Comparative Study of Extrapyramidal Side Effects, Sexual Dysfunctions and Hyperprolactinaemia Using Typical and Atypical Antipsychotic Medications Among Patients with Schizophrenia in Maidugri

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Falmata Baba Shettima
Musa Abba Wakil
Taiwo Lateef Sheikh
Isa Bukar Rabbebe
Mohammed Abdulaziz
Said Jidda
Asma’u Mohammed Chibado Dahiru


Schizophrenia, sexual dysfunction, extra-pyramidal side effects, hyperprolactinaemia, typical antipsychotics, atypical antipsychotics.


Background: Extra-pyramidal side effects, sexual dysfunctions and hyperprolactinaemia are major side effects with the use of antipsychotic medications that impede treatment adherence leading to relapse, increased cost of care and rehospitalization among patients with schizophrenia on antipsychotic medications. The study aims to compare the prevalence of extra-pyramidal side effects (EPSE), sexual dysfunctions (SD) and hyperprolactinaemia (HPRL) among patients with schizophrenia spectrum disorders on typical and atypical antipsychotic medications. The secondary aim is to determine if any associations exist between extra-pyramidal side effects, sexual dysfunctions and hyperprolactinaemia.

Methodology: A cross-sectional hospital-based survey involving 209 patients with schizophrenia were interviewed with structured instruments for the assessment of sexual dysfunction, EPSE and the estimation of serum prolactin was done using Enzyme-linked Immunosorbent Assay. Frequencies and Chi-square analysis were used to compare differences in EPSE, SD & HPRL.

Result: The study revealed non-statistically significant differences as a group between typical and atypical antipsychotic medication in terms of extra-pyramidal side effects, sexual dysfunction and hyperprolactinaemia. However, a significant association was observed when individual drugs were compared with haloperidol causing the highest frequency of hyperprolactinaemia (χ2 = 14.9, P = 0.011). A significant relationship between sexual dysfunction and hyperprolactinaemia, sexual dysfunction and extra-pyramidal side effects as well as extra-pyramidal and hyperprolactinaemia was found when individual items for sexual functionin were used.

Conclusion: The significant relationships between sexual dysfunction only in the domains of sexual desire and arousal with hyperprolactinaemia and extrapyramidal side effects as well as hyperprolactinaemia with extrapyramidal side effects point to a common anti-dopaminergic activity of antipsychotics via different pathways. Prospective studies among a larger sample of patients with schizophrenia are needed to unfold these relationships.

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1. Carpenter WT, Koenig JI. The evolution of drug development in schizophrenia: Past issues and future opportunities Neuropsychopharmacology. 2008; 33 (9): 2061-79.

2. de Greef R, Maloney A, Olsson-Gisleskog, Schoemaker J, Panagides J. Dopamine D2 occupancy as a biomarker for antipsychotics: quantifying the relationship with efficacy and extrapyramidal symptoms. AAPS J. 2011; 13 (1):121-30.

3. Nasrallah H. A review of the effects of antipsychotics on weight. Psychoneuroendocrinology. 2003; 28:83-96.

4. Marsden CD, Jenner P. The pathophysiology of extrapyramidal side effects of neuroleptic drugs. Psychol Med 1980; 10 (1): 55-72.

5. Kapur S and Mamo D. Half a century of antipsychotics and still a central role for dopamine D2 receptors. Prog Neuropshchopharmacol Biol Psychiatry. 2003; 27 (7): 1081-90.

6. Liu H, Kinon BJ, Tennant CJ, Sniadecki J, Volavka J. Sexual dysfunction in patients with schizophrenia treated with conventional antipsychotics or risperidone. Neuropsychiatric Disease and Treatment 2009; 5: 47–54.

7. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353(12): 1209–23

8. Jones PB, Barnes TR, Davies L, Dunn G, Lloyd H, Hayhurst KP, Murray RM, Markwick A, Lewis SW. Randomized controlled trials of effect on quality of life of second-vs first generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic drugs in Schizophrenia Study (CUtLASS1). Arch Gen Psychiatry. 2006; 63:1079-87.

9. Leucht S, Corves C, Arbter D, Engel RR, Li C and Davis JM. Second- generation versus first-generation antipsychotic drugs for schizophrenia:a meta-analysis. Lancet. 2009; 373(9657): 31–41.
10. Hartling L, Abou-Setta AM, Dursun S, Mousavi SS, Pasichnyk D, Newton AS. Antipsychotics in adults with schizophrenia: comparative effectiveness of first-generation versus second-generation medications: A systematic review and meta-analysis. Ann Intern Med. 2012; 157(7): 498-511.
11. McCreadie RG, Ohaeri JU. Movement disorder in never and minimally treated Nigerian schizophrenic patients. BJP. 1994; 164: 184-189.
12. Oyekanmi AK, Adelufosi AO, Abayomi Olukayode and Adebowale TO. Demographic and clinical correlates of sexual dysfunction among Nigerian male outpatients on conventional antipsychotic medications. BMC Res Notes. 2012; 5: 267.
13. Guy W. ECDEU Assessment manual for psychopharmacology. Washington DC: US Government Printing Office, 1976: 534–7.

14. Schooler NR, Kane JM. Research diagnosis for tardive dyskinesia. Arch Gen Psy. 1982;39:486-487.

15. Smith JM, Kucharski LT, Oswald WT, Waterman LJ. A systematic investigation of TD in inpatients. Am J Psychiatry 1979; 136(7): 918–22.

16. Simpson GM, Angus JWS. A rating scale for extrapyramidal side effects. Acta Psych Scand 1970; 212S: 11–9.

17. Hansen L, Kingdom D. Akathisia as a risk factor for suicide. BJP 2006; 188: 190-194.

18. Barnes TR. A rating scale for drug-induced akathisia. Br J Psychiatry 1989; 154: 672–6.

19. Barnes TR. The Barnes Akathisia Rating Scale-revisited. J Psychopharmacology. 2003; 17(4): 365-370.

20. McGahuey CA, Gelenberg AJ, Laukes CA, Moreno FA, Delgado PL, McKnight KM, Manber R. The Arizona Sexual Experience Scale (ASEX): reliability and validity. J Sex Marital Ther. 2000; 26(1): 25-40.

21. Nunes LVA, Dieckmann LHJ, Lacaz FS, Bressans Rodrigo, Matsuo T, Mari JJ. .The accuracy of the Arizona Sexual Experience Scale (ASEX) to identify sexual dysfunction in patients of the schizophrenia spectrum. Rev Psiq Clin. 2009; 36 (5): 182-189.

22. Tietz N. Clinical guide to laboratory test, WB Saunders, Philadelphia London 2nd Ed 1992.

23. Nunes Mahmoud A, Hayhurst KP, Drake RJ, Lewis SW. Second generation antipsychotics improve sexual dysfunction in schizophrenia. A randomized control trial. 2011;Schizophrenia Research and Treatment.

24. Saad A, Khalifa DA, El-Missiry M, El-Batrawy A and Taha S. Sexual dysfunction related to typical and atypical antipsychotics in drug naive psychotic patients. Middle East Current Psychiatry 2015, 22:76–82

25. Knegtering H, Boks M, Bligd C, Castelein S, van den Bosch RJ, Wiersma D. A randomized open-label comparison of the impact of olanzepine versus risperidone on sexual functioning. J Sex Marital Ther. 2006; 32:315 -326.

26. Baggaley M. Sexual dysfunction in schizophrenia: focus of recent evidence. Hum. Psychopharmacol. 2008; 23: 201–209.

27. Kelly DL, Conley RR: Sexuality and schizophrenia: a review. Schizophr Bull. 2004; 30 (4): 767-779.

28. Serretti A, Chiesa A. A meta-analysis of sexual dysfunction in psychiatric patients taking antipsychotics doi: 10.1007/s40263-014-0157-3 Int Clin Psychopharmacol 2011;26(3):130-40.

29. Serretti A, Chiesa A. Sexual side effects of pharmacological treatment of psychiatric diseases. Clin Pharmacol Ther 2011;89(1):142-7.

30. Nebhinani N, Grover S, Avasthi A. Sexual dysfunction in male subjects receiving trifluoperazine, risperidone or olanzepine: Rates vary with assessment questionnaire. Prim Care Companion CNS Disord. 2012;14(2): PCC.11m01199

31. Malik P, Kemmler G, Hummer M, et al. Sexual dysfunction in first-episode schizophrenia patients: Results from european first episode schizophrenia trial. J Clin Psychopharmacol. 2011;31:274–280.

32. Nebhinani N, Grover S, Avasthi A. Sexual dysfunction in male subjects receiving trifluoperazine, risperidone, or olanzapine: Rates vary with assessment questionnaire. Prim Care Companion CNS Disord. 2012;14:pii–PCC11m01199.

33. Kumar S and Vinod Sinha VK. Comparative study of sexual dysfunction and serum prolactin level associated with olanzapine, risperidone, and clozapine in patients with remitted schizophrenia. Indian Journal of psychiatry, 2015; 57(4): 386-391.

34. Baggaley M. “Sexual dysfunction in schizophrenia: focus on recent evidence,” Human Psychopharmacology, 2008; 23(3): 201–209.

35. Kahn RS, Fleischhacker WW, Boter H, Davidson M, Vergouwe Y, Keet IP, et al. EUFEST study group 2008.Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 371 (9618):1085-1097.

36. Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM; Second-generation versus first generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet, 2009; 373: 31-41

37. Kane JM, Woerner M, Borenstein M, Wegner J, Lieberman J. Integrating incidence and prevalence of tardive dyskinesia. Psychopharmacol Bull.1986;22:254-8.

38. Miller DD, Caroff SN, Davis SM, Rosenheck RA, McEvoy JP, Saltz BL, et al. Extrapyramidal side-effects of antipsychotics in a randomisedtrial.Br J Psychiatry. 2008; 193: 279–88.

39. Hugenholtz GW, Heerdink ER, Stolker JJ, Meijer WE, Egberts AC, Nolen WA. Haloperidol dose when used as active comparator in randomized controlled trials with atypical antipsychotics in schizophrenia: comparison with officially recommended doses. J Clin Psychiatry 2006; 67: 897–903.

40. Peluso MJ, Lewis SW, Barnes TRE and Jones PB. Extrapyramidal motor side-effects of first- and second-generation antipsychotic drugs. The British Journal of Psychiatry. 2012 May;200(5):387-92.

41. Crossley NA and Constante M. Efficacy of atypical vs. typical antipsychotics in the treatment of early psychosis: meta-analysis. Br J Psychiatry. 2010;196(6):434-439.

42. Woods SW, Morgenstern H, Saksa JR, Walsh BC, Sullivan MC,Money Ret al. Incidence of tardive dyskinesia with atypical vs conventional antipsychotic medications: a prospective cohort study. J Clin Psychiatry. 2010; 71: 463–474.

43. Smith SM: The impact of hyperprolactinaemia on sexual function in patients with psychosis. J Psychopharmacol. 2008; 22 (2 suppl.): 63-9.

44. Toire DL, Falorni A. Pharmacological causes of hyperprolactinaemia. Ther Clin Risk Manag. 2007; 3(5): 929-51.

45. Veronica O'Keane. Antipsychotic-induced hyperprolactinaemia, hypogonadism and osteoporosis in the treatment of schizophrenia. J Psychopharmacol. 2008 22: 70.

46. Montgomery J, Winterbottom E, Jessani M, Jessani M, Kohegyi E, Fulmer J, Seamonds B, Josiassen RC. Prevalence of hyperprolactinemia in schizophrenia: association with typical and atypical antipsychotic treatment. J Clin Psychiatry. 2004; 65:1491–8.

47. Kinon BJ and Halbreich UM. Hyperprolactinaemia in response to antipsychotic drugs: characterization across comparative clinical trials. Psychoendocrinology. 2003; 28(2):69-82.

48. Esel E, Basturk M, Saffet Gonul A, Kula M, Tayfun Turan M, Yabanoglu I, Sofuoglu S. Effects of olanzapine and haloperidol on serum prolactin levels in male schizophrenic patients. Psychoneuroendocrinology. 2001 Aug;26(6):641-7.

49. Volavka J, Czobor P, Cooper TB, Sheitman B, Lindenmayer JP, Citrome L, McEvoy JP, Lieberman JA. Prolactin levels in schizophrenia and schizoaffective disorder patients treated with clozapine, olanzapine, risperidone, or haloperidol. J Clin Psychiatry. 2004 Jan;65(1):57-61.

50. Kondo T, Ishida M, Tokinaga N, Mihara K, Yasui-Furukori N, Ono S, Kaneko S. Association between side effects of nemonapride and plasma concentrations of the drug and prolactin. Prog Neuropsychopharmacol Biol Psychiatry. 2002; 26(2):287-91.

51. Eberhard J, Lindstro¨m E, Holstad M, Levander S. Prolactin level during 5 years of risperidone treatment in patients with psychotic disorders. Acta Psychiatr Scand 2007; 115: 268–276.

52. Johnsen E, Kroken Rune, Loberg EM, Kjelby E, Jorgensen HA. Sexual dysfunction and Hyperprolactinaemia in male psychotic inpatients: A cross-sectional study. Adv Urol. 2011: 686924.

53. vanBruggen 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(7):989-95.

54. Bobes J, Garc A-Portilla MP, 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(2):125-47

55. 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(6):711-15.

56. Ali S, Miller KK, Freudenreich O. Management of psychosis associated with a prolactinoma: case report and review of the literature. Psychosomatics 2010;51(5):370-6

57. Peveler RC, Branford D, Citrome L, et al. Antipsychotics and hyperprolactinaemia:clinicalrecommendations. J Psychopharmacol2008;22(2 Suppl):98-103

58. Peluso MJ, Lewis SW, Barnes TR, 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(1-3):80-6.

59. 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(3):281-301

60. Yasui-Furukori N. Update on the development of lurasidone as a treatment for patients with acute schizophrenia. Drug Des Devel Ther 2012;6:107-15.

61. Kelly DL, Wehring HJ, Earl AK, et al. Treating symptomatic hyperprolactinemiain women with schizophrenia: presentation of the ongoing DAAMSEL clinical trial (Dopamine partial Agonist, Aripiprazole, for the Management of Symptomatic Elevated prolactin). BMC Psychiatry 2013; Published online 22 August 2013, doi: 10.1186/1471-244X-13-214.

62. De Boer M.K, Castelein S , Wiersma D, Schoevers R.A, and Knegtering H. Fact about sexual (Dys)function in schizophrenia: An overview of clinically relevant findings. Schizophrenia Bulletin vol. 41 no. 3 pp. 674–686, 2015.

63. P. Malik, “Sexual dysfunction in schizophrenia,” Current Opinion in Psychiatry, 2007; 20(2): 138–142.