Clozapine in hyperactive delirium

Psychiatry On-Line 1999


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Dr. T.N. Srinivasan Psychiatrist, Dr. Rangarajan Memorial hospital, Sundaram Medical Foundation, Chennai- 600 040. INDIA


Pharmacotherapy has become the cornerstone in the behavioural management of hyperactive delirious states. Phenothiazines, butyrophenones and benzodiazepines have been used in such states (Smith,1992). Although no drug is ideal, butyrophenones like haloperidol have become the drug of choice for control of agitation in acute delirium (Ayd,1978).

Clozapine, an atypical antipsychotic was indicated mainly for schizophrenia patients who were not responding or were intolerant to typical antipsychotics (Remschmidt et al,1994). More recently there has been an increase in the number of conditions for which the drug is used effectively. It has been used for mood disorders (Woyshville & Meltzer,1994). An emerging body of literature suggests that clozapine may be preferable to typical neuroleptics for treating psychosis in certain neurologic disorders (Musser & Akil 1996) as well as in the treatment of movement disorders that are caused by or are a result of the pharmacologic treatment of some neurologic illnesses. (Safferman et al 1994).

I would like to report here my experience in using the drug with good effect for acute hyperactive delirium in five cases, three male and two female patients who were under treatment for a medical disorder in the hospital.

The medical conditions for which these patients were admitted in the hospital were heat hyperpyrexia, enteric fever, cerebral malaria, chronic obstructive airway disease with acute respiratory failure and diabetic ketoacidosis . During the hospital stay they developed acute delirium with confusion, disorientation, visual and auditory hallucinations, restlessness, fear, insomnia and aggressive behaviour. Besides complicating the primary medical condition, the delirious state was also disrupting treatment process like maintenance of intravenous line and administration of medication.

After baseline evaluation the patients were put on a low dose of clozapine. The dose used was 12.5 to 50mgms as a single night-time dose or bid dosage. Clozapine was used as the first-choice drug for these patients. A good level of sedation was attained rapidly and the hyperactive delirious state was brought under control within a mean period of 12 hours and full remission within 3 days. The drug was stopped as soon as the delirium cleared.

The general hesitation in using clozapine is because of its potential for producing haematological disorder. As was experienced by me with its use in delirium, the drug seemed effective in small doses and needed to be used for a short period. Many of the delirious states due to toxic or metabolic disorders are short-lived. Hence the risk of haematological complications could be negligible when used for such conditions.

Clozapine may not still warrant itself to be used as the first choice in hyperactive delirious states. With clozapine being increasingly used for conditions other than treatment-resistant schizophrenia, its use in controlling acute hyperactive delirious states could be considered an effective alternative especially where the use of conventional neuroleptics or benzodiazepines is ineffective, contraindicated or caused adverse effects.



Ayd FJ (1978) Haloperidol: 20 years clinical experience. Journal of Clinical Psychiatry 39:807-814

 Musser WS, Akil M.(1996). Clozapine as a treatment for psychosis in Parkinson's  disease: A review. Journal of Neuropsychiatry and Clinical Neurosciences 8,1-9.

 Remschmidt HE, Schulz E, Martin M, Warnke A, Trott GE (1994) Childhood-onset schizophrenia. History of the concept and recent studies. Schizophrenia Bulletin 20, 727-745

Safferman AZ, Kane JM, Aronowitz JS, Gordon MF, Pollack S ,Lieberman JA (1994) The use of clozapine in neurologic disorders. Journal of Clinical Psychiatry: 55 (SupplementumB), 98-101

Smith J (1992) Organic brain syndrome. In: Rosen P, Barkin RM, Braen GR et al, eds. Emergency medicine: Concepts and clinical practice.3rd ed.. St. Louis: Mosby Yearbook: 1766-1786

Woyshville MJ, MeltzerHY (1994) Clozapine in treatment refractory mood disorders. Journal of Clinical Psychiatry:55( Supplementum B), 91-93.

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