Improvement of serum prolactin and sexual function after switching to aripiprazole from risperidone in schizophrenia: A case series

Authors


Cheng-Yuan Chen, MD, Department of Psychiatry, Armed Forces Taichung General Hospital, Number 348, Section 2 Jhongshan Road, Taiping City, Taichung County 411, Taiwan. Email: ayuan329@yahoo.com.tw

Abstract

This study examined prolactin levels, sexual function and clinical improvement after switching to aripiprazole from risperidone. Nine schizophrenic male Chinese patients who reported risperidone-induced sexual dysfunction were studied. Clinical Global Impression Scale Scores for Severity (CGI-S), Clinical Global Impression Scale Scores for Improvement (CGI-I), Arizona Sexual Experience Scale results and serum prolactin concentrations were determined over 16 weeks. After treatment with aripiprazole, all patients showed reduced serum prolactin (26.54 ± 17.03 ng/mL to 3.71 ± 1.87 ng/mL, P = 0.008) and five reported improved sexual function. Mean baseline CGI-S (5.11 ± 0.93) decreased to 3.78 ± 1.39 (P = 0.010) by week 16. Compared to baseline (4.0), the mean CGI-I significantly declined by the end of the study (3.44 ± 0.53, P = 0.025).

HYPERPROLACTINEMIA IS A leading cause of antipsychotic-induced sexual dysfunction.1–4 Antipsychotics block D2 receptors in the anterior pituitary, with the resultant hyperprolactinemia in men provoking hypogonadism and decreasing testosterone, thereby impairing libido and inducing impotence. These disturbances can outweigh the benefits of antipsychotics and affect patient compliance.1,2

Among current atypical antipsychotic agents, risperidone has the greatest propensity to provoke hyperprolactinemia.1,5,6 Its prolactin-elevating effects occur in most male patients taking risperidone and are dose-dependent.1,5 Aripiprazole (Abilify; Otsuka Pharmaceutical, Tokyo, Japan) is as effective as other antipsychotics in treating schizophrenia. Aripiprazole has a unique mechanism, acting as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors and an antagonist at serotonin 5-HT2A receptors. Therefore, aripiprazole could normalize prolactin, alleviate hyperprolactinemia and sexual dysfunction induced by previous antipsychotics. A meta-analysis by Baggaley2 found that, of all antipsychotics, risperidone had the greatest impact on sexual dysfunction and prolactin-sparing aripiprazole had the least impact. A study by Hanssens et al.7 showed that aripiprazole spared prolactin better than risperidone; however, to the best of our knowledge, no previous study has demonstrated that the substitution of aripiprazole could relieve sexual dysfunction induced by risperidone.

METHODS

Participants

Nine adult male patients admitted to the authors' institution between March and August 2007 were studied. Participants had a mean age of 48.33 ± 8.17 years and a mean duration of illness of 17.89 ± 9.06 years. All were chronic schizophrenic patients treated with risperidone who complained of sexual dysfunction on that medication.

Patient data were collected at baseline and every 4 weeks. During the 16 weeks, aripiprazole was given after risperidone was tapered over the first 8 weeks. No adverse reactions were observed.

Indices of clinical efficacy and sexual function

Clinical efficacy was assessed with the Clinical Global Impression Scales for Severity (CGI-S) and Improvement (CGI-I)8 and sexual function was assessed with the Arizona Sexual Experience Scale (ASEX).9 Validated Chinese versions of these instruments did not exist. For this study, they were translated from the original English by the authors.

Prolactin measurements

Peripheral venous blood samples were obtained to determine serum prolactin levels, using the immunoradiometric assay Prolactin Riabead II (Abbot Laboratories, North Chicago, IL, USA) and an AxSYM analyzer (Abbott Laboratories, North Chicago, IL, USA). Hyperprolactinemia in men was defined as a fasting value of ≥20 ng/mL 2 h after waking.

Statistical analyses

Continuous data are presented as means with standard deviations. The repeated measures anova was used to determine the trends in CGI-S, CGI-I, ASEX and prolactin concentrations over time. All statistical assessments were two-tailed and performed using spss 15.0 (spss, Chicago, IL, USA). P < 0.05 was considered significant.

Results

The average daily dose of aripiprazole was 13.89 ± 3.33 mg. All patients, including those who did not present with hyperprolactinemia at baseline, showed reduced serum prolactin levels at week 4, and these decreased throughout the study (Table 1). The mean prolactin level was significantly decreased over time (P = 0.045). The initial mean prolactin level (26.54 ± 17.03 ng/mL) significantly decreased to 13.78 ± 6.51 ng/mL (P = 0.017), 9.56 ± 4.99 ng/mL (P = 0.009), 5.32 ± 4.99 ng/mL (P = 0.003) and 3.71 ± 1.87 ng/mL (P = 0.003) at weeks 4, 8, 12 and 16, respectively. The mean ASEX score was also significantly decreased over time (P < 0.001). Compared with baseline ASEX scores, all patients showed decreased scores at week 16 (P < 0.001). In addition, five patients returned to the normal range at the end of the study. The mean baseline CGI-S score (5.11 ± 0.93) decreased to 4.89 ± 0.93 (P = 0.169), 4.44 ± 1.51 (P = 0.050), 4.00 ± 1.12 (P = 0.001) and 3.78 ± 1.39 (P < 0.001) at weeks 4, 8, 12 and 16, respectively. CGI-I scores fell moderately in five patients by week 16. The mean CGI-I score was significantly lower by the end of the study (baseline [4.0] and week 16 [3.44 ± 0.53]; P = 0.013).

Table 1.  Patient characteristics (n = 9)
Patient no.Age (years)Duration of illness (years)Serum prolactin at baseline (ng/mL)Serum prolactin at 16 weeks (ng/mL)CGI-S at baselineCGI-S at 16 weeksCGI-I at baselineCGI-I at 16 weeksASEX at baselineASEX at 16 weeksASEX differenceASEX improved
  • The definition of ASEX improved is total ASEX score <19 at week 16.

  • All patients were male.

  • ASEX, Arizona Sexual Experience Scale; CGI-I, Clinical Global Impression Scale Scores for Improvement; CGI-S, Clinical Global Impression Scale Scores for Severity; SD, standard deviation.

1531428.242.87544425196No
2522020.136.51534420155Yes
3452327.64.32434319145Yes
451912.42.8654326215No
55553.750.68424320155Yes
6331563.984.326443271512Yes
7411618.243.18424320155Yes
8452335.496.28664430255No
9603629.022.4654427225No
Mean48.3317.8926.543.715.113.784.003.4423.7817.895.89 
SD8.179.0617.031.870.931.3900.534.063.982.32 

DISCUSSION

Serum prolactin levels of all nine patients were significantly lower at week 4 whether or not they had clinical hyperprolactinemia at baseline. The results suggested that the switch to aripiprazole alleviated hyperprolactinemia induced by risperidone as five of nine patients showed improved sexual function. Mean CGI-S scores decreased from markedly ill (at baseline) to mildly ill (at week 16) and there was also a significant decrease in CGI-I scores over that period. Both scores indicated a significant improvement in clinical symptoms. These results were consistent with the Schizophrenia Trial of Aripiprazole study.7 ASEX scores showed a significant improvement in sexual function at week 8. One study reported normalized prolactin levels in 84.6% of patients treated with aripiprazole and a significant decrease in prolactin-related adverse effects.10 The reduction in prolactin reflects the known pharmacodynamic mechanism of aripiprazole, namely, its partial D2-receptor agonist activity on the anterior pituitary lactotrophs, which lie outside the blood–brain barrier.11 Limitations of the present study include its small sample size, open-label design and absence of control subjects. For schizophrenic patients suffering from risperidone-induced sexual dysfunction, switching to aripiprazole can reduce serum prolactin levels and may improve sexual function, patient compliance, and quality of life.

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