Pharmacologic Treatment of Sex Offenders With Paraphilic Disorder
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- Garcia, F.D., Delavenne, H.G., Assumpção, A.F.A. et al. Curr Psychiatry Rep (2013) 15: 356. doi:10.1007/s11920-013-0356-5
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Sexual offending is both a social and a public health issue. Evidence demonstrates that a combination of pharmacological and psychotherapeutic approaches may reduce or even eliminate deviant sexual behavior in sex offenders with paraphilic disorders. In this article, we will review pharmacological treatment options for sex offenders with paraphilias. Both serotonin selective reuptake inhibitors (SSRIs) and antiandrogen treatments have been used with reported success in decreasing recidivism. SSRIs have been used in mild types of paraphilias and juvenile paraphilias. Antiandrogen treatments seem to be effective in severe sex offenders with paraphilic disorders in order to reduce victimization. Combined pharmacological and psychotherapeutic treatment is associated with better efficacy. Imaging studies may improve the knowledge of paraphilic disorders and the mechanisms of action of current treatments. In spite of existing evidence, there is a need for independent, large-scale and good quality studies assessing the long-term efficacy and tolerance of treatments.
KeywordsSex OffenderParaphiliaPedophiliaPharmacologic TreatmentSelective Serotonin Reuptake InhibitorSSRIAndrogen Deprivation TherapySteroidal Antiandrogen TreatmentsMedroxyprogesterone AcetateMPACyproterone AcetateCPAGonadotropin-Releasing Hormone AnalogGnRHaGoserelinLeuprorelinTriptorelinSexual DisordersPsychiatry
Sex offending is a major public health concern. There are significant levels of psychiatric morbidity in survivors of sexual offences. This has been indirectly demonstrated by significant losses of quality of life and productivity and by increased mental health care expenses observed in victims . Although the prevalence of sexual offences can only be estimated using indirect data, such as the number of incarcerations related to sex offending, international data have suggested an increase in the recognition of the widespread prevalence of sexual offences [2, 3]. Comprehensive treatment of offenders with paraphilic disorders may be an alternative to incarceration if it reduces recidivism. Not all sex offenders have a paraphilic disorder, and not all individuals with a paraphilic disorder are sex offenders. In this article, current pharmacologic treatment of sexual offenders with paraphilic disorders will be reviewed, and the authors will update information published in their previous reviews on this topic [4, 5••, 6••].
Comprehensive Treatment Programs
Follow-up data have suggested that incarceration alone does not reduce sexual violence. Several meta-analyses have reported an increase in reoffending rates ranging from 15 % after 5 years of follow-up to 27 % after 20 years in the absence of treatment [7–10]. Sex offenders who are sexually attracted to unrelated boys present a higher risk of reoffending (35 % at 15 years) than those who are exclusively interested in unrelated girls (16 % at 15 years) as compared with incestuous sex offenders (13 % at 5 years) .
A cost-benefit analysis has demonstrated that effective treatment of sex offenders with paraphilic disorders is a cost-effective approach that reduces health care expenses . This inference is based on a direct comparison of the treatment costs with the incarceration costs without counting the cost of potential reoffences. Moreover, a recent meta-analysis evaluating controlled trials conducted in sexual offenders with paraphilic disorders concluded that treatment is associated with a reduction of in recidivism rates of about one third .
Prior to treatment, each individual should be carefully examined by at least one mental health professional in order to identify and evaluate a paraphilic disorder (especially the number and type of paraphilias and the previous response to treatment if any) and if necessary to adequately treat offenders who are suffering from a major mental illness or intellectual disability.
Comprehensive treatment plans for sexual offenders with paraphilic disorders has to be individualized and adaptable. It should include both pharmacological and psychotherapeutic approaches. The combination of pharmacological and psychotherapeutic treatments is reported to be more effective than either used alone [6••, 9, 14, 15].
Pharmacological interventions should be part of a more comprehensive treatment plan including psychotherapy and, in most cases, cognitive behavior therapy . Successful treatment of sex offenders with paraphilic disorders opens the possibility of preventing the commission of sex crimes thus reducing individual and social burden . Moreover, reducing libido seems to make some offenders with paraphilic disorder more responsive to psychotherapy . The goal of the treatment is to reduce or suppress deviant sexual fantasies and behaviors, preclude sexual urges, which may reduce the risk of further victimization, while maintaining and enhancing normophilic sexual interests [6••]. Ideally, this treatment has minimal or no adverse side effects . Current treatments decrease, in an unspecific manner, deviant (criminal) sexual arousal level and behavior.
Three major classes of medications can be used for the treatment of sexual offenders with a paraphilic disorder in association with psychotherapy: antidepressants, steroidal antiandrogens and gonadotropin-releasing hormone (GnRH) analogs or agonists.
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin inhibits sexual arousal and reduces orgasmic and ejaculatory capacities . Sexual effects of serotonin are receptor type dependent (i.e., the activation of 5-HT1A receptors accelerates ejaculation, the activation of 5-HT2C receptors inhibits ejaculation) . Low cerebrospinal fluid (CSF) concentrations of 5-HIAA (5-hydroxyindoleacetic acid), a serotonin metabolite, were reported in men with impulsive aggression [20, 21]. Some evidence for an upregulation of 5-HT2A and 5-HT2C was described in one study evaluating eight pedophiles .
Selective serotonin reuptake inhibitor treatment (SSRI) may be a pharmacological alternative to androgen deprivation therapy . Four possible mechanisms of action of SSRIs may be useful in the treatment of sex offenders: (1) non-specific inhibition of sexual interest; (2) reduction of impulsiveness; (3) decrease of obsessive-compulsive symptoms; (4) treatment of concurrent depressive symptoms .
SSRIs have demonstrated clinical efficacy for the treatment of sexual offenders with a paraphilic disorder in a systematic review of the available evidence. Although the quality of available studies is limited by methodological biases (e.g., subjective outcomes, insufficient follow-up duration and heterogeneity of the samples) . Patients presenting with exhibitionism, compulsive masturbation and pedophilia without acting on their interests seemed to most benefit from SSRI treatments [5••, 26]. Compliance was higher with SSRIs as compared to antiandrogen treatment in sex offenders . Moreover, SSRIs seem most effective in sex offenders with a diagnosed paraphilia who report difficulty resisting sexual urges or who have subjective distress .
The most studied SSRIs for the treatment of paraphilias and sex offenders are fluoxetine and sertraline [5••]. SSRIs are typically initiated in low doses. The doses needed to achieve satisfactory clinical efficacy are close to the doses used to treat obsessive-compulsive disorders. Of studies describing the use of fluoxetine, the most frequently used strategy was dose titration until a significant reduction or the absence of symptoms was reached. The mean used dose of fluoxetine was 40 mg (range 20-80 mg) and the time to treatment switch was 4 to 6 weeks [5••]. Long-term randomized controlled studies are needed to confirm SSRIs utility in the treatment of sex offenders with paraphilias.
Androgen Deprivation Therapy
Androgens, like testosterone and dihydrotestosterone, influence sexual behavior, particularly in men. Moreover, androgens enhance the sensitivity of dopaminergic receptors and modulate 5-HT1A and 5-HT1B receptor effects on impulsive aggression .
A significant reduction of androgen effects is the cornerstone of hormonal treatment in sex offenders with paraphilic disorders . For example, surgical castration has been shown to be associated with reduced recidivism rates of sex offenders . Pharmacological antiandrogen treatment is a reversible and more ethically acceptable treatment.
Not every sex offender is a candidate for antiandrogen treatment, even if it has the benefit of being reversible once discontinued. For sex offenders presenting with paraphilias, characterized by intense and frequent deviant sexual desire and arousal, which highly predispose the patient to severe paraphilic behaviors (such as pedophilia or serial rapes), a hormonal intervention may be needed. In subjects with a paraphilia at high risk of victimization, pharmacological treatment in combination with psychotherapy should be used as a first line treatment option [6••].
Steroidal Antiandrogen Treatments
Medroxyprogesterone Acetate (MPA)
MPA is a progesterone derivative that acts as a progestogen and, like testosterone itself, exerts negative feedback on the hypothalamic-pituitary axis, resulting in a decrease in both gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) release. More than 600 cases have been reported among different studies including 12 case reports, 13 open or controlled studies, including three double-blind cross-over studies comparing MPA and placebo. The oral dosage ranges are 100 to 400 mg per day and parental dosage starts at 300 mg given weekly and then is titrated in frequency and dosage to achieve total and free plasma androgen levels that are prepubertal . In most cases, reduction of sexual behavior and complete disappearance of deviant sexual behavior and fantasies is observed after 1–2 months of treatment.
Pulmonary embolism is the most severe side effect reported , and no studies have evaluated bone mineral loss using osteodensitometry. Other adverse effects of MPA are: weight gain, headache, nausea, asthenia, gynecomastia, lethargy, insomnia, leg cramps, spermogram abnormalities, erectile dysfunction, increased blood pressure, hot flushes, diabetes mellitus, gallstones, transient increased levels of hepatic enzymes, depressive syndrome, adrenal suppression, decrease in testicular volume, Cushing’s syndrome and thromboembolic phenomena .
Cyproterone Acetate (CPA)
Cyproterone acetate (CPA) is a synthetic steroid, similar to progesterone, which has progestational and antiandrogenic actions. CPA acts through its binding to a variety of androgen receptors, including brain receptors, blocking intracellular testosterone uptake and metabolism. CPA is a competitive inhibitor of testosterone and dihydrotestosterone (DHT) at androgen receptor sites. CPA has a strong progestational action causing the inhibition of GnRH secretion and a decrease in both GnRH and LH release [34, 35]. CPA is authorized in more than 20 countries for the moderation of sexual drive in adult men and is the most widely studied pharmacological agent for treating sex offenders with paraphilic disorders .
Concerning the efficacy of CPA, more than 700 men have been included in different studies (for review of the studies see [6••]). Most of the studies reported that CPA intramuscular (i.m.) injection depot form 200-400 mg once weekly or every 2 weeks during a follow-up of 4 to 12 weeks caused a drop in reported sexual fantasies and activity in 80 to 90 % of subjects. At the end of the follow-up, the average rate of reoffending was 6 % after treatment compared to 85 % without treatment. Most of the re-offenses were committed by subjects who did not follow the treatment prescription .
CPA can be prescribed in either intramuscular (i.m.) depot form, 100 mg/ml (200–400 mg once weekly or every 2 weeks) or per os in tablets of 50 and 100 mg (50–200 mg/day). Side effects are related to hypoandrogenism: asthenia, sleep disorders, depressive symptoms or disorders, hot flushes, hair loss and pilosity, decreased sebum excretion, leg cramps, spermatogenesis reduction (reversible), erectile dysfunction, decrease of sexual activity and fantasies, reduced ejaculate volume and osteoporosis. Side effects related to CPA are : headache, dyspnea, weight gain, gynecomastia (20 % of cases, surgically reversible in most of cases), increased level of prolactin, adrenal insufficiency or hyperplasia (0.5 % of cases, in juveniles), hypertension, cardiac insufficiency, decreased glucose tolerance, kidney dysfunction, pituitary dysfunction, anemia, local pain at the injection site (depot formulation), nausea, hepatocellular damage (but serious hepatotoxicity is uncommon, less than 1 %) and thromboembolic phenomena. A history of venous thromboembolism or recent surgery or trauma increased the risk by 4- to 13-fold, respectively. The effect of CPA is entirely reversible 1 or 2 months after treatment interruption .
Gonadotropin-releasing hormone analogs (GnRHa) are GnRH agonists acting at the level of pituitary GnRH receptors, interrupting the normal pulsatile stimulation and leading to a desensitization of GnRH receptors. GnRHa indirectly downregulate the secretion of LH and follicle-stimulating hormone (FSH) leading to hypogonadism and thus to a significant reduction in testosterone levels. It should be noticed that GnRHa cause, during the first weeks of treatment, an initial testosterone surge that theoretically may be associated with increased deviant sexual arousal, fantasies and behavior. CPA or flutamide may be concurrently used for the first weeks of GnRHa treatment to prevent the behavioral consequences of this flare-up effect.
Patients treated with GnRHa may present side effects such as hot flushes, asthenia, nausea, weight gain (2-13 %), transient pain or cutaneous reaction at the site of injection, decreased facial and body hair growth (2-23 %), blood pressure variations, decreased glucose tolerance, decreased testicular volume (4–20 %), episodic painful ejaculation, diffuse muscular tenderness, sweating, depressive symptoms and mild gynecomastia (2–7 %). Bone mineral loss should be regularly measured using osteodensitometry in patients receiving GnRHa treatment and treated if necessary .
Although no randomized controlled studies were published and some biases have been observed in open trials conducted with GnRHa, in most cases GnRHa has shown a better efficacy as compared to previous treatments with psychotherapy, SSRIs or other antiandrogens. In fact, in spite of their efficacy, MPA and CPA treatments are associated with a high percentage of side effects, which considerably limit their use, especially for MPA in Europe. Moreover, poor compliance is frequently observed with oral CPA treatment. In contrast, long-acting GnRHa is more potent than CPA or MPA. In addition, they induce fewer side effects except for those related to hypoandrogenism . Long-acting GnRHa can be administered parentally once every 1 to 3 months, which may increase treatment compliance. Some authorities have recommended that GnRHa treatments should be used after other alternatives have been ruled out or when there is a high risk of sexual violence.
Three GnRHa compounds are currently available: triptorelin, leuprorelin and goserelin. To the best of our knowledge, no studies have compared the efficacy of these three medications.
Triptorelin is a synthetic decapeptide developed as a pamoate salt (3 mg, 1-month formulation or 11.25 mg, 3-month formulation), recently approved in Europe for the reversible decrease in plasma testosterone to castration levels in order to reduce drive in sexual deviations of adult men (Triptorelin Long Acting 11.25 mg). A total of 72 paraphilic men were included in several studies [16, 39, 41–43]. In all studies, during GnRHa treatment, no deviant sexual behavior was observed, and no sexual offences were committed except for one case. Concurrently, with a rapid and sharp decrease of testosterone and LH levels, reduction of deviant and non-deviant sexual fantasies and behavior was observed, and the maximal effect (absence of reported deviant sexual fantasies or behaviors) occurred after 1 to 3 months.
Leuprorelin was developed as daily i.m. or monthly depot injections (3.75 or 7.5 mg, 1-month formulation or 11.25 or 22.5 mg, 3-month formulation). Leuprorelin efficacy has been described in 101 male patients with paraphilic behaviors included in six studies that reported a rapid drop of deviant sexual fantasies and behavior. Schober et al.  have compared behavioral therapy with leuprolide acetate or with placebo in a cross-over study including five pedophiles. In three cases, during the placebo phase, deviant sexual fantasies reappeared while testosterone levels were returning to baseline levels.
Duration of Treatment
There is no consensus about the minimal duration of treatment. Some authors and international guidelines suggest a minimal duration of 3 to 5 years of antiandrogen treatment in cases of severe paraphilia with a high risk of sexual violence [6••]. It is argued that this is the minimal duration necessary for the development of a therapeutic relationship between the patient and his doctor and for the patient’s acceptance of his diagnosis. However, paraphilias are chronic disorders and lifelong treatment might be necessary.
Ethical Issues of Pharmacological Treatment of Sex Offenders
The main ethical dilemma in the treatment of sex offenders with paraphilic disorder is the balance between the need for public safety and treatment, even when treatment is appropriate and effective [46, 47]. The use of pharmacological treatment is justifiable in light of the high rate of sexual victimization by offenders. While medication can lower the intensity of pathological sexual urges and may help patients improve self-control, medication cannot make patients develop a conscience and a sense of moral responsibility.
A second dilemma is the conflict between coercion and free will, which is present in many cases. Informed consent states that a patient must be competent to make a decision, must be fully informed of the potential consequences of his decision and be allowed to decide without coercion . This raises the question of the validity of informed consent in incarcerated subjects or when a sex offender with paraphilic disorder is subjected to coercive treatment. Sexual activity is psychologically and socially related to a sense of gender, vitality and gratification. Depriving a person from these psychological benefits to reduce the risk of his potential dangerousness is another dilemma.
To minimize conflicts some ethics boards have published recommendations concerning the use of antiandrogen treatment , the patient may be prescribed hormonal treatment only if all of the following conditions are met: (1) the person has a paraphilic disorder diagnosed by a psychiatrist after a careful psychiatric examination; (2) the hormonal treatment addresses specific clinical signs, symptoms and behaviors and is adapted to the person’s state of health; (3) the person’s condition represents a significant risk of serious harm to his health or to the physical or psychological integrity of other persons; (4) no less intrusive treatments are available; (5) the psychiatrist in charge of the patient agrees to inform the patient and receive his or her consent, to take the responsibility for the indication of the treatment and for the follow-up including somatic aspects with the help of a consulting physician, if necessary; and finally, (6) the hormonal treatment is part of a written treatment plan to be reviewed at appropriate intervals and, if necessary, revised .
The brain actions of androgens and the neuronal circuitry involved in paraphilic behaviors are not fully understood. A recent study using neuroimaging in pedophilic patients has demonstrated that brain activation, stimulated by pictures representing boys, was decreased in patients under leuprorelin treatment. This study suggests that leuprorelin treatment may decrease neuronal activity in brain regions that mediate the perceptual, motivational and affective responses to visual sexual stimuli .
Sexual offending is both a social and a public health issue. Evidence demonstrates that a combination of pharmacological and psychotherapeutic approaches may reduce or even suppress deviant sexual behavior in sex offenders with paraphilic disorders. Both SSRIs and antiandrogen treatment efficacy has been reported in populations of sex offenders with paraphilias. Despite the major social cost of paraphilic behavior, paraphilia disorders still remain under-researched. Imaging studies may improve the knowledge about paraphilic disorders. In spite of existing evidence, there is a need for independent, large-scale and good quality studies assessing the long-term efficacy and tolerance of the currently used treatments.
Conflict of Interest
F.D. Garcia declares that he has no conflict of interest.
H.G. Delavenne declares that she has no conflict of interest.
A.F.A. Assumpção declares that she has no conflict of interest.
F. Thibaut declares that she has no conflict of interest.