Mirtazapine for Concurrent Depression and Anxiety

Abstract & Commentary

Synopsis: This small open study suggests that the antidepressant mirtazapine (Remeron) may be effective in patients with both depression and generalized anxiety disorder.

Source: Goodnick PJ, et al. J Clin Psychiatry 1999;60: 446-448.

A high proportion of patients with depression have comorbid anxiety disorder, which is associated with increased severity, poorer outcome, and increased risk of suicide. Selective serotonin reuptake inhibitors (SSRIs), nefazodone (Serzone), venlafaxine (Effexor XR), and tricyclic antidepressants (e.g., imipramine) have been shown to be efficacious for these comorbid disorders. Mirtazapine (Remeron) is a relatively new antidepressant that enhances both noradrenergic and serotonergic transmission while simultaneously antagonizing postsynaptic 5-HT2 and 5-HT3 receptors. Post synaptic 5HT2 antagonism may limit activation and contribute to its anxiolytic and sleep-enhancing properties. Post synaptic 5HT3 antagonism is a pharmacologic target for treating nausea. For example, odansetron (Zofran) is a post synaptic 5HT3 antagonist.

In the current study, 10 patients with major depression comorbid with general anxiety disorder, and without any other Axis I diagnosis, received mirtazapine 15 mg QHS for one week, 30 mg QHS for three weeks, and then 45 mg QHS for four weeks. Assessments were carried out at baseline, 1, 2, 4, and 8 weeks of therapy, including the Hamilton Rating Scale for Anxiety (HAM-A), the Hamilton Rating Scale for Depression (HAM-D), the Beck Depression Inventory (BDI), and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).

There was significant improvement in scores on all rating scales used with improvement noted after the first week of therapy and continuing to improve over the eight-week period. A 50% reduction in the HAM-A score from baseline occurred for three patients after one week, five patients after four weeks, and all 10 patients at eight weeks. The most common adverse events were sedation in four patients (mostly occurring early) and blurred vision in two patients. Side effects common to SSRIs (e.g., sexual dysfunction, insomnia, gastrointestinal distress, diarrhea, and agitation) were not noted with mirtazapine.

Comment by Donald M. Hilty, MD

It appears that mirtazapine (Remeron) is a viable option for depression with anxiety, although the current findings must be replicated with a suitable double-blind, placebo-controlled design and with a larger number of subjects. SSRIs and nefazodone are the treatment of choice for these patients in the primary care setting, though with further trials this may well be reconsidered. Mirtazapine may have a valuable place in the treatment of these patients since, like nefazodone, it avoids many typical side effects of SSRIs because it antagonizes post synaptic 5HT-2. Its most significant side effects appear to be sedation and weight gain, both of which can be of marked severity in some patients early in treatment. Interestingly, in open trials the sedation appears less at 30 mg QHS than 15 mg QHS; many clinicians start at the higher dose accordingly. (Dr. Hilty is Assistant Professor of Clinical Psychiatry, University of California—Davis, Sacramento, CA.)