Uygunsuz hiperseksüel davranışlar otizmi olan bireylerde sıklıkla bildirilmesine rağmen, yazında bu davranışların kontrol altına alınması ile ilgili yeterli bilgi bulunmamaktadır. Bu yazıda otistik bozukluğu ve zekâ geriliği olan bir ergen olguda aşırı uygunsuz cinsel davranışların risperidonparoksetin kombinasyonu ile tedavisi sunulmuştur. Otizmi olan kişilerde aşırı cinsel uğraşlar aile ve çevre için stres kaynağı oluşturabilir, bu nedenle uygun tedavi yaklaşımları önemlidir. (Nöropsikiyatri Arflivi 2012; 49: 311-313)Inappropriate hypersexual behaviors have been frequently reported in subjects with autism, however, literature on management of such behaviors in this group is very limited. In this paper, we describe an adolescent with autistic disorder and mental retardation who developed severe inappropriate sexual behaviors and has been treated successfully with risperidone-paroxetine combination. As presence of hypersexual behaviors in individuals with autism is a distressing factor for their family and social environment, appropriate management seems to be essential. (Archives of Neuropsychiatry 2012; 49: 311-313

Erdinç, Çiçek

Hergüner, Arzu

Hergüner, Sabri

Nöro Psikiyatri Arşivi

Necmettin Erbakan University Institutional Repository

Sabri HERGÜNER1, Arzu HERGÜNER1, Erdinç ÇİÇEK21Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi, Çocuk ve Ergen Psikiyatri Anabilim Dalı, Konya, Türkiye 2Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi, Psikiyatri Anabilim Dalı, Konya, TürkiyeOtizm ve Zekâ Geriliği olan Bir Ergende Uygunsuz Cinsel Davranışlar içinRisperidone ve Paroxetine Birlikte KullanımıCombination of Risperidone and Paroxetine for Inappropriate Sexual Behaviors in an Adolescent with Autismand Mental RetardationOlgu Sunumu / Case Report 311Cor res pon den ce Ad dress/Ya z›fl ma Ad re si: Dr. Sabri Hergüner, Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi, Çocuk ve Ergen Psikiyatri Anabilim Dalı, Konya, Türkiye  Gsm: +90 533 742 81 50 E-mail: cocukergen@yahoo.com Re cei ved/Ge liş ta ri hi: 15.05.2011 Ac cep ted/Ka bul ta ri hi: 05.08.2011       © Arc hi ves of Neu ropsy chi atry, pub lis hed by Ga le nos Pub lis hing. / Nö rop si ki yat ri Ar fli vi Der gi si, Ga le nos Ya y› ne vi ta ra f›n dan ba s›l m›fl t›r. ÖZET Uygunsuz hiperseksüel davranışlar otizmi olan bireylerde sıklıkla bildirilmesinerağmen, yazında bu davranışların kontrol altına alınması ile ilgili yeterli bilgibulunmamaktadır. Bu yazıda otistik bozukluğu ve zekâ geriliği olan bir ergenolguda aşırı uygunsuz cinsel davranışların risperidon–paroksetin kombinasyonuile tedavisi sunulmuştur. Otizmi olan kişilerde aşırı cinsel uğraşlar aile ve çevreiçin stres kaynağı oluşturabilir, bu nedenle uygun tedavi yaklaşımları önemlidir.(Nö rop si ki yat ri Ar fli vi 2012; 49: 311-313)Anah tar ke li me ler: Otistik bozukluk, hiperseksüalite, seçici serotonin geri alıminhibitörleri, paroksetin, risperidonÇıkar çatışması: Yazarlar bu makale ile ilgili olarak herhangi bir çıkar çatışmasıbildirmemişlerdir.ABS TRACTInappropriate hypersexual behaviors have been frequently reported in subjectswith autism, however, literature on management of such behaviors in this groupis very limited. In this paper, we describe an adolescent with autistic disorderand mental retardation who developed severe inappropriate sexual behaviorsand has been treated successfully with risperidone-paroxetine combination.As presence of hypersexual behaviors in individuals with autism is a distressingfactor for their family and social environment, appropriate management seemsto be essential. (Arc hi ves of Neu ropsy chi atry 2012; 49: 311-313) Key words: Autistic disorder, hypersexuality, selective serotonin reuptakeinhibitors, paroxetine, risperidoneConflict of interest: The authors reported no conflict of interest related to this article.Doi: 10.4274/npa.y6173IntroductionAutistic disorder (AD) is characterized by qualitative impairmentin social interaction and communication, along with restricted,repetitive, and stereotyped patterns of behaviors, interests andactivities (1). In addition to these core features, individuals withautism frequently exhibit interfering behavioral symptoms, includingself-injury, irritability, aggression, severe tantrums, and hyperactivity.Over the past ten years, psychopharmacological studies havedemonstrated moderate success on management of thesebehavioral problems (2). Inappropriate sexual behaviors (ISB), suchas undressing and masturbating in public, touching his/her ownprivate body areas in public, and touching others inappropriatelyhave also been reported in individuals with AD (3,4). However,information on the treatment of ISB is very limited. Several researchers recommend beginning with behavioral,psychological and environmental interventions for the managementof ISB (5). However, in many cases, pharmacotherapy is often thepreferred first-line treatment because of its ease to administration,perceived efficacy and decreased use of staff time (6). Several drugsincluding leuprolide (a gonadotropin-releasing hormone analogue)(7), oral estrogen (8) and mirtazapine (4) are reported to be effectivefor the treatment of ISB in subjects with AD. Some reports indicate that selective serotonin reuptakeinhibitors (SSRIs), such as paroxetine (9), sertraline (10) andcitalopram (11) might be an alternative in controllinghypersexual behaviors. Several authors have suggested that theefficacy of SSRIs might be due to their anti-libidinal, anti-depressant, and/or anti-obsessional effects. Antipsychoticdrugs are also thought to decrease ISB by their dopamine-blocking effects and possibly by increasing prolactin levels,thereby decreasing sexual urges (12).We report an adolescent with autism and mental retardationwho had severe ISB and has been treated successfully withparoxetine and risperidone combination.CaseSK, a  17-year-old boy with AD and moderate mental retardation,was referred to our outpatient clinic for his aggressive, overactiveand self-injurious behaviors, and insomnia. The main complaint ofhis parents was his ISB. He was masturbating manually and/orrubbing himself everyday for nearly two hours and ejaculatingafterwards. He was touching breasts of his mother and kissing heron her lips. When his mother tried to prevent him he was becomingangry and irritable. Because he was doing same behaviors towardshis female teacher, his education program was discontinued. Thesebehaviors began nearly six months ago and increased within thepast two months. He had no sexual acts toward males including hisfather and other family members. We initiated risperidone and increased the dose up to 2 mg/day.His hyperactivity, irritability and self-injurious behaviors decreasedand his sleep disturbance diminished during the treatment withrisperidone. Although he was on this medication for two months, hisISB showed no improvement and we subsequently addedparoxetine 20 mg/day to his treatment regimen. Two weeks after theinitiation of paroxetine, his ISB disappeared totally. Thisimprovement was maintained during the six-month period when hewas on risperidone–paroxetine treatment and his parents reportedno substantial side effect. Discussion We described treatment of ISB in an adolescent with AD andmental retardation. It is not possible to attribute  the improvement inISB directly to paroxetine, as he was receiving both risperidone andparoxetine. However, there was no change in his sexual acts whenhe was on risperidone monotherapy. Here, we discuss the probablemechanisms to explain the mode of action of risperidone–paroxetine combination in the treatment of ISB.The mesolimbic system was found to have a substantial role insexual interest, and dopamine has been suggested as an importantneurotransmitter required for maintaining sexual desire. Selectiveserotonin reuptake blockade was found to reduce dopamineactivity in the mesolimbic system through the 5-HT2 receptors,suggesting a possible mechanism of action for SSRI - induceddesire dysfunction. Arousal dysfunction can also be explained bythe inhibition of peripheral spinal reflexes of the sympathetic andparasympathetic systems (13,14). Paroxetine is the most potentserotonin reuptake inhibitor of the antidepressants and hasdopamine (D2) blocking properties. It also inhibits nitric oxidesynthase activity which is required for penile vasodilatation anderection. Sexual dysfunction, such as erectile dysfunction, delayedejaculation, delayed orgasm, anorgasmia and diminished libido, isa common side effect of SSRIs that occurs in at least one third ofpatients (15). In this subject, efficacy of paroxetine on ISB might bedue to its direct anti-libidinal properties.Risperidone has been reported to be effective for the treatmentof irritability, aggression or self-injurious behavior in children andadolescents with autism (16). It binds with high affinity to 5-HT2,dopamine D2, and α1-adrenergic receptors. Ejaculatorydisturbances, diminished sexual desire, and erectile dysfunctionassociated with risperidone have been reported and severalmechanisms including central dopaminergic receptor blockade, α-adrenergic antagonism, and prolactin elevation have beenproposed (17,18,19,20). However, in our case, ISB were decreasedafter the addition of paroxetine to risperidone. One explanation forthis may be that paroxetine increased the plasma risperidoneconcentration (21).A relationship between depressive symptoms and ISB wassuggested (14,22). Because the diagnosis of depressiondepends primarily on communication skills, assessment ofdepression in non-verbal subjects with autism depends moreon the presence of vegetative signs than depressed mood.These signs include aggression, irritability, and sleep andappetite disturbances (23). Along with overactivity, irritability,and insomnia, ISB might be a manifestation of depression inthis case and paroxetine might be effective in controlling ISBthrough its antidepressant effect.Finally, at a neurobiological and phenomenological level, asignificant relationship between hypersexual behaviors andobsessive-compulsive disorder was suggested. The beneficialeffects of SSRIs on ISB can be explained by the effectiveness of thisclass of medications in obsessive-compulsive spectrum disorders(24). Several studies on subjects with AD reported that SSRIs mightbe an effective choice of treatment for repetitive, compulsive, andstereotypic behaviors (25). Paroxetine might be beneficial inameliorating ISB in the reported case by its anti-obsessional effect.Presence of ISBs in individuals with autism is a distressingfactor for their family and social environment. Therefore, appropriatemanagement seems to be essential. Further studies are needed toestablish the efficacy and safety of pharmacological approaches intreating such behaviors.References1. American Psychiatric Association: Diagnostic and Statistical Handbookand Mental Disorders, 4th edition (DSM-IV). Washington (DC): AmericanPsychiatric Association, 1994.2. Matson JL, Dempsey T. Autism spectrum disorders: Pharmacotherapy forchallenging behaviors. J Dev Phys Disabil 2008; 20:175-191.3. Stokes MA, Kaur A. High-functioning autism and sexuality: A parentalperspective. Autism 2005; 9:266-289.4. Coskun M, Karakoc S, Kircelli F, Mukaddes NM. Effectiveness ofmirtazapine in the treatment of inappropriate sexual behaviors inindividuals with autistic disorder. J Child Adolesc Psychopharmacol 2009;19:203-206.5. Koller R. Sexuality and adolescents with autism. Sexuality and Disability2000; 18:125-135.6. Harris L, Wier M. Inappropriate sexual behavior in dementia: a review ofthe treatment literature. Sex Disabil 1998; 16:205-217. 7. Realmuto GM, Ruble LA. Sexual behaviors in autism: Problems of definitionand management. J Autism Dev Disord 1999; 29:121-127.8. Jones MC, Okere K. Treatment of hypersexual behavior with oral estrogenin an autistic male. South Med J 2008; 101:959-960.Hergüner  et al.Risperidone-Paroxetine Combination for Inappropriate Sexual Behaviors in anAdolescent with Autism and Mental RetardationNö rop si ki yat ri Ar fli vi 2012; 49: 311-313Arc hi ves of Neu ropsy chi atry 2012; 49: 311-3133129. Stewart JT, Shin KJ. Paroxetine treatment of sexual disinhibition indementia. Am J Psychiatry 1997; 154:1474.10. Anneser JM, Jox RJ, Borasio GD. Inappropriate sexual behavior in a caseof ALS and FTD: successful treatment with sertraline. Amyotroph LateralScler 2007; 8:189-190.11. Tosto G, Talarico G, Lenzi GL, Bruno G. Effect of citalopram in treatinghypersexuality in an Alzheimer's disease case. Neurol Sci 2008; 29(4):269-270. 12. Wirshing DA, Pierre JM, Marder SR, Saunders CS, Wirshing WC. Sexualside effects of novel antipsychotic medications. Schizophr Res 2002;56:25-30.13. Serretti A, Chiesa A. Treatment-emergent sexual dysfunction related toantidepressants: a meta-analysis. J Clin Psychopharmacol. 2009;29:259-266.14. Kafka M. Psychopharmacologic treatments for nonparaphilic compulsivesexual behaviors. CNS Spectr 2000; 5:49-59.15. Werneke U, Northey S, Bhugra D. Antidepressants and sexual dysfunction.Acta Psychiatr Scand 2006; 114:384-397.16. West L, Waldrop J. Risperidone use in the treatment of behavioralsymptoms in children with autism. Pediatr Nurs 2006; 32:545-549. 17. Yılmazer EE, Güler J, İncesu C. Sexual side effects caused by psychotropicmedications. Archives of Neuropsychiatry 2011; 48(Suppl)1: 7-15 .18. Doğu B, Kocabıyık A, Karson F, Çıtak S, İncesu C. The intersexual differences ofsexual functions and prolactin levels in schizophrenia patients underantipsychotic medication. Archives of Neuropsychiatry 2011; 48 (Suppl 1): 35-38.19. Cutler AJ. Sexual dysfunction and antipsychotic treatment.Psychoneuroendocrinology 2003; 28 (Suppl) 1: 69-82.20. Wadoo O, Chalhoub N. Risperidone-induced sexual dysfunction in aprepubertal child - a case report. J Psychopharmacol 2009; 23: 727-728. 21. Saito M, Yasui-Furukori N, Nakagami T, Furukori H, Kaneko S. Dose-dependent interaction of paroxetine with risperidone in schizophrenicpatients. J Clin Psychopharmacol 2005; 25:527-532.22. Kafka MP. Sertraline pharmacotherapy for paraphilias and paraphilia-related disorders: an open trial. Ann Clin Psychiatry 1994; 6:189-195.23. Ghaziuddin M, Ghaziuddin N, Greden J. Depression in persons with autism:Implications for research and clinical care. J Autism Dev Disord 2002;32:299-306.24. Bradford JM. The neurobiology, neuropharmacology, and pharmacologicaltreatment of the paraphilias and compulsive sexual behavior. Can JPsychiatry 2001; 46:26-34. 25. West L, Brunssen SH, Waldrop J. Review of the evidence for treatment ofchildren with autism with selective serotonin reuptake inhibitors. J SpecPediatr Nurs 2009; 14:183-191.Nö rop si ki yat ri Ar fli vi 2012; 49: 311-313Arc hi ves of Neu ropsy chi atry 2012; 49: 311-313 313Hergüner  et al.Risperidone-Paroxetine Combination for Inappropriate Sexual Behaviors in anAdolescent with Autism and Mental Retardation

Combination of Risperidone and Paroxetine for Inappropriate Sexual Behaviors in an Adolescent with Autism and Mental Retardation

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