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Plasma concentration of neuroleptic and serum prolactin in patients chronically receiving depot fluphenazine: No evidence of tolerance

The authors determined neuroleptic dose, plasma level of drug, and serum prolactin in 76 outpatients receiving depot fluphenazine. The patients had received neuroleptic treatment for periods ranging from 3 to 23 years (median 13 years). Plasma level of drug correlated with dose (rs = 0·73, p>0·0001). Prolactin levels were linearly correlated with dose (rs = 0·42, p = 0·0001) and plasma level of drug (rs = 0·64, p>0·0001). There was a tendency for dose and, concomitantly, plasma level of drug, to decrease with age (rs = −0·29, p = 0·01, for each). However, dose, plasma level of drug adjusted for dose, and serum prolactin adjusted for plasma level of drug did not correlate with duration of treatment. Neither did any of these measures correlate with treatment duration when adjusted for age. The findings suggest that while older patients were given lower doses of medication, changes in the metabolism of fluphenazine or tolerance to its prolactin‐elevating effects did not occur during extended treatment.