Letters to the Editor
Hypnopompic Hallucinations During Olanzapine Treatment
Dear Editor:
A young man, aged 22 years, was taken for a psychiatric consultation after he had expressed death threats toward his cousin. From the information supplied, it was deduced that he had dramatically reduced his social contacts over the past 3 years and had given up all the activities that he previously enjoyed. After the consultation, we were able to draw a clinical picture that was characterized by indifference, bizarre behaviour, serious relational difficulties, and withdrawal from activities and interests. Judging from the current symptomology and from the clinical history, we diagnosed schizophrenia. As the main symptoms were negative, we decided to prescribe olanzapine. The starting dosage was 5 mg daily, gradually increased to 20 mg daily over a 1-month period. Our patient had never taken any psychotropic drug. Apart from the disappearance of paranoid symptoms (which had manifested themselves as death threats toward his cousin) a few days after the patient reached the olanzapine dosage of 20 mg daily, we also noticed improvement in the bizarre behaviour that had affected some of his daily activities. His social contacts also improved significantly. However, the therapy made the patient complain of a persistent sedative state and, strangely enough, he reported that upon waking he saw large spiders walking across the ceiling. Having noticed great therapeutic results despite the patient’s complaints of sedative effects, and because he did not complain about the hypnopompic hallucinations, we continued olanzapine therapy for about 2 more months. The patient then started to complain more vociferously about sedation and continued to refer to the visual hallucinations mentioned above, which he had previously tolerated. Because these symptoms were totally discordant with the clinical picture drawn before treatment, we decreased the dosage from 20 to 15 mg, and then to 10 mg daily, over a 1-month period. Both sedation and hypnopompic hallucinations persisted at 10 mg daily, but above all, the clinical picture worsened, particularly with regard to social withdrawal. We therefore decided to discontinue olanzapine and replace it with risperidone.
We believe that olanzapine induced the hypnopompic hallucinations claimed by the patient. With regard to olanzapine’s side effects, the drug literature has never reported imperceptive symptoms such as hypnopompic hallucinations. Conversely, cases of hypnopompic hallucinations have been reported during therapy with imipramine, amitriptyline, maprotiline, and donezepil. Schlauch has reported a case of hypnopompic hallucinations during therapy with imipramine and has suggested that such hallucinations may be connected to the decrease in rapid eye movement (REM) sleep caused by imipramine (1). Hemmingsen and Rafaelsen reported 4 cases of hypnopompic and hypnagogic hallucinations during therapy with amitriptyline (2). According to these authors, there is a connection between amitriptyline effects on the brain, sleep patterns, and clinical condition. In our case, hallucinations appeared after a few days of treatment with olanzapine and continued for approximately 2 more months, manifesting themselves every morning as the patient woke up. The patient had never previously suffered hallucinations. They disappeared after the discontinuation of olanzapine therapy and did not reappear when another antipsychotic was administered.
The discontinuation of therapy was not determined by the hallucinations, which our patient tolerated, but by sedative side effects. Olanzapine at a dosage of 5 mg daily significantly increases slow wave sleep, probably by blocking 5-HT2C receptors; it improves the continuity of sleep and the subjective quality of sleep. At a dosage of 10 mg, olanzapine significantly increases the latency of REM sleep and also decreases its duration. Such effects may be a consequence of the antagonist effects of olanzapine at muscarinic cholinergic receptors (3). Inhibition of REM sleep, as we have mentioned above, is a common property of tricyclics.The manifestation of hypnopompic hallucinations caused by olanzapine could be similar to that described for tricyclics and is therefore probably linked to REM-sleep suppression.
References
1. Schlauch R. Hypnopompic hallucinations and treatment with imipramine. Am J Psychiatry 1979;136:219–20.
2. Hemmingsen R, Rafaelsen OJ. Hypnagogic and hypnopompic hallucinations during amitriptyline treatment. Acta Psychiatr Scand 1980;62:364–8.
3. Sharpley Al, Vassallo CM, Cowen P. Olanzapine increases slow wave sleep: evidence for blockade of central 5-HT2C receptors in vivo. Biol Psychiatry 2000;47:468–70.
Iginia Mancinelli, MD
Maurizio Pompili, MD
Amedeo Ruberto, MD
Roberto Tatarelli, MD
Rome, Italy
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