Review Article

Prolactin and Psychopathology in Schizophrenia: A Literature Review and Reappraisal

Table 4

Studies examining the relationship between measures of prolactin and antipsychotic response in schizophrenia.

Study and authorsPatient sample and drug usedResults

Gruen et al., 1978 [89]15 patients with schizophrenia; high-dose butaperazine or loxapine for 6 weeksTransient prolactin elevation during the untreated admission period; consistent elevation in all patients following treatment but no relationship between levels and response

Markianos et al., 1991 [90]12 patients with schizophrenia; haloperidol 30–60 mg for one monthIncreases in baseline prolactin were significantly correlated with reduction in the BPRS total score

Zhang et al., 2002 [42]30 male patients with “chronic schizophrenia”; risperidone 6 mg/day for 12 weeksA significant association was found between increases in prolactin level and the positive subscore of the Positive and Negative Symptom Scale (PANSS)

Zhang et al., 2005 [91]78 in-patients with schizophrenia; randomized to risperidone 6 mg/day or haloperidol 20 mg/day for 12 weeksChange in prolactin levels was significantly related to improvement in the PANSS positive score in patients on risperidone but not haloperidol

Otani et al., 1994 [92]24 patients with schizophrenia (12 male, 12 female); zotepine 100 mg/day for 1 week, then 200 mg/day for 3 weeksSignificant relationship between increases in prolactin and positive symptom improvement as measured by the BPRS but only in male patients

Kitamura et al., 1988 [93]100 patients (96 with schizophrenia) receiving fluphenazine decanoate for at least 12 weeksHigher prolactin to plasma fluphenazine ratio was associated with a better outcome (out-patient versus in-patient status)

Larsson et al., 1984 [94]4 patients with schizophrenia; thioridazine with or without alpha-methyl tyrosine, 2 g/dayPositive correlation between the antipsychotic response to thioridazine and changes in prolactin

Chou et al., 1998 [95]23 patients with acute exacerbations of schizophrenia or schizoaffective disorder; haloperidol titrated to achieve “low to moderate” plasma levels for 3 weeksIncreases in prolactin were associated with fewer symptoms at the end of treatment

Van Putten et al., 1991 [33]73 drug-free male in-patients with schizophrenia; haloperidol 5–20 mg/day for 4 weeksPosttreatment prolactin levels were significantly related to treatment outcome, but this reached a plateau at levels of 30 ng/mL (achieved with a dose of around 10 mg/day)

Mohr et al., 1998 [96]23 in-patients (11 male, 12 female) with schizophrenia; haloperidol for 4 weeksAn exaggerated basal prolactin response to TRH predicted a worse response to haloperidol across several domains (positive, negative, anxiety-depression, and total BPRS scores)

Jones et al., 1998 [41]20 patients with schizophrenia; clozapineBlunting of the prolactin response to fenfluramine after clozapine treatment was significantly correlated with reductions in total positive symptoms, delusions, and hallucinations as measured by the Scale for the Assessment of Positive Symptoms (SAPS)

Lieberman et al., 1994 [97]Patients with schizophrenia; clozapineBlunting of the prolactin response to apomorphine after clozapine treatment was associated with a better response

Meltzer and Busch, 1983 [98]Drug-free patients with schizophrenia; chlorpromazine 100 mg bid for 1 week and 200 mg bid for 1 weekAt doses of 200 mg of chlorpromazine, prolactin elevation was negatively correlated with the severity of hallucinations

Awad et al., 1990 [43]Patients with schizophrenia; remoxipride (high- and low-dose) and haloperidolHigher basal prolactin predicted responses to both drugs but only in male patients

Wang et al., 2007 [34]118 patients with schizophrenia (78 female, 40 male); risperidone 2–8 mg for 8 weeksNo relationship between changes in plasma prolactin and the response to risperidone

Volavka et al., 2004 [35]157 patients with treatment-resistant schizophrenia (133 male, 24 female); randomized to clozapine, olanzapine, risperidone, or haloperidol for 14 weeksNo relationship between prolactin levels and clinical improvement

Rimon et al., 1985 [37]28 patients with “acute symptoms” of schizophrenia; fluphenazine for 8 weeksNo correlation between changes in either plasma or CSF prolactin and response to fluphenazine

Smith et al., 1984 [99]Patients with schizophrenia; haloperidolNo relationship between changes in prolactin level and response to haloperidol

Meltzer et al., 1983 [36]21 drug-free in-patients with schizophrenia (10 female, 11 male); chlorpromazine 200 mg for 1 week, then 400 mg for 1 weekNo relationship between prolactin levels and clinical outcome

Meco et al., 1983 [38]23 out-patients (11 male, 12 female) with schizophreniform disorder; haloperidol decanoate 50–250 mg once in 4 weeks for 12 monthsNo relationship between prolactin levels and clinical improvement

Jørgensen et al., 1982 [39]9 patients with chronic schizophrenia; flupenthixol decanoateNo correlation between prolactin levels and changes in clinical ratings

Kolakowska et al., 1979 [40]19 patients with acute psychoses, including schizophrenia; chlorpromazine Plasma prolactin did not differentiate between patients with a good or poor treatment outcome