The Treatment of Sexual Deviation Using a Pharmacological Approach.

In a recent editorial in the New England Journal of Medicine, this author decried the need for government and pharmaceutical industry support for research in the treatment of sexually deviant behavior (Bradford, 1998). There are a number of reasons for this, including the case of Kansas v. Hendricks (1997) where the U.S. Supreme Court upheld the civil commitment of sexually violent predators for treatment as constitutional. This means that the most seriously sexually deviant individuals are now to be held in psychiatric hospitals or special facilities for the treatment of their sexual deviation prior to their release. It is these individuals who need to be treated using a pharmacological approach in addition to cognitive behaviourial therapy. Further, pedophilia alone is a very severe public health problem of staggering proportions, with between 6 and 62% of girls and 10 to 30% of boys being the victims of sexual abuse in childhood according to various studies (Peters, Wyatt, & Finkelhor, 1986). Furthermore, in the United States the costs of incarcerating individuals convicted of sexually abusing children is staggering, with more than two billion dollars spent in 1990, while at the same time there is no evidence that the deterrence of incarceration has any impact on the problem (Pithers et al., 1995).

At this time, no one is certain of the cause of pedophilia and other sexual deviations. In addition, the actual incidence and prevalence of the paraphilias is unknown. The level of sexual abuse victimization of children in the general population today is fairly consistent with that reported by Kinsey (Gebhard & Johnson, 1979). In a study completed in the 1940s, 24% of 4,000 females surveyed disclosed a sexual interaction with a male at least five years older than them when they were 14 years of age or younger (Gebhard & Johnson, 1979). Sexual intercourse occurred in 93% of cases, and in 31% of cases there was mild petting or fondling without involvement of the genitals. A national survey by the Federal Government of Canada on sexual violence against children and adolescents found that 18.1% of children (23.5% of females and 12.8% of males) were victims of childhood sexual abuse. In only 20% of cases were the perpetrators strangers, with friends, acquaintances, parents, and other family members being the perpetrators in the majority of cases (Federal Government of Canada, 1984). The actual levels of the prevalence of pedophilia in the general population is unknown, but it could be at least at the same levels as obsessive compulsive disorder, or most likely even higher (Bradford, 1999). Despite this convincing evidence of a serious public health problem, the support for research into the causes and treatment of pedophilia (and other sexual deviations) is very weak, with little or no pharmaceutical industry support and poor government support. In a study of sexual fantasies by Crepault and Couture (1980) it was reported that over 60% of males reported heterosexual pedophilic fantasies and 33% of males had rape fantasies. While this may be a high estimate, even if this is partially accurate the prevalence of mild cases of pedophilia in the general population is staggering. The onset of paraphilic sexual fantasies and urges is usually well established by age 18 (Abel & Rouleau, 1990). This means the risk of sexually acting out is present in late adolescence, yet there are only a few programs dedicated to the treatment of sexual deviation in adolescence. Generally, mental health professionals working

with this segment of the population are not aware of this serious problem, and therefore not enough is being done to treat these conditions before they are well established. In addition, there is considerable comorbidity between the various paraphilias (Bradford, Boulet, & Pawlak, 1992). This means that for a treatment to be successful it has to be able to simultaneously reduce multiple paraphilic behaviours. All of these factors strongly support a pharmacological treatment option as being the most important intervention in the treatment of paraphilias.

The treatment of paraphilias using pharmacological agents is well established (Bradford, 1991, 1994, 1995). It is a treatment approach that is effective in all types of sexual deviations, including the simultaneous presence of multiple sexual deviations. In addition, it is the treatment of choice for the most serious sexual deviations, such as sexual sadism. The paraphilias or sexual deviations are deviant sexual behaviors that have common clinical features, specifically sexual fantasies, leading to sexual urges and then, ultimately, to the deviant sexual behavior. Ideally, if a treatment were to be successful the sexually deviant behavior would be completely suppressed, while at the same time nondeviant sexual behavior (normophilic behavior) would remain intact or would even be enhanced. As outlined later in this article various pharmacological treatment approaches have been shown to have that capability. In addition an ideal treatment would be one that was able to suppress the psychological component of sexual deviation (sexual fantasies) while at the same time having an impact on physiological components of sexual deviation (sexual arousal).

The success of any form of treatment is highly dependent on a detailed evaluation of the behaviour and the establishment of the appropriate diagnosis. In the case of the paraphilias, this is even more critical because of the comorbidity of the paraphilias and the associated comorbidity with other psychiatric problems such as alcoholism. In the author's sexual behaviors clinic (a research clinic that was established 20 years ago), close to 3,000 individuals with paraphilias have been assessed and treated. In specialized clinics such as this one there is a usually a standardized evaluation. This consists of a psychiatric evaluation with a detailed psychiatric history and mental status examination to diagnose associated psychiatric and other medical conditions. The assessment specific to sexual behaviors then consists of (a) a sex hormone profile, (b) sexual questionnaires, and (c) physiological testing of sexual preference. Although it is beyond the scope of this paper, a detailed evaluation is critical to establishing the appropriate treatment intervention. In brief, the sex hormone profile is used to establish a baseline level for possible future treatment with an antiandrogen, as well as screening for abnormal hormone levels. The sexual questionnaires consist of computerized self-generated diagnosis based on DSM criteria (American Psychiatric Association, 1994), sexual history questionnaires, questionnaires to measure cognitive distortions in relation to rape and coercive sexual traits as well as pedophilia, questionnaires to measure types and levels of sexual fantasies, sexual drive measures as well as measures of general sexual functioning, questionnaires on aggression and impulsivity, and questionnaires on alcohol and drug abuse. Physiological measures of sexual arousal are used to measure sexual preferences such as rape proneness, pedophilia and sexual sadism. Penile tumescence techniques and visual reaction time are the physiological measures used.

Sex is a basic biological drive, and understanding this helps to conceptualize the pharmacological treatment approach to sexual deviation. In this framework the paraphilias are similar to eating disorders, where a basic biological drive is also involved. It is also well accepted how difficult it is to treat eating disorders. In eating disorders there is a basic biological drive expressed as hunger and this drive can be disturbed, leading to obesity if it is overactive or anorexia if it is underactive. Thoughts of certain types of food can predominate these disorders as a disturbed directional component to the drive, and the associated behaviour is very difficult to control. It is obvious from the multi-million dollar diet industry in North America how difficult it is for the average person to control their appetite. Sex is also a biological drive with sexual drive the equivalent of hunger and where it can be disturbed both in intensity and direction. Unlike hunger sex is not essential for survival, other than ensuring the procreation of the species. Nonetheless the intensity of the sexual drive is similar to hunger. If this concept is considered in relation to the sexual deviation, then the biomedical approach would involve reducing sexual drive (the equivalent of hunger) and redirecting the drive toward normal sexual behavior and away from deviant sexual interests. There is considerable scientific evidence that the biological components of sexual drive are hormones and neurotransmitters (Bancroft, 1989). Using this knowledge the traditional pharmacological treatment approach has been aimed at sex drive reduction using antiandrogens or hormonal agents. This has been closely related to other biological interventions such as surgical castration and stereotaxic neurosurgery. Stereotaxic neurosurgery is of only historical interest. Surgical castration is of significant interest as it closely parallels antiandrogen treatments which are aimed at reducing plasma testosterone (Bradford, 1985). Surgical castration involves removal of the testes and results in a significant reduction in plasma testosterone levels (Bradford, 1985). The effect of this intervention is seen in the long term outcome studies of surgical castration. These studies, usually involving very serious sexual offenders (mostly pedophiles and rapists) who had already shown high rates of recidivism resulted in follow-up rates of recidivism ranging from 1.3% to slightly over 10% with follow-up periods in some studies being over 20 years (Bremer, 1959; Cornu, 1973; Heim & Hursch, 1979; Langeluddeke, 1963, Le Maire, 1956; Ortman 1980, 1984a; Sturup 1968, 1972).

Testosterone is the principle androgen produced by the testes of most animal species, and is also the most important androgen in influencing male sexual behavior and, to a lesser extent, female sexual behavior (Davidson, Smith, & Damassa, 1977). As the mammalian species studied become more complex, there appears to be a weakening of the direct influence of hormones on sexual behaviors, although in the male sexual behavior tends to remain androgen dependent regardless of the species, including man (Bancroft, 1989). The effects of testosterone occurs through action on the intracellular androgen receptors in various parts of the body (Liang, Tymoczko, Chan, Hung, & Liao, 1977). Testosterone may also be converted to estrogens in the brain and then have an action on estrogen receptors, and in this way influence sexual drive in both males and females (Naftolin, Ryan, & Petro, 1972). It is these biological factors that are the focus of pharmacological treatments targeting hormones.

More recently the neurochemistry of sexual behavior has been studied, and it is clear that central serotonin metabolism also has a significant effect on sexual behavior (Greenberg & Bradford, 1997). Decreased central serotonin levels in experimental animals are associated with an increase in sexual drive. Contrastingly, increased serotonin levels reduce sexual drive. In humans the role of serotonin in sexual behavior is extremely complex, and in addition there are a variety of serotonin receptors that are present (Bradford, 1999; Greenberg & Bradford, 1997).

Utilizing these factors, it has been possible to establish an algorithm for the treatment of the paraphilias. This algorithm is also based on a classification of the severity of a given paraphilia. Although severity might vary according to the type of paraphilia, the following classification covers most paraphilias. In order to establish the degree and severity of a paraphilia, formal training in the assessment of treatment of the paraphilias is imperative. This scheme follows the criteria for severity of manifestations of a specific paraphilia in DSM IIIR, with the addition of additional category of catastrophic as the highest category of severity. (DSM IIIR 1987).

The paraphilias can be graded from mild to catastrophic as follows, based in part on the severity criteria set forth in DSM IIIR (DSM IIIR 1987).

Mild. "The person is markedly distressed by the recurrent paraphilic urges but has never acted on them" (DSM IIIR 1987). Mild cases would include deviant sexual fantasies and urges but no history of any hands-on victimization. Deviant sexual preference as measured by sexual arousal tests may show evidence of a deviation, but no evidence of severe paraphilias such as sexual sadism. Most of the hands-off paraphilias such as exhibitionism would be classified here. Hands-on paraphilias such as pedophilia would be limited to deviant sexual fantasies and urges.

Moderate. "The person has occasionally acted on the paraphilic urges" (DSM IIIR 1987). These would be cases where victimization has occurred in terms of the hands-on paraphilias, although the numbers of victims would remain low and the degree of victimization would be confined to nonintrusive fondling (i.e., no penetration). A low number of victims would usually be classified as less than three victims. Sexual arousal would show deviant sexual preference but no arousal to coercive paraphilias or sexual sadism. The hands-off paraphilias would have problems controlling their deviant sexual urges.

Severe. "The person has repeatedly acted on the paraphilic urges" (DSM IIIR 1987). Severe cases would involve greater than three victims and there would be an increased level of intrusiveness in the victimization, where there would be penetration to some degree. Sexual arousal tests would show deviant sexual arousal with a mild coercive component to it but no frank evidence of sexual sadism. There may be mild sexually sadistic fantasies present. The hands-off paraphilias would have serious difficulties with control.

Catastrophic. There would be clear evidence of sexual sadism in terms of fantasies, urges, history, and behavior in these cases. There may have been victimization and, if this was the case, it would mean this is the highest level of risk in all categories. If there is no victimization, this designation would result from evidence of predatory stalking behavior with sadistic urges, homicidal urges, and urges to torture. It is classified as catastrophic as any acting out would result in injury and/or death to the victim. Sexual arousal testing would show evidence of sexual sadism, with high levels of arousal to coercive stimuli.

THE AIMS OF PHARMACOLOGICAL TREATMENT:

The aims of treatment in all levels of severity would be the same: (a) to suppress deviant sexual fantasies, (b) to suppress deviant sexual urges and behavior, and (c) to reduce the risk of further victimization. The treatment algorithm would then be as follows:

Level 1: Cognitive behaviourial treatment and relapse prevention treatment. This would always be given regardless of the severity of the paraphilia.

Level 2: Pharmacological treatment would start with specific serotonin reuptake inhibitors (SSRIs) and is indicated in most cases of mild paraphilias.

Level 3: If SSRIs are not effective in 4 to 6 weeks when at adequate dosage levels, then a small dose of an antiandrogen would be added, such as Sertraline 200 mg daily and 50 mg of Medroxyprogesterone Acetate daily. This would be used in mild and moderate paraphilias.

Level 4: Full antiandrogen treatment or hormonal treatment given orally, e.g. 50 to 300 mg of Medroxyprogesterone Acetate per day or 50 to 300 mg of Cyproterone Acetate per day. This would be used in moderate cases and in some cases of severe paraphilias.

Level 5: Full antiandrogen treatment or hormonal treatment given intramuscularly, such as 300 mg of Medroxyprogesterone Acetate given intramuscularly per week or 200 mg of Cyproterone Acetate given intramuscularly every, two weeks. This would be used in severe cases of paraphilias.

Level 6: Complete androgen suppression and sex drive suppression by giving Cyproterone intramuscularly, such as Cyproterone Acetate 200 to 400 mg intramuscularly given weekly or a luteinizing hormone-releasing hormone agonist. This is for severe cases of paraphilia and the only treatment in catastrophic cases.

The impact of this treatment algorithm on sexual behavior would be as follows:

1. Suppression of deviant sexual fantasies, urges, and behavior with a minor impact on sexual drive occurring at Level 1 and Level 2.

2. Suppression of deviant sexual fantasies, urges, and behavior with a moderate reduction in sexual drive. Normophilic behavior will occur but at a low level. This will be seen at Levels 2 and 3, but is dose dependent.

3. Suppression of deviant sexual fantasies, urges, and behavior with a severe reduction of sexual drive, so that normophilic behavior occurs but at a very low level. This would be seen at Levels 4 and 5.

4. The complete suppression of sexual drive with no paraphilic or normophilic sexual behavior, creating an asexual individual. This would be seen at Level 6.

In the case of the majority of paraphilias, Level 1 and Level 2 of the algorithm would be sufficient for treatment. This would cover most of the hands-off paraphilias such as exhibitionism, voyeurism, and others where there is not a direct physical contact involving a victim. Caution should prevail however, because of the high levels of comorbidity and crossover between hands-off paraphilias and hands-on paraphilias. This emphasizes the importance of a detailed evaluation prior to implementing treatment. In the case of hands-on paraphilias involving direct physical contacts with victims, such as frotteurism and pedophilia, the treatment intervention would start at Levels 1 and 2, but would move quickly move to Levels 3 and 4 depending on the effectiveness of treatment outcome. For example, in the cases of mild pedophilia Level 1 and Level 2 would be sufficient treatment intervention. In contrast, for more severe cases of pedophilia Levels 3 and 4 of the algorithm would be the pharmacological treatment needed in order to reach adequate control. More serious cases and cases involving sexual sadism of various degrees would start with a Level 4 intervention would move through to Level 5 and Level 6 depending on the degree of risk and the severity of the paraphilia.

This algorithm can only be used if there is a full understanding of the pharmacology of the various agents used in the treatment. It is also important to think of the paraphilia and the type of treatment as independent variables and that the final treatment outcome can be affected by a variety of mediator variables. These mediator variables are various factors that could cause a relapse of paraphilic behavior. These include (a) abuse of substances, specifically alcohol but also nonprescription drugs; (b) mood disorders, specifically depression but any variation of mood disorder can disinhibit sexual behavior; (c) noncompliance with pharmacological treatment; and (d) noncompliance with relapse prevention interventions.

THE SPECIFIC SEROTONIN REUPTAKE INHIBITORS (SSRIs)

The most recent advance in the treatment of paraphilias has been the use of drugs that affect serotonin (5HT) (Greenberg & Bradford, 1997). By decreasing brain serotonin, animal research has shown that the sexual behavior of animals is affected with an increased sexual drive and, specifically, increased mounting behavior. It is also known that increasing the brain levels of 5HT would reduce sexual drive and behavior. Although sexual behavior in humans is always regarded as being much more complicated than in animals, drugs affecting 5HT levels were seen as possibly being useful in the treatment of sexually deviant behavior by suppressing sexual drive (Greenberg & Bradford, 1997). An early report by Bianchi (1990) described an exhibitionist treated with fluoxetine hydrochloride, and reported a reduction in paraphilic fantasy and urges. Other case reports soon followed, mostly using fluoxetine hydrochloride as the pharmacological agent (Emmanuel, Lydiard, & Ballenger 1991; Lorefice 1991; Perilstein, Lipper, & Friedman 1991; Zohar, Kaplar, & Benjamin 1994). Kafka (1991) studied four patients with nondeviant hypersexuality treated with fluoxetine hydrochloride and reported significant reductions in sexual drive observed clinically. He also reported on three cases of sexual deviation treated with Fluoxetine hydrochloride over a 3-month period and reported considerable improvement. Kafka and Prentky (1992) completed an outpatient study (n = 16), where 50% of the study population suffered from a sexual deviation or paraphilia and the rest suffered from nonparaphilic hypersexuality. All of the patients improved over a 12-week period with a mean dose of 39 mg of fluoxetine hydrochloride per day. Stein et al. (1992) treated five paraphilic males and in contrast reported that none had shown decreased sexual fantasies and urges or masturbation to deviant sexual fantasies when treated with fluoxetine hydrochloride. Also, Coleman, Cesnik, Moore, and Dwyer (1992) completed a retrospective study of 13 paraphilic males and reported improvement in all aspects of sexually deviant behavior when treated with fluoxetine hydrochloride. Kafka (1994) reported on an open clinical trial of both men suffering from paraphilia (n = 13) and nonparaphilic hypersexuality (n = 11). The study showed a significant reduction in sexually deviant fantasies, urges, masturbation, and sexual behavior. The specific serotonin reuptake inhibitor was Sertraline and there was about a 50% clinical response rate. The nonresponders were offered an alternative specific serotonin reuptake inhibitor, fluoxetine hydrochloride, and two thirds showed some clinical improvement. The Sertraline was used for a mean duration of treatment of 17.4 weeks (SD [+ or -] 18.6 weeks) and the mean dosage of Sertraline was approximately 100 mg per day. The mean dosage of fluoxetine hydrochloride in the second phase of the clinical study was 51.1 mg per day (SD [+ or -] 19.6) and the duration of treatment was 30.5 weeks (SD [+ or -] 16.8 weeks). Bradford, Greenberg, Gojer, Martindale, and Goldberg (1995) reported on a 12-week open label dose titrated study of pedophilia (n = 20) using Sertraline. The mean effective dosage of Sertraline was 131 mg per day. Eighty-six percent of patients completed the study and no patients were discontinued due to an inadequate treatment response. Overall the severity of the pedophilia rated by the physicians in the study decreased dramatically over and this was a statistically significant decrease. A high proportion (86%) of patients were rated as responders. Various sexual behaviors were significantly reduced over the duration of the study while heterosexual coitus actually showed a small increase during the study. Physiological measures of sexual arousal showed decreases in pedophilic arousal and improved or maintained normophilic arousal. Although this was an open label study, it did show evidence of improvement or maintenance of normophilic behavior in the treatment of pedophilia, which would be a highly desirable outcome. In another study Greenberg, Bradford, Curry, and O'Rourke (1996) completed a retrospective study of the treatment of a variety of paraphilias using three different serotonin reuptake inhibitors in a sample of paraphilic males (n = 58). The aim of the study was to see the relative efficacy of three different SSRIs in their ability to reduce deviant sexual behavior. In this particular study, the three SSRIs, sertraline hydrochloride