Mirtazapine-Induced Nightmares

Abstract

Sir: Mirtazapine is classed as a noradrenergic and specific serotonergic antidepressant (NaSSA). It acts by blocking α2 receptors on noradrenergic neurons and enhancing norepinephrine release.1 Increased levels of norepinephrine act on α1-adrenoceptors on serotonergic cell bodies, increasing serotonergic firing.1 Nightmares occur only in rapid eye movement (REM) sleep. Most antidepressants suppress REM sleep; hence, nightmares are not a commonly reported side effect of therapy with antidepressants. We report the first ever case, to our knowledge, of a patient who developed severe nightmares on initiation of therapy with mirtazapine, which necessitated stopping the drug. Case report. Mr. A, a 52-year-old white man, presented in 2006 with depressive symptoms including low mood, poor sleep and appetite, loss of weight, hopelessness, and fatigue. Because of his symptom profile, he was started on mirtazapine, 15 mg at night. One day later, he reported vivid nightmares of being murdered and his body being cut up. These nightmares woke him from sleep and left him feeling very scared and upset. He recalled that he had been treated with mirtazapine 2 years ago and it had to be discontinued because of similar distressing nightmares. After 4 days of therapy and experiencing nightmares every night, he requested that the medication be stopped. The nightmares disappeared 1 day after cessation of mirtazapine. He denied ever experiencing such distressing nightmares in the past, except when he was taking mirtazapine. His only other concurrent medication was hydroxymorphone. The temporal relationship between the initiation of treatment with mirtazapine and onset of nightmares and their disappearance with discontinuation of the drug, and also their occurrence during a previous episode of mirtazapine treatment, suggest a causal etiology. Most antidepressants suppress REM sleep.2 Mirtazapine has been shown to increase REM sleep even with acute administration, i.e., at 2 days.3 It has also been shown to increase total sleep time, sleep efficiency, and stage 2 and slow wave sleep. These effects persisted after 5 weeks of treatment.3 Vivid dreams and nightmares have been reported with other antidepressants that increase REM sleep, such as bupropion.4 It is possible that mirtazapine increased REM sleep in this patient, which may have induced nightmares. Clinicians should be aware of this side effect, as it can potentially affect treatment adherence.