Clozapine Therapy for a Patient With a History of Hodgkin's Disease

To the Editor: Research has shown that clozapine is the most effective neuroleptic for treatment-refractory psychosis (1), especially when psychosis is associated with a mood disorder (2). Therefore, it was appropriate to consider using clozapine for a 20-year-old African-American woman who was hospitalized for the fourth time in four years with a DSM-IV diagnosis of schizoaffective disorder, bipolar type. Prominent symptoms for the previous four years were paranoid delusions, auditory and visual hallucinations, and mania. The episodes of mania occurred once or twice a week, and each episode lasted several hours.

For four months before hospitalization the patient was treated with 6 mg of risperidone and 1,000 mg of valproic acid a day. Nevertheless she continued to have delusions, hallucinations, and mania.

Clozapine was not prescribed because of the patient's medical history. At age 13 she had had Hodgkin's disease (stage 1), which was treated with radiation (left axilla only) and splenectomy, but with no radiation elsewhere or chemotherapy. She achieved complete remission in six months and had maintained remission up to the present—for seven years.

The patient's oncologist, the medical director's office at Sandoz Pharmaceuticals (now Novartis), and a consulting hematologist all cleared use of clozapine for her. The patient's blood counts were normal—the white cell count was 7,800/μL and the absolute neutrophil count 4,200/μL. Liver profile, kidney profile, and blood chemistries were within normal limits. Clozapine titration was started at 12.5 mg a day on day 1, increasing by 25 mg a day. Valproic acid was continued at 1,000 mg a day, and risperidone was phased out over one week.

On day 9 of clozapine, when her clozapine dosage was 200 mg a day and risperidone had been phased out, the patient reported that she no longer believed her paranoid delusions and that hallucinations and manic episodes had stopped. On day 14 of clozapine (350 mg a day), the absolute neutrophil count was 1,300/μL, and clozapine was stopped. On day 21 the absolute neutrophil count was 2,600/μL, and clozapine was restarted with the same titration schedule. On day 28 of clozapine (150 mg a day) the count was 1,100/μL. All three consultants advised stopping clozapine permanently. Risperidone was restarted at 4 mg a day.

At discharge one week later, the patient was still free of delusions, hallucinations, and mania. At one-year follow-up, she remained free of these symptoms while taking 4 mg of risperidone and 1,000 mg of valproic acid a day. She was able to work and live independently.

Use of clozapine for a patient with a history of Hodgkin's disease has not been reported previously. The consultants could not distinguish between four possible causes of the leukopenia: prior Hodgkin's disease, prior treatment of Hodgkin's disease (splenectomy and local radiation), clozapine-induced leukopenia, and the predisposition of young African-American women to have low absolute neutrophil counts (3).

This case provides an alert but not a conclusion about the use of clozapine for a patient with a history of Hodgkin's disease in remission. The patient also had a clozapine-induced remission that was sustained with risperidone, which contradicts previous findings (4)