Clinical and biochemical effects of melperone (100rag • 3) and thiothixene (10 mg• 3) were studied in women with psychoses of schizophrenic or paranoid type. Psychotic morbidity and side effects were determined by rating scales. Concentrations of the major monoamine metabolites homovanillic acid (HVA), 4-hydroxy-3-methoxyphenyl-ethylene glycol (MOPEG), and 5-Hydroxy-3-indoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) were measured by mass fragmentography. Concentrations of prolactin in CSF and plasma were determined by radioimmunoassay (RIA). Measurements were performed before and after 2 and 4 weeks of drug treatment.
The drugs did not differ in antipsychotic effect, but thiothixene treatment caused greater elevation of HVA and prolactin than melperone. The measures of dopaminergic activity did not correlate significantly with therapeutic outcome in either of the treatment groups. Treatment with melperone, but not thiothixene, reduced MOPEG levels, but only during thiothixene treatment was MOPEG reduction related to clinical improvement. In both treatment groups clinical improvement correlated significantly with an increase in the 5-HIAA/MOPEG ratio. Extrapyramidal side effects correlated negatively with HVA and HVA/MOPEG in the thiothixene, but not in the melperone group.
It is concluded that there is no simple relationship between alteration of dopaminergic transmission and therapeutic outcome in drug-treated psychotic patients. In addition to dopamine (DA) receptor blockade, alteration of norepinephrine (NE) mechanisms may play a role in the antipsychotic effect. It is suggested that the balance of activity between central serotonin (5-HT) and NE systems should be considered in the mechanism of action of antipsychotic drugs and the pathophysiology of psychosis.