Proserotonergic Pharmacotherapy

As previously described in this chapter, anxious and depressive symptoms and disorders have been identified in paraphilic sex offenders, nonoffender paraphilic men, and men with PRDs. DSM-IV (American Psychiatric Association 1994) notes that symptoms of depression can be associated with an increased frequency and intensity of sexual impulsivity in paraphilic individuals. In addition, there are subgroups of depressed males who self-report increased sexual behavior (Nofzinger et al. 1993). In particular, in my clinical research, dysthymic disorder, early-onset subtype, may accompany hypersexual disorders and be clinically overlooked (Kafka and Prentky 1992b, 1994, 1998). Prior to 1988, there were only a handful of case reports (e.g., Bartova and Nahanek 1979; Snaith 1981; Ward 1975) suggesting that mood or anxiety disorders and PAs might be comorbid and that thymoleptic treatment could ameliorate depressive and anxious symptoms as well as deviant fantasies, urges, and sexual behaviors. Since 1989, however, multiple case reports, open clinical trials, and retrospective chart reviews have indicated that serotonergic antidepressants - in particular, SSRIs - can ameliorate both PAs and PRDs, even in the absence of a concurrent mood disorder diagnosis.

Fluoxetine (Bianchi 1990; Bradford 1995a; Emmanuel et al. 1991; Kafka 1991a, 1991b; Kafka and Prentky 1992b; Lorefice 1991; Perilstein et al. 1991), sertraline (Bradford 1995b; Kafka 1994b), clomipramine (Kruesi et al. 1992; Ruby et al. 1993), fluvoxamine (Greenberg et al. 1996; Zohar et al. 1994), and paroxetine (Abouesh and Clayton 1999) may be effective for the amelioration of both PAs and PRDs when prescribed at the usual antidepressant doses. Citalopram, an SSRI that has been prescribed in continental Europe for over a decade, was recently released in the United States. In my experience, it is as efficacious as the aforementioned medications.

Analogous to the onset of the effects of antiandrogens, a distinct effect on sexual arousal and target symptoms is usually apparent by week 4 after initiating pharmacotherapy with SSRIs (Bradford 1995b; Kafka and Prentky 1992b). In addition, antidepressant pharmacotherapy may diminish the vulnerability to “negative affective states” (e.g., irritability, depressed mood) commonly reported to precede sex-offending behaviors (Marques and Nelson 1989) and to alleviate low self-esteem and social anxiety that frequently accompany social skills deficits in males with sexual impulse disorders (Baxter et al. 1984; Levin and Stava 1987; Marshall 1989). Because of these effects on nonsexual target symptoms and syndromes associated with PAs and PRDs, SSRIs and other proserotonergic drugs may offer distinct therapeutic benefits in comparison with antiandrogens when clinically indicated.

Mr. M was a 30-year-old married man who was self-referred after his wife of 8 years discovered that he was dressing in female attire and insisted that he stop that behavior. Mr. M reported that he had noticed sexual feelings and excitement even prior to the onset of puberty when he played with his older sister’s undergarments. During adolescence, he began wearing women’s underpants, then lingerie, and finally dresses as well for sexual pleasure. In his early 20s, Mr. M masturbated every day, using either women’s undergarments or pornography. Although he was heterosexual, he acknowledged having sexual fantasies, while cross-dressed, of being an attractive female seducing a man.
At the time of referral, Mr. M was diagnosed with major depression, social phobia, and alcohol abuse. His lifetime sexual diagnoses included compulsive masturbation and transvestic fetishism. In addition to receiving psychoeducational material describing treatments for paraphilias, Mr. M was instructed to completely abstain from alcohol use. He was subsequently prescribed fluoxetine, adjusted to 30 mg/day, and his cross-dressing behavior became markedly reduced in frequency. In addition, Mr. M reported that he was much more patient at work and with his children, had better motivation to finish household tasks, and experienced less social anxiety. Mrs. M was included in a supportive psychotherapy that helped her to understand that her husband’s sexual behavior was a “stress reliever” associated with vulnerability to a mixture of anxious and depressive symptoms. She became less angry and more able to empathize with her husband, because she herself had also experienced a depressive disorder. Over time, without further additional psychotherapeutic treatment, Mr. and Mrs. M’s relationship restabilized.

Several caveats apply in regard to the efficacy and clinical indications for serotonergic drugs or other antidepressants in comparison with antiandrogens for sex-offending paraphilic individuals. With one exception (Kruesi et al. 1992), no systematic studies have examined the efficacy of tricyclic antidepressants or monoamine oxidase inhibitors in the treatment of sexual impulsivity disorders. Although SSRIs have the clinical advantage, in comparison with antiandrogens, of being more readily prescribed and accepted by both the medical and patient communities (Federoff 1995), there have been no published double-blind or placebo-controlled studies of their use in either incarcerated or outpatient paraphilic individuals. Pharmacotherapy with serotonergic antidepressants requires highly motivated patient compliance, given that no antidepressant is currently available in parenteral form. The antiandrogens, in contrast, can be administered parenterally or orally, and serum testosterone determination can help to monitor efficacy and compliance. There are currently no data on recidivism rates or long-term remission rates in sex offenders treated with antidepressants, although some studies report treatment outcomes after more than 1 year of pharmacotherapy (Greenberg et al. 1996; Kafka 1994b). It remains to be determined when or if serotonin-enhancing pharmacotherapy should be tapered after a successful course of cognitive-behavioral or other psychotherapy. Although the cumulative data regarding SSRI antidepressants are encouraging, more rigorous empirical study is needed.

In contrast to the reported continuous efficacy of antiandrogens, pharmacological tolerance to the mitigating effects of SSRIs on sexual impulsivity disorders has been described (Kafka 1994b). A similar loss of efficacy for SSRIs has been reported in samples of patients treated for mood disorders as well (Bryne and Rothschild 1998; Fava et al. 1995; Mischoulon et al. 1999). In the event that tolerance develops, I have had good treatment results in adolescents and adults with PAs and PRDs by combining noradrenergic/dopaminergic agonists - such as the dextroamphetamine salts, methylphenidate, magnesium pemoline, and bupropion hydrochloride - with SSRIs. This combination has been efficacious not only when tolerance develops to an SSRI (Mischoulon et al. 1999) but also to counteract certain SSRI side effects such as fatigue, to treat residual depressive symptoms (Bodkin et al. 1997; Nierenberg et al. 1998; Stoll et al. 1996), and, most importantly, to treat residual ADHD (Kafka and Prentky 1998). Inasmuch as dopaminergic agonists can intensify or disinhibit sexual appetitive behavior (Angrist and Gershon 1976; Bell and Trethowan 1961), rigorous SSRI pretreatment followed by cautious titration of a dopaminergic agonist is indicated during the administration of this combination of drugs to males and females with PAs and PRDs (Kafka and Hennen 2000).

Mr. N was a 42-year-old married man who was referred to me after his wife discovered that he had incurred a phone bill in excess of $400 for phone sex. She was outraged, threatening to divorce him unless he received treatment. In addition, Mr. N had been a compulsive masturbator who persistently downloaded pornography over the Internet, even when such behavior jeopardized his employment. In the past, Mr. N had been repetitively promiscuous with both men and women and had unsuccessfully tried to completely suppress these behaviors during his marriage. He reported no PAs.
Mr. N met diagnostic criteria for dysthymic disorder, late-onset subtype, and had a prior history of marijuana dependence. Although he did not meet the retrospective diagnostic threshold for ADHD, his early school history was notable for underachievement, daydreaming, and failure to complete assignments. Currently, at work, he characterized himself as disorganized, sexually distracted, deadline driven, and chronically anxious.

Mr. N was resistant to participation in group or individual psychotherapy, because he had undergone (prior to his marriage) several years of such therapies (including 12-Step groups), with only modest results. He was prescribed sertraline adjusted to 150 mg/day. On this regimen, he did much better clinically but still complained of distracting sexual thoughts, procrastination, and compulsive use of pornography at work. Three months into this treatment, however, he reported that his mood and sexual symptoms were insidiously returning and that “something had to be done.” Methylphenidate SR 20 mg/day was added to his pharmacological treatment, with substantial clinical effects. On this combination, not only was he no longer sexually symptomatic, but his mood disorder remained under good control and he no longer reported significant distraction, procrastination, and disorganization. His wife noticed and commented on the improvement as well, and they initiated marital therapy together.

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Revision date: July 9, 2011
Last revised: by Dave R. Roger, M.D.