Commentary

Paraphilic disorders: A better understanding

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Historically, removal of the testes (surgical castration) had been the only effective way to reliably lower testosterone. Today, this can be achieved pharmacologically. Use of a sex drive–lowering medication should be considered when either the clinician or the patient is concerned that a nonpharmacologic approach may be inadequate. In all instances, a patient with a paraphilic disorder should be informed that pharmacologic treatment is an option. A protocol for the pharmacologic treatment of paraphilic disorders that is based on my clinical experience is summarized in Table 2.

Paraphilic disorders: Protocol for pharmacologic treatment

Leuprolide. A depot form of leuprolide is the most commonly employed agent to pharmacologically lower testosterone to treat a paraphilic disorder.13 When injected into muscle, leuprolide binds to it before gradually being released into the bloodstream. Previously, a depot medroxyprogesterone (a form of progesterone) had been used to treat paraphilic disorders.14 However, that had required weekly rather than monthly injections, and carried an increased risk of thrombotic emboli.

Prescribing leuprolide to treat a paraphilic disorder falls under FDA guidelines regarding the use of an approved drug for an “off-label” indication, and therefore is not considered investigational. For treating a paraphilic disorder, an effective dosage of leuprolide is 7.5 mg IM every 4 weeks. Long-term treatment is generally required, analogous to the management of diabetes. Because the initial injection of the series can cause a transient increase in testosterone (prior to its sustained decline), flutamide, a testosterone receptor blocking agent, is ordinarily prescribed for the first 14 days only, following initiation of treatment with depot leuprolide.15 Using flutamide in this fashion prevents the transient increase in testosterone from transiently increasing sexual drive. Flutamide should be discontinued after 14 days because long-term use can result in liver toxicity.

Some clinicians have been hesitant to prescribe leuprolide because of negative connotations associated with the term “chemical castration.” Unlike surgical castration, use of leuprolide is not a physically irreversible intervention, and does not result in sterility (although there may be an increase of atypical sperm and a decrease in total sperm production). The dosage can sometimes be titrated without a loss of efficacy.

In general, leuprolide’s safety protocol is well within the range associated with psychotropic medications.13 Low-risk adverse effects, such as hot flashes or cold sweats, may occur, especially during the period when hormone levels are in transition. There are no absolute contraindications to the use of leuprolide.

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