Relationship between Serum Aripiprazole, Dehydroaripiprazole, Prolactin and Testosterone Concentrations and Clinical Response to Aripiprazole in Male Schizophrenic Patients

Aripiprazole is an atypical antipsychotic with partial agonist activity at dopamine D2 receptors. Antipsychotics generally have the potential to induce sexual dysfunction through blockade of D2 receptors in the tuberoinfundibular pathway, leading to elevated prolactin levels. However, aripiprazole is documented as a prolactin-sparing antipsychotic. We studied the association between aripiprazole dosage, serum drug levels, serum prolactin and sex hormones levels and clinical response.

A total of 30 male schizophrenic patients (15 treated and 15 un-treated) of reproductive age were recruited. Aripiprazole dosage ranged from 5 to 20mg per day. Drug monitoring of serum aripiprazole and its major metabolite dihydroaripiprazole levels by HPLC and measurement of prolactin and sex hormones (testosterone, oestrogen, progesterone, SHBG and DHEAS) using ELECSYS were performed at baseline and at the end of each week. Patients were followed up to end of 8th week medication. The clinical status of the patients was assessed every week using PANSS and CGI.

Aripiprazole dosage had effect on serum testosterone levels at the end of week 3 (F=13.43; p=0.035). Prolactin levels reduced significantly after the first (T=3.005; p=0.006), the third (T=2.527; p=0.02) and the fifth week (T=3.314;p=0.005). Basal prolactin levels and prolactin change after aripiprazole treatment showed correlations with PANSS-negative score change (R=0.782; p=0.001), PANSS-global score change (R=0.78; p=0.001) and CGI change (R=0.831, p=0.041) after the treatment. Smoking (F=7.72; p=0.021) and number of cigarettes consumed per day (F=6.004, p=0.037) showed significant effect on change of prolactin levels.

The results indicated that aripiprazole treatment can normalise the high basal prolactin level and thus indirectly induce positive effect on testosterone sparing in male schizophrenic patients. However, this prolactin sparing effect showed no significant effect on the clinical response.