Olanzapine withdrawal/discontinuation-induced hyperthermia in rats

In female rats olanzapine (4 mg/kg b.i.d., i.p.) induced acute hypothermia, followed by very rapid full tolerance. With more prolonged treatment (over > 10 days) the hypothermic effect of olanzapine was reinstated. Subsequent withdrawal after 18 days of treatment induced very rapid onset (within 1 day) hyperthermia, which was time limited, dissipating completely over 3-4 days. These findings are similar to previous findings with clozapine [Goudie A Smith J Robertson A Cavanagh C (1999). Clozapine as a drug of dependence. Psychopharmacology; 142: 369-374.]. Although the mechanism(s) involved in the secondary hypothermic effect of olanzapine are, at present, unclear; the withdrawal hyperthermia observed represents the first report of a clear discontinuation effect of olanzapine. Such discontinuation effects are probably observed with many antipsychotic drugs. Since they have been suggested to facilitate relapse to psychosis and to interfere with subsequent clinical responses to antipsychotics, they merit further detailed analysis in both clinical and preclinical studies.