Mirtazapine for Concurrent Depression and Anxiety
Abstract & Commentary
Synopsis: This small open study suggests that the antidepressant mirtazapine (Remeron) may be effect in patients with both depression and generalized anxiety disorder.
Source: Goodnick PJ, Puig A, DeVane CL, et al: Mirtazapine in major depression with comorbid general anxiety disorder. 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 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 15mg QHS for one week, 30mg QHS for three weeks, and then 45mg 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.
Commentary 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. Mirtazepine may have a valuable place in the treatment of these patients because, like nefazodone, it avoids many typical side effects of SSRIs because it antagonizes post synaptic 5HT-2. Its most significant side effects appears 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 30mg QHS than 15mg QHS; many psychiatrists start at the higher dose accordingly.
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