Neuronale Korrelate sexueller Funktionen unter Antidepressiva

Zusammenfassung

Sexuelle Funktionsstörungen treten häufig in der Therapie mit monoaminerg wirksamen Antidepressiva, insbesondere unter der Einnahme von selektiven Serotoninwiederaufnahmehemmern auf und beeinträchtigen neben der Lebensqualität in erheblichem Maße die Therapieadhärenz der Betroffenen. Trotz der zunehmenden klinischen Relevanz dieser unerwünschten Arzneimittelwirkung (UAW) konnten die zentralen Mechanismen der sexuellen Dysfunktion unter antidepressiver Medikation nicht hinreichend aufgeklärt werden. In einem umfangreichen Forschungsprogramm untersuchten wir gesunde männliche Probanden mit pharmakologisch gestützter funktioneller Magnetresonanztomografie (pharmako-fMRT) und visueller erotischer Stimulation unter der Einnahme verschiedener antidepressiv wirksamer Substanzen, um die monoaminergen Wirkprinzipien auf neuronalen Korrelate sexueller Stimulation aufzuklären und stellen unsere Ergebnisse in dem folgenden Übersichtsartikel dar.

Summary

Sexual dysfunction is a major side-effect of monoaminergic antidepressant agents, e. g. the selective serotonin reuptake inhibitors (SSRIs) and substantially affects quality of life, adherence to medication and hence therapeutic success. Despite of the clinical relevance of this side-effect, the central mechanism of antidepressant-related sexual dysfunction remain unclear. Within an extensive scientific program, we investigated healthy male subjects by pharmacological functional magnet-resonance tomography (pharmaco-fMRI) under visual erotic stimulation and after intake of different classes of antidepressant agents to clarify monoaminergic principles on neural correlates of sexual behaviour. The respective results are illustrated in the following review article.

Schlüsselwörter

fMRT - SSRI - sexuelle Funktion

Keywords

fMRI - SSRIs - sexual function

• Literatur

• 1 La Torre A, Conca A, Duffy D, Giupponi G, Pompili M, Grozinger M. Sexual dysfunction related to psychotropic drugs: a critical review part II: antipsychotics. Pharmacopsychiatry 2013; 46 (06) 201-8.
• 2 La Torre A, Giupponi G, Duffy D, Conca A. Sexual dysfunction related to psychotropic drugs: a critical review – part I: antidepressants. Pharmacopsychiatry 2013; 46 (05) 191-9.
• 3 La Torre A, Giupponi G, Duffy DM, Pompili M, Grozinger M, Kapfhammer HP. et al. Sexual dysfunction related to psychotropic drugs: a critical review. Part III: mood stabilizers and anxiolytic drugs. Pharmacopsychiatry 2014; 47 (01) 1-6.
• 4 Serretti A, Chiesa A. Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. J Clin Psychopharmaco 2009; 29 (03) 259-66.
• 5 Gregorian RS, Golden KA, Bahce A, Goodman C, Kwong WJ, Khan ZM. Antidepressant-induced sexual dysfunction. Ann Pharmacother 2002; 36: 1577-89.
• 6 Bossini L, Fortini V, Casolaro I, Caterini C, Koukouna D, Cecchini F. et al. [Sexual dysfunctions, psychiatric diseases and quality of life: a review]. Psychiatr Pol 2014; 48 (04) 715-26.
• 7 Montejo AL, Llorca G, Izquierdo JA, Rico-Villademoros F. 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. 03) 10-21
• 8 La Torre A, Giupponi G, Duffy D, Conca A, Catanzariti D. Sexual dysfunction related to drugs: a critical review. Part IV: cardiovascular drugs. Pharmacopsychiatry 2015; 48 (01) 1-6.
• 9 Clayton A, Kornstein S, Prakash A, Mallinckrodt C, Wohlreich M. Changes in sexual functioning associated with duloxetine, escitalopram, and placebo in the treatment of patients with major depressive disorder. J Sex Med 2007; 4 (04) 917-29.
• 10 Clayton AH, Pradko JF, Croft HA, Montano CB, Leadbetter RA, Bolden-Watson C. et al. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry 2002; 63: 357-66.
• 11 Coleman CC, Cunningham LA, Foster VJ, Batey SR, Donahue RM, Houser TL. et al. Sexual dysfunction associated with the treatment of depression: a placebo-controlled comparison of bupropion sustained release and sertraline treatment. Ann Clin Psychiatry 1999; 11 (04) 205-15.
• 12 Croft H, Settle Jr. E, Houser T, Batey SR, Donahue RM, Ascher JA. A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline. Clin Ther 1999; 21 (04) 643-58.
• 13 Langworth S, Bodlund O, Agren H. Efficacy and tolerability of reboxetine compared with citalopram: a double-blind study in patients with major depressive disorder. J Clin Psychopharmacol 2006; 26 (02) 121-7.
• 14 Segraves RT, Kavoussi R, Hughes AR, Batey SR, Johnston JA, Donahue R. et al. Evaluation of sexual functioning in depressed outpatients: a double-blind comparison of sustained-release bupropion and sertraline treatment. J Clin Psychopharmacol 2000; 20 (02) 122-8.
• 15 Assem-Hilger E, Kasper S. Psychopharmaka und sexuelle Dysfunktion. Journal für Neurologie, Neurochirurgie und Psychiatrie 2005; 6 (02) 30-6.
• 16 Haddad PM, Sharma SG. Adverse effects of atypical antipsychotics differential risk and clinical implications. CNS Drugs 2007; 21 (11) 911-36.
• 17 Baldwin D, Mayers A. Sexual side-effects of antidepressant and antipsychotic drugs. Advances in Psychiatric Treatment 2003; 9: 202-10.
• 18 Merims D, Giladi N. Dopamine dysregulation syndrome, addiction and behavioral changes in Parkinson’s disease. Parkinsonism Relat Disord 2008; 14 (04) 273-80.
• 19 Wingo TS, Evatt M, Scott B, Freeman A, Stacy M. Impulse control disorders arising in 3 patients treated with rotigotine. Clin Neuropharmacol 2009; 32 (02) 59-62.
• 20 Thase ME, Haight BR, Richard N, Rockett CB, Mitton M, Modell JG. et al. Remission rates following antidepressant therapy with bupropion or selective serotonin reuptake inhibitors: a meta-analysis of original data from 7 randomized controlled trials. J Clin Psychiatry 2005; 66 (08) 974-81.
• 21 Angst J. Treated versus untreated major depressive episodes. Psychopathology 1998; 31 (01) 37-44.
• 22 Kennedy SH, Rizvi S. Sexual dysfunction, depression, and the impact of antidepressants. J Clin Psychopharmacol 2009; 29 (02) 157-64.
• 23 Arnow BA, Desmond JE, Banner LL, Glover GH, Solomon A, Polan ML. et al. Brain activation and sexual arousal in healthy, heterosexual males. Brain 2002; 125 (Suppl. 05) 1014-23.
• 24 Georgiadis JR, Farrell MJ, Boessen R, Denton DA, Gavrilescu M, Kortekaas R. et al. Dynamic subcortical blood flow during male sexual activity with ecological validity: a perfusion fMRI study. Neuroimage 2010; 50 (01) 208-16.
• 25 Metzger CD, Eckert U, Steiner J, Sartorius A, Buchmann JE, Stadler J. et al. High field FMRI reveals thalamocortical integration of segregated cognitive and emotional processing in mediodorsal and intralaminar thalamic nuclei. Front Neuroanat 2010; 4: 138.
• 26 Mouras H, Stoleru S, Bittoun J, Glutron D, Pelegrini-Issac M, Paradis AL. et al. Brain processing of visual sexual stimuli in healthy men: a functional magnetic resonance imaging study. Neuroimage 2003; 20 (02) 855-69.
• 27 Park K, Kang HK, Seo JJ, Kim HJ, Ryu SB, Jeong GW. Blood-oxygenation-level-dependent functional magnetic resonance imaging for evaluating cerebral regions of female sexual arousal response. Urology 2001; 57 (06) 1189-94.
• 28 Redoute J, Stoleru S, Gregoire MC, Costes N, Cinotti L, Lavenne F. et al. Brain processing of visual sexual stimuli in human males. Hum Brain Mapp 2000; 11 (03) 162-77.
• 29 Stoleru S, Gregoire MC, Gerard D, Decety J, Lafarge E, Cinotti L. et al. Neuroanatomical correlates of visually evoked sexual arousal in human males. Arch Sex Behav 1999; 28 (01) 1-21.
• 30 Graf H, Walter M, Metzger CD, Abler B. Antidepressant-related sexual dysfunction – perspectives from neuroimaging. Pharmacol Biochem Behav 2014; 121: 138-45.
• 31 Masters WH, Johnson VE. Die sexuelle Reaktion. Frankfurt a. M.: Akademische Verlagsgesellschaft; 1967
• 32 Agmo A. Functional and dysfunctional sexual behavior: a synthesis of neuroscience and comparative psychology. London: Elsevier Academic; 2007
• 33 Kranz GS, Kasper S, Lanzenberger R. Reward and the serotonergic system. Neuroscience 2010; 166: 1023-35.
• 34 Serretti A, Chiesa A. Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. J Clin Psychopharmacol 2009; 29 (03) 259-66.
• 35 Clayton AH, Pradko JF, Croft HA, Montano CB, Leadbetter RA, Bolden-Watson C. et al. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry 2002; 63 (04) 357-66.
• 36 Abler B, Seeringer A, Hartmann A, Gron G, Metzger C, Walter M. et al. Neural correlates of antidepressant-related sexual dysfunction: a placebo-controlled fMRI study on healthy males under subchronic paroxetine and bupropion. Neuropsychopharmacology 2011; 36 (09) 1837-47.
• 37 Diekhof EK, Gruber O. When desire collides with reason: functional interactions between anteroventral prefrontal cortex and nucleus accumbens underlie the human ability to resist impulsive desires. J Neurosci 2010; 30 (04) 1488-93.
• 38 Abler B, Gron G, Hartmann A, Metzger C, Walter M. Modulation of frontostriatal interaction aligns with reduced primary reward processing under serotonergic drugs. J Neurosci 2012; 32 (04) 1329-35.
• 39 Graf H, Metzger CD, Walter M, Abler B. Serotonergic antidepressants decrease hedonic signals but leave learning signals in the nucleus accumbens unaffected. Neuroreport 2016; 27 (01) 18-22.
• 40 Graf H, Abler B, Hartmann A, Metzger CD, Walter M. Modulation of attention network activation under antidepressant agents in healthy subjects. Int J Neuropsychopharmacol 2013; 16 (06) 1219-30.
• 41 Dosenbach NU, Fair DA, Cohen AL, Schlaggar BL, Petersen SE. A dual-networks architecture of top-down control. Trends Cogn Sci 2008; 12 (03) 99-105.
• 42 Bermpohl F, Fregni F, Boggio PS, Thut G, Northoff G, Otachi PT. et al. Effect of low-frequency transcranial magnetic stimulation on an affective go/no-go task in patients with major depression: role of stimulation site and depression severity. Psychiatry Res 2006; 141 (01) 1-13.
• 43 Dosenbach NU, Fair DA, Miezin FM, Cohen AL, Wenger KK, Dosenbach RA. et al. Distinct brain networks for adaptive and stable task control in humans. Proc Natl Acad Sci USA 2007; 104 (26) 11073-8.
• 44 Dosenbach NU, Visscher KM, Palmer ED, Miezin FM, Wenger KK, Kang HC. et al. A core system for the implementation of task sets. Neuron 2006; 50 (05) 799-812.
• 45 Fox MD, Greicius M. Clinical applications of resting state functional connectivity. Front Syst Neurosci 2010; 4: 19.
• 46 Metzger CD, Wiegers M, Walter M, Abler B, Graf H. Local and global resting state activity in the noradrenergic and dopaminergic pathway modulated by reboxetine and amisulpride in healthy subjects. Int J Neuropsychopharmacol. 2015 19. (2).
• 47 Metzger CD, Walter M, Graf H, Abler B. SSRI-related modulation of sexual functioning is predicted by pre-treatment resting state functional connectivity in healthy men. Arch Sex Behav 2013; 42 (06) 935-47.
• 48 Graf H, Wiegers M, Metzger CD, Walter M, Gron G, Abler B. Erotic stimulus processing under amisulpride and reboxetine: a placebo-controlled fMRI study in healthy subjects. Int J Neuropsychopharmacol. 2015 18. (2).
• 49 Miller EM, Shankar MU, Knutson B, McClure SM. Dissociating motivation from reward in human striatal activity. J Cogn Neurosci 2014; 26 (05) 1075-84.