Safeguards in the treatment of schizophrenia with propranolol

Early results for an uncontrolled study of 555 patients with florid schizophrenia suggest that propranolol can be used safely in high dosage, and in a proportion of cases it appears to control schizophrenic symptoms. This method of treatment is now being submitted to controlled trial. Evdence from this uncontrolled study suggests that there was a therapeutic dose range in which symptoms steadily improved as a low dose was ineffective and a high dose, particularly if reached too rapidly, caused toxic effects. Rapid increases (400-800 mg) in the daily total intake when given in divided doses (4 to 10/day) produced gross toxic effects that included ataxia with unprotected falls, drop attacks, visual hallucinations, and confusional states. Severe toxic effects were uncommon when the dose was raised by regular, gradual increments (e.g. by 40-80 mg/day), when propranolol was given twice daily, when the dose was held steady as the patient started to improve, and when the daily total dose was reduced if the fall in pulse rate or blood pressure was excessive, or if there was evidence of toxicity. The observation of gradual, progressive improvement was the most valuable positive guide to the dose of propranolol. All schizophrenic symptoms remitted, at least temporarily, in 26 of 55 patients (in 15 of 17 patients who had been ill for less than one year and in 11 of 38 patients who had been ill for longer than a year). Patients who then stopped propranolol usually relapsed within hours or days.