Abstract
Harpreet S. Duggal and S. Haque Nizamie, Department of Psychiatry, Central Institute of Psychiatry, Ranchi, India:
Among the psychiatric effects of isonicotinic acid hydrazide (INH) [1], is its potential to induce or aggravate manic psychosis. Most clinicians, in such a scenario, would prefer to stop prescription of INH [1]. The role of novel antipsychotic drugs (APDs), including risperidone, in treating manic psychosis aggravated by INH, without cessation of the INH, is discussed.
PK, an 18-year-old youth was admitted for treatment of bipolar disorder, his second episode of mania, with psychotic features. Due to significant extrapyramidal symptoms, he had to be maintained on 200 mg per day of chlorpromazine and 4 mg per day trihexyphenidyl. Lithium, at 900 mg per day, was added for prophylaxis. Seven days after admission, the patient was found to be lethargic, prostrated and with an increased respiratory rate. Radiographic and invasive techniques revealed a right-sided tuberculous pleural effusion. Antituberculous therapy (ATT) including 300 mg per day INH, 450 mg per day rifampicin, 800 mg per day ethambutol and 1000 mg per day pyrazinamide, was commenced. Blood investigations showed no abnormality other than a significantly raised erythrocyte sedimentation rate. Serum lithium level was 1.0 mmol/L.
A week after commencing ATT, PK experienced increased agitation, grandiosity and worsening of psychosis. A further increase in the dose of chlorpromazine was impossible due to marked extrapyramidal symptons (EPS). In the ensuing 6 weeks the patient showed only little improvement as evident from a 33%% and 27%% reduction in the scores of Brief Psychiatric Rating Scale (BPRS) and the Young Mania Rating Scale (YMRS), respectively, since admission. Treating it as a case of INH-aggravated mania with psychosis, 8 weeks after admission, chlorpromazine was replaced with risperidone increased to 4 mg per day in divided doses and trihexyphenidyl was tapered and stopped as his EPS decreased. Two weeks later a 66%% and 60%% reduction from day 1 levels in BPRS and YMRS scores respectively was noted. Significantly, his grandiosity and psychosis, which had hitherto shown no apparent change, also decreased. All through this time the patient was still on INH. Subsequently, he was discharged on lithium carbonate 900 mg/day, risperidone 4 mg/day and the ATT.
The patient's recovery could not be due to the natural course of mania, as his earlier episode had persisted for 3 months. Moreover, the iatrogenic exacerbation could have only prolonged the course. Whether risperidone or other atypical APDs have a specific role in treating INH-related psychosis needs attention. The posited mechanism for INH-induced psychosis is its inhibition of the enzyme glutamic acid decarboxylase (GAD) which decreases gamma-aminobutyric acid (GABA) [2]. Furthermore, decrease in GABA contributes to the aetiology of psychosis [3]. This, when viewed in the light of Meltzer's proposed mechanism of action for clozapine facilitating GABA release [4], indicates a more specific action of atypical antipsychotics in the treatment of INH-related psychosis. Such a mechanism for risperidone and other atypical antipsychotics, although not documented, needs exploration considering the reports that novel APDs down-regulate GABAA receptors in animal studies [5].
Thus, treatment with INH may lead to a deterioriation of psychotic illness. A clinician in a similar situation may consider starting treatment with safer atypical APDs. This being a preliminary observation, further trials are encouraged for examining the role of newer APDs in managing patients with psychosis concurrently on INH.