Plasma fluphenazine levels and clinical response in newly admitted schizophrenic patients.

Seventy-two newly readmitted, drug-free men with the diagnosis of schizophrenia by DSM-III were assigned randomly to receive fluphenazine hydrochloride at 5 mg, 10 mg, or 20 mg daily for 4 weeks. Fluphenazine (FLU), fluphenazine sulfoxide, 7-hydroxyfluphenazine, and fluphenazine N-oxide were measured by highly specific and sensitive radioimmunoassays. Data were analyzed by logistic regression using the Clinical Global Impressions Disabling Side Effects and Global Improvement as the outcome measures. Disabling side effects were defined as "side effects that significantly interfered with patient's functioning" or "side effects that outweigh therapeutic effects" (National Institute of Mental Health 1985, p. 839). Higher plasma FLU levels (up to 4.23 ng/mL) were significantly (p = .015) associated with a higher rate of global improvement. However, close to 90 percent of these acute patients had disabling side effects at a plasma FLU level of 2.7 ng/mL. At least in the patient's view, these disabling side effects negated or compromised the improvement in psychosis. Fluphenazine N-oxide may be a toxic metabolite in that it was more powerfully associated with side effects than was the parent FLU.

Neuroleptic plasma levels.

There is enormous variation in plasma levels of most neuroleptics in patients on the same dose. Much of the past research on the relation between plasma levels of antipsychotic drugs and clinical change, however, has been difficult to interpret. It does appear that decreased bioavailability, at least in public institutions, is rarely the cause of treatment failure. Aberrantly low plasma levels are more likely due to surreptitious noncompliance or drug interactions with enzyme inducers such as carbamazepine. Therapeutic plasma level ranges, in which good antipsychotic effect occurs without undue side effects, have been tentatively identified for perphenazine, haloperidol, fluphenazine, and chlorpromazine. The extent to which aberrantly high plasma levels are associated with inferior antipsychotic response is unclear. Antipsychotic plasma levels may be most useful when the distinction between side effects and worsening psychosis is unclear. The utility of high neuroleptic plasma levels in the treatment-resistant patient is unclear.