Olanzapine, a thienobenzodiazepine, is a new "atypical" antipsychotic drug. Olanzapine's pharmacologic properties suggest it would be effective for headaches, and its propensity for inducing acute extrapyramidal reactions or tardive dyskinesia is relatively low. We thus decided to assess the value of olanzapine in the treatment of chronic refractory headache.

We reviewed the records of 50 patients with refractory headache who were treated with olanzapine for at least 3 months. All previously had failed treatment with at least four preventative medications. The daily dose of olanzapine varied from 2.5 to 35 mg; most patients (n = 19) received 5 mg or 10 mg (n = 17) a day.

Treatment resulted in a statistically significant decrease in headache days relative to baseline, from 27.5 +/- 4.9 before treatment to 21.1+/-10.7 after treatment (P <.001, Student t test). The difference in headache severity (0 to 10 scale) before treatment (8.7+/-1.6) and after treatment (2.2 +/- 2.1) was also statistically significant (P <.001).

Olanzapine may be effective for patients with refractory headache, including those who have failed a number of other prophylactic agents. Olanzapine should receive particular consideration for patients with refractory headache who have mania, bipolar disorder, or psychotic depression or whose headaches previously responded to other neuroleptic medications.