Abstract
Clozapine is an atypical antipsychotic with efficacy attributed to its antagonist actions at serotonin (5HT1) and dopamine (D1 and D2) receptors. Abrupt clozapine withdrawal has been associated with nausea, vomiting, diarrhoea and agitation postulated to occur as a result of cholinergic rebound [1,2] Catatonia as a clozapine withdrawal syndrome has not been well documented. We report a case of catatonia developing within a week of sudden withdrawal of clozapine.
A 29 year old man suffering from schizophrenia presented with a history of predominantly negative symptoms for 9 years. He had been trialled on trifluoperazine, haloperidol and olanzapine in adequate dosage for adequate duration. Minimal response of his negative symptoms to the above treatment prompted institution of clozapine. The patient was stabilized on clozapine 250 mg/day and a response was noted in the form of ward participation, increased productivity of spontaneous speech and motivation to carry out daily activities. Initial blood counts were within normal limits. After 3 months in the ward, his blood count revealed a sudden drop in total leukocyte count (1100/cu mm) and absolute neutrophil count (540/cu mm) along with a fever (37.8°C). Clozapine was immediately stopped. His fever was treated conservatively and it resolved within 2 days. There were no signs of autonomic instability or muscle rigidity to suspect neuroleptic malignant syndrome. Antipsychotic medication was not started for 2 days during which the patient remained quiet, sitting or standing in the same position for long periods of time and refusing to eat his meals. He stopped talking completely and would maintain postures such as psychological pillow for 4–5 h at a time. Clinical examination revealed mutism, posturing, passive obedience, waxy flexibility, negativism and nil oral intake. A diagnosis of catatonia was made and he was given lorazepam for 2 days followed by electroconvulsive therapy (ECT) on day 3. After 4 ECT treatments he started showing significant improvement. He started eating, making spontaneous movements and speaking a few words. Within the next two days, all signs of catatonia resolved and he was discharged on risperidone (4 mg/day).
Catatonia as a clozapine withdrawal syndrome has been rarely documented. There is evidence that clozapine withdrawal is associated with rapid onset of psychotic symptoms, known as ‘rebound psychosis’, which is now believed to be distinct from the relapse of the underlying disorder and due to increased dopamine activity in the limbic system [3]. To our knowledge only 3 cases have been reported [2,4,5]. Two of the cases [2,5] presented with a malignant excited catatonic syndrome with prominent autonomic abnormality. In another case, the patient presented in a stuporous state with no significant elevation of temperature and prominent autonomic disturbances, along with myoclonus, hyperreflexia, and hyperactive bowel sounds [4]. Our patient developed a catatonic syndrome following abrupt discontinuation of clozapine. Though the episode was not associated with other features of clozapine withdrawal such as cholinergic or serotonergic hyperactivity, the temporal relationship between the abrupt cessation of clozapine dose and the emergence of catatonic symptoms in this patient prompted the association.