Although chronic insomnia is an established risk factor for suicidal ideation in depressive disorders,1–3 the therapeutic benefit of targeting insomnia per se in such patients remains understudied. We report an initial case and a series of patients in whom treatment of insomnia with mirtazapine proved highly therapeutic.
A 60-year-old man presented with a 5-year history of distress due to nonrestorative sleep despite having adequate sleep time and good environmental sleep conditions. His Clinically Useful Depression Outcome Scale (CUDOS)4 score (50/64) indicated severe depression. After 3 weeks of treatment with low-dose mirtazapine (7.5 mg at bedtime), his CUDOS score (11/64) declined into the minimal depression range, whereas suicidal ideation and insomnia symptoms resolved. He attributed his improvement in mood primarily to regaining restorative sleep.
We then administered mirtazapine (7.5–30 mg at bedtime) on a clinical basis primarily to treat insomnia in patients who (1) were referred to the mental health clinic for significant depressive symptoms, (2) met International Classification of Diseases, 10th Revision criteria for insomnia, and (3) endorsed subjective suicidal ideation. The subsequent chart review was approved by the Institutional Review Board.
A total of 28 male patients (age 40–75 years) were started on mirtazapine. In six patients, mirtazapine was discontinued because of side effects (somnolence in four; tinnitus in one; dermatitis in one). However, significant improvement (n = 15) or complete resolution (n = 7) of both insomnia and suicidal ideation was achieved in the remaining 22 patients. For the group as a whole, the change in CUDOS score (mean ± standard deviation of the mean: baseline 42.39 ± 7.07; 4 to 6 weeks 19.5 ± 3.06; 6 to 8 weeks 16.89 ± 2.59) was significant by repeated-measures analysis of variance (F34,2 = 65.7, P < .0001).
Both in the index patient and most patients in the case series, insomnia, depressive symptoms, and suicidal ideation resolved in parallel during treatment with mirtazapine at bedtime in the low-dose range (7.5 mg, n = 2; 15 mg, n = 18; 30 mg, n = 2). The pivotal original studies supported an FDA-approved antidepressant indication for mirtazapine 15–45 mg/d. While the drug is commonly used off-label at lower doses (7.5 to 15 mg at bedtime) primarily for a soporific effect, antidepressant effects at doses of 7.5 mg/d have been reported.5,6 One possibility is that our data merely confirm the established antidepressant actions of mirtazapine. However, the relationship between depression, suicidal ideation, and insomnia is complex. Insomnia often precedes the onset of depression and constitutes a powerful independent risk factor for development of depression, suicidality, executive impairment, and impulsive behavior.7–9 We postulate that at least in some patients, targeting and effectively treating insomnia may lead to secondary resolution of concomitant suicidal ideation and other depressive symptoms. Our report underscores the importance of recognizing and treating insomnia in patients with depression and suicidal ideation. When insomnia is present concomitantly with suicidal ideation, antidepressant selection should be guided at least in part by the goal of providing restorative sleep.
All authors have seen and approved the manuscript. Work for this study was performed at the Louis Stokes VA Medical Center. The views expressed in this letter do not necessarily represent the views of the Department of Veterans Affairs or of the US Federal Government. The authors report no conflicts of interest.
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