Nightmares with mirtazapine - A case report

Sir,

Mirtazapine is known to have noradrenergic (NA) and specific serotonergic properties, making it a drug of choice for the treatment of major depression. It helps with rapid and sustained clinical improvement in this condition and is relatively safe in the elderly patients. Nightmare is a documented side-effect of this drug, reported in around 1% of the patients being treated.[1,2] Interestingly, while around 25% of patients suffering from depressive disorders might voluntarily report nightmares with mirtazapine, this could increase with specific probing.[1]

We encountered a 52 years old man in our clinic, with 4 weeks' history of depressive symptoms (first presentation) and sleep disturbances. The latter was in the form of initial insomnia, significantly interfering with his daily functioning and job. There were no psychotic symptoms or history of substance abuse (except long-established 15 cigarettes/day). He did not have any known medical comorbidity, was not taking any other regular medicine, and did not have any significant past or family history.

He was started on mirtazapine 15 mg at night and was followed up in a week's time to monitor side effects. He reported new-onset nightmares-frightening and lucid-beginning with the first dose of mirtazapine and occurring every night. Mirtazapine was discontinued after a week's use, with relief in distressing symptoms over the next 2 nights. Naranjo Adverse Drug Reaction Probability Scale[3] score of 5 suggested a probable relationship between nightmares and Mirtazapine. The patient was subsequently stabilized on Sertraline.

The available literature warrants deeper research into the actions of mirtazapine at a molecular level. Its unique receptor profile theoretically engenders multisite action increased sympathomimetic activity and serotonin release through presynaptic alpha-2-receptor blockade, with preferential activation of 5HT1-receptors by antagonizing 5HT2/5HT3-receptors.[4] While compounds with high affinity to serotonin receptors generally reduce REM (Rapid Eye Movement) sleep, it appears to be different with mirtazapine, given the nonrarity of nightmares, and thus pointing toward the role of the NA system.[5] This predominant manifestation of NA action in the production of nightmares indicates a phenomenon of NA hijacking the REM sleep control centers, at least in a subgroup of predisposed individuals who are treated with mirtazapine.

This is a hypothesis and requires further evidence through research. In addition, if studies show that the nightmares could reduce with continued therapy and dose hike[1]– thus indicating possible receptor desensitization – a short-term use of benzodiazepines (for REM suppressant effects) might be considered as an alternative.

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Conflicts of interest

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