Sexual Dysfunction Related to Psychotropic Drugs: A Critical Review Part II: Antipsychotics

Abstract

Sexual dysfunction is a potential side effect of antipsychotic drugs: this article presents a critical review of the current literature. Although many studies have been published on the subject, only some used a validated sexual function rating scale and most lacked either a baseline or placebo control or both. In addition, many of the studies on sexual dysfunction associated with antipsychotic medication are limited by other methodological flaws. However, there is consistent evidence to suggest that a large number of antipsychotic drugs adversely affect one or more of the 3 phases of sexual response (desire, arousal and orgasm). Among the antipsychotics, the so called “prolactin-raising” are probably most associated with sexual dysfunction, even if further studies to confirm this are needed: the reviewed literature shows no consistent evidence that any one antipsychotic drug has a significantly superior side effect profile over another and current information on this topic is often based on methodologically weak research. Clinicians must be aware of drug-induced sexual dysfunction, since its presence can have important consequences for clinical management and compliance.

Key words

antipsychotic drugs - sexual dysfunction - sexual side effects - treatment-emergent sexual dysfunction

• References

• 1 Berner MM, Hagen M, Kriston L et al. Management of sexual dysfunction due to antipsychotics drug therapy. Cochrane Database of Systematic Reviews 2007; 1-24
• 2 Compton MT, Miller AH. Antipsychotic-induced hyperprolactinemia and sexual dysfunction. Psychopharmacol Bull 2002; 36: 143-164
• 3 Knegtering H, Van den Moolen AEGM, Castelein S et al. What are the effects of antipsychotics on sexual dysfunction and endocrine functioning?. Psychoneuroendocrinology 2003; 28: 109-123
• 4 Labbate LA. Psychotropics and sexual dysfunction: the evidence and treatments. Adv Psychosom Med 2008; 29: 107-130
• 5 Gitlin M. Sexual dysfunction with psychotropic drugs. Expert Opin Pharmacother 2003; 4: 2259-2269
• 6 Tardieu S, Micallef J, Bonierbale M et al. Sexual behaviour in schizophrenic patients: the impact of antipsychotics. Encephale 2006; 32: 697-704
• 7 Akhtar S, Thompson Jr JA. Schizophrenia and sexuality: a review and a report of twelve unusual cases, part I. J Clin Psychiatry 1980; 41: 134-142
• 8 Akhtar S, Thompson Jr JA. Schizophrenia and sexuality: a review and a report of twelve unusual cases, part II. J Clin Psychiatry 1980; 41: 166-174
• 9 Peuskens J, Sienaert P, De Hert M. Sexual dysfunction: the unspoken side effect of antipsychotics. Eur Psychiatry 1998; 13: 23s-30s
• 10 Dervaux A, El Omari F. Sexual dysfunction in schizophrenics patients, the role of antipsychotics. Presse Med 2005; 34: 529-532
• 11 Serretti A, Chiesa A. A meta-analysis of sexual dysfunction in psychiatric patients taking antipsychotics. Int Clin Psychopharmacol 2011; 26: 130-140
• 12 Serretti A, Chiesa A. Sexual side effects of pharmacological treatment of psychiatric diseases. Clin Pharmacol Ther 2011; 89: 142-147
• 13 Brugnoli R, Novick D, Belger M et al. Effectiveness of antipsychotic treatment for schizophrenia: Italian results of the pan-European Schizophrenia Outpatient Health Outcomes (SOHO) study after 12 months. Giornale Italiano di Psicopatologia 2006; 12: 283-292
• 14 Dossenbach M, Erol A, el Mahfoud Kessaci M et al. Effectiveness of antipsychotic treatments for schizophrenia: interim 6-month analysis from a prospective observational study (IC-SOHO) comparing olanzapine, quetiapine, risperidone, and haloperidol. IC-SOHO Study Group. J Clin Psychiatry 2004; 65: 312-321
• 15 Eberhard J, Lindström E, Holstad M et al. Prolactin level durin 5 years of risperidone treatment in patients with psychotic disorders. Acta Psychiatr Scand 2007; 115: 268-276
• 16 Haro JM, Salvador-Carulla L. The SOHO (Schizophrenia Outpatient Health Outcome) study. Implications for the treatment of schizophrenia. CNS Drugs 2006; 20: 293-301
• 17 Mullen B, Brar JS, Vagnucci AH et al. Frequency of sexual dysfunction in patients with schizophrenia on haloperidol, clozapine, or risperidone. Schizophr Res 2001; 48: 155-158
• 18 Treuer T, Anders M, Bitter I et al. Effectiveness and tolerability of schizophrenia treatment in central and eastern Europe: results after 1 year from a prospective, observational study (IC-SOHO). Int J Psychiatr Clin Pract 2006; 10: 78-90
• 19 Assalian P, Fraser R, Tempier R et al. Sexuality and quality of life of patients with schizophrenia. Int J Psychiatr Clin Pract 2000; 4: 29-33
• 20 Compton MT, Miller AH. Sexual side effects associated with conventional and atypical antipsychotics. Psychopharmacol Bull 2001; 35: 89-108
• 21 Higgins A, Barker P, Begley CM. Neuroleptic medication and sexuality: the forgotten aspect of education and care. J Psychiatr Ment Health Nurs 2005; 12: 439-446
• 22 Kelly DL, Conley RR. Sexuality and schizophrenia: a review. Schizophr Bull 2004; 30: 767-779
• 23 Murthy S, Wylie K. Sexual problems in patients on antipsychotic medication. Sex Relation Ther 2007; 22: 97-107
• 24 Lukoff D, Gioia-Hasick D, Sullivan G et al. Sex education and rehabilitation with schizophrenic male outpatients. Schizophr Bull 1986; 12: 669-677
• 25 Cutler AJ. Sexual dysfunction and antipsychotics treatment. Psychoneuroendocrinology 2003; 28: 69-82
• 26 Dossenbach M, Hodge A, Anders M et al. Prevalence of sexual dysfunction in patients with schizophrenia: international variation and underestimation. Int J Neuropsychopharmacol 2005; 8: 195-201
• 27 Fortier P, Mottard JP, Trudel G et al. Study of sexuality-related characteristics in young adults with schizophrenia treated with novel neuroleptics and in a comparison group of young adults. Schizophr Bull 2003; 29: 559-572
• 28 Nnaji RN, Friedman T. Sexual dysfunction and schizophrenia: psychiatrist’ attitudes and training needs. Psychiatric Bull 2008; 32: 208-210
• 29 Apantaku-Olajide T, Gibbons P, Higgins A. Drug-induced sexual dysfunction and mental health patients’ attitude to psychotropic medications. Sex Relation Ther 2011; 26: 145-155
• 30 Baggaley M. Sexual dysfunction in schizophrenia: focus on recent evidence. Hum Psychopharmacol 2008; 23: 201-209
• 31 Dossenbach M, Dyachkova Y, Pirildar S et al. Effects of atypical and typical antypsichotic treatments on sexual function in patients with schizophrenia: 12-month results from the Intercontinental Schizophrenia Outpatients Health Outcomes (IC-SOHO) study. Eur Psychiatry 2006; 21: 251-258
• 32 Hamer S, Haddad PM. Adverse effects of antipsychotics as outcome measures. Br J Psychiatry 2007; 191: s64-s70
• 33 Kelly DL, Conley RR. Evaluating sexual function in patients with treatment-resistant schizophrenia. Schizophr Res 2003; 63: 195-196
• 34 Khawaja MY. Sexual dysfunction in male patients taking antipsychotics. J Ayub Med Coll Abbottabad 2005; 17: 73-75
• 35 Lambert M, Conus P, Eide P et al. Impact of present and past antipsychotic side effects on attitude toward typical antipsychotic treatment and adherence. Eur Psychiatry 2004; 19: 415-422
• 36 Rosenberg KP, Bleiberg KL, Koscis J et al. A survey of sexual side effects among severely mentally ill patients taking psychotropic medications: impact on compliance. J Sex Marital Ther 2003; 29: 289-296
• 37 Smith SM, O’Keane V, Murray R. Sexual dysfunction in patients taking conventional antipsychotic medication. Br J Psychiatry 2002; 181: 49-55
• 38 Macdonald S, Halliday J, MacEwan T et al. Nithsdale schizophrenia surveys 24: sexual dysfunction. Case-control study. Br J Psychiatry 2003; 182: 50-56
• 39 Fan X, Henderson DC, Chiang E et al. Sexual functioning, psychopatology and quality of life in patients with schizophrenia. Schizophr Res 2007; 94: 119-127
• 40 Ghadirian AM, Chouinard G, Annable L. Sexual dysfunction and plasma prolactin levels in neuroleptic-treated schizophrenic outpatients. J Nerv Ment Dis 1982; 170: 453-467
• 41 Fujii A, Yasui-Furukori N, Sugawara N et al. Sexual dysfunction in Japanese patients with schizophrenia treated with antipsychotics. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 288-293
• 42 Knegtering H, Blijd C, Boks MPM. Sexual dysfunction and prolactin levels in patients using classical antipsychotics, risperidone or olanzapine. Schizophr Res 1999; 36: 355-356
• 43 Haddad PM, Sharma SG. Adverse effects of atypical antipsychotics: differential risk and clinical implications. CNS Drugs 2007; 21: 911-936
• 44 Haddad PM, Wieck A. Antipsychotic-induced hyperprolactinaemia. Mechanisms, clinical features and management. Drugs 2004; 64: 2291-2314
• 45 Knegtering H. Antipsychotic treatment and sexual functioning, the role of prolactin. University of Groningen; The Netherlands: 2003. Available on line at http://irs.ub.rug.nl/ppn/254939104
• 46 Knegtering H, Bruggeman R. What are the effects of antipsychotics on sexual functioning?. Prim Psychiatry 2007; 14: 51-56
• 47 Westheide J, Cohen S, Bender S et al. Sexual dysfunction in psychiatric inpatients the role of antipsychotic medication. Pharmacopsychiatry 2007; 40: 140-145
• 48 Stahl SM. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. (third edition). New York: Cambridge University Press; 2008
• 49 Nasrallah HA. Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry 2008; 13: 27-35
• 50 Andersohn F, Schmedt N, Weinmann S et al. Priapism associated with antipsychotics: role of alpha1 adrenoceptor affinity. J Clin Psychopharmacol 2010; 30: 68-71
• 51 Bhuvaneswar CG, Baldessarini RJ, Harsh VL et al. Adverse endocrine and metabolic effects of psychotropic drugs. CNS Drugs 2009; 23: 1003-1021
• 52 Goodnick PJ, Rodriguez L, Santana O. Antipsychotics: impact on prolactin levels. Exp Opin Pharm 2002; 3: 1381-1391
• 53 Madhusoodanan S, Parida S, Jimenez C. Hyperprolactinemia associated with psychotropics. A review. Hum Psychopharmacol Clin Exp 2010; 25: 281-297
• 54 Maguire GA. Prolactin elevation with antipsychotic medications: mechanisms of action and clinical consequences. J Clin Psychiatry 2002; 63: 56-62
• 55 Potkin SG, Saha AR, Kujawa MJ et al. Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder. Arch Gen Psychiatry 2003; 60: 681-690
• 56 Conley RR, Kelly DL. Second-generation antipsychotics for schizophrenia: a review of clinical pharmacology and medication-associated side effects. Isr J Psychiatry Relat Sci 2005; 42: 51-60
• 57 Hummer M, Huber J. Hyperprolactinaemia and antipsychotic therapy in schizophrenia. Curr Med Res Opin 2004; 20: 189-197
• 58 Liu-Seifert H, Kinon BJ, Tennant CJ et al. Sexual dysfunction in patients with schizophrenia treated with conventional antipsychotics or risperidone. Neuropsychiatr Dis Treat 2009; 5: 47-54
• 59 Montejo AL. Prolactin awareness: an essential consideration for physical health in schizophrenia. Eur Neuropsychopharmacol 2008; 18: S 108-S 114
• 60 Rettenbacher MA, Hofer A, Ebenbichler C et al. Prolactin levels and sexual adverse effects in patients with schizophrenia during antipsychotic treatment. J Clin Psychopharmacol 2010; 30: 711-715
• 61 Smith SM. The impact of hyperprolactinaemia on sexual function in patients with psychosis. J Psychopharmacol 2008; 22: 63-69
• 62 Howes OD, Wheeler MJ, Pilowsky LS et al. Sexual function and gonadal hormones in patients taking antipsychotic treatment for schizophrenia or schizoaffective disorder. J Clin Psychiatry 2007; 68: 361-367
• 63 Hummer M, Kemmler G, Kurz M et al. Sexual disturbances during clozapine and haloperidol treatment for schizophrenia. Am J Psychiatry 1999; 156: 631-633
• 64 Kleinberg DL, Davis JM, de Coster R et al. Prolactin levels and adverse events in patients treated with risperidone. J Clin Psychoharmacol 1999; 19: 57-61
• 65 Konarzewska B, Wolczyński S, Szulc A et al. Effect of risperidone and olanzapine on reproductive hormones, psychopathology and sexual functioning in male patients with schizophrenia. Psychoneuroendocrinology 2009; 34: 129-139
• 66 Johnsen E, Kroken R, Loberg EM et al. Sexual dysfunction and hyperprolactinemia in male psychotic inpatients: a cross-sectional study. Adv Urol 2011; article ID 686924
• 67 Yasui-Furukori N, Fujii A, Sugawara N et al. No association between hormonal abnormality and sexual dysfunction in Japanese schizophrenia patients treated with antipsychotics. Hum Psychopharmacol 2012; 27: 82-89
• 68 Knegtering H, Van den Bosch R, Castelein S et al. Are sexual side effects of prolactin-raising antipsychotics reducible to serum prolactin?. Psychoneuroendocrinology 2008; 33: 711-717
• 69 Westheide J, Cvetanovska G, Albrecht C et al. Prolactin, subjective well-being and sexual dysfunction: an open label observational study comparing quetiapine with risperidone. J Sex Med 2008; 5: 2816-2826
• 70 Istikoglou C, Vlissides D, Michelidakis K et al. Quality of life: sexual dysfunction in young people with schizophrenia treated with ziprasidone. Eur Neuropsychopharm 2009; 19: S511
• 71 Van Bruggen M, Van Amelsvoort T, Wouters L et al. Sexual dysfunction and hormonal changes in first episode psychosis patients on olanzapine or risperidone. Psychoneuroendocrinology 2009; 34: 989-995
• 72 Dickson RA, Glazer WM. Neuroleptic-induced hyperprolactinemia. Schizophr Res 1999; 35: S75-S86
• 73 Wieck A, Haddad M. Antipsychotic-induced hyperprolactinaemia in women: pathophysiology, severity and consequences. Selective literature review. Br J Psychiatry 2003; 182: 199-204
• 74 Marder SR, Essock SM, Miller AL et al. Physical health monitoring of patients with schizophrenia. Am J Psychiatry 2004; 161: 1334-1349
• 75 Smith S, Wheeler MJ, Murray R et al. The effects of antipsychotic-induced hyperprolactinaemia on the hypotalamic-pituitary-gonadal axis. J Clin Psychopharmacol 2002; 22: 109-114
• 76 American Psychiatric Association. Practise guidelines for the treatment of patients with schizophrenia. Second edition. April 2004. Available on line at http://www.psychiatryonline.com/pracGuide/pracGuideTopic_6.aspx
• 77 Conley RR, Mahmoud R. A randomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder. Am J Psychiatry 2001; 158: 765-774
• 78 Chrzanowski WK, Marcus RN, Torbeyns A et al. Effectiveness of long-term aripripazole therapy in patients with acutely relapsing or chronic, stable schizophrenia: a 52-week, open-label comparison with olanzapine. Psychopharmacology 2006; 189: 259-266
• 79 Volavka J, Czobor P, Cooper TB et al. Prolactin levels in schizophrenia and schizoaffective disorder patients treated with clozapine, olanzapine, risperidone, or haloperidol. J Clin Psychiatry 2004; 65: 57-61
• 80 Potkin SG. Asenapine: a critical overview. J Clin Psychiatry 2011; 72: 14-18
• 81 Weber J, McCormack PL. Asenapine. CNS Drugs 2009; 23: 781-792
• 82 Citrome L. Iloperidone: a critical overview. J Clin Psychiatry 2011; 72: 19-23
• 83 Kane L. Lurasidone: a critical overview. J Clin Psychiatry 2011; 72: 24-28
• 84 Montgomery J, Winterbottom E, Jessani M et al. Prevalence of hyperprolactinemia in schizophrenia: association with typical and atipical antipsychotic treatment. J Clin Psychiatry 2004; 65: 1492-1498
• 85 Baldwin D, Mayers A. Sexual side-effects of antidepressant and antipsychotic drug. Adv Psychiatric Treatment 2003; 9: 202-210
• 86 Aizenberg D, Zemishlany Z, Dorfman-Etrog P et al. Sexual dysfunction in male schizophrenic patients. J Clin Psychiatry 1995; 56: 137-141
• 87 Boora K, Chiappone K, Dubovsky S et al. Ziprasidone-induced spontaneous orgasm. J Psychopharmacol 2010; 24: 947-948
• 88 Freeman SA. Iloperidone-induced retrograde ejaculation. Int Clin Psychopharmacol 2013; [Epub ahead of print]
• 89 Orazzo C, Bortolotti F, Monteleone P. Gli psicofarmaci e la funzionalità sessuale nella pratica clinica. Available on line at http://www.psychiatryonline.it/ital/riviste/quaderni/orazzo.htm (latest access on 18 february 2013)
• 90 Kotin J, Wilbert DE, Verburg D et al. Thioridazine and sexual dysfunction. Am J Psichiatry 1976; 133: 82-85
• 91 Degen K. Sexual dysfunction in women using major tranquilizers. Psychosomatics 1982; 23: 959-961
• 92 Compton MT, Miller AH. Priapism associated with conventional and atypical antipsychotic medications: a review. J Clin Psychiatry 2001; 62: 362-366
• 93 Mago R, Anolik R, Johnson RA et al. Recurrent priapism associated with use of aripiprazole. J Clin Psychiatry 2006; 67: 1471-1472
• 94 Penaskovic KM, Haq F, Raza S. Priapism during treatment with Olanzapine, Quetiapine, and Risperidone in a patient with schizophrenia: a case report. Prim Care Companion J Clin Psychiatry 2010; 12 PCC.09l00939
• 95 Torun F, Yilmaz E, Gumus E. Priapism due to a single dose of quetiapine. Turk Psikiyatri Derg 2011; 22: 195-199
• 96 Kaufman KR, Stern L, Mohebati A et al. Ziprasidone-induced priapism requiring surgical treatment. Eur Psychiatry 2006; 21: 48-50
• 97 Reeves RR, Kimble R. Prolonged erections associated with ziprasidone treatment: a case report. J Clin Psychiatry 2003; 64: 97-98
• 98 Malik P. Sexual dysfunction in schizophrenia. Curr Opin Psychiatry 2007; 20: 138-142
• 99 Malik P. Sexual dysfunction in schizophrenia. Focus 2008; 6: 234-238
• 100 Rico-Villademoros F, Calandre EP. Antipsychotic-induced sexual dysfunction and the strength of the evidence. J Clin Psychiatry 2005; 66: 1074-1075
• 101 Kelly DL, Conley RR. A randomized double-blind 12-week study of quietapine, risperidone or fluphenazine on sexual functioning in people with schizophrenia. Psychoneuroendocrinology 2006; 31: 340-346
• 102 Knegtering H, Boks M, Blijd C et al. A randomized open-label comparison of the impact of olanzapine versus risperidone on sexual functioning. J Sex Marital Ther 2006; 32: 315-326
• 103 Bobes J, Garcia-Portilla MP, Rejas J et al. 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. J Sex Marital Ther 2003; 29: 125-147
• 104 Uçok A, Incensu C, Aker T et al. Sexual dysfunction in patients with schizophrenia on antipsychotic medication. Eur Psychiatry 2007; 22: 328-333
• 105 Nakonezny PA, Byerly MJ, Rush AJ. The relationship between serum prolactin level and sexual functioning among male outpatients with schizophrenia or schizoaffective disorder: a randomized double-blind trial of risperidone vs. quetiapine. J Sex Marital Ther 2007; 33: 203-216
• 106 Byerly MJ, Nakonezny PA, Bettcher BM et al. Sexual dysfunction associated with second-generation antipsychotics in outpatients with schizophrenia or schizoaffective disorder: an empirical evaluation of olanzapine, risperidone, and quetiapine. Schizophr Res 2006; 86: 244-250
• 107 Nagaraj AK, Pai NB, Rao S. A comparative study of sexual dysfunction involving risperidone, quetiapine, and olanzapine. Indian J Psychiatry 2009; 51: 265-271
• 108 Byerly MJ, Nakonezny PA, Rush AJ. Sexual functioning associated with quetiapine switch vs. risperidone continuation in outpatients with schizophrenia or schizoaffective disorder: A randomized double-blind pilot trial. Psychiatry Res 2008; 159: 115-120
• 109 Strous RD, Kupchik M, Roitman S et al. Comparison between risperidone, olanzapine, and clozapine in the management of chronic schizophrenia: a naturalistic prospective 12-week observational study. Hum Psychopharmacol 2006; 21: 235-243
• 110 Bitter I, Basson BR, Dossenbach MR. Antipsychotic treatment and sexual functioning in first-time neuroleptic-treated schizophrenic patients. Int Clin Psychopharmacol 2005; 20: 19-21
• 111 Mahmoud A, Hayhurst KP, Drake RJ et al. Second generation antipsychotics improve sexual dysfunction in schizophrenia: a randomised controlled trial. Schizophrenia Research and Treatment 2011; Article ID 596898
• 112 Montejo AL, Majadas S, Rico-Villademoros F et al. Frequency of sexual dysfunction in patients with a psychotic disorder receiving antipsychotics. J Sex Med 2010; 7: 3404-3413
• 113 Cookson J, Hodgson R, Wildgust HJ. Prolactin, hyperprolactinaemia and antipsychotic treatment: a review and lessons for treatment of early psychosis. J Psychopharmacol 2012; 26: 42-51
• 114 Paparrigopoulos T, Liappas J, Tzavellas E. Amisulpride-induced hyperprolactinemia is reversible following discontinuation. Prog Neuropsychoparmacol Biol Psychiatry 2007; 31: 92-96
• 115 Raj R, Sidhu BS. Hyperprolactinaemia with amisulpride. Indian J Psychiatry 2008; 5: 54-56
• 116 Kerwin R, Millet B, Herman E et al. A multicentre, randomized, naturalistic, open-label study between aripripazole and standard of care in the management of community-treated schizophrenic patients. Schizophrenia Trial of Aripripazole: (STAR) study. Eur Psychiatry 2007; 22: 433-443
• 117 Montejo AL, Campos MC, Fombellida C et al. Prospective, multicenter, open-label, observational study of sexual function in patients beginning aripiprazole treatment. Eur Psychiatry 2008; 23: S133-S134
• 118 Mir A, Shivakumar K, Williamson RJ et al. Change in sexual dysfunction with aripiprazole: a switching or add-on study. J Psychopharmacol 2008; 22: 244-253
• 119 Casey DE, Carson WH, Saha AR et al. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Psychopharmacol 2003; 166: 391-399
• 120 Lee BH, Kim YK, Park SH. Using aripiprazole to resolve antipsychotic-induced symptomatic hyperprolactinemia: a pilot study. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 714-717
• 121 Marder SR, McQuade RD, Stock E et al. Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term, placebo-controlled trials. Schizophr Res 2003; 61: 123-136
• 122 Aizenberg D, Modai I, Landa A et al. Comparison of sexual dysfunction in male schizophrenic patients maintained on treatment with classical antipsychotics versus clozapina. J Clin Psychiatry 2001; 62: 541-544
• 123 Deschenes S, Courtois F, Lafond J. Potential side effects of clozapine on the sexual function of schizophrenic man. J Sex Educ Ther 2001; 26: 334-339
• 124 Breier AF, Malhotra AK, Su T-P et al. Clozapine and risperidone in chronic schizophrenia: effects on symptoms, Parkinsonian side effects, and neuroendocrine response. Am J Psychiatry 1999; 156: 294-298
• 125 Yusufi B, Mukherjee S, Flanagan R et al. Prevalence and nature of side effects during clozapine maintenance treatment and the relationship with clozapine dose and plasma concentration. Int Clin Psychopharmacol 2007; 22: 238-243
• 126 Grootens KP, Van Veelen NM, Peuskens J et al. Ziprasidone versus olanzapine in recent-onset schizophrenia and schizoaffective disorder: results of an 8-week double-blind randomized controlled trial. Schizophr Bull 2011; 37: 352-361
• 127 Costa AM, de Lima MS, Faria M et al. A naturalistic, 9-month follow-up, comparing olanzapine and conventional antipsychotics on sexual function and hormonal profile for males with schizophrenia. J Psychopharmacol 2007; 21: 165-170
• 128 Kinon BJ, Ahl J, Liu-Seifert H et al. Improvement in hyperprolactinemia and reproductive comorbidities in patients with schizophrenia switched from conventional antipsychotics or risperidone to olanzapine. Psychoneuroendocrinology 2006; 31: 577-588
• 129 Knegtering R, Castelein S, Bous H et al. A randomized open-label study of the impact of quetiapine versus risperidone on sexual functioning. J Clin Psychopharmacol 2004; 24: 56-61
• 130 Atmaca M, Kuloglu M, Tezcan E. A new atypical antipsychotic: quetiapine-induced sexual dysfunctions. Int J Imp Res 2005; 17: 201-203
• 131 Byerly MJ, Lescouflair E, Weber MT et al. An open-label trial of quetiapine for antipsychotic-induced sexual dysfunction. J Sex Marital Ther 2004; 30: 325-332
• 132 Menon A, Williams RH, Watson S. Increased libido associated with quietiapine. J Psychopharmacol 2006; 20: 125-127
• 133 Montejo González AL, Rico-Villademoros F, Tafalla M et al. A 6-month prospective observational study on the effects of quetiapina on sexual functioning. J Clin Psychopharmacol 2005; 25: 533-538
• 134 Wirshing DA, Pierre JM, Marder SR et al. Sexual side effects of novel antipsychotic medications. Schizophr Res 2002; 56: 25-30
• 135 Peuskens J. Risperidone in the treatment of patients with chronic schizophrenia: a multinational, multicentre, double-blind, parallel-group study versus haloperidol. Br J Psychiatry 1995; 166: 712-726
• 136 David SR, Taylor CC, Kinon BJ et al. The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia. Clin Ther 2000; 22: 1085-1096
• 137 Berwaerts J, Cleton A, Rossenu S et al. A comparison of serum prolactin concentrations after administration of paliperidone extended-release and risperidone tablets in patients with schizophrenia. J Psychopharmacol 2010; 24: 1011-1018
• 138 Montejo AL, Rico-Villademoros F. Changes in sexual function for outpatients with schizophrenia or other psychotic disorders treated with ziprasidone in clinical practice settings: a 3-month prospective, observational study. J Clin Psychopharmacol 2008; 28: 568-570
• 139 Rossi A, Vita A, Tiradritti P et al. Assessment of clinical and metabolic status, and subjective well-being, in schizophrenic patients switched from typical and atypical antipsychotics to ziprasidone. Int Clin Psychopharmacol 2008; 23: 216-222
• 140 Duncan D, Taylor D. Treatment of psychotropic-induced hyperprolactinaemia. Psychiatric Bull 1995; 19: 755-757
• 141 Gopalakrishnan R, Jacob KS, Kuruvilla A et al. Sildenafil in the treatment of antipsychotic-induced erectile dysfunction: a randomized, double-blind, placebo-controlled, flexible-dose, two-way crossover trial. Am J Psychiatry 2006; 163: 494-499
• 142 Kodesh A, Weizman A, Aizenberg D et al. Selegiline in the treatment of sexual dysfunction in schizophrenic patients maintained on neuroleptics: a pilot study. Clin Neuropharmacol 2003; 26: 193-195
• 143 Costa AM, Lima MS, Mari Jde J. A systematic review on clinical management of antipsychotic-induced sexual dysfunction in schizophrenia. Sao Paulo Med J 2006; 124: 291-297
• 144 Inder WJ, Castle D. Antipsychotic-induced hyperprolactinaemia. Aust N Z J Psychiatry 2011; 45: 830-837
• 145 Nunes LV, Moreira HC, Razzouk D et al. Strategies for the treatment of antipsychotic-induced sexual dysfunction and/or hyperprolactinemia among patients of the schizophrenia spectrum: a review. J Sex Marital Ther 2012; 38: 281-301
• 146 Schmidt HM, Hagen M, Kriston L et al. Management of sexual dysfunction due to antipsychotic drug therapy. Cochrane Database Syst Rev 2012;