198 - References

References

200 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 1 The evidence base supporting the use of ‘antidotes’ is often poor and specific to particular drug-­induced problems.33,106 The generalisability of results from positive trials is limited by small sample sizes, short trial durations and lack of controlling for confounding factors (age, concurrent medication, antipsychotic switches for reasons other than baseline sexual dysfunction).106 Comparison of data between studies is further complicated by the use of varying assessment tools to measure outcomes.107 Drugs such as sildenafil (Viagra) or alprostadil (Caverject) are effective only in the treatment of erectile dysfunction (they have no effect on libido or central arousal). Psychological approaches used by sexual dysfunction clinics may be difficult for clients with mental health problems to engage in.9 References

1. Korchia T, et al. Sexual dysfunction in schizophrenia: a systematic review and meta-­analysis. JAMA Psychiatry 2023; 80:1110–1120.
2. Montejo AL, et  al. Frequency of sexual dysfunction in patients with a psychotic disorder receiving antipsychotics. J Sex Med 2010; 7:3404–3413.
3. Olfson M, et al. Male sexual dysfunction and quality of life in schizophrenia. J Clin Psychiatry 2005; 66:331–338.
4. Montejo AL, et al. Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-­Related Sexual Dysfunction. J Clin Psychiatry 2001; 62 Suppl 3:10–21.
5. Souaiby L, et  al. Sexual dysfunction in patients with schizophrenia and schizoaffective disorder and its association with adherence to ­antipsychotic medication. J Ment Health 2020; 29:623–630.
6. Baggaley M. Sexual dysfunction in schizophrenia: focus on recent evidence. Hum Psychopharmacol 2008; 23:201–209.
7. Ucok A, et al. Sexual dysfunction in patients with schizophrenia on antipsychotic medication. Eur Psychiatry 2007; 22:328–333.
8. Patel R, et al. Oral and long-­acting injectable antipsychotic discontinuation and relationship to side effects in people with first episode psychosis: a longitudinal analysis of electronic health record data. Ther Adv Psychopharmacol 2023; 13:20451253231211575.
9. Segraves RT. Effects of psychotropic drugs on human erection and ejaculation. Arch Gen Psychiatry 1989; 46:275–284.
10. Pollack MH, et al. Genitourinary and sexual adverse effects of psychotropic medication. Int J Psychiatry Med 1992; 22:305–­327.
11. Stahl SM. The psychopharmacology of sex, part 1: neurotransmitters and the 3 phases of the human sexual response. J Clin Psychiatry 2001; 62:80–81.
12. Garcia-­Reboll L, et al. Drugs for the treatment of impotence. Drugs Aging 1997; 11:140–151.
13. Bitter I, et al. Antipsychotic treatment and sexual functioning in first-­time neuroleptic-­treated schizophrenic patients. Int Clin Psychopharmacol 2005; 20:19–21.
14. Dembler-­Stamm T, et al. Sexual dysfunction in unmedicated patients with schizophrenia and in healthy controls. Pharmacopsychiatry 2018; 51:251–256.
15. Vargas-­Cáceres S, et al. The impact of psychosis on sexual functioning: a systematic review. J Sex Med 2021; 18:457–­466.
16. Macdonald S, et al. Nithsdale Schizophrenia Surveys 24: sexual dysfunction. Case-­control study. Br J Psychiatry 2003; 182:50–56.
17. Howard LM, et al. The general fertility rate in women with psychotic disorders. Am J Psychiatry 2002; 159:991–­997.
18. Peluso MJ, et al. Non-­neurological and metabolic side effects in the Cost Utility of the Latest Antipsychotics in Schizophrenia Randomised Controlled Trial (CUtLASS-­1). Schizophr Res 2013; 144:80–86.
19. Byerly MJ, et  al. An empirical evaluation of the Arizona sexual experience scale and a simple one-­item screening test for assessing antipsychotic-­related sexual dysfunction in outpatients with schizophrenia and schizoaffective disorder. Schizophr Res 2006; 81:311–316.
20. Serretti A, et  al. A meta-­analysis of sexual dysfunction in psychiatric patients taking antipsychotics. Int Clin Psychopharmacol 2011; 26:130–140.
21. Zhang Y, et al. Prolactin and thyroid stimulating hormone (TSH) levels and sexual dysfunction in patients with schizophrenia treated with conventional antipsychotic medication: a cross-­sectional study. Med Sci Monit 2018; 24:9136–9143.
22. Martínez-­Giner G, et al. Sexual dysfunction in people treated with long-­acting injectable antipsychotics in monotherapy or polypharmacy: a naturalistic study. Int J Ment Health Nurs 2022; 31:576–590.
23. Nunes LV, 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.
24. Edinoff AN, et al. Hyperprolactinemia, clinical considerations, and infertility in women on antipsychotic medications. Psychopharmacol Bull 2021; 51:131–148.
25. Adverse effects of the atypical antipsychotics. Collaborative Working Group on Clinical Trial Evaluations. J Clin Psychiatry 1998; 59 Suppl 12:17–22.
26. Knegtering H, et al. Are sexual side effects of prolactin-­raising antipsychotics reducible to serum prolactin? Psychoneuroendocrinology 2008; 33:711–717.
27. Hanssens L, et al. 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 (NCT00237913). BMC Psychiatry 2008; 8:95.
28. Mir A, et al. Change in sexual dysfunction with aripiprazole: a switching or add-­on study. J Psychopharm 2008; 22:244–253.

Schizophrenia and related psychoses CHAPTER 1 29. Byerly MJ, et al. Effects of aripiprazole on prolactin levels in subjects with schizophrenia during cross-­titration with risperidone or olanzapine: analysis of a randomized, open-­label study. Schizophr Res 2009; 107:218–222. 30. Montejo AL, et al. Management strategies for antipsychotic-­related sexual dysfunction: a clinical approach. J Clin Med 2021; 10:308. 31. Aldridge SA. Drug-­induced sexual dysfunction. Clin Pharm 1982; 1:141–147. 32. Fond G, et al. Sexual dysfunctions are associated with major depression, chronic inflammation and anticholinergic consumption in the real-­ world schizophrenia FACE-­SZ national cohort. Prog Neuropsychopharmacol Biol Psychiatry 2019; 94:109654. 33. Baldwin D, et al. Sexual side-­effects of antidepressant and antipsychotic drugs. Adv Psychiatr Treat 2003; 9:202–210. 34. Rykmans V, et al. P0106: A comparision of switching strategies from risperidone to aripiprazole in patients with schizophrenia with insufficient efficacy/tolerability on risperidone (cn138-­169). Eur Psychiatry 2008; 23 Suppl 2:S111. 35. Potkin SG, et al. Reduced sexual dysfunction with aripiprazole once-­monthly versus paliperidone palmitate: results from QUALIFY. Int Clin Psychopharmacol 2017; 32:147–154. 36. Kelly DL, et al. Analysis of prolactin and sexual side effects in patients with schizophrenia who switched from paliperidone palmitate to aripiprazole lauroxil. Psychiatry Res 2021; 302:114030. 37. Kelly DL, et al. Adjunct aripiprazole reduces prolactin and prolactin-­related adverse effects in premenopausal women with psychosis: results from the DAAMSEL clinical trial. J Clin Psychopharmacol 2018; 38:317–326. 38. Chen CY, et al. Improvement of serum prolactin and sexual function after switching to aripiprazole from risperidone in schizophrenia: a case series. Psychiatry Clin Neurosci 2011; 65:95–97. 39. Vrignaud L, et al. [Hypersexuality associated with aripiprazole: a new case and review of the literature]. Therapie 2014; 69:525–527. 40. Ajmal A, et al. Psychotropic-­induced hyperprolactinemia: a clinical review. Psychosomatics 2014; 55:29–36. 41. Kane JM, et al. A multicenter, randomized, double-­blind, controlled phase 3 trial of fixed-­dose brexpiprazole for the treatment of adults with acute schizophrenia. Schizophr Res 2015; 164:127–135. 42. Citrome L. Brexpiprazole for schizophrenia and as adjunct for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antipsychotic – what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Int J Clin Pract 2015; 69:978–997. 43. Nasrallah HA, et al. The safety and tolerability of cariprazine in long-­term treatment of schizophrenia: a post hoc pooled analysis. BMC Psychiatry 2017; 17:305. 44. Barabássy Á, et  al. Safety and tolerability of cariprazine in patients with schizophrenia: a pooled analysis of eight phase II/III studies. Neuropsychiatr Dis Treat 2021; 17:957–970. 45. Coward DM. General pharmacology of clozapine. Br J Psychiatry Suppl 1992; 160:5–11. 46. Meltzer HY, et al. Effect of clozapine on human serum prolactin levels. Am J Psychiatry 1979; 136:1550–1555. 47. Aizenberg D, et al. Comparison of sexual dysfunction in male schizophrenic patients maintained on treatment with classical antipsychotics versus clozapine. J Clin Psychiatry 2001; 62:541–544. 48. Crawford AM, et al. The acute and long-­term effect of olanzapine compared with placebo and haloperidol on serum prolactin concentrations. Schizophr Res 1997; 26:41–54. 49. Mitchell JE, et al. Antipsychotic drug therapy and sexual dysfunction in men. Am J Psychiatry 1982; 139:633–637. 50. Serretti A, et al. Sexual side effects of pharmacological treatment of psychiatric diseases. Clin Pharmacol Ther 2011; 89:142–147. 51. Citrome L, et al. Long-­term safety and tolerability of lurasidone in schizophrenia: a 12-­month, double-­blind, active-­controlled study. Int Clin Psychopharmacol 2012; 27:165–176. 52. Clayton AH, et al. Safety of flibanserin in women treated with antidepressants: a randomized, placebo-­controlled study. J Sex Med 2018; 15:43–51. 53. Dossenbach M, et al. Effects of atypical and typical antipsychotic treatments on sexual function in patients with schizophrenia: 12-­month results from the Intercontinental Schizophrenia Outpatient Health Outcomes (IC-­SOHO) study. Eur Psychiatry 2006; 21:251–258. 54. Aurobindo Pharma  -­ Milpharm Ltd. Summary of Product Characteristics. Olanzapine 10  mg tablets 2023 (last checked May 2024); http://www.medicines.org.uk/emc/medicine/27661/SPC/Olanzapine++10+mg+tablets/. 55. Montalvo I, et al. Changes in prolactin levels and sexual function in young psychotic patients after switching from long-­acting injectable risperidone to paliperidone palmitate. Int Clin Psychopharmacol 2013; 28:46–49. 56. Shiloh R, et al. Risperidone-­induced retrograde ejaculation. Am J Psychiatry 2001; 158:650. 57. Smith S. Effects of antipsychotics on sexual and endocrine function in women: implications for clinical practice. J Clin Psychopharmacol 2003; 23(3 Suppl 1):S27–S32. 58. Loh C, et  al. Risperidone-­induced retrograde ejaculation: case report and review of the literature. Int Clin Psychopharmacol 2004; 19:111–112. 59. Thompson JW, Jr., et al. Psychotropic medication and priapism: a comprehensive review. J Clin Psychiatry 1990; 51:430–433. 60. Peuskens J, et  al. A comparison of quetiapine and chlorpromazine in the treatment of schizophrenia. Acta Psychiatr Scand 1997; 96:265–273. 61. Bobes 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. 62. Byerly MJ, et al. An open-­label trial of quetiapine for antipsychotic-­induced sexual dysfunction. J Sex Marital Ther 2004; 30:325–332. 63. Knegtering R, et  al. A randomized open-­label study of the impact of quetiapine versus risperidone on sexual functioning. J Clin Psychopharmacol 2004; 24:56–61. 64. Montejo Gonzalez AL, et  al. A 6-­month prospective observational study on the effects of quetiapine on sexual functioning. J Clin Psychopharmacol 2005; 25:533–538. 65. Atmaca M, et al. A new atypical antipsychotic: quetiapine-­induced sexual dysfunctions. Int J Impot Res 2005; 17:201–203.

202 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 1 66. Kelly DL, et al. A randomized double-­blind 12-­week study of quetiapine, risperidone or fluphenazine on sexual functioning in people with schizophrenia. Psychoneuroendocrinology 2006; 31:340–346. 67. Tran PV, et al. Double-­blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders. J Clin Psychopharmacol 1997; 17:407–418. 68. Raja M. Risperidone-­induced absence of ejaculation. Int Clin Psychopharmacol 1999; 14:317–319. 69. Smith SM, et al. Sexual dysfunction in patients taking conventional antipsychotic medication. Br J Psychiatry 2002; 181:49–55. 70. Aizenberg D, et al. Sexual dysfunction in male schizophrenic patients. J Clin Psychiatry 1995; 56:137–141. 71. Correll CU, et al. Safety and tolerability of lumateperone 42 mg: an open-­label antipsychotic switch study in outpatients with stable schizophrenia. Schizophr Res 2021; 228:198–205. 72. Correll CU, et al. Efficacy and safety of lumateperone for treatment of schizophrenia: a randomized clinical trial. JAMA Psychiatry 2020; 77:349–358. 73. Cruz MP. Pimavanserin (Nuplazid): a treatment for hallucinations and delusions associated with Parkinson’s disease. P T 2017; 42:368–371. 74. Freeman MP, et al. Improvement of sexual functioning during treatment of MDD with adjunctive pimavanserin: a secondary analysis. Depress Anxiety 2020; 37:485–495. 75. Peuskens J, et al. The effects of novel and newly approved antipsychotics on serum prolactin levels: a comprehensive review. CNS Drugs 2014; 28:421–453. 76. Subeesh V, et al. Novel adverse events of iloperidone: a disproportionality analysis in US Food and Drug Administration Adverse Event Reporting System (FAERS) Database. Curr Drug Saf 2019; 14:21–26. 77. Freeman SA. Iloperidone-­induced retrograde ejaculation. Int Clin Psychopharmacol 2013; 28:156. 78. Theleritis C, et al. Sexual dysfunction and central obesity in patients with first episode psychosis. Eur Psychiatry 2017; 42:1–7. 79. Yoshida K, et  al. Dose-­dependent effects of antipsychotics on efficacy and adverse effects in schizophrenia. Behav Brain Res 2021; 402:113098. 80. Besag FMC, et al. Is adjunct aripiprazole effective in treating hyperprolactinemia induced by psychotropic medication? A narrative review. CNS Drugs 2021; 35:507–526. 81. Terevnikov V, et al. Add-­on mirtazapine improves orgasmic functioning in patients with schizophrenia treated with first-­generation anti­ psychotics. Nord J Psychiatry 2017; 71:77–80. 82. Kodesh A, et al. Selegiline in the treatment of sexual dysfunction in schizophrenic patients maintained on neuroleptics: a pilot study. Clin Neuropharmacol 2003; 26:193–195. 83. Davis SR, et al. Testosterone for low libido in postmenopausal women not taking estrogen. N Engl J Med 2008; 359:2005–2017. 84. Schover LR. Androgen therapy for loss of desire in women: is the benefit worth the breast cancer risk? Fertil Steril 2008; 90:129–140. 85. Baldwin DS, et al. Effects of antidepressant drugs on sexual function. Int J Psychiatry Clin Pract 1997; 1:47–58. 86. Krzystanek M, et al. Amantadine in the treatment of sexual inactivity in schizophrenia patients taking atypical antipsychotics: the pilot case series study. Pharmaceuticals (Basel) 2021; 14:947. 87. Valevski A, et al. Effect of amantadine on sexual dysfunction in neuroleptic-­treated male schizophrenic patients. Clin Neuropharmacol 1998; 21:355–357. 88. Gross MD. Reversal by bethanechol of sexual dysfunction caused by anticholinergic antidepressants. Am J Psychiatry 1982; 139:1193–1194. 89. Masand PS, et al. Sustained-­release bupropion for selective serotonin reuptake inhibitor-­induced sexual dysfunction: a randomized, double-­ blind, placebo-­controlled, parallel-­group study. Am J Psychiatry 2001; 158:805–807. 90. Rezaei O, et al. The effect of bupropion on sexual function in patients with Schizophrenia: a randomized clinical trial. Eur J Psychiatry 2017; 32:11–15. 91. Rothschild AJ. Sexual side effects of antidepressants. J Clin Psychiatry 2000; 61 Suppl 11:28–36. 92. Lauerma H. Successful treatment of citalopram-­induced anorgasmia by cyproheptadine. Acta Psychiatr Scand 1996; 93:69–70. 93. IBM Watson Health. IBM Micromedex Solutions. 2024; https://www.ibm.com/watson-­health/about/micromedex. 94. Clayton AH, et al. Effect of lurasidone on sexual function in major depressive disorder patients with subthreshold hypomanic symptoms (mixed features): results from a placebo-­controlled trial. J Clin Psychiatry 2018; 79:18m12132. 95. Nurnberg HG, et  al. Sildenafil for women patients with antidepressant-­induced sexual dysfunction. Psychiatr Serv 1999; 50:1076–1078. 96. Salerian AJ, et  al. Sildenafil for psychotropic-­induced sexual dysfunction in 31  women and 61  men. J Sex Marital Ther 2000; 26:133–140. 97. Gopalakrishnan R, 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. 98. Mazzilli R, et al. Erectile dysfunction in patients taking psychotropic drugs and treated with phosphodiesterase-­5 inhibitors. Arch Ital Urol Androl 2018; 90:44–48. 99. de Boer MK, et al. Efficacy of tadalafil on erectile dysfunction in male patients using antipsychotics: a double-­blind, placebo-­controlled, crossover pilot study. J Clin Psychopharmacol 2014; 34:380–382. 100. Nunes LV, et al. Adjunctive treatment with lodenafil carbonate for erectile dysfunction in outpatients with schizophrenia and spectrum: a randomized, double-­blind, crossover, placebo-­controlled trial. J Sex Med 2013; 10:1136–1145. 101. Mitsonis CI, et al. Vardenafil in the treatment of erectile dysfunction in outpatients with chronic schizophrenia: a flexible-­dose, open-­label study. J Clin Psychiatry 2008; 69:206–212. 102. Jacobsen FM. Fluoxetine-­induced sexual dysfunction and an open trial of yohimbine. J Clin Psychiatry 1992; 53:119–122.

Schizophrenia and related psychoses CHAPTER 1 103. Michelson D, et al. Mirtazapine, yohimbine or olanzapine augmentation therapy for serotonin reuptake-­associated female sexual dysfunction: a randomized, placebo controlled trial. J Psychiatr Res 2002; 36:147–152. 104. Woodrum ST, et al. Management of SSRI-­induced sexual dysfunction. Ann Pharmacother 1998; 32:1209–1215. 105. Kingsberg SA, et al. Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials. Obstet Gynecol 2019; 134:899–908. 106. Allen K, et al. Management of antipsychotic-­related sexual dysfunction: systematic review. J Sex Med 2019; 16:1978–1987. 107. Basson R, et  al. Women’s sexual dysfunction associated with psychiatric disorders and their treatment. Womens Health 2018; 14:1745506518762664.