© POL.it 2000 QUADERNI ITALIANI DI PSICHIATRIA

GLI PSICOFARMACI E LA FUNZIONALITA'SESSUALE NELLA PRATICA CLINICA

Catello Orazzo, Francesca Bortolotti e Palmiero Monteleone

Istituto di Psichiatria,

Seconda Università di Napoli

1) INTRODUZIONE

2) LE DISFUNZIONI SESSUALI SECONDARIE A TRATTAMENTO CON PSICOFARMACI E IL DSM IV

3) BASI BIOLOGICHE DELLE FUNZIONI SESSUALI

4) GLI ANTIDEPRESSIVI E LA FUNZIONALITA' SESSUALE

5) GLI ANTIPSICOTICI E LA FUNZIONALITA' SESSUALE

6) I SALI DI LITIO E LA FUNZIONALITA' SESSUALE

7) LE BENZODIAZEPINE E LA FUNZIONALITA' SESSUALE

8) CONCLUSIONI

9) BIBLIOGRAFIA E TABELLE

Bibliografia

11. AHLENIUS S, LARSSON K, SVENSSON L, et al. Effects of a new type of 5-HT receptor agonist on male rat sexual behaviour. Pharmacol Biochem Behav 1981; 15, 785-92.

12. AIZENBERG D et al. Painful ejaculation associated with antidepressants in four patients. J Clin Psychiatry 1991; 52, 461-463.

13. AIZENBERG D, ZEMISHLANY Z, DORFMAN-ETROG P, WEIZMAN A. Sexual dysfunction in male schizophrenic patients. Clin Psychiatry 1995; 56(4), 137-141.

14. AMERICAN PSYCHIATRIC ASSOCIATION. Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition. 1994; 519-522.

15. BALDWIN D. Sexual function in depression. VIII Congresso dell'European College of Neuropsychopharmacology. Venezia (1995).

16. BALON R, YERAGANI VK, POHL R. Sexual dysfunction with antidepressant treatment. J Clin Psychiatry 1993; 54: 209-212.

17. BANCROFT J. Psychophysiology of sexual dysfunction. In Handbook of Biological Psychiatry. Edited by Van Praag HM. New York. Marcel Dekker, 1980.

18. BARDIN ED, KRIEGER JN. Pharmacological priapism: comparison of trazodone and papaverine associated cases. Int Urol Nephrol 1990; 22: 147-152.

19. BELLANTUONO C, TANSELLA M. Gli psicofarmaci nella pratica terapeutica. Il Pensiero Scientifico Editore. Terza edizione. Ottobre 1993.

10. BELLANTUONO C, TANSELLA M. Gli psicofarmaci nella terapia delle sindromi schizofreniche. In: Gli psicofarmaci nella pratica terapeutica, tabella 11, 2, pag 455. Il Pensiero Scientifico Editore, 1994.

11. BENASSI-BENELLI A, FERRARI F, PELLEGRINI-QUARANTOLLI B. Penile erection induced by apomorphine and N-n-propylnonapomorphine in rats. Arch Int Pharmacodyn Ther 1979; 241: 128-134.

12. BERENDSEN HHG, BROEKKAMP CLE. Behavioural evidence for functional interactions between 5-HT receptor subtypes in rats and mice. Br J Pharmacol 1990; 101: 667-73.

13. BEUMONT PJV et al. The effects of phenothiazines on endocrine function. I. Patients with inappropriate lactation and amenorrhoea. Br J Psychiatry 1974; 124: 413-419.

14. BITRAN D, HULL EM. Pharmacological analysis of male rat sexual behaviour. Neurosci Biobehav Rev 1987; 11: 365-389.

15. BORS E, COMARR AE. Neurological disturbances of sexual function with special reference to 529 patients with spinal cord injury. Urol Surv 1960; 10: 191-222.

16. BURNES TR et at. Psychotropic drugs and sexual behaviour. Br J Hospital Medicine 1979; 21: 594-600.

17. CHAPELLE PA, DURANT J, LACERT P. Penile erection following complete spinal cord injury in man. Brit J Urol 1980; 52: 216-219.

18. CHARNEY DS., MENKES DB, HENINGER GR. Receptor sensitivity and the mechanism of action of antidepressant treatment. Implications for the etiology and therapy of depression. Arch Gen Psychiatry 1981; 38: 1160-1180.

19. CLAUS A, BOLLEN J, DeCUYPED H, et al. Risperidone versus haloperidol in the treatment of chronic schizophrenic patients; a multicenter double-blind comparative study. Acta Psychiatr Scand 1992; 85: 255-305.

20. COLLINS AC, KELLNER R. Neuroleptics and sexual functioning. Integrative Psychiatry 1986; 4: 96-108.

21. DE CASTRO RM. Reversal of MAOI-induced anorgasmia with Cyproeptadine. Am J Psychiatry 1985; 142: 783.

22. DEGEN K. Sexual dysfunction in women using major tranquilizers. Psychosomatics 1982; 23: 959-961.

23. DUA S, Mac LEAN PD. Localization for penile erection in medial frontal lobe . Am J Physiol 1964; 207: 1425-1434.

24. EVERETT HC. The use of bethanechol chloride with tricyclic antidepressants. Am J Psychiatry 1975; 132: 1202.

25. Fabian JL. Psychotropic medication and priapism. American Journal of Psychiatry 1993; 150: 249-350.

26. FEDER R. Reversal of antidepressant activity of fluoxetine by cyproheptadine in three patients. J Clin Psychiatry 1991; 52: 163-164.

27. FOREMAN MM, HALL JL. Effects of D2-dopaminergic receptor stimulation on male rat sexual behavior. J Neural Trans 1987; 68: 153-170.

28. FRATTA W, BIGGIO G, GESSA GI. Homosexual mounting behavior induced in male rats by a triptophan free diet. Life Sci 1977; 21: 379.

29. GARDNER EA, JOHNSTON JA. Bupropion: an antidepressant without sexual pathophysiological action. J Clin Psychopharmacol 1985; 5: 24-29.

30. GHADIRIAN AM, ANNABLE L, BELANGER MC. Lithium, benzodiazepines, and sexual function in bipolar patients. Am J Psychiatry 1992; 149: 801-805.

31. GHADIRIAN AM, CHOUINARD G, ANNABLE L. Sexual dysfunction and plasma prolactin levels in neuroleptic-treated schizophrenic outpatients. J Nerv Ment Dis 1982; 170: 463-467.

32. GLASS RM. Ejaculatory impairment from both phenelzine and imipramine with tinnitus from phenelzine. J Clin Psychopharmacol 1981; 1: 152-154.

33. GORZALKA BB, MENDELSON SD, WATSON NV. Serotonin receptor subtypes and sexual behaviour. Ann NY Acad Sci 1990; 600: 435-46.

34. GREENBERG HR. Inhibition of ejaculation by chlorpromazine. J Nerv Ment Dis 1971; 152: 364-366.

35. HARRISON WM, RABKIN JG, EHRHARDT AA, STEWART JM, McGRATH PJ, ROSS D, QUITKIN FM. Effects of antidepressant medication on sexual function: a controlled study. J Clin Psychopharmacol 1986; 6: 144-149.

36. HARRISON WM, STEWART J, EHRHARDT AA, RABKIN J, McGRATH P, LIEBOWITZ M, QUITKIN FM. A controlled study of the effects of antidepressants on sexual function. Psychopharmacol Bull 1985; 21: 85-88.

37. HASEN S. Spinal control of sexual behavior: Effects of intrathecal administration of lisuride. Neurosci Lett 1982; 33: 329-332.

38. HEALTH RG. Pleasure and brain activity in man. J Nerv Ment Dis 1972; 154: 3-10.

39. HERZOG DB, NORMAN DK, GORDON C, AND PEPOSE M. Sexual conflict and eating disorders in 27 males. Am J Psychiatry 1984, 141: 989-990.

40. HOROWITZ JD, GOBLE AJ. Drug and impaired male sexual function. Drugs 1979; 18: 206-217.

41. HUGHES JM. Failure to ejaculate with chlordiazepoxide. Am J Psychiatry 1964; 121: 610-611.

42. HYYPPA M, RINNE O.K, SONNINE V. The activating effect of L-DOPA treatment on sexual functions and its experimental background. Acta Neurol Scand 1970; 43(s): 46, 223.

43. JACOBSEN FM. Fluoxetine-induced sexual dysfunction and an open trial of yohimbine. J Clin Psychiatry 1992; 53: 119-122.

44. KAPLAN HS. Nuove terapie sessuali. VII Edizione Studi Bompiani; 1991.

45. KEDIA K, MARRLAND C. Effect of sympathectomy and drugs on ejaculation. In: Sciarra JJ, Markland C, Speidel JJ (eds).: Control of Male Fertility. New York, Harper and Row Publishers Inc, 1975; 240-248.

46. KLINGE E, SJOSTRAND NO. Contraction and relaxation of the retractor penis muscle and the penile artery of the bull. Acta Physiol Scand 1974; 420 (suppl), 1-88.

47. KOLODNY R., MASTERS W., JOHNSON V. Textbook of sexual medicine. Little Brown, Boston 1979.

48. KOTIN J, WILBERT DE, VELBURG D. Thioridazine and sexual dysfunction. Am J Psychiatry 1976; 133: 82-85.

49. KOWALSKI A et al. The sexual side effects of antidepressant medication: a double-bind comparison of two antidepressants in a non- psychiatric population. Br J Psychiatry 1985; 413-418.

50. KOWALSKI A, STANLEY RO, DENNERSTEIN L, et al. The sexual side-effects of antidepressant medication: a double-blind comparison of two antidepressants in a non-psychiatric population. Br J Psychiatry 1985; 147: 413-418.

51. KRANE RJ, SIROKY MB. Neurophysiology of erection. Urol Clin North Am 1981; 8: 91-102.

52. LAI S, ACKMAN D, THAVUNDAYIL JX, KIELY ME, ETIENNE P. Effect of apomorphine, a dopamine receptor agonist, on penile tumescence in normal subjects. Prog Neuropsychopharmacol Biol Psychiatry 1984; 8: 695-699.

53. MacLEAN PD. Brain mechanisms of primal sexual functions and related behavior. In: Sandler M, Gessa GL (eds): Sexual Behavior: Pharmachology and Biochemistry. New York, Haven Press, 1975; 1-12.

54. MacLEAN PD. New findings relevant to the evolution of psychosexual functions of the brains. The Journal of Nervous and Mental Disease 1962; 4: 135.

55. MALMNAS C. Monoaminergic influence on testosterone-activated copulatory behavior in the castrated male rat. Acta Physiol Scand Suppl. Suppl 1973; 1: 395.

56. MALMNAS C, MEYERSON B. P-chlorophenylalanine and copulatory behavior in the castrated male rat. Nature 1971; 232: 398.

57. MITCHELL JE et al. Antidepressant drug therapy and sexual sex dysfunction in men. A review. J Clin Psychopharmacol 1983; 3(2): 76-79.

58. MOINFAR N, GOAD S, BRINK DD, et al. Clozapine-related priapism. Hosp Commun Psychiatry 1994; 45: 1044.

59. MONTEIRO WO, NOSHIRVANI HF, MARKS IM, LELLIOTT PT. Anorgasmia from clomipramine in obsessive-compulsive disorder: a controlled-trial. Br J Psychiatry 1987; 151: 107-112.

60. MONTGOMERY SA. Safety of mirtazepina: a review. Int Clin Psychopharmacol 1995; 10 (suppl 2), 37-45.

61. NININGER JE. Inhibition of ejaculation by amitriptyline. Am J Psychiatry 1978; 135: 750-751.

62. NUMBERG HG, LEVINE PE. Spontaneous remission of MAOI-induced anorgasmia. Am J Psychiatry 1987; 144: 805-807.

63. PENTTILA O. Acetylcholine, biogenic amines and enzymes involved in their metabolism in penile erectile tissue. Ann Med Exp Biol Fenn 1966; 44 (suppl 9), 7-42.

64. RILEY AJ, RILEY EJ. Cyproheptadine and antidepressant-induced anorgasmia. BR J Psychiatry 1986; 148: 217-218.

65. RILEY AJ, RILEY EJ. The effect of single dose diazepam on female sexual response induced by masturbation. Sexual and Marital Therapy (UK) 1986; 1: 49-53.

66. RISBY ED, et al. The mechanism of action of lithium. Effects on adenylate cyclase activity and beta-adrenergic receptor binding in normal subjects. Archives of general psychiatry 1991; 48: 513-524.

67. RIVARD DJ. Anathomy, physiology, and neurophysiology of male sexual function. In: Bennett AH (ed): Management of Male Impotence. Baltimore, Williams and Wilkins, 1982; 1-25.

68. RODRIGUEZ M, CASTRO R, HERNADEZ G, MAS M. Different roles of catecholaminergic and serotoninergic neurons of the medial forebrain bundle on male rat sexual behavior. Phisiol Behav 1984; 33: 5-11.

69. ROSEN RC, ASHTON AK. Prosexual drugs: empirical status of the "new aphrodisiacs". Arch Sex Behav 1993; 22: 521-543.

70. SAENZ DE TEJADA I, et al. Pathophysiology of prolonged penile erection associated with trazodone use. J Urol. 1991; 145: 60.

71. SCHWARTZ MF, BAUMAN JF, MASTERS WH. Hyperprolactinemia and sexual disorders in men. Biol Psychiatry 1982; 17: 861-876.

72. SEFTEL AD, DE TEJADA IS, SZETELA B, et al. Clozapine - associated priapism: a case report. J Urol 1992; 147: 146-148.

73. SEGRAVES RT. Drugs and desire, In: Sexual Desire Disorders. Edited by Leiblum SR, Rosen RC. New York, Guilford 1988; 313-347.

74. SEGRAVES RT. Effects of psychotropic drugs on human erection and ejaculation. Arch Gen Psychiatry 1989; 46: 275-284.

75. SEGRAVES RT. Treatment of premature ejaculation with lorazepam. Am J Psychiatry 1987; 144(9): 1420.

76. SEGRAVES RT. Treatment-emergent sexual dysfunction in affective disorder: a review and management strategies. J Clin Psychiatry Monogr Ser 1993; 11: 7-63.

77. SELVINI PALAZZOLI M. L'anoressia mentale, dalla terapia individuale alla terapia familiare. Feltrinelli, VIII edizione, 1995.

78. SICUTERI F. Serotonin and sex in man. Pharmacol Res Commun 1974; 6: 403-411.

79. SITLAND-MARKEN PA, WELLS BG, FROEMMING JH, et al. Psychiatric applications of bromocriptine therapy. J Clin Psychiatry 1990; 51: 68-82.

80. SJOERSDMA A, LOVENBERG W, ENGELMAN K, CARPENTER WT, WYATT RJ, GESSA GL. Serotonin now: Clinical implications of inhibiting its synthesis with para-chlorophenylalanine. Ann Intern Med 1970; 73: 607-629.

81. SOVNER R. Treatment of tricyclic antidepressant-induced orgasmic inhibition with cyproheptadine. J Clin Psychopharmacol 1984; 4: 169.

82. TAGLIAMONTE A, FRATTA W, DEL FIACCO M, et al. Evidence that brain dopamine stimulates copulatory behavior in the male rats. Riv Farm Ter 1973; 4: 177.

83. TAGLIAMONTE A, TAGLIAMONTE P, GESSA G L, et al. Compulsive sexual activity induced by P-chlorophenylalanine in normal and pinealectomized rats. Science 1969; 166: 1433.

84. TENNENT G, BANCROFT J, CASS J. The control of deviant sexual behavior by drugs: a double-blind controlled study of benperidol, chlorpromazine, and placebo. Arch Sex Behav 1974; 3: 261-271.

85. THOMPSON JW, WARE MR, BLASHFIELD RK. Psychotropic medication and priapism: a comprehensive review. Journal of Clinical Psychiatry 1990; 51: 430-433.

86. VINAROVA E, UHLIR O, STIKA L, VINAR O. Side effects of lithium administration. Activ Nerv Sup 1972; 14: 105-107.

87. WAGNER G, BRINDLEY GS. The effect of atropine, and beta blockers on human penile erection: a controlled pilot study. In: Zorgniott A, Rossi G (eds): Vasculogenic Impotence. Springfield. III, Charles C Thomas Publishers, 1980; 77-82.

88. WAGNER G, GREEN R: Impotence. New York, Plenum Press, 1981.

89. WAKADE AR, KIRRERAR SM. Chemical and histochemical studies on the sympathetic innervation of the vas deferens and seminal vesicle of the guinea pig. J Pharmacol Exp Ther 1971; 178: 432-441.

90. WALKER PW, COLE JO, GARDNER EA, et al. Improvement in fluoxetine-associated sexual dysfunction in patients switched to bupropion. J Clin Psychiatry 1993; 54: 459-465.

91. WASS JOH, THORNER MO, MORRIS DV, et al. Long term treatment of acromegalia with bromocriptine. Brit Med J 1977; I (?): 875.

92. WILSON CA. Pharmacological targets for the control of male and female sexual behaviour. In: Riley AJ, Peet M, Wilson C editors. Sexual pharmacology. Oxford. Oxford Medical Publications. 1993; 1: 58.

93. ZAJECKA J, FAWSETT J, SCHAFF M, et al. The role of serotonin in sexual dysfunction: fluoxetine-associated orgasm dysfunction. J Clin Psychiatry 1991; 52: 66-68.

94. ZIEGLER J, BEHAR D. Clozapine induced priapism. Am J Psychiatry 1992; 149: 272-273.

TABELLE

TABELLA I
Possibile ruolo dei neurotrasmettitori

TraSMETTITORI	EFFETTO SULL'ANIMALE	EFFETTO SULL'UOMO
SEROTONINA	inibizione della risposta eiaculatoria inibizione della risposta sessuale	inibizione dell'attività sessuale (osservazioni cliniche: mancano dati sperimentali attendibili)
DOPAMINA	abbassamento della soglia del riflesso erettile ed eiaculatorio aumento della reattività sessuale	miglioramento della reattività sessuale o nessuna interferenza con la risposta sessuale
NORADRENALINA	- induzione dell'erezione	inibizione dell'erezione facilitazione dell'eiaculazione
ACETILCOLINA	- inibizione dell'erezione in seguito a stimolazione elettrica dei nervi parasimpatici sacrali	modulazione della risposta sessuale agli altri neurotrasmettitori possibile facilitazione dell'orgasmo (la microinfusione nella regione settale di donna epilettica ha provocato orgasmi ripetuti)

TABELLA II
Psosibili interventi farmacologici

INTERVENTO	CONSEGUENZE	COMMENTO
Riduzione della posologia	Ripresa della sintomatologia depressiva
Trattamento con neostigmina	Mioclonie, sudorazione, scialorrea, pollachiuria, nausea, vomito, diarrea	Rimedio valido soprattutto per i disturbi dell'eiaculazione (7,5-15 mg per os prima del rapporto sessuale)
Trattamento con yoimbina (da 4 a 7,5 mg per os, prima del rapporto sessuale)	Ansia, aumento della pressione arteriosa, irritabilità, tremore, pollachiuria, nausea, vomito	Non è in commercio in Italia Rimedio valido soprattutto in caso di ridotta libido o di inibizione dell'orgasmo da farmaci serotoninergici
Sostituzione del farmaco con bupropione	Irritabilità, insonnia, cefalea, perdita di peso	- Non è in commercio in Italia
Sostituzione con nefazodone	Xerostomia, nausea, cefalea
Sostituzione con trazodone	Rischio di priapismo	Rimedio valido soprattutto nelle disfunzioni erettili
Sostituzione con mirtazepina	Xerostomia, stipsi, sonnolenza, sedazione	Scarsa documentazione Rimedio valido soprattutto nelle disfunzioni erettili e nei disturbi dell'orgasmo
Trattamento con ciproeptadina	Possibilità di antagonizzare l'effetto antidepressivo secondario all'uso di farmaci serotoninergici	Rimedio valido soprattutto nei disturbi dell'orgasmo (4-8 mg per os, 1 o 2 ore prima del rapporto sessuale)

TABELLA III
Disturbi della funzionalità sessuale nel corso di trattamenti antipsicotici

UOMO	DONNA
Ginecomastia	Galattorrea
Disturbi dell'orgasmo	Amenorrea
Impotenza	Irregolarità mestruali
Riduzione del volume dell'eiaculato	Disturbi dell'orgasmo
Riduzione della libido	Riduzione della libido
Priapismo

TABELLA IV
Possibili interventi terapeutici per le DSSP da antipsicotici

Trattamento	Possibili conseguenze
Sospensione del trattamento o riduzione della posologia	Ricomparsa dei sintomi psicotici
Sostituire un farmaco ad alta azione adrenolitica con uno a bassa azione
Sospensione dell'anticolinergico o sostituzione con amantadina	Ricomparsa delle manifestazioni extrapiramidali
Trattamento con bromocriptina	Ricomparsa dei sintomi psicotici

TABELLA V
Trattamento dei DSSP da sali di litio

Intervento	Conseguenze	Commento
Riduzione della posologia	Ricomparsa del disturbo dell'umore	Controllare la litiemia prima della riduzione posologica
Sostituzione del litio con altri stabilizzatori dell'umore	Ricomparsa del disturbo dell'umore
Passare da un intervento preventivo ad un intervento curativo	Aumento del numero degli episodi patologici
Prolungare il trattamento con i sali di litio	Scarsa compliance	In genere dopo 2-3 mesi di trattamento con i sali di litio i sintomi sessuali regrediscono

RED CRAB DESIGN

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