Abstract
Raju G.V.L., Ramesh Kumar T.C. and Sumant Khanna, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India:
Twenty to thirty per cent of schizophrenia patients are considered treatment-resistant when they have failed to respond to two classes of antipsychotics in doses of at least 1000 mg chlorpromazine equivalents over three periods of time spanning 6 weeks each. Clozapine is the only drug approved by the FDA for the treatment of such patients, however, about 30% are non-responders even to clozapine [1]. We report two cases in which combination of clozapine and risperidone proved to be beneficial when neither of the two drugs seemed effective when used alone.
In case one, a 26-year-old male diagnosed with paranoid schizophrenia of 6 years duration was given a trial of risperidone (12 mg/day) for 5 weeks and parenteral fluphenthixol (80 mg fortnightly) for 8 weeks, to which he did not respond. He was considered treatment-resistant and was started on clozapine, a dose of 800 mg/day was reached and maintained for 5 weeks with no change in positive and negative symptoms scale (PANSS) scores. Risperidone was added to clozapine at a dose of 2 mg/day and increased to 10 mg/day. At the end of 8 weeks on this combination, the patient had improved remarkably and his PANSS scores fell from 41 to 32. The patient tolerated this combination well and continues to maintain the improvement on follow-up 7 months after discharge.
Case two was an 18-year-old male with no past history of seizure disorder, diagnosed with schizophrenia not otherwise specified of 2.5 years' duration, was given a trial of parenteral haloperidol (100 mg/month, intramuscular, for 2 months), risperidone (8 mg/day) for 5 weeks, a combination of risperidone (8 mg/day) and parenteral fluphenthixol (40 mg fortnightly) for 8 weeks, a combination of parenteral fluphenthixol (80 mg fortnightly) and pimozide (12 mg/day) for 8 weeks, and olanzapine (20 mg/day) for 5 weeks. He proved unresponsive to all these treatments and was started on clozapine. A doseof 800 mg/day was reached over 4 weeks when patient had a generalized tonic-clonic seizure, following which the dose was decreased to 400 mg/day. The dose was later increased to 600 mg/day after a normal electroencephalogram. When there was no change in PANSS scores even after 6 weeks, risperidone was added at a doseof 2 mg/day and was increased to 10 mg/day following which within the next 4 weeks PANSS scores fellfrom 84 to 47. The patient tolerated this combination well and improved further on follow up, 3 months after discharge.
Risperidone has been used successfully to augment clozapine in treatment-resistant cases [2, 3], but in such cases, there was always a doubt that the augmentor, given in monotherapy, might have had the same effects [3]. In the above cases, it is very clear that patients improved only when the combination was used. The rationale of such combination stems mainly from pharmacodynamic interactions between the two drugs, however, the exact mechanism is still unclear.
Case reports have indicated sudden appearance of agranulocytosis [4] and atrial ectopics [5] when this combination was used. No such adverse effects were observed in our cases.
Thus, this combination can be safely tried with careful monitoring in treatment-resistant schizophrenia.