d-Cycloserine therapy of psychosis by symptom provocation

The demonstration that cycloserine, an accepted therapeutic agent in the treatment of pulmonary tuberculosis, induces neurotoxic effects and behavioral changes at high doses suggested its therapeutic trial in a group of long-term severe mentally ill. Cycloserine was given to ten patients in dosages from 1.0 to 2.0 grams per day for 18 days to 16 weeks (mean, 50 days). Increases in psychotic symptoms and psychomotor excitement, confusion, and alterations of mood, affect and vigilance were the principal behavioral changes observed. Seizures and muscular twitching occurred in 2 patients. While the therapeutic benefits of cycloserine treatment alone were poor, subsequent treatment with active psychotropic drugs resulted in marked behavioral improvement, with 6 patients discharged and 3 working in the hospital six months after the study. This sequence of treatments (activation followed by psychotropic drug treatment) has been described as “symptom-provocation” therapy. Blood levels of cycloserine were related to the daily dosage and inversely related to weight. Blood levels below 45 mcg./ml. were accompanied by few behavioral changes, while levels above 65 mcg./ml. were accompanied by neurotoxic phenomena, suggesting a symptom-provocation range for cycloserine between 45 and 65 mcg./ml. The EEG patterns with cycloserine were those of desynchronization, increased fast frequencies and increased variability. These are similar to the patterns seen with other compounds inducing behavioral alerting, heightened affect and, in higher than therapeutic doses, hallucinations, delusions and excitement. d -cycloserine is an effective agent for symptom provocation with the unique advantage that an effective range can be defined by simple blood level estimations.