By 2030, depression is predicted to be the leading cause of disability in high-income countries. Antidepressants are often the first line treatment, however, many patients do not respond to treatment with one study finding that half of those treated failed to experience at least a 50% reduction in depressive symptoms after 12-14 weeks of treatment with a single antidepressant.
Clinical guidelines recommend reconsidering treatment options if the patient shows no response after 4-6 weeks of antidepressant use. Further treatment options are varied and include increasing the dose, switching antidepressants, combining two antidepressants, and including another psychotropic drug, such as lithium or an antipsychotic. A new treatment option is the drug mirtazapine, which is a selective noradrenaline α2 adrenoreceptor and serotonin receptors 2 and 3 antagonist. The present trial determined the effects on depression and quality of life of adding mirtazapine to existing antidepressant medication compared to placebo in treatment resistant depression.
Patients were identified from general practices in the UK. Eligible participants were at least 18 years, had used a serotonin-noradrenaline reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI) antidepressant for at least six weeks, were adherent to treatment, had a Beck Depression Inventory, second revision (BDI II) score of 14 or more and met the ICD-10 criteria for depression. Patients were excluded who had bipolar disorder, psychosis, major alcohol or substance misuse and a diagnosis of dementia.
Following informed consent, eligible participants were randomised to either one 15mg capsule of mirtazapine daily for two weeks followed by two 15 mg capsules of mirtazapine for up to 50 weeks, or to identical placebo. Participants were followed up at 6, 12, 24, and 52 weeks. The primary outcome was BDI II at 12 weeks. Analysis was by intention-to-treat.
856 patients were identified as eligible for the baseline assessment and of these 105 declined to take part. A total of 751 attended the baseline interview, but a large number (271) were determined to be ineligible (mostly due to not meeting the depression severity criteria). A total of 480 were randomised comprising 241 randomised to mirtazapine and 239 to placebo.
The two groups had similar baseline characteristics, but some evidence showed that participants in the mirtazapine group had more severe depression. For the primary outcome the mean BDI II score at 12 weeks in those randomised to mirtazapine was 18.0 (SD 12.3) compared to 19.7 (12.4) in those allocated to placebo. After adjustment for the baseline BDI II score and stratification and minimisation variables the confidence interval included the null (adjusted difference in means -1.83, 95% confidence interval -3.92 to 0.27, P=0.09).
For the secondary outcomes the adjusted difference in BDI II score between the groups at 24 and 52 weeks was smaller and included the null (24 weeks: adjusted difference in means −0.85 (−3.12 to 1.43); 52 weeks: adjusted difference in means 0.17 (−2.13 to 2.46). For the other secondary outcomes, the adjusted difference in scores between the groups was small and with only two exceptions included the null. Patients in the mirtazapine were more likely to report adverse events and stop taking treatment.
In conclusion, the authors state that the trial did not find convincing evidence of a clinically important benefit of mirtazapine over placebo when given in addition to an SSRI or SNRI antidepressant for patients who remained depressed after at least six weeks of antidepressant treatment.
You can read the full report here.