Mirtazapine may induce nightmares, case series reports rare side-effect of antidepressant treatment

Sleep disturbance and insomnia are some of the most frequent complaints in patients suffering from depression. Mirtazapine, because of its antihistaminergic action,is associated with sedative properties and can quickly improve sleep quality. Despite these documented beneficial effects, Dell’Osso et al have reported five elderly patients in whom the aforesaid antidepressant triggered dramatic nightmares. These cases were published in Hindawi Journal recently.

The five cases of elderly patients had age ranging from 69 to 79 with various diagnoses and comorbidities (severe or recurrent depression, general anxiety disorder, borderline personality disorder, and Parkinson's disease) assessed during clinical daily routine for whom the use of mirtazapine was linked to the onset of nightmares so impressive and dramatic that made it necessary to interrupt the treatment.

The typical course in four patient was reporting a significant improvement of the sleeping time and depressive symptoms within few days of initiating mirtazapine treatment but following this was sudden and progressive appearance of nightmares, so disturbing that the patients autonomously decided to stop the treatment. Soon after the discontinuation of the drug, the nightmares disappeared and the insomniac pattern came back.

In the fifth patient, with diagnosis of general anxiety disorder with recurrent depressive episodes, mirtazapine led to nightmares and progressive increase of anxiety symptoms, and at least one time, a full blown panic attack happened during the night. Mirtazapine’s discontinuation became necessary and led to the disappearance of any sleep disturbance and of night time panic attacks.

The authors mention that while this drug’s ability to block α2-autoreceptors could lead to impaired REM sleep and to a disruption of sleep continuity, its inhibition on the 5-HT2 and, to a lesser extent, H1 receptors may tend to promote sleep.

Nightmares can be considered a “REM sleep-related behavior disturbance” (RBD) and thus a kind of parasomnia that may include the loss of the normal muscle hypotonia present during REM sleep, portrayed by a dream enactment and the appearance of terrific and realistic issues.

Therefore, hypothesizing that nightmares can be caused generically by an alteration or even repression of REM sleep, a great contradiction arises, since mirtazapine, unlike many other antidepressants, commonly has no repressive effect on REM sleep.

Globally, further studies in wide samples and with a longitudinal design are needed to clarify the positive and negative impacts of mirtazapine on nightmares in different populations.

Source: Case Rep Psychiatry. 2023; 2023: 8843206.