British Experience With High-Dose Olanzapine for Treatment-Refractory Schizophrenia

To the Editor: We read with interest the letter by Brian B. Sheitman, M.D., and colleagues (1) reporting the use of olanzapine at doses above the recommended upper limit in patients with refractory schizophrenia. Although the maximum recommended dose for olanzapine is 20 mg/day, Reus (2) cited unpublished trials using a higher dose.

During the first 8 months of use of olanzapine at St. Andrew’s Hospital, Northampton, U.K., 23 (62%) of 37 patients given olanzapine fulfilled the criteria for treatment-resistant schizophrenia. Eight patients with resistant schizophrenia were difficult to treat within the recommended olanzapine dose range. For these patients, the prescribing consultants felt justified in using a higher maximum dose (60 mg/day), which did not produce any increase in the incidence or severity of side effects. Olanzapine had an acceptable degree of overall tolerability, and there were no cases of treatment-emergent extrapyramidal side effects.

Eleven (48%) of 23 patients with resistant schizophrenia were continued on a regimen of olanzapine because of an appreciable degree of clinical improvement. A greater proportion of the patients who had never taken clozapine demonstrated an improvement in overall symptoms than did those who had previously been treated unsuccessfully with clozapine. There were seven clozapine-naive patients. Six of these patients were continued on a regimen of olanzapine at a mean dose of 33.3 mg/day (range=20–60) and a mean duration of treatment of 4.8 months (range=3–8) by the end of June 1997. Five clozapine-na�ve patients improved. In the patients who were started on olanzapine following an unsuccessful trial of clozapine (16 patients), seven patients continued on olanzapine treatment with a mean dose of 31.4 mg/day (range=10–60) and a mean duration of treatment of 7.4 months (range=5–8) by June 1997. Six of these patients exhibited moderate to marked improvement comparable to the improvement of the five clozapine-na�ve patients. The remaining nine patients were withdrawn from olanzapine after a mean duration of treatment of 2.2 months (range=0.3–5.7) and a mean dose of 18.9 mg/day (range=10–30) at the time of stopping. Patient refusal to take olanzapine or any other oral antipsychotic medication was a common cause for withdrawal from treatment. This highlights the importance of developing an atypical antipsychotic preparation in depot form to ensure compliance.