Stynke Castelein

What are the effects of antipsychotics on sexual dysfunctions and endocrine functioning

The literature is reviewed and preliminary results of new studies are presented showing that treatment with classical antipsychotics, as well as risperidone, induces sexual dysfunctions in 30-60% of the patients. These antipsychotics also frequently induce amenorrhoea and galactorrhoea. Although comparative studies are rare, it is likely that prolactin-sparing antipsychotics, as recently shown in a randomized trial of olanzapine versus risperidone, induce less sexual side effects.From these studies, it becomes apparent that prolactin elevation induced by classical antipsychotics and risperidone is probably a factor in inducing sexual dysfunctions, amenorrhoea and galactorrhoea. The role of other factors inducing sexual dysfunctions like sedation, proportional, variant -blockade, testosterone, dopamine, and serotonin is discussed. Finally, it is concluded that sexual and hormonal effects of antipsychotics, although clearly important, are often neglected in research as in clinical practice. Lowering the dosage or switching to a prolactin-sparing antipsychotic often reduces sexual side effects, amenorrhoea, and galactorrhoea.

A randomized open-label study of the impact of quetiapine versus risperidone on sexual functioning

Objective: To compare sexual functioning in patients treated with quetiapine or risperidone. Methods: This open-label study included patients with schizophrenia or a related psychotic illness who were randomized to quetiapine (200-1200 mg/d) or risperidone (1-6 mg/d) for 6 weeks. Sexual dysfunction was assessed by a semistructured interview, the Antipsychotics and Sexual Functioning Questionnaire (ASFQ), based upon the Utvalg for Kliniske Undersogelser (UKU). Results: Four of 25 quetiapine-treated patients (16%) and 12 of 24 risperidone-treated patients (50%) reported sexual dysfunction (χ 2 = 6.4; df = 1; P = 0.006) on the ASFQ. Six patients (11.7%; 4 on risperidone, 2 on quetiapine) spontaneously reported sexual dysfunction. The mean ± SD dose was 580 ± 224 mg/d for quetiapine and 3.2 ± 1.3 mg/d for risperidone. Mean ± SD prolactin levels in quetiapine- and risperidone-treated patients were 13.8 ± 17.9 and 57.7 ± 39.7 ng/mL, respectively. Conclusion: Sexual dysfunction was less common in patients treated with quetiapine than with risperidone. Direct questioning about sexual functioning is necessary to avoid underestimating the frequency of sexual side effects in patients with schizophrenia and related psychotic disorders.

The effectiveness of peer support groups in psychosis: a randomized controlled trial

Objective:  To investigate the effect of a (minimally) guided peer support group (GPSG) for people with psychosis on social network, social support, self‐efficacy, self‐esteem, and quality of life, and to evaluate the intervention and its economic consequences.

Two subdomains of negative symptoms in psychotic disorders: Established and confirmed in two large cohorts

Negative symptoms of schizophrenia are normally grouped into a single category. However, the diversity of such symptoms suggests that they are actually made up of more than one dimension. The DSM-V proposes two negative symptom domains, namely expressive deficits and avolition/asociality. We investigated whether the negative symptoms do indeed have two dimensions. An exploratory factor analysis was carried out based on interviews with the PANSS (664 patients). We restricted our analysis to items that had been described as negative symptoms in previous factor analyses. The symptom structure was then tested for stability by performing a confirmatory factor analysis on PANSS interviews from a separate cohort (2172 patients). Exploratory factor analysis yielded a two-factor structure of negative symptoms. The first factor consisted of PANSS items Flat affect, Poor rapport, Lack of spontaneity, Mannerisms and posturing, Motor retardation, and Avolition. The second factor consisted of Emotional withdrawal, Passive/apathetic social withdrawal, and Active social avoidance. The first factor could be related to expressive deficits, reflecting a loss of initiative, and the second factor to social amotivation, related to community interaction. This factor structure supports the DSM-V classification and may be relevant for pathophysiology and treatment of schizophrenia and other psychotic disorders.

A Randomized Open-Label Comparison of the Impact of Olanzapine Versus Risperidone on Sexual Functioning

The objective of this study was to compare sexual functioning in patients treated with olanzapine or risperidone. This open-label trial included 46 patients randomized to olanzapine (5–15 mg/d) or risperidone (1–6 mg/d) for 6 weeks. We used sexual dysfunction was assessed by a semistructured interview based on the items of the UKU side effect rating scale. Three olanzapine-treated patients (12.0%), compared with 11 risperidone-treated patients (52.4%), reported sexual dysfunctions (p = .008) in the semistructured interview. Only 4 patients (8.7%) spontaneously reported sexual dysfunction. The mean dose was 9.4 mg/d for olanzapine and 3.4 mg/d for risperidone. The mean (±SD) prolactin levels (ng/mL) in olanzapine-and risperidone-treated patients were 25.1 (± 23.5) and 43.5 (± 26.1), respectively. Less sexual dysfunction occurred in the group treated with olanzapine compared with the risperidone group. Direct questioning about sexual functioning is necessary to avoid underestimating the frequency of sexual side effects in patients with schizophrenia and related psychotic disorders.

Are sexual side effects of prolactin-raising antipsychotics reducible to serum prolactin?

OBJECTIVE To assess the degree to which sexual side effects (SSE) are associated with prolactin-raising antipsychotics, and to what degree such SSE are reducible to serum prolactin levels. METHOD A large sample (n=264) of patients treated for 6 weeks with prolactin-raising and prolactin-sparing antipsychotics was assessed for changes in sexual performance in terms of libido, arousal and orgasm using the Antipsychotics and Sexual Functioning Questionnaire. For men also erection and ejaculation were evaluated. At 6 weeks, prolactin levels were assessed and analyzed in relation to sexual performance. RESULTS Men and women reported SSE (libido and orgasm) with about the same frequency. Prolactin-raising medication induced significantly more SSE than prolactin-sparing medication (adjusted OR=3.4, 95% CI: 1.8, 6.5) with 43% of emerging SSE attributable to prolactin-raising medication. When adjusted for serum prolactin, the association between prolactin-raising medication and SSE was reduced but remained significant (OR=2.1, 95% CI: 1.0, 4.5); 27% of emerging SSE remained attributable to prolactin-raising medication. For erectile and ejaculatory dysfunction in men, the attributable fraction due to prolactin-raising medication was 32% before, and 11% after adjustment for serum prolactin. CONCLUSIONS Around 40% of emerging SSE in schizophrenia are attributable to the prolactin-raising properties of antipsychotic medication. Of this attributable fraction, around one-third to two-thirds is directly reducible to the effects of serum prolactin.

The Facts About Sexual (Dys)function in Schizophrenia: An Overview of Clinically Relevant Findings

A limited number of studies have evaluated sexual functioning in patients with schizophrenia. Most patients show an interest in sex that differs little from the general population. By contrast, psychiatric symptoms, institutionalization, and psychotropic medication contribute to frequently occurring impairments in sexual functioning. Women with schizophrenia have a better social outcome, longer lasting (sexual) relationships, and more offspring than men with schizophrenia. Still, in both sexes social and interpersonal impairments limit the development of stable sexual relationships. Although patients consider sexual problems to be highly relevant, patients and clinicians not easily discuss these spontaneously, leading to an underestimation of their prevalence and contributing to decreased adherence to treatment. Studies using structured interviews or questionnaires result in many more patients reporting sexual dysfunctions. Although sexual functioning can be impaired by different factors, the use of antipsychotic medication seems to be an important factor. A comparison of different antipsychotics showed high frequencies of sexual dysfunction for risperidone and classical antipsychotics, and lower frequencies for clozapine, olanzapine, quetiapine, and aripiprazole. Postsynaptic dopamine antagonism, prolactin elevation, and α1-receptor blockade may be the most relevant factors in the pathogenesis of antipsychotic-induced sexual dysfunction. Psychosocial strategies to treat antipsychotic-induced sexual dysfunction include psychoeducation and relationship counseling. Pharmacological strategies include lowering the dose or switching to a prolactin sparing antipsychotic. Also, the addition of a dopamine agonist, aripiprazole, or a phosphodiesterase-5 inhibitor has shown some promising results, but evidence is currently scarce.

Measuring Empowerment Among People With Psychotic Disorders: A Comparison of Three Instruments

OBJECTIVE This study compared three instruments that are used to measure empowerment of people with psychotic disorders. The study evaluated internal consistency, discriminant and convergent validity, sensitivity to symptom levels, and clinical usefulness. METHODS Fifty patients in the Netherlands were administered the Empowerment Scale (ES), the Personal Empowerment Scale (PES), and the Mental Health Confidence Scale (MHCS). RESULTS The MHCS had good internal consistency, whereas the levels for the ES and PES were just below what would be considered acceptable. The instruments demonstrated moderate correlations between total scores; correlations between subscale scores were weaker. Scores for all three instruments were comparably associated with symptom severity. CONCLUSIONS All three instruments measure some aspect of empowerment among persons with severe mental illness. However, empowerment is too broadly defined to allow these instruments to have convergent validity. Among patients with psychotic disorders, the MHCS is recommended because it has good psychometric qualities and is clinically useful.

The Antipsychotics and Sexual Functioning Questionnaire (ASFQ): Preliminary evidence for reliability and validity

The aim of this study is to describe the psychometric properties of the Antipsychotics and Sexual Functioning Questionnaire (ASFQ). Internal reliability, test-retest reliability, inter-rater reliability, validity and sensitivity to change were calculated in a sample of 30 patients with schizophrenia or a schizophrenia spectrum disorder using antipsychotics. The ASFQ is a semistructured interview, with good face validity and content validity, that takes on average about 10min to complete. The ASFQ has good internal reliability (Cronbachs alpha 0.84) and good test-retest reliability (mean Spearmans rho=.76). The inter-rater reliability is good for questions about libido, orgasm, erection and ejaculation. Correlation coefficients for calculating convergent validity were modest to good when comparing the ASFQ with the corresponding items on the Subjects Response to Antipsychotics (SRA) questionnaire and the Arizona Sexual Experience Scale (ASEX). Based on preliminary evidence, it can be concluded that the Antipsychotics and Sexual Functioning Questionnaire has reasonable reliability and is available for clinical use and research.

A Systematic Review of Instruments to Measure Sexual Functioning in Patients Using Antipsychotics

Sexual dysfunction is a frequent side effect of antipsychotics, but information is scant regarding the psychometric properties and clinical usefulness of currently existing questionnaires. This systematic review compares the psychometric properties and content of questionnaires for assessment of sexual functioning in patients using antipsychotics. A systematic literature search was performed using three electronic databases (PubMed, Embase, and PsycINFO) with predefined search terms. We identified six validated instruments for assessment of sexual functioning in patients using antipsychotics: the Antipsychotic Non-Neurological Side Effects Rating Scale (ANNSERS), the Arizona Sexual Experience Scale (ASEX), the Antipsychotics and Sexual Functioning Questionnaire (ASFQ), the Changes in Sexual Function Questionnaire-14 (CSFQ-14), the Nagoya Sexual Function Questionnaire (NSFQ), and the Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ). The ASFQ, CSFQ-14, and PRSexDQ cover all stages of sexual functioning, which makes these questionnaires preferable to the other three questionnaires described. The ASFQ and PRSexDQ are clinician-administered and ask for a change in sexual functioning related to medication. The ASFQ assesses improvement as well as deterioration of sexual functioning, and includes items about hyperprolactinemia. The CSFQ-14 is useful when self-report is desired but contains more items.