identified: the hard work of managing depression, uncertainties over the value of a second antidepressant, help-seeking at a point of crisis, and attainment and maintenance of a hard-won equilibrium.    Conclusions  Exploring reasons for declining to participate in a trial of a second antidepressant in people who had not responded to one antidepressant suggests that people who are already taking one antidepressant may be reluctant to take a second, being wary of possible side-effects, but also being unconvinced of the logic behind such a combination. In addition, people describe being in a state of equilibrium and reluctant to make a change, reflecting that this equilibrium is ‘hard-won’ and they are unwilling to risk disturbing this. This makes some people reluctant to enrol in a clinical trial. Understanding a patient’s view on medication is important for GPs when discussing antidepressants.    Trial registration  MIR Trial Registration:  ISRCTN 06653773 .

bmc family practice

The value of an embedded qualitative study in a trial of a second antidepressant for people who had not responded to one antidepressant: understanding the perspectives of patients and general practitioners