'Milestone' Study Shows Promise for Pedophilic Disorder

Testosterone-suppressing treatment with the gonadotropin-releasing hormone (GnRH) antagonist degarelix may reduce dynamic risk factors for sexual offense in men with pedophilic disorder, new research suggests.

In a first-of-its-kind randomized controlled trial of 52 help-seeking men with the disorder, degarelix vs placebo significantly dampened two critical risk factors for committing abuse: high sexual desire and sexual attraction to children. In addition, effects were noticeable within 2 weeks.

"The medicine is quick-acting, not only on biological systems but also on thoughts and behavior," coinvestigator and corresponding author Christoffer Rahm, MD, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden, told Medscape Medical News.

"The effect lasts and increases after 10 weeks, and especially so in the small group of high-risk individuals," Rahm added.

The study findings were published online April 29 in JAMA Psychiatry.

Opportunity for Prevention

Although all men with pedophilic disorder do not commit a sexual offense, those who do generally report struggling with their sexual urges for 10 years before committing a sexual crime, the investigators note.

This presents an opportunity for prevention by treating high-risk individuals without prior convictions. Effective treatment could prevent child sexual abuse and reduce psychosocial stress for the individual with pedophilic disorder, the researchers write.

GnRH antagonists are considered effective in reducing paraphilic symptoms, but their use has been limited to correctional settings. The current study is the first randomized controlled trial to include self-identified, help-seeking men — and not just convicted men from prison and the probation system.

"It means the conclusions from the study are applicable to the patients you meet on sexual medicine and general psychiatry clinics too," Rahm said.

The study included 52 men with a pedophilic disorder diagnosis and no contraindications to the intervention. All had contacted PrevenTell, the Swedish national telephone helpline for unwanted sexuality.

Half of the participants were randomly assigned to receive two subcutaneous 120 mg injections of degarelix acetate, while the other half received an equal volume of placebo.

The primary endpoint was efficacy at 2 weeks after injection in reducing a composite risk score of five domains for committing child sexual abuse; this risk score ranged from 0 to 15 points (each domain could be rated 0 to 3). Secondary endpoints included efficacy at 2 and 10 weeks in the composite score, each risk domain, quality of life, self-reported effects, and adverse events.

"Positive Effects"

At 2 weeks, the composite risk score decreased from 7.4 to 4.4 in the degarelix group and from 7.8 to 6.6 in the placebo group, which was a mean between-group difference of –1.8 (95% confidence interval [CI], –3.2 to –0.5; P = .01).

Compared with placebo, the degarelix group also showed a decrease in the composite score at 10 weeks (−2.2; 95% CI, −3.6 to −0.7), in the domains of pedophilic disorder at 2 weeks (−0.7; 95% CI, −1.4 to 0.0) and 10 weeks (−1.1; 95% CI, −1.8 to −0.4), and in sexual preoccupation at 2 weeks (−0.7; 95% CI, −1.2 to −0.3) and 10 weeks (−0.8; 95% CI, −1.3 to −0.3).

There were no between-group differences in the other domains of self-rated risk, low empathy, and impaired self-regulation at 2 or 10 weeks, or in quality of life.

Injection site reactions were more common with degarelix than placebo (88% vs 4%, respectively), as were hepatobiliary enzyme level elevations (44% vs 8%). Two patients in the degarelix group were hospitalized as a result of increased suicidal ideation, suggesting "vigilance for the risk of exacerbating suicidality in predisposed individuals is warranted," the researchers write.

"Most patients tolerated it well, many experienced what they thought were positive effects on sexuality, and a majority wanted to continue with the medicine after the study was over and have another injection," Rahm said.

Sexual Science Milestone

In an accompanying editorial, Peer Briken, MD, Institute for Sex Research, Sexual Medicine and Forensic Psychiatry, University Medical Centre, Hamburg, Germany, writes that the innovative potential of this study should "not be underestimated."

It has previously been thought that randomized controlled trials were not possible because it might be unethical to withhold therapy from high-risk participants and thus risk sexual assaults on children in a control group, Briken notes.

With the current study, "the situation has changed, which marks a milestone in clinical sexual science and the field of forensic psychiatry," he writes.

However, the "great benefit" of the study, which is the proof of feasibility of an RCT in this special group of patients and use of a new drug, comes with some "important limitations," he adds.

Only three participants in each treatment group were in the high-risk subgroup. In addition, the most important long-term outcome criterion — reduction in recidivism in high-risk individuals — could not be investigated, he points out.

Briken writes that he agrees with the investigators that risk of suicidal tendencies during rapid testosterone withdrawal requires attention.

Despite its limitations, this study is "certainly the most important contribution to the field of pharmacotherapy of pedophilic disorders since Rösler and Witztum's study on GnRH-agonists in 1998. Also, a relevant number of the study participants (58%) were in favor of further application," he concludes.

The study was funded by the Swedish Society of Medicine, the Söderström-Königska Foundation, the Fredrik and Ingrid Thuring Foundation, the Centre for Psychiatric Research at Karolinska Institutet, the Gothenburg Society of Medicine, Skaraborg Hospital research unit, Region Stockholm, and the Swedish Society for Medical Research. Rahm and Briken have disclosed no relevant financial relationships.

JAMA Psychiatry. Published online April 29, 2020. Full text, Editorial

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