There is no data to suggest that pharmacological intervention cans specifically target or ameliorate underlying paraphilic mechanisms. Rather, pharmacological interventions are either symptom focused or directed toward ameliorating or managing comorbid conditions. For example, where hypersexuality is a factor, pharmacological treatments are commonly implemented to lower libidinal drive; where concurrent mania fosters hypersexuality, mood stabilizing agents are indicated; where comorbid depression or anxiety exacerbates paraphilic urges and behaviors, pharmacological intervention to lower affective distress may be a crucial early treatment; where paraphilic behavior is driven by underlying psychotic or delusional processes, the obvious first line treatment is pharmacological management of the psychotic state. As exemplified in these scenarios, pharmacological interventions for the paraphilias fall into three primary categories: antidepressants, antiandrogens, and neuroleptics and other agents.
Some individuals with a paraphilia experience distressingly high drive and hyperarousability. Pharmacological interventions to lower libidinal urges are not only sometimes useful, but frequently essential, particularly the offending disorders such as pedophilia (136). The side-effect of diminished sexual desire, arousability, and behavior has been well documented in the specific serotonin reuptake inhibitors (SSRIs). Although the precise mechanism of action is unknown, it is thought that the SSRIs lower drive by increasing levels of serotonin (10,137,138). The SSRIs are often utilized in cases where high biological drive is a significant contributing factor (139). They are, of course, also helpful in reducing comorbid depressive and anxiety symptoms as well as intrusive sexual preoccupation. The clinical evidence for serotonin agonists include numerous reports of treatment success using fluoxetine, sertraline, and paroxetine for fetishism, voyeurism, exhibitionism, and pedophilia (18,137,140-146).
It has been hypothesized that for a subset of individuals, paraphilias may be secondary to obsessive-compulsive related disorders, for which the SSRIs have been found to be effective. A study comparing the effectiveness of the SSRI flu-voxamine to the heterocyclic desipramine in the treatment of exhibitionism found that fluvoxamine effectively reduced the paraphilic urges and behavior, whereas desipramine was associated with relapse (147). A study comparing the effectiveness of fluvoxamine, fluoxetine, and sertraline in paraphilics found all three effective in reducing the severity of fantasies and no significant differences in overall efficacy (138). Kafka and Hennen reported on the successful use of psychostimulants in combination with SSRIs in the treatment of individuals with paraphilias and comorbid adult symptoms of ADHD (148).
Although most studies regarding the use of antidepressants in the treatment of the paraphilias have focused on the SSRIs, there have been case reports of the effective use of other antidepressants. The tricyclic clomipramine, which has significant serotonin reuptake inhibition, has been reported to be effective in treating exhibitionism (149-151). Another case report described the remission of exhibitionism with trazodone, although the precise mechanism of action in this agent is not fully understood (152).
The number of studies regarding antidepressants in the treatment of the paraphilias remains small and more studies are needed in order to clarify the effects of SSRIs compared with other psychopharmacological interventions. Further, it is unclear whether the SSRIs are selectively useful in individuals with a clear obsessive-compulsive disorder component, comorbid anxiety, or depressive disorder underlying the paraphilia or, rather, they have a more generalized usefulness for the paraphilias.
In paraphilias where elevated sexual drive does not remit to other treatments, the use of antiandrogens is indicated. In contrast to the SSRIs and other antidepress-ants, where the effects on libido are indirect, the antiandrogens have a direct suppressing effect on testosterone levels. Most of the current knowledge regarding the use of antiandrogens stems from research with sex offending populations, although the use of testosterone reducing agents has also been reported in transvestic individuals who cannot control cross-dressing behaviors (153). Use of antiandrogenic medications in the treatment of paraphilias usually must be long-term. Relapse is common upon cessation of the medication. Treatment with antiandrogens may result in erectile dysfunction, although many individuals maintain adequate sexual functioning. As with the SSRIs, the goal of antiandro-gen medications is to augment the individual's ability to achieve behavioral control (10).
Methoxyprogesterone acetate (MPA) is the most commonly used hormonal agent for the reduction of sex drive in the United States (140,146,154,155). It does not compete with androgens at the receptor level but blocks levels of testosterone by inducing hepatic testosterone reductase. The goal of this strategy is to reduce baseline testosterone to 50% of initial values. Common dosages are 50-300 mg orally or 300-400 weekly via intramuscular injections with reduction to 100 mg weekly for a maintenance program. Depot preparations of methoxyprogesterone are also available. Side-effects include weight gain, hyper-glycemia due to an exaggerated insulin response to a glucose load, headaches and increased risk of deep vain thromboses.
Cyproterone acetate (CPA) is also frequently used to suppress sex drive in individuals with paraphilias. CPA blocks androgen receptors, directly decreasing the biological effects of testosterone. It is not available in the United States and most of the research regarding this agent derives from Germany (156). CPA can be given orally 100 mg daily or 200 mg every other week via intramuscular injection. Reports clearly demonstrate that CPA reduces sexual drive and erectile ability. Possible side effects include weight gain, depression and feminization (157,158).
Some researchers argue that long-acting gonadotropin-releasing hormone (GnRH) agonist analoges are the most potent antiandrogens, have the fewest side-effects, and therefore are the most promising pharmacological treatment for the future (159). Either leuprolide or triptorelin is given intramuscularly in doses of 3.75 or 7.5 monthly. These agents suppress testosterone via decreasing the number of pituitary GnRH receptors and testicular LH receptors, thereby desensitizing the testes to LH. It more completely suppresses androgen than MPA or CPA. In an open trial of 30 sex offenders, triptorelin administered on a monthly basis (3.75 mg per dose) diminished paraphilic fantasies and drives according to self-report at 8-months follow-up. In another report, triptorelin treatment resulted in complete cessation of paraphilic behavior and significant decreases in paraphilic fantasies in five of six subjects (160). Termination of the treatment resulted in relapse to paraphilic fantasies in some subjects and in behavioral relapse in others. When a GnRH agonist is initially given, a "flare" phenomenon may result in that there is a transient rise in testosterone levels before receptor down regulation (161). To manage this, nonsteroidal antiandro-gens such as flutamide may be helpful.
Neuroleptic agents have been reported to diminish paraphilic behaviors and fantasies. One early report described the successful treatment of a case of familial exhibitionism in Tourette's syndrome with haloperidol (162). Additionally, there have been case reports of other pharmacological interventions for the paraphilias. A report described success in eliminating pedophilic cognitions and behaviors with a combination of the anticonvulsant carbamazepine and the benzodiazepine clonazepam (163). These were selected to specifically target the patient's mixed depression and anxiety as well as his sexual impulsivity. Lithium has also been reported to be effective in reducing inappropriate sexual behaviors. However, the diagnostic classification of subjects in many studies has been vague and the use of mood stabilizers may reflect a comorbid mania or other psychotic state as the actual target of intervention (164,165).
Although more research is needed, the current knowledge base regarding reduction of sexual drive and sexual preoccupation through pharmacological means is compelling. Further, due to the high comorbidity between the paraphi-lias and other psychiatric disorders, the need for pharmacological support in the treatment of the paraphilias is significant. In sum, pharmacological interventions are today a critical component of state-of-the-art treatment of paraphilias, especially the offending paraphilias. Most often, these medications are coupled with, and signifiantly enhance the effects of, concomitant psychological treatment, to be discussed in the following section.
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