Use of High-Dose Olanzapine in Refractory Psychosis
To the Editor: The recent introduction of olanzapine as an antipsychotic has enlarged the pharmacological armamentarium of clinicians. The literature on olanzapine concerns doses of 10 mg to 20 mg, and I am not aware of any literature on its efficacy above 30 mg. This letter reports two cases of refractory psychosis that responded to high levels of olanzapine.
Mr. A was a patient diagnosed with schizoaffective disorder starting in his teens. He had a mild stroke at age 37 and had some left-side residual weakness. He initially was on a regimen of fluphenazine hydrochloride, 15 mg b.i.d. orally, benztropine, 2 mg b.i.d. orally, and paroxetine hydrochloride, 50 mg in the morning. Because he had developed tardive dyskinesia, he was tapered off of the fluphenazine hydrochloride, taken off of the benztropine, and started on a regimen of propranolol hydrochloride, 10 mg b.i.d. orally, for tremors. A dose of risperidone was only partially effective up to 6 mg. Above that dose, the patient developed dystonias. A regimen of olanzapine was tried (gradually replacing risperidone), starting at 10 mg a week and increased gradually over several months to a dose of 50 mg. At this dose, his hallucinations and delusions disappeared. They reappeared when the dose was reduced to 40 mg. He had some dystonias at this dose but felt them preferable to hallucinations.
Mr. B was a patient in a locked psychiatric facility with a history of violence and psychosis. His diagnosis was schizoaffective disorder. Initially, he was on a regimen of fluphenazine hydrochloride, 20 mg q.i.d. orally, trihexyphenidyl, 5 mg q.i.d., and divalproex sodium, 250 b.i.d. orally. Mr. B had tardive dyskinesia and was floridly psychotic and aggressive. He had previously failed a trial of clozapine. His dose of divalproex sodium was increased to a therapeutic level (500 mg b.i.d. orally); the trihexyphenidyl and fluphenazine hydrochloride were phased out as a trial of risperidone (ultimately unsuccessful) was made. Doses of propranolol hydrochloride were added to try to reduce aggressive behavior, eventually reaching 20 mg in the morning, 10 mg in the evening, and 10 mg h.s. Risperidone was tapered off and olanzapine was gradually introduced and eventually increased to a dose of 50 mg. At this point, his violent behavior disappeared, and his hallucinations were reduced. (He said he could no longer hear Santa Claus but still had regular communication with God and the disciples.) More important, Mr. B began to have better concentration and could carry on appropriate conversations lasting 2 to 3 minutes. He did not have any side effects at this dose.
Laboratory monitoring of both patients did not indicate abnormal liver or kidney function. CBCs remained within normal levels. It is possible that in certain refractory psychotic patients olanzapine, at doses up to 50 mg, may have a positive therapeutic effect.
