The Effect of Antipsychotic Medication on Sexual Function and Serum Prolactin Levels in Community-treated Schizophrenic Patients: Results From the Schizophrenia Trial of Aripiprazole (STAR) Study

Linda Hanssens; Gilbert L'Italien; Jean-Yves Loze; Ronald N. Marcus; Miranda Pans; Wendy Kerselaers


BMC Psychiatry 

In This Article


The STAR study was designed to allow comparison of aripiprazole with SOC treatment in a setting close to daily clinical practice, and also to assess the patient and caregiver perspective on the treatment received. The primary outcome measure in the STAR study was the IAQ total score, which takes into account both the efficacy and tolerability of an antipsychotic medication and thus is a measure of effectiveness rather than merely efficacy.[21] The results of STAR demonstrated clearly that at all time points, treatment with aripiprazole was associated with significantly better effectiveness compared with SOC treatment, in the form of one of three atypical agents chosen by the clinician as optimal treatment for the individual patient.

The results of the ASEX evaluation in the STAR study showed that patients treated with aripiprazole experienced significantly less sexual dysfunction at the end of the treatment period compared with patients receiving SOC. These findings are consistent with the existing body of evidence for atypical antipsychotics, as discussed below. When considering the agents within the SOC group individually, olanzapine and quetiapine were associated with less sexual dysfunction at the end of treatment and risperidone was associated with the least improvement in sexual dysfunction, which is in agreement with the Intercontinental Schizophrenia Outpatient Health Outcomes IC-SOHO study.[13]

Whilst sexual dysfunction has traditionally run the risk of being underestimated in clinical trials due to the lack of self-reporting and unwillingness to discuss the issue, there is increasing awareness amongst clinicians and allied mental health care professionals that sexual dysfunction is a common and distressing side effect of antipsychotic medication.[22] A survey carried out by the UK patient advocacy group Rethink (formerly the National Schizophrenia Fellowship) showed that 66% of patients who had experienced sexual dysfunction felt that this side effect was 'bad' or 'very bad'.[23] Men appear to suffer more than women.[22] However, in this study female patients showed less improvement in sexual function than their male counterparts who experienced greater improvement in ASEX score. There is evidence that sildenafil is able to address such antipsychotic related sexual dysfunction in men including those patients who also report raised serum prolactin levels. In the study by Gopalakrishnan et al,[4] 77% reported improved erections and 74% (24 patients) felt they would use the medication in future compared with 26% of the placebo group. However, it may be possible to improve sexual dysfunction in both male and female by changing antipsychotic medication rather than adding further medication to the treatment regimen of schizophrenia patients.

Overall, around half of all patients treated with antipsychotics experience sexual dysfunction; the associated distress and frustration may have a profound effect on the quality of life of the patient as well as making personal relationships more difficult, and sexual dysfunction may lead to non-compliance with the antipsychotic treatment regimen.[24,25,26] In fact, if considering QLS the aripiprazole group reported a greater increase in total QLS and in QLS related to interpersonal relations ( Table 3 ) compared to the SOC group. This may be in part related to the greater improvement in ASEX score also observed in these patients.

Prolactin plays a key role in the regulation of sexual behaviour and activity,[27] and elevated serum prolactin levels associated with antipsychotic medication are known to cause erectile dysfunction, orgasmic difficulties, amenorrhoea and gynaecomastia.[11,28] The serum prolactin measurements also demonstrated that patients in the aripiprazole treated group were more likely to have normal serum prolactin levels at the end of the treatment period compared with patients receiving SOC. Given previous risperidone data, it is not surprising that this was the only agent in the SOC treatment group associated with an increase in mean serum prolactin level at week 26.

The implications of sexual dysfunction for treatment compliance and the prevention of relapse, together with the potential link between primary and secondary prolactinaemia and breast cancer and/or decreased bone mineral density[29] makes serum prolactin an important endpoint in the assessment of antipsychotic therapy. A growing evidence base indicates that, with the exception of risperidone, the atypical antipsychotics are less associated with hyperprolactinaemia than conventional antipsychotics. Some agents, including quetiapine, olanzapine and clozapine, were shown previously to cause no significant or sustained increase in serum prolactin in adult patients.[6,7,8,9,10] More recently, a systematic review of short-term clinical trials with aripiprazole showed that the effect of aripiprazole on serum prolactin levels was comparable to that of placebo, and significantly lower than that of risperidone.[14] The IC-SOHO study demonstrated that a reduction in the incidence of elevated serum prolactin translates to a reduced potential for sexual side effects.[13] Switching patients from conventional antipsychotics or risperidone to an antipsychotic with less potential for prolactin elevation is therefore likely to be an effective measure for improving treatment compliance and reducing the risk of symptomatic relapse in patients experiencing sexual dysfunction during antipsychotic therapy.

One major limitation to the interpretation of the findings is that the STAR study employed an open-label design and both patients and physicians would have been aware as to whether they were receiving study medication or not. Moreover, physicians could choose the SOC medication. This may have introduced bias in subjective measures such as the ASEX, and caution should thus be exercised when interpreting these results.


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