Isr J Relat Sci - Vol. 49 - No 4 (2012) Pharmacological Treatment of

Florence Thibaut , MD, PhD

Psychiatric Department, University Hospital Ch. Nicolle, INSERM U 614, Rouen, France

unclear despite years of research. Numerous psycho- logical, developmental, environmental, genetic, and Abstract organic factors have been discussed, but none of the Background: The psychiatrist’s main role is to provide theories fully explains paraphilic behaviors. The causes care to the paraphilic patient and to reduce personal are probably multifactorial, rendering treatment dif- distress. However, in cases of associated with ficult. Recidivism of sex offences is a major concern sexual offences, reducing paraphilic behavior is critical in in the treatment of paraphilias such as . an approach to preventing and reducing Most people recognize that incarceration alone will victimization. This review will focus on this specific not solve sexual violence. Indeed, treating the sexual population. offenders with a diagnosis of paraphilia is critical in an approach to preventing sexual violence and reducing Method: We discuss the recently published recom- victimization. This paper was intended to present and mendations for the treatment of paraphilias of the World summarize pharmacological treatment of paraphilias Federation of Societies of Biological Psychiatry which and will focus on paraphilias associated with a risk of were based on a review of the available literature about sexual offending such as pedophilia or . pharmacological treatment of paraphilias (1970-2010).

Results and Conclusion: , and mostly GnRH analogues, significantly reduce the intensity and Definition of Paraphilias frequency of deviant and behavior, although According to the Diagnostic and Statistical Manual informed is necessary in all cases. GnRH analogue Disorder, Fourth Edition, Text Revision (DSM IV-TR) treatment constitutes the most promising treatment or to the International Classification of Mental Diseases for sex offenders at high risk of sexual violence, such as (ICD 10th), paraphilias are defined as sexual disorders pedophiles or serial rapists. SSRIs remain an interesting which are characterized by “recurrent, intense, sexually option in adolescents, in patients with depressive or OCD arousing fantasies, sexual urges or behaviors, generally disorders, or in mild paraphilias such as exhibitionism. involving (1) non-human objects, (2) the suffering or Pharmacological interventions should be part of a more humiliation of oneself or one’s partner, or (3) chil- comprehensive treatment plan including dren or other nonconsenting individuals, that occur and, in most cases, behavior therapy. over a period of 6 months” (criterion A), which “cause clinically significant distress or impairment in social, occupational, or other important areas of functioning” (criterion B). DSM IV-TR describes eight specific disor- ders of this type (exhibitionism, fetishism, , pedophilia, sexual masochism, sexual sadism, voyeur- Treatment of paraphilias began during the late nine- ism and ) along with a residual teenth century at a similar time, though not directly category called “paraphilia not otherwise specified.” connected, to the new concept of sexual deviance as is not included in this classification, because it a medical condition. Etiology of paraphilias remains represents an heterogeneous behavior and an expression

Address for Correspondence: Prof. F. Thibaut, Psychiatric Dept., University Hospital Ch. Nicolle, 1 rue de Germont, 76031 Rouen, France [email protected] Potential conflict of interest: consultant for Debiopharm, Swiss

297 Pharmacological Treatment of Paraphilias of rather than a specific paraphilia. However, (GnRH) agonists. These compounds reduce a small number of rapists may meet the criteria for to very low levels and result in very low having a paraphilia (e.g., exhibitionism or pedophilia, levels of recidivism.There is also emerging evidence sexual sadism). Simply having paraphilia is not illegal, for the use of selective serotonin reuptake inhibitors but acting in response to certain paraphilic urges may (SSRIs)A pharmacological approach is essential in the be illegal and, in some cases, subjects the person with treatment of patients with severe paraphilias, but a paraphilia to severe sanctions. Conversely, not all sex psychotherapeutic context to the treatment is equally offenders meet the criteria for a paraphilic disorder. necessary (especially cognitive behavioral therapy). Some paraphilic subjects show evidence of comorbid major axis I mental illness which may require specific treatment, in most cases: affective disorders (3-95%), Ethical Considerations substance use disorders (8-85%), anxiety disorders Treatment for paraphilia should reduce or eliminate (3-64%) and less often: or other psychotic paraphilic fantasies and behaviors and decrease the level disorders (1-16%) (1-4), or other cognitive of distress of paraphilic subjects, permitting them to disorders (for review, 2). Attention deficit and hyper- live a normal sexual life, it should not have significant activity disorders (ADHD) may also represent 36% of side-effects and, most importantly, it should prevent the cases and eating disorders 10% of cases. Paraphilia may risk of acting out and victimization in case of pedophilia also be secondary to major axis I mental disorders (e.g., or exhibitionism, for example. The optimal treatment schizophrenia or manic episodes), in these cases, anti- for paraphilias is currently unavailable and treatments psychotic treatment and/or mood stabilizers are used already used decrease, in an unspecific manner, sexual as first line treatment. In cases of comorbid depressive arousal level and behavior. In the case of hormonal or anxiety disorders, antidepressant treatment may treatment, deviant but also non-deviant (if any) sexual be used as first line treatment or in combination with behavior and fantasies are largely decreased in most treatment if necessary. subjects. An explanation of the sexual side effects associ- Paraphilias may also occur within the context of ated with hormonal treatment and obtaining informed axis II disorders, the prevalence of personality disor- consent of the patient are considered by many authors ders may vary from 33 to 52% (among them antisocial a necessary prerequisite (2). is the most frequently observed) Paraphilic sex offenders referred for hormonal treat- (3-5). Heterogeneity of both the samples and the diag- ment are often the object of some external coercion, be nosis criteria may have contributed to the discrepancies it from a court decision or under the pressure of their observed in terms of prevalence between the studies. family, employers or other involved persons. From an These personality disorders may be addressed with ethical point of view, the patient may be subjected to psychological therapies such as behavioral or cognitive hormonal treatment only if all of the following condi- treatments. tions are met:

• The person has a paraphilic disorder diagnosed by a History of Treatments psychiatrist after a careful psychiatric examination. Surgical was first used in 1892 in Switzerland. • The person’s condition represents a significant risk By the 1940s, some attempts had been made to treat of serious harm to his health or to the physical or paraphilias using oestrogens, but due to feminiz- moral integrity of other persons. ing side-effects, this was supplanted in the 1960s by • No less intrusive treatment means of providing care medications reducing testosterone levels (cyproterone are available. acetate [CPA] is available in most countries, while in • The psychiatrist in charge of the patient agrees to the U.S., medroxyprogesterone acetate [MPA] is the inform the patient and receive his or her consent, drug of choice). Unlike surgical castration, the effects to take the responsibility for the indication of the of antilibido medication are reversible on discontinua- treatment and for the follow up including somatic tion. A more recent and promising development in the aspects with the help of a consultant endocrinolo- treatment of paraphilias at high risk of sexual offend- gist, if necessary. ing is the use of gonadotrophin hormone releasing In some cases, coerced treatment may be used in sex

298 Florence Thibaut offenders with paraphilia. The decision to subject a violence in incarcerated sex offenders. The comparison to coerced treatment should be taken by between studies is often difficult due to methodologi- a court or another competent body. The court or other cal differences between studies such as: heterogeneity competent body should: of paraphilias included; different durations of follow up; different definitions of recidivism (sexual or non • Act in accordance with procedures provided by law sexual offences); the presence or absence of previous based on the principle that the person concerned offences and/or previous convictions which (if any) should be seen and consulted; may increase the recidivism risk; the retrospective or • Not specify the content of the treatment (hormonal prospective design of the study; outpatients or prisoners or not) but force the person to comply with the treat- may be included which may interfere with treatment ment plan negotiated with the psychiatrist; compliance and with the recidivism risk; and finally, in • The decision to subject this person to hormonal most cases, statistical analyses are not conducted due treatment must be taken by a psychiatrist with the to small sample sizes and cross over designs. requisite competence and experience and not by the This review, based on the published recommenda- judge, after examination of the person concerned tions for the treatment of paraphilias of the World and only after his or her informed consent has been Federation of Societies of Biological Psychiatry (2), obtained. While treatment may facilitate improve- focused on pharmacological treatment of male adult ment and release or discharge, this may not be neces- paraphilic subjects at risk for sexual offending. Female sarily the case; sex offenders and female paraphilic subjects were • In some cases, failure of the offender to accept any excluded from this review. kind of treatment could lead to sanctions by the court.

The Belgian Advisory Committee on has Pharmacological Treatment published some guidelines in this field in 2006 (www. Paraphilia is not a synonym for sex offender. Conversely, health.fgov.be/bioeth). not all sex offenders suffer from a paraphilia. Paraphilic patients may only suffer from deviant sexual fantasies or urges and their deviant sexual behavior does not Methodological Limitations necessarily involve a non-consenting person or a child. Most reports on the treatment of paraphilias are case In these latter cases, treatment may open a possibility reports or series. In general, controlled treatment for prevention of acting out and victimization, thus efficacy studies in this field are extremely difficult to reducing individual and social burden of this disease. conduct for several reasons: those who suffer from We will focus the review on these latter cases. paraphilia rarely seek treatment voluntarily; ethical considerations would not easily allow performing The primary aims of the treatment are: double-blind placebo-controlled studies in paraphilic • To control paraphilic fantasies and behaviors (this subjects at risk of sex offending (such as pedophilic will help to decrease the risk of sexual offences espe- subjects or exhibitionists). cially in cases of pedophilia or rape); Methodological biases were observed in many stud- • To decrease the level of distress of the paraphilic ies. The small size of the samples and the short duration subject. of follow up make statistical analyses in most of the studies difficult. The outcome measurements usually In addition to psychological and behavioral therapies, used, such as self reports of conventional and paraphilic several pharmacological treatment options are avail- sexual activity, are subjective and not always reliable. able. The treatment choice will essentially depend on: (using audio or visual erotic stimuli videos including children, or adults) may • The patient’s previous medical history, be used but, according to Marshall and Fernandez • The patient’s compliance, (6), many methodological flaws may limit the use of • The intensity of paraphilic sexual fantasies and the this technique. In contrast, Howes (7) reported that risk of sexual violence. plethysmography may be used to assess the risk of In case of psychiatric , pharmacological

299 Pharmacological Treatment of Paraphilias and/or psychological treatment of these comorbidities (insight-oriented treatment, therapeutic communities, must be used. Hormonal treatment may be coprescribed other psychosocial programs) do not seem to reduce in case of lack of efficacy of adequate treatment of the recidivism (18). Moreover, the longer the observation psychiatric disease on deviant sexual behavior, in order periods, the higher the recidivism rates, leaving the to control paraphilic behavior. However, antiandrogen impression that the durability of psychological therapies treatment may increase psychotic symptoms (8). is limited. Randomized controlled trials are needed. The evaluation of a subject with paraphilia must No randomized controlled trials have documented include demographic characteristics (including being the efficacy of psychotropic medications such as antide- in contact with children in case of pedophilia), informa- pressants, antipsychotics or mood stabilizers, in para- tion about deviant and non-deviant sexual behavior and philic behaviors. Concerning the use of antipsychotics fantasies (type, frequency of sexual activity and fantasies, and mood stabilizers, there are only anecdotal reports presence or absence of sexual violence fantasies), past (for review see 2). In general their use is only recom- and current psychiatric history, history of previous sexual mended in case of psychiatric comorbidities treatment. and non-sexual offences, past history of sexual or physi- One double-blind non-controlled study comparing cal abuse, history of previous treatment of paraphilic clomipramine and desipramine was conducted in a behavior if any. The diagnosis of paraphilia includes: sample of 15 patients with different types of paraphilias. the number and type of paraphilias; with Only 8 patients completed the study and both medica- axis 1 or axis 2 of the DSM classification (especially tions equally reduced the paraphilic symptoms (19). addictive disorders or personality disorders), if any; The efficacy of SSRIs and clomipramine side effects comorbidity with somatic diseases if any. Impulsivity have limited the use of clomipramine in the treatment and are also important to assess. of paraphilic disorders. Some risk factors such as: comorbid psychiatric disorders, personality disorders, alcohol or substance SSRIs abuse, type of paraphilia (pedophilia with sexual interest The rationale for their use in these indications is based in boys), young age of onset of paraphilia, past history on their sexual side effects (inhibitory) and on the of sexual or physical abuse, previous history of sexual similarities between OCD and some paraphilic behav- offences may increase the risk of recidivism. Some of iors. Despite the increasing clinical use of SSRIs for these risk factors may be addressed during psychother- paraphilias and hypersexuality (for review see 20), apy. Some scales, like Static-99, Rapid Risk Assessment double-blind controlled trials with these agents are for Sexual Offence Recidivism, Sex Offender Risk still lacking. Appraisal Guide (SORAG), Sexual Violence Risk–20 Most of the available data are case reports and open and, more recently, Stable 2000 (using dynamic items) or retrospective studies and a systematic review con- have been proposed to evaluate these risks (9-12). In cerning the use of SSRIs in paraphilic subjects found meta-analyses all these instruments have shown a good only nine case series for analysis (21). The efficacy predictive validity, supporting the utility and predictive of SSRIs in the reduction of fantasies and paraphilic validity of actuarial risk assessment complementary to behaviors has previously been described for the treat- treatment efforts to reduce risk (13). Static risk assess- ment of pedophilia, exhibitionism, paraphilias in gen- ment tools that use historical or unchangeable risk eral, and fetishism (for a review of studies: variables (Static 99 or SORAG) are expected to be less 24 case reports, 3 retrospective studies including 76 accurate than dynamic tools in measuring risk changes patients, 5 open studies including 141 patients - see despite their overall strong predictive validity (14). 20). Pedophilia was clearly reported in 72 males and Antiandrogens or GnRH analogues, if necessary, sexual sadism was reported in one case. The dosages have to be prescribed by a physician after appropriate may be increased up to the dosages usually used in medical assessment and informed consent is required. OCD patients in case of lack or insufficiency of efficacy Meta-analyses and reviews concerning the efficacy at 4th or 6th week. The maximal duration of follow up of cognitive behavioral therapy for sex offenders with was 12 months but, in most cases, the duration was paraphilia indicate a modest reduction in recidivism less than 3 months. Mostly fluoxetine (20-80 mg/d) (15), but this is doubted by studies with longer follow- and sertraline (100-200 mg/d), but also paroxetine up periods (16, 17). However, the other approaches and fluvoxamine (300 mg/d) have shown efficacy in

300 Florence Thibaut reducing paraphilic sexual fantasies and behavior in Antiandrogen treatment these patients. Lack or insufficient therapeutic response Steroidal antiandrogens such as medroxyprogester- to fluoxetine was described in one retrospective study one acetate (MPA) or (CPA) have concerning patients with paraphilias (22) and a case progestogenic activities in addition to their effects as report concerning a patient with exhibitionism and antiandrogens, resulting in a decrease in circulating one with sexual sadism (23). levels of both testosterone and dihydrotestosterone Kafka and Prentky (24) used fluoxetine (30 mg/d-12 (DHT). These compounds interfere with the binding of weeks) in ten patients with paraphilias and ten patients DHT to receptors and they have been shown with hypersexual disorder and obtained a significant to block the cellular uptake of . reduction in unconventional sexual behavior. Another trial obtained 70% remission of paraphilias (n=13) and MPA paraphilia related disorders (n=11) after a two-stage Many paraphilic subjects received MPA treatment, treatment program of sertraline followed by fluoxetine although most studies were not controlled, and some (25). Fedoroff et al. (26) obtained almost 95% remission biases were observed (32). Among the thirteen studies of symptoms in a treatment combining fluoxetine and reported in Thibaut et al.’s review (2 ), three were double psychotherapy versus psychotherapy alone (n=51). One blind cross over studies (comparing MPA and placebo) trial noted a reduction in the total sexual outlet and the including 51 pedophiles and 8 sex offenders (33-35), nine time spent in paraphilic behaviors with a combination were open studies and one was a retrospective study (275 of fluoxetine and methylphenidate (n=26) (27). sex offenders) (36). Reduction of sexual behavior and A 12-week open label dose titrated study of sertraline complete disappearance of deviant sexual behavior and for the treatment of pedophilia (n=20) obtained reduc- fantasies were observed after one to two months in the tions in sexual drive, sexual fantasies, and other sexual majority of cases, in spite of maintained erectile function behaviors. These authors reported a reduction of sexual during plethysmography in some studies. In twelve cases, arousal patterns with suppression of deviant arousal, recidivism of deviant sexual behavior during MPA treat- coupled with a maintenance or relative increase in non- ment was reported using different criteria. Some studies pedophilic arousal in consenting sex with adults (28). A reported increased recidivism after MPA was stopped. retrospective study concerning 25 patients treated with The re-offence rate for 334 individuals taking depot sertraline for pedophilia or other paraphilias found a MPA was greater than with CPA, with a mean rate of significant decrease in paraphilic fantasies (29). Another 27% at the end of the follow-up (range 6 months to 13 study described 50% remission of paraphilic symptoms years) as compared with 50% before treatment (37). in an open label study using 100 mg of sertraline during Money et al. (38), using MPA, reported no reduction a mean follow up of 17 weeks (27). in non-sexual crimes in sex offenders with antisocial Efficacy of fluvoxamine has been described for behavior. McConaghy et al. (39) reported a lower effi- the treatment of 16 patients with pedophilia (29). cacy of MPA in juveniles. Escitalopram was also useful for the treatment of one Severe side effects (pulmonary embolism, weight gain, patient with transvestic fetishism (30). diabetes mellitus, transient increased levels of hepatic Paraphilias usually start at adolescence and are lim- enzymes, increased blood pressure, depressive disorders, ited to deviant fantasies related to between Cushing syndrome or adrenal suppression, etc.) were 12 and 18 years. SSRIs given at this stage could help to observed with MPA. The benefit/risk ratio did not favor prevent acting out of deviant behaviors (31). the use of MPA which was abandoned in Europe. Taking into account clinical data, Bradford and Fedoroff (31) and Kafka (25), recommended SSRIs CPA prescription in mild paraphilias especially in cases Many subjects received CPA treatment but only a few of exhibitionism, in juvenile subjects with paraphilia, studies were controlled, and some biases were observed. or in cases that have comorbidity with OCD and/or Among the ten studies aimed to evaluate CPA treat- depression. Though not formally approved, their off ment, two were double blind cross-over comparative label use has become a standard of care. studies (CPA vs ethinyl or MPA, 40, 41); two However, controlled studies demonstrating efficacy were double blind cross-over studies comparing CPA are needed. with placebo (42, 43); one was a single blind study, CPA

301 Pharmacological Treatment of Paraphilias vs placebo (44); and five were open studies. In these In total, 75 male subjects (aged from 15 to 57 years) with comparative studies, CPA, ethinyl-estradiol and MPA paraphilia were included in two prospective open studies showed similar efficacy and CPA was superior to placebo. (n=41), two retrospective studies (n=30 + 3) and one case CPA (50 – 300 mg/day per os or i.m. 300 – 600 mg report. These subjects were receiving depot triptorelin every 1 or 2 weeks) was associated with a significant for some months to 7 years (3.75 mg/month). During decrease of self-reported sexual fantasies or activity and triptorelin treatment, no deviant sexual behavior was a disappearance of deviant sexual behavior in about observed and no sexual offences were committed except in 80 – 90% of cases within 4-12 weeks. The efficacy was one case (45). One third of cases (13/41 cases) had previ- maintained as long as the treatment was used and in ously received CPA without efficacy. No plethysmography some cases for up to 8 years. was used. However, in all cases but one, triptorelin was Several studies examined the re-offence rates of successful and the deviant sexual behavior completely individuals taking CPA. A mean rate of 6% was found disappeared during GnRH analogue treatment. at the end of the follow-up period (less than the rate In Czerny et al.’s study (48), similar efficacies were observed with MPA), as compared with 85% before observed with CPA and triptorelin. treatment, with a duration of follow up ranging from 2 months to 4.5 years. Many re-offences were committed by individuals who did not comply with therapy (37). Three open studies using leuprorelin (1- or 3-month Plasma testosterone levels were moderately decreased formulations) were performed in patients with para- and could not be used as a marker of compliance. philic behaviors (48-53). In addition, CPA has antiaggressive and anxiolytic Forty-five male subjects (20 to 61 years old) with para- properties that may be of interest in these populations. philias received leuprolide acetate; they were included CPA has shown positive but inconsistent results in in three prospective studies including a cross-over study the treatment of paraphilic subjects. In some countries, (52) (28 cases), one naturalistic study comparing CPA the oral form is the only form available and treatment and GNRH analogues (48) (58 cases, 11 with leuprorelin compliance may be erratic. Because of a substantial acetate) and 15 case reports. Maximal duration of follow number of side effects (in addition to those related up was 57 months (mean duration about 1 year). to hypoandrogenism), including gynecomastia (20%, In addition to the outcome measures used, such as which is not always completely reversible), weight gain, self report of deviant and non-deviant sexual behavior depressive mood, thrombo-embolic phenomena and and fantasies (type, frequency, intensity) or testosterone hepatocellular damage (severe cases < 1%), there was a and LH levels, plethysmography was used in Schober need for other effective treatments with fewer side effects. et al.,s study (53). However, in one case report (54) the patient relapsed while treated with leuprorelin treatment GnRH analogues and committed a sex offence. Gonadotrophin-releasing hormone (GnRH) analogues In conclusion, there were no controlled studies, and act initially at the level of the pituitary to stimulate some biases were observed. The efficacy observed in LH release, resulting in a transient increase in serum these open studies, though, was clear. In most cases, testosterone levels (flare-up). After an initial stimula- subjects were previously treated with psychotherapy or tion, GnRH analogues cause rapid desensitization of other antiandrogens such as CPA without efficacy. In GnRH receptors, resulting in reduction of LH and most of the cases, CPA or flutamide were concurrently testosterone to castrate levels within 2 to 4 weeks. Two used for the first weeks of GnRH agonist in order to analogues of the gonadotrophin-releasing hormone prevent the behavioral consequences of a flare-up effect were preferentially used in paraphilic subjects: trip- and concurrent psychotherapy was used. Concomitantly torelin and leuprorelin. They were developed as 1- or to the rapid decrease of testosterone levels, a reduction 3-month formulations. of non-deviant sexual behavior was observed and devi- ant sexual fantasies disappeared with a maximal effect Triptorelin after 1 or 3 months in more than 90% of cases. Two open prospective studies and one retrospective The duration of treatment and the conditions of study using triptorelin 1-month formulation were per- treatment interruption remain controversial. For some formed in sex offenders or paraphilic subjects(45- 47). patients, a life-long treatment may be necessary.

302 Florence Thibaut

Among the side effects observed with GnRHa, bone violence was proposed (2) . Medical survey (including mineral loss is the most problematic side effect and needs osteodensitometry at least every two years) is necessary to be carefully checked at least every two years and even during hormonal treatment (for detailed information, 2). more frequently in case of osteoporosis. Calcium and Until now, there have been no pharmacological stud- vitamin D or biphosphonates may be prescribed in the ies conducted in sexual murderers, and in women, only event of osteoporosis (for a review of these side effects few case reports have been described. see 2, 32). Decreased values of vertebral and femoral Hormonal agents cannot be easily used in the treat- bone densities (0.95 and 0.8 g/cm³, respectively), without ment of juvenile sex offenders with paraphilia owing to clinical signs but requiring medical supervision, were possible interference with the development of . recorded during the third year of triptorelin treatment In these subjects, behavioral therapy and SSRIs are the in one patient aged 27, among 6 cases in Thibaut et al.’s first choice treatment (for review, 59). study (45) (normal ranges: 1.15 ± 0.15 and 0.9 ± 0.1 g/ cm³, respectively). In Rösler and Witztum study (47) two patients among 30 cases had progressive demin- Duration of Treatment eralization and were given oral calcium and vitamin D Paraphilia is a chronic disorder. According to the major- supplements after completing 24 months of triptorelin ity of authors, a minimal duration of treatment of three therapy. Hoogeveen and Van der Veer (55) reported bone to five years for severe paraphilia with a high risk of demineralization in one patient aged 35 years after 37 sexual violence is necessary. Hormonal treatment must months of triptorelin treatment in spite of biphospho- not be stopped abruptly. In case of mild paraphilia, a nates and calcium treatment. Krueger and Kaplan (51) treatment of at least two years might be used, after which observed three cases of demineralization at 35 and 57 the patient must be carefully followed up following months respectively among 12 patients aged from 20 treatment stopping. Treatment must be resumed in to 48, receiving leuprolide acetate. Czerny et al. (48) case of recurrence of paraphilic sexual fantasies. reported one case of bone mineral loss among 29 patients receiving GnRH analogues for a mean duration of 10 months. Dickey (56) observed demineralization after Conclusion three years of leuprolide acetate treatment in a 28-year-old In paraphilic subjects, pharmacological interventions patient. Calcium and vitamin D were used. Grasswick should be part of a more comprehensive treatment plan and Bradford (57) focused their study on bone mineral including psychotherapy and, in most cases, behavior survey and reported demineralization in 2/4 cases with therapy (20, 60). In paraphilic subjects at high risk of CPA, 1/1 with leuprorelin and 2/2 with surgical castra- victimization, pharmacological treatment should even be tion, the follow-up duration was four years. used as first line treatment. Not every sex offender with patients may also complain of hot flushes, asthenia, paraphilia is a candidate for hormonal treatment, even if it nausea, weight gain (2–13%), transient pain or site has the benefit of being reversible once discontinued. For reaction at the site of injection, decreased and paraphilias, characterized by intense and frequent deviant body hair growth, blood pressure variations, decreased sexual desire and arousal, which highly predispose the glucose tolerance, decreased testicular volume (4–20%), patient to severe paraphilic behavior (such as pedophilia episodic painful , diffuse muscular tender- or serial rapes), a hormonal intervention may be needed. ness, sweating, depressive symptoms and finally mild Antiandrogens or GnRH analogues have to be prescribed gynecomastia (2-7%) (for review of their frequency of by a physician, after appropriate medical assessment, and occurrence see 32, 48). informed consent must be obtained. GnRH analogues When properly administered, with an appropriate reduce testosterone levels, more dramatically and more protocol in place to detect and treat side effects should consistently, and produced less variable results in the they develop, GnRHa treatments constitute no more treatment of paraphilic behaviors than MPA or CPA. or less of a risk than most other forms of frequently GnRH analogue treatment probably constitutes the most prescribed pharmacological agents (58). promising treatment for sex offenders at high risk of An algorithm which distinguishes six levels of treat- sexual violence, such as pedophiles or serial rapists. ment for different categories of paraphilias according In contrast, SSRIs remains an interesting option in to the severity of the paraphilia and the risk of sexual patients with depressive or OCD disorders, in mild

303 Pharmacological Treatment of Paraphilias paraphilias such as exhibitionism or in juvenile para- Psychiatry 2006;17: 442–466. 19. Kruesi MJ, Fine S, Valladares L, Phillips RA, Jr., Rapoport JL. Paraphilias: philic subjects. A double-blind crossover comparison of clomipramine versus Collaborative studies including large cohorts of desipramine. Arch Sex Behav 1992 ;21: 587-593. well-defined paraphilic subjects with long durations 20. Garcia F, Thibaut F. Current concepts in the pharmacotherapy of of follow up are clearly needed. paraphilias. Drugs 2011;71:771-790. 21. Adi Y, Ashcroft D, Browne K, Beech A, Fry-Smith A, Hyde C. Clinical effectiveness and cost–consequences of selective serotonin reuptake Acknowledgements inhibitors in the treatment of sex offenders, Health Technol Assess The author thanks Prof. Rösler for his valuable advice regarding this 2002;6:1-66. manuscript and Richard Medeiros, Medical Editor, Rouen University Hospital 22. Stein DJ, Hollander E, Anthony DT, Schneier FR, Fallon BA, Liebowitz for editing the final manuscript. MR, et al. Serotonergic medications for , sexual addictions, and paraphilias. J Clin Psychiatry 1992;53: 267-271. 23. Casals-Ariet C, Cullen K. Exhibitionism treated with clomipramine. References Am J Psychiatry 1993;150: 1273-1274. 24. Kafka MP, Prentky R. Fluoxetine treatment of non-paraphilic sexual 1. Marshall WL. Diagnostic problems with sexual offenders In: Marshall addictions and paraphilias in men. J Clin Psychiatry 1992;53: 351–358. WL, Fernandez YM, Marshall LE, Serran GA, editors. Sexual offender treatment: Controversial issues. Chichester: Wiley, 2006: pp. 33-43. 25. Kafka MP. Sertraline pharmacotherapy for paraphilias and paraphilia- related disorders: An open trial. Ann Clin Psychiatry 1994;6: 189-195. 2. Thibaut F, Torres de la Barra F, Gordon H, Bradford JMW, Cosyns P, the WFSBP Task Force on Sexual Disorders. The World Federation of 26. Fedoroff JP. Antiandrogens vs serotonergic medications in the treatment Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological of sex offenders: A preliminary compliance study. Can J Hum Sexuality Treatment of Paraphilias. World J Biol Psychiatry 2010;11: 604-655. 1995;4: 111–123. 3. Kafka MP, Prentky R. Attention-deficit/hyperactivity disorder in males 27. Kafka MP, Hennen J. Psychostimulant augmentation during treatment with paraphilias and paraphilia-related disorders: A comorbidity study. with selective serotonin reuptake inhibitors in men with paraphilias and J Clin Psychiatry 1998,59: 388-396. paraphilia-related disorders: A case series. J Clin Psychiatry 2000;61: 4. Dunsieth N, Nelson M, Brusman–Lovens L Holcomb JL, Beckman D, 664-670. Welge JA, Roby D, Taylor P Jr, Soutullo CA, McElroy SL. Psychiatric and 28. Bradford JM, Martindale JJ, Goldberg M, Greenberg D, Lane JG. legal features of 113 men convicted of sexual offenses. J Clin Psychiatry Sertraline in the treatment of pedophilia: An open label study. New 2004,65: 293-300. Research Program Abstracts, NR 441, APA Annual Meeting 1996, 5. Raymond N, Coleman E, Ohlerking F. Psychiatric comorbidity in Miami, FL, 1996. pedophilic sex offenders. Am J Psychiatry 1999,156: 786-788. 29. Greenberg DM, Bradford JM, Curry S, O'Rourke A. A comparison of 6. Marshall WL, Fernandez YM. Phallometric testing with sexual offenders: treatment of paraphilias with three serotonin reuptake inhibitors: a Limits to its value. Clin Psychol Rev 2000,20: 807-822. retrospective study. Bull Am Acad Psychiatry Law 1996;24: 525-532. 7. Howes RJ. Measurement of risk of sexual violence through phallometric 30. Phahaj SK. Escitalopram treatment of transvestic fetishism: Case report. testing. Leg Med (Tokyo) 2009, S1:368-369. German J Psychiatry 2004;7: 20-21. 8. Thibaut F, Kuhn JM, Colonna L. A possible antiaggressive effect of 31. Bradford J, Fedoroff P. Pharmacological treatment of the juvenile sex cyproterone acetate. Br J Psychiatry 1991; 159: 298-299. offender. In: Barbaree H, Marshall W, editors. The juvenile sex offender. 9. Hanson RK. The development of a brief actuarial risk scale for sexual Second Edition. U.S.A.: Guilford, 2006: Chapter 16, pp. 358-382. offense recidivism (User Report No. 1997-04). In: DotSGo, editor. 32. Guay DRP. Drug treatment of paraphilic and non paraphilic sexual Ottawa, 1997. disorders. Clin Ther 2009;31: 1-31. 10. Boer DP, Hart SD, Kropp PR, Webster CD. Manual for the Sexual 33. Wincze JP, Bansal S, Malamud M. Effects of medroxyprogesterone acetate Violence Risk–20: Professional guidelines for assessing risk of sexual on subjective arousal, arousal to erotic stimulation, and nocturnal penile violence. Vancouver: The Law & Policy Institute, 1997. tumescence in male sex offenders. Arch Sex Behav 1986,15: 293-305. 11. Hanson RK, Thornton D. Static-99: Improving actuarial risk assessments for 34. Hucker S, Langevin R, Bain J. A double-blind trial of sex drive reducing sex offenders (User Report No. 1999-02). In: DotSGo, editor. Ottawa, 1999. medication in pedophiles. Ann Sex Res 1988, 1: 227-247. 12. Quinsey VL, Harris GT, Rice ME, Cormier C. Violent offenders: 35. Kiersch TA. Treatment of sex offenders with Depo Provera. Bull Am Appraising and managing risk. Washington, DC: American Psychological Acad Psychiatry Law 1990,18: 179-187. Association, 2006. 36. Maletzky BM, Tolan A, McFarland B. The Oregon depo-Provera program: 13. Hanson RK, Morton-Bourgon KE. The accuracy of recidivism risk A five-year follow-up. Sex Abuse 2006,18: 206-316. assessments for sexual offenders: A meta-analysis of 118 prediction 37. Meyer JW, Cole CM. Physical and of sex offenders: studies. Psychol Assess 2009; 21: 1-21. A review. J Off Rehab 1997;25: 1–18. 14. Olver ME, Wong SCP. A comparison of static and dynamic assessment 38. Money J, Wiedeking C, Walker P, Migeon C, Meyer W, Borgaonkar D. 47, of sexual offender risk and need in a treatment context. Criminal Justice XYY and 46, XY males with antisocial and/or sex offending behaviour: and Behaviour 2011;38: 113-126. antiandrogen therapy plus counselling. Psychoneuroendocrinology 15. Losel F, Schmucker M. The effectiveness of treatment for sexual offenders: 1975,1: 165-178. A comprehensive meta-analysis. J Exp Criminol 2005;1: 117-146. 39. McConaghy N, Blaszczynski A, Armstrong MS. Resistance to treatment 16. Kenworthy T, Adams CE, Bilby C, Brooks-Gordon B, Fenton M. of adolescent sex offenders. Arch Sex Behav 1989,18: 97-107. Psychological interventions for those who have sexually offended or 40. Bancroft J, Tennent G, Loucas K, Cass J. The control of deviant sexual are at risk of offending. Cochrane Database Syst Rev 2004;3: CD 004858. behaviour by drugs. I. Behavioural changes following estrogens and 17. Maletzki BM, Steinhauser C. A 25-year follow-up of cognitive-behavioural antiandrogens. Br J Psychiatry 1974;125: 310-315. therapy with 7,275 sexual offenders. Behav Modif 2002;26: 123-147. 41. Cooper AJ, Sandhu S, Losztyn S, Cernovsky Z. A double-blind placebo 18. Brooks-Gordon B, Bilby C, Wells H. A systematic review of psychological controlled trial of medroxyprogesterone acetate and cyproterone acetate interventions for sexual offenders I. Randomised control trials. J Forensic with seven pedophiles. Can J Psychiatry 1992;37: 687-693.

304 Florence Thibaut

42. Cooper AJ. A placebo controlled trial of the antiandrogen cyproterone 52. Schober JM, Kuhn PJ, Kovacs PG, Earle JH, Byrne PM, Fries RA. acetate in deviant hypersexuality. Compr Psychiatry 1981;22: 458-465. Leuprolide acetate suppresses pedophilic urges and arousability. Arch 43. Bradford JM, Pawlak A. Double-blind placebo crossover study of Sex Behav 2005;34: 691-705. cyproterone acetate in the treatment of the paraphilias. Arch Sex Behav 53. Schober JM, Byrne P, Kuhn PJ. Leuprolide acetate is a familiar drug 1993;22: 383-402. that may modify sex-offender behaviour: The urologist's role. BJU Int 44. Cooper AJ, Cernovsky Z. The effects of cyproterone acetate on sleeping 2006;97: 684-686. and waking penile in pedophiles: Possible implications for 54. Briken P, Hill A, Berner W. A relapse in pedophilic sex offending and treatment. Can J Psychiatry 1992;37: 33-39. subsequent suicide attempt during luteinizing hormone-releasing 45. Thibaut F, Cordier B, Kuhn JM. Effect of a long-lasting gonodatrophin hormone treatment. J Clin Psychiatry 2004,65: 1429. hormone-releasing hormone agonist in six cases of severe male paraphilia. 55. Hoogeveen GH, Van Der Veer E. Side effects of pharmacotherapy on Acta Psychiatr Scand 1993;87: 445-450. bone with long-acting gonadorelin agonist triptorelin for paraphilia. J 46. Thibaut F, Cordier B, Kuhn J. Gonadotrophin hormone releasing Sex Med 2008,5: 626-630. hormone agonist in cases of severe paraphilia: A lifetime treatment? 56. Dickey R. Case report: the management of bone demineralization Psychoneuroendocrinology 1996;21: 411-419. associated with long term treatment of multiple paraphilias with long 47. Rösler A, Witztum E. Treatment of men with paraphilia with a long- acting LHRH agonists. J Sex Marital Ther 2002,28: 207-210. acting analogue of gonadotropin-releasing hormone. N Eng J Med 57. Grasswick LJ, Bradford JM. Osteoporosis associated with the treatment 1998;338: 416-422. of paraphilias: A clinical review of seven case reports. J Forensic Sci 48. Czerny JP, Briken P, Berner W. Antihormonal treatment of paraphilic patients 2003,48: 849-855. in German forensic psychiatric clinics. Eur Psychiatry 2002;17: 104-106. 58. Berlin F. Sex offender treatment and legislation. J Am Acad Psychiatry 49. Briken P, Nika E, Berner W. Treatment of paraphilia with luteinizing Law 2003;31: 510-513. hormone-releasing hormone agonists. J Sex Marital Ther 2001;27: 45-55. 59. Gerardin P, Thibaut F. Epidemiology and treatment of juvenile sexual 50. Briken P. Pharmacotherapy of paraphilias with luteinizing hormone- offending. Paediatric Drugs 2004;6: 79-91. releasing hormone agonists. Arch Gen Psychiatry 2002;59: 469-470. 60. Hanson RK, Morton-Bourgon KE. The characteristics of persistent 51. Krueger RB, Kaplan MS. Depot-leuprolide acetate for treatment of sexual offenders: A meta-analysis of recidivism studies. J Consult Clin paraphilias: A report of twelve cases. Arch Sex Behav 2001;30: 409-422. Psychol 2005,73: 1154-1163.

List of reviewers for Israel Journal of Psychiatry, 2012 The Editors would like to thank the following for their contribution as reviewers of manuscripts during 2012

Henry Abramovitch Silvana Fennig Arturo Lerner Joav Merrick Gal Shoval Alan Apter Laurence French Vladimir Lerner David Miklowitz Emi Shufman Rachel Bachner-Melman David Galameau Andrea Letamendi Chanoch Miodownik Michael Silverman Moshe Bensimon Annette Gallant Itzhak Levav Piper Myers Zahava Solomon Oded Ben-Arush Marc Gelkopf Stephen Levine Eitan Nahshoni Eli Somer Howard Berger Lucas Giner Dafna Levinson Ora Nakash Daniel Stein Avi Bleich Doron Gothelf Alon Liberman Shaul Navon Elian Sommerfeld Ehud Bodner Michal Granot Pesach Lichtenberg Ross Norman Jennifer Torr Gabrielle Carlson Ilanit Hasson-Ohayon Gadi Lubin Femi Oyebode Tom Trauer Efrat Dagan Sol Jaworowski Paul Lysaker Torsten Passie Anne-Marie Ulman Adam Darnell Sean Kidd Iris Manor Alan Pincus Carol Veneziano Giancarlo Dimaggio Arad Kodesh Saed Maree Norman Relkin Knut Wester Zipi Dolev Anatoly Kreinin Cherie Marvel Jamie Ringer Zvi Zemishlany Rimona Durst Sefi Kronenberg James Megna Abraham Rudnick Gadi Zerach Adrienne Einarson Ellen Leibenluft Yuval Melamed Michael Seto Avner Elizur Vadim Leibovitch Shlomo Mendlovic Leah Shelef

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