Abstract
Shashjit Varma, and Kris Achan, Grampians Psychiatric Services, Ballarat, Vic., Australia:
Clozapine is a useful drug in treating patients who have not responded to conventional neuroleptics, and it is quite safe except for agranulocytosis and seizures that can become a concern. Unlike typical neuroleptics, it does not cause acute extrapyramidal side effects (hence the term ‘atypical') or hyperprolactemia. Neuroleptic malignant syndrome is rare and tardive dyskinesia (TD) is uncommon. In fact, clozapine may improve symptoms of TD in those patients already showing signs of the syndrome [1]. Cardiovascular side effects are not common but orthostatic hypotension, tachycardia, cardiomyopathy [2], myocardial failure [3] and electrocardiogram changes have been reported [4].
We report a patient who developed ventricular and atrial fibrillation after 2 weeks of clozapine therapy. A Medline search did not report any such adverse effects of clozapine.
A 44-year-old man, known to have chronic schizophrenia first diagnosed in 1988, subsequently had multiple admissions to a psychiatric facility. Recently, he had not been keeping well. He had negative symptoms, withdrawal and isolation, paranoid ideation and sleep disturbances. His cognitive functions were also not satisfactory. He was maintained on depot neuroleptics. Later, he was admitted to hospital to introduce clozapine and to gradually withdraw the depot neuroleptic.
His past and family history was unremarkable. There was no history of any medical problems. Physical examination at the time of admission was within normal limits. The Mental State Examination revealed an indifferent attitude; he was not interested in the interview, replied in very few words and was circumstantial. He had ideas of self-harm and low self-esteem. There were no other positive symptoms. His judgement was impaired.
Pre-clozapine investigations were normal and clozapine was started on 19 May 1998. On 31 May 1998, he developed a fever (38.5°C) and pallor and was lethargic. Urgent full blood examinations did not reveal any abnormality. He became weaker and macular rashes were noted on his forearms and feet. His chest revealed bibasal crepts. Electrocardiogram (ECG) showed ST elevation in leads V2 and V3. His lactate dehydrogenase level was 731 on 1 June 1998. He was transferred to the emergency department where he developed ventricular tachycardia that needed active resuscitative measures, including central line lignocaine amiodarone infusions, and he was kept in coronary care unit (CCU). He also developed atrial fibrillation for 24 h, which resolved subsequently. Gradually, he settled in CCU and on 7 June 1998 he was transferred back to the psychiatric ward. His ECG showed a global hypokinetic heart. Retrospectively, he reported to have a few spells of sweating and palpitations but did not feel it important enough to report. The impression of the cardiologists was that this episode might be the result of rhythm disturbance possibly due to clozapine.
It is always very difficult to establish the causal relationship of an uncommon side effect. This patient was asymptomatic until he was started on clozapine. Clozapine may have contributed to the development or worsening of an undiagnosed cardiac condition. Leo et al. [2] report cases of cardiorespiratory complications of clozapine and some had been even fatal.
Undoubtedly, clozapine has been shown to be beneficial to patients refractory to conventional neuroleptics; caution is advised in patients with medical disease, especially cardiac disease. As in our case, cardiac complications may arise in patients with no significant cardiac history.