Frequency of Sexual Dysfunction in Patients with Schizophrenia
David Cohen, M.D.·Published 6 January 2011·9 min read
Key points
Abstract Atypical antipsychotics seem to differ mainly in their tolerability profile.
This study has been funded by Laboratorios Pfizer SA, Madrid, Spain.
We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks.
We assessed 636 evaluable patients out of 669 recruited.
Frequency of Sexual Dysfunction and Other Reproductive Side-effects in Patients with Schizophrenia Treated with Risperidone, Olanzapine, Quetiapine, or Haloperidol: The Results of the EIRE Study
Abstract Atypical antipsychotics seem to differ mainly in their tolerability profile. The aim of this cross-sectional study, the Estudio de Investigaci n de Resultados en Esquizofrenia (Outcomes Research Study in Schizophrenia; EIRE study), was to assess in a clinical setting the frequency of several side-effects related to haloperidol, risperidone, olanzapine, and quetiapine. This article addresses sexual dysfunction and other reproductive side-effects (gynecomastia, menorrhage, amenorrhea, and galactorrhea).
We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks. During a single visit, we collected data, including demographic and clinical characteristics, current antipsychotic and concomitant treatment, and adverse effects listed in a modified version of the UKU Scale. We used a Chi-squared test to determine pairs comparisons of the frequency of adverse reactions between treatments. To estimate risk of a given adverse reaction with a given treatment, we used a logistic regression method.
We assessed 636 evaluable patients out of 669 recruited. Frequency of sexual dysfunction was high with haloperidol (38.1%) and also with olanzapine (35.3%), quetiapine (18.2%), and risperidone (43.2%). We found the frequency of other reproductive side-effects to be relatively low with all four drugs: haloperidol (6.9%), olanzapine (6.4%), quetiapine (2.7%), and risperidone (11.7%).
Sexual dysfunction appeared to be dose-related with haloperidol, risperidone, and olanzapine. Risperidone and olanzapine showed a higher risk of sexual dysfunction and other reproductive sideeffects than haloperidol. Quetiapine showed a lower risk of sexual dysfunction during short-term treatment ( 12 weeks) are lacking. Our results suggest that none of the atypical antipsychotics that we studied significantly improved sexual dysfunction and other reproductive side-effects of the conventional antipsychotic, haloperidol, in stabilized patients during long-term treatment. Quetiapine appears to improve this profile during short-term treatment; however, longterm data, with larger samples, are required with this latter drug.
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Study in Schizophrenia; EIRE study), was to assess in a clinical setting the frequency of several side-effects related to haloperidol, risperidone, olanzapine, and quetiapine. This article addresses sexual dysfunction and other reproductive side-effects (gynecomastia, menorrhage, amenorrhea, and galactorrhea). We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks. During a single visit, we collected data, including demographic and clinical characteristics, current antipsychotic and concomitant treatment, and adverse effects listed in a modified version of the UKU Scale. We used a Chi-squared test to determine pairs comparisons of the frequency of adverse reactions between treatments. To estimate risk of a given adverse reaction with a given treatment, we used a logistic regression method. We assessed 636 evaluable patients out of 669 recruited. Frequency of sexual dysfunction was high with haloperidol (38.1%) and also with olanzapine (35.3%), quetiapine (18.2%), and risperidone (43.2%). We found the frequency of other reproductive side-effects to be relatively low with all four drugs: haloperidol (6.9%), olanzapine (6.4%), quetiapine (2.7%), and risperidone (11.7%).
Written and revised by
David Cohen, M.D.
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Sexual dysfunction appeared to be dose-related with haloperidol, risperidone, and olanzapine. Risperidone and olanzapine showed a higher risk of sexual dysfunction and other reproductive sideeffects than haloperidol. Quetiapine showed a lower risk of sexual dysfunction during short-term treatment (≤ 12 weeks).
However, data on longer-term treatment (> 12 weeks) are lacking. Our results suggest that none of the atypical antipsychotics that we studied significantly improved sexual dysfunction and other reproductive side-effects of the conventional antipsychotic, haloperidol, in stabilized patients during long-term treatment. Quetiapine appears to improve this profile during short-term treatment; however, longterm data, with larger samples, are required with this latter drug.
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Sexual dysfunction is a common problem among the general population as well as among those suffering for psychiatric disorders and/or receiving psychotropic drugs. Research on sexual dysfunction with the exception of male erectile dysfunction is scarce. There are various aspects that make assessment of sexual dysfunction related to psychotropic drugs difficult. These include the potential biases associated with (a) patient selection (The study may include a greater number of patients who pay more attention to sexual matters and/or who are more willing to report on such matters.); (b) the assessment procedure used (self-report, questionnaire, or direct questioning); (c) the type of measurements used (objective versus subjective measurements); (d) the gender differences in the assessment (Sexual effects of psychotropic drugs are better documented in men than in women.); and (e) the lack of a baseline assessment (Demyttenaere, De Fruy, & Sienaert, 1998). An added difficulty is the differentiation between the effects of psychopathology and its course and the effects of psychotropic medication (Peuskens, Sienaert, & de Hert, 1998).
However, in spite of these limitations in the evaluation and the bias involved, most published studies agree that patients with schizophrenia treated with antipsychotics have a high prevalence of sexual dysfunction, ranging from 25% to 60% (Demyttenaere et al., 1998; Peuskens et al., 1998), and of problems derived from hyperprolactinemia, such as amenorrhea, with an incidence in women even higher than 50% (Ghadirian, Chouinard, & Annable, 1982; Sandison, Whitelaw, & Currier, 1960).
Sexual dysfunction and other reproductive problems have been given particularly little attention and often are underestimated in daily clinical practice with schizophrenic patients. This is partly because for years it was assumed that these patients had little sexual activity (Peuskens et al., 1998).
However, the few data available, obtained from research on risk behaviors associated with HIV infection, show that 50–60% of these patients have some type of sexual activity (Cournos et al., 1994; Demyttenaere et. al. 1998, Kelly et al., 1992; Susser et al., 1995; Thompson et al., 1997). It has recently been reported that approximately 80% of stabilized psychotic patients of both sexes have partner relations, and over 75% of men have masturbatory activity (Dickson & Glaser, 2000). It was also assumed for years that schizophrenic patients have sexual problems and deviant sexual behavior; however, no clinical evidence has been found to support this assumption (Demyttenaere et al., 1998). On the other hand, until clozapine was introduced in 1975, it was also assumed that hyperprolactinemia was an unavoidable problem associated with antipsychotic treatment.
However, with the introduction of clozapine and more recently with the marketing of new atypical antipsychotics the situation seems to have changed; in addition to clozapine, atypical antipsychotics such as olanzapine, quetiapine, and ziprasidone do not appear to be associated with a significant increase in prolactin levels, sexual dysfunction, and other reproductive-related side-effects (Petty, 1999). The data currently available suggest that the incidence of sexual dysfunction differs depending on the antipsychotic used (Knegtering, Blijd, & Boks, 1999; Montejo, 2000; Montejo, Llorca, & Izquierdo, 2000). On one hand, various studies had already shown that the incidence of sexual dysfunction was high, 25–60%, in patients treated with conventional antipsychotics such as thioridazine (Kotin, Wilbert, Verburg, & Soldinger, 1976; Sandison et al., 1960), with conventional drugs other than thioridazine (Ghadirian et al., 1982), with conventional drugs also including thioridazine (Sullivan & Lukoff, 1990), or with risperidone (David, Crawford, & Breier, 1998; Knegtering et al., 1999; Montejo, 2000; Shiwach & Carmody, 1998).
On the other hand, the data available suggest atypical antipsychotics are different not only from classical ones (Aizenberg, Modai, Landa, Gil-Ad, & Weizman, 2001); furthermore, data available suggests that atypical ones differ from one another (David et al., 1998; Knegtering et al., 1999; Montejo, 2000). Systematic data on quetiapine and ziprasidone are lacking; however, in registrational clinical trials with these drugs, frequency of sexual dysfunction appears to be very low (Physicians’ Desk Reference, 2001).
Although clinical trials are essential in assessing the effect and value of an intervention because they provide researchers a methodological control on potential confounding factors and maximize the internal validity, inclusion and exclusion criteria are so limiting, the conditions of treatment administration are so optimized, and the results are so narrowly defined that it is difficult to generalize them (Norquist, Lebowitz, & Hyman, 1999).
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In addition, in the specific case of sexual dysfunction, findings from clinical trials clearly underestimate this problem because of the nonspecific assessment of these adverse effects; the incidence of sexual dysfunction has been shown to increase when specific assessment measures are used (Knegtering, Boks, & Brink, 1998; Monteiro, Noshirvani, Marks, & Lelliott, 1987; Montejo et al., 1996). Therefore, clinical trials are not always applicable to clinical practice (Fleischhacker & Hummer, 1999). More naturalistic studies are therefore required to test the clinical value of these drugs in routine daily clinical practice as well as to ascertain how the drugs are actually used and how the sideeffects are managed by physicians at their offices. This was the purpose of the Estudio de Investigacion de Resultados en Esquizofrenia (Outcomes Research Study in Schizophrenia; EIRE study), conducted in Spain. The results of this study are partially reported in this article. The objectives of this crosssectional study were to assess the frequency of different adverse effects—extrapyramidal, weight changes, and sexual dysfunction and other reproductive side-effects—that occur with the antipsychotics most commonly used in Spain and to evaluate the management of such adverse effects by the clinical psychiatrist. This article addresses sexual dysfunction and other reproductive side-effects.
This study has been funded by Laboratorios Pfizer SA, Madrid, Spain. Preliminary results were presented at the American Psychiatric Association (APA) Annual Meeting, New Orleans, May 5–10, 2001 and at the International Society for Pharmacoeconomics and Outcomes Research Fourth Annual European Congress (ISPOR), Cannes, France, November 11–13, 2001. The authors have written this article on behalf of the EIRE Study Group, whose member include S. Álvarez (Asturias), P. Álvarez (Valladolid), M. T. Bascarán (Asturias), M. Bernardo (Barcelona), J. A. Blanco (Valladolid), J. Bobes (Asturias), J. Busto (Badajoz), F. Campo (Cádiz), M. S. Casares (Madrid), S. Catarineu (Barcelona), M. Cavero (Barcelona), E. Daniel (Cáceres), C. Deza (Burgos), V. Elvira (Alicante), J. C. Espín (Madrid), Z. Fernández (Sevilla), C. Fernández (Zamora), J. I. Franch (Valladolid), F. Galán (Badajoz), M. T. Gallego (Zamora), G. García (Barcelona), M. García (Baleares), M. A. Garzón (Salamanca), J. Gómez-Trigo (Madrid), M. P. G.-Portilla (Asturias), M. González-Quirós (Asturias), L. Gutiérrez (Orense), M. Hemmings (Zamora), O. Herreros (Santa Cruz de Tenerife), C. Iglesias (Asturias), J. J. López (Granada), E. Martín (Madrid), M. Martín (Navarra), F. Martín (Burgos), J. M. Martínez (Zamora), M. J. Martínez (Zamora), J. Matías (Salamanca), J. Medina (Madrid), M. Á. Medina (Burgos), P. Megía (Palencia), M. J. Merino (Asturias), A. Monforte (Zamora), J. Mons (Burgos), A. L. Montejo (Salamanca), J. M. Montes (Madrid), M. A. More (Madrid), A. Muñoz (Madrid), F. Orengo (Madrid), A. Pérez (Pontevedra), J. L. Pérez-Iñigo (Madrid), J. I. Portilla (Asturias), I. Rubio (Madrid), V. Rubio (Zaragoza), F. Ruíz (Palencia), O. Sanz (Burgos), M. Silvestre (Badajoz), J. A. Solana (Salamanca), A. Soto (Valladolid), J. R. Valle (Sevilla), A. Varona (Burgos), F. Vicente (Madrid).
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