Abstract
Sedation is one of the common unwanted effects of clozapine. This letter reports a case of extreme sedation. A 29-year-old physically healthy man started clozapine after recovering in hospital from a particularly severe episode of accelerated psychosis. He had had several years of affective and perceptual instability punctuated by episodes of psychotic ideas of supernatural power and connection to other worlds. Despite his intelligent insight into his illness, these psychotic ideas continued to exert their disruptive and mystical pull even when he was relatively well. Lithium and variable doses of amisulpride had moderated the intensity of symptoms but neither suppressed them and their disabling effect, nor prevented episodic frank psychosis.
The initial trial dose of 12.5 mg prostrated him. He maintained that dose at night for 2 weeks despite incapacitating enervation and hypersomnia. Alternate day dosing reduced the prostration on the medication-free day when some possible benefit of the medication could be seen through the sedation haze. We then tried 6.25 mg (quarter tablets) with continuing prostration.
Heroically, we had 1 mg tablets compounded for him. While on 1 mg daily the hypersomnia was less extreme but the oppressive daytime enervation continued. It remained intolerable and aversive so that after 6 weeks of willing and insightful cooperation he finally decided he could not continue. He went back to lithium which, along with all other medications, had been stopped for the trial. At no time did he show any tolerance to the sedation effect and no response to a trial dose of dexamphetamine that is supported in the literature (Burke and Sebastian, 1993).
Previously he had tolerated amisulpride but had found quetiapine extremely sedating. This suggests that the effect may be mediated by D2, D3 or 5HT1D receptors to which clozapine and quetiapine have high affinity but not amisulpride (Richtand et al., 2007). The patient is not inclined to further explore different medicines to elucidate this.
Neither I nor my colleagues nor the manufacturers have seen this intense and sustained sedation in our extensive experience with clozapine. A literature search reports that sedation is common but has no reports to this degree.
It would be interesting to know how commonly sedation of this degree is seen in clinical practice.