L-dopa helps positive but not negative features of neuroleptic-insensitive chronic schizophrenia

L-dopa (Sinemet-110 in a final dose equivalent to - 4 g per day) added to maintenance chlorpromazine, produced a small antipsychotic effect in a group of eight severely impaired male chronic schizophrenic in-patients. Negative symptoms were unaffected by L-dopa, although the improvement in psychotic behaviour and positive symptoms was restricted to the four patients with the most severe negative symptoms measured during the control treatment period. These L-dopa responders also tended to improve slightly when the dose of chlorpromazine was halved, an indication of their poor, or even counter-therapeutic response to conventional neuroleptic medication given in relatively high dosage. Signs of increased dopaminergic activity (raised eye blink rate and reduced plasma prolactin) were not observed in subjects showing an antipsychotic response to L-dopa. This raises the possibility that L-dopa may exert an antipsychotic effect in neuroleptic-insensitive subjects by altering noradrenergic activity in the brain.