The Dopamine Hypothesis of Schizophrenia: A Review*

• Serum prolactin levels were studied before and during longterm administration of phenothiazines on a twice daily schedule to 27 newly admitted schizophrenic patients. An increase in serum prolactin is believed to be a reflection of inhibition of dopamine receptors in the hypothalamopituitary axis. By 72 hours after the initiation of treatment, all 27 patients had persistently elevated serum prolactin levels averaging 3.2-fold and 3.8-fold in men and women, respectively. There was a lag between clinical response and dopamine blockade, as indicated by serum prolactin levels in most patients. Serum prolactin levels remained elevated during the one- to three-month period subjects were studied, suggesting there was no tolerance to this effect of phenothiazines. Serum prolactin levels tended to be higher with thioridazine than on equivalent doses of chlorpromazine or trifluoperazine hydrochloride. There was some evidence that the magnitude of the serum prolactin elevation correlated with clinical response. After cessation of phenothiazines, serum prolactin levels rapidly reverted to normal within 48 to 96 hours.

The effect of neuroleptics on serum prolactin in schizophrenic patients.

In a series of 36 patients with acute schizophrenia flupenthixol dosage was blindly adjusted to give a fixed level of sedation. Patients were than randomly allocated to procyclidine or placebo. The patients receiving procyclidine experienced more positive schizophrenic symptoms and less severe extrapyramidal features by comparison with placebo patients. Blood levels of prolactin and flupenthixol estimated by radioimmunoassay were not significantly changed by the addition of procyclidine. Flupenthixol dosage and levels and prolactin levels were significantly related. There was no significant association between clinical and laboratory measures, with the exception that a curvilinear (inverted U) relationship was demonstrated between flupenthixol levels and antipsychotic and extrapyramidal effects. This relationship may be due to the fact that, in a study of this design, patients resistant to the effects of neuroleptic medication are likely to be given the highest doses. The findings support earlier claims that anticholinergic medication has adverse effects on schizophrenic symptoms.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0033291700047942

Adverse effects of anticholinergic medication on positive schizophrenic symptoms

Dopamine and norepinephrine activity in schizophrenia. An integrative perspective.

Dopamine and schizophrenia

Plasma levels of chlorpromazine (CPZ) and prolactin were measured repeatedly in 14 psychiatric patients throughout CPZ treatment. Mean prolactin level was elevated in 11 subjects (all six women and five of eight men). Mean plasma prolactin correlated significantly with mean plasma CPZ but not with the dose of the drug. Only patients with mean plasma prolactin above 35 ng/ml developed Parkinsonian side-effects.

A. S. McNeilly

Papers

Correlation between plasma levels of prolactin and chlorpromazine in psychiatric patients.