Neuroendocrine changes in acute schizophrenia as a function of clinical state and neuroleptic medication.

Changes in levels of prolactin, growth hormone, luteinizing hormone, and follicle stimulating hormone in serum, and testosterone in plasma, have been studied in 38 patients with acute schizophrenic illnesses in a 4-week double-blind comparison of the 2 isomers of flupenthixol and placebo. Only prolactin showed changes which could be related either to changes in clinical state or to the effects of medication. Prolactin levels increased during treatment with the therapeutically active alpha-isomer of flupenthixol but were unchanged with the inactive beta-isomer and placebo. Although there was a significant relationship between prolactin level and antipsychotic effect in patients on alpha-flupenthixol, in the individual case prolactin level was not a strong predictor of therapeutic response; and in patients on inactive medication changes in prolactin level could not be related to sympton change. There was a time lag of at least 2 weeks between the increase in prolactin secretion in patients on alpha-flupenthixol and the therapeutic effect attributable to medication. This delay suggests that if the antipsychotic effect is dependent upon dopamine receptor blockade it is not a direct consequence of this action. Perhaps dopamine receptor blockade permits other, and slower, changes to take place and it is these changes, rather than dopamine receptor blockade itself, which are reflected in clinical improvement.