Commentary on guidelines for the pharmacological treatment of paraphilic disorders

In this issue of the Journal, Thibaut et al. and the World Federation of Biological Psychiatry (WFSBP) Task Force on Paraphilias provide an update (Thibaut et al. 2020) to the original article (Thibaut et al. 2010) by this group. These articles provide information on the treatment of adults who have paraphilic disorders; a companion report on the treatment of adolescents who have committed sexual offences has also been provided by this author and her colleagues. (Thibaut et al. 2016). Although the main focus of each of these reviews is on the biological treatment of these disorders, psychological and behavioural treatment, often inextricable from the treatment of this population, is also included. Each of these reports is notable for its exhaustive references and extensive detail, not only reporting on pharmacotherapy, but also on epidemiological, aetiological, diagnostic, risk assessment, evaluation and treatment information. An enormous number of studies is well organised and presented in these extensive documents, which will serve as go-to resources for clinicians and investigators for years to come. An algorithm is also proposed with different levels of treatment for different categories of paraphilic disorders with different risk levels. This will undoubtedly be modified as research evolves.

Although atypical sexual behaviour has been recounted since biblical times (Aggrawal 2009), the mechanisms and biology of such behaviour have remained difficult to explain. Darwin lamented in 1862 (Darwin 1862) ‘We do not even in the least know the final cause of sexuality… The whole subject is as yet hidden in darkness.’ (pp 94 & 95). The 20th and 21st centuries have seen the growth of the field of behavioural endocrinology, which encompasses sexual and aggressive behavior (Nelson and Kriegsfeld 2017) and the development of a significant body of research on paedophilia and the sexual abuse of children (Seto 2018). The design of such research studies has been limited, however. (Langstrom et al. 2013) reviewed 1447 abstracts concerning interventions designed to prevent reoffending among known abusers and individuals at risk of abusing children; of 167 full text studies retrieved only 8 of these were considered to be of low to moderate risk of bias. None of these included pharmacological studies.

Significant challenges to the study of this population exist. Randomised, double-blind and placebo-controlled studies are the gold standard for evaluating the efficacy of pharmacological treatments. These have been difficult to conduct because of the lack of interest in the treatment or research of such populations in academic medical centres, the forensic nature of such study populations (with many being incarcerated or under the control of the legal system), and lack of funding. In the United States, for instance, few academic medical centres have programs for the treatment of individuals with paraphilic sexual behaviour. This population is often incarcerated or under the supervision of the legal system. Such populations are considered vulnerable to abuse and require a higher level of ethical review and protection. For instance, a proposed randomised placebo-controlled study of triptorelin (a synthetic analogue of gonadotropin-releasing hormone that reduces testosterone) and psychotherapy in the German forensic system (Briken et al. 2012) was not allowed because it was determined that it was not ethical to conduct research on patients detained in a forensic psychiatric hospital. Another issue is the fact that for most drug studies, the outcome of interest involves the individual studied; for studies targeting aggressive sexual behaviour, outcomes may involve the individual, but also potential victims (as documented by criminal charges). Such studies and ethical conundrums might involve consideration of the risks and benefits both to the individual and to society.

Drug companies have rejected study proposals designed to control atypical sexual behaviour, expressing concern that there is not an adequate market for their medication or objecting to a design that would demonstrate that their drug was effective at reducing sexual drive, which would place them at a disadvantage compared with competitors advertising lack of sexual side effects. Government-funded support for the study of pharmacological agents to treat aggressive sexual behaviour has also been extremely limited; the author had the experience of, after careful clearance from a grant review officer, having the United States National Institute of Justice return without review a proposed grant involving the study of sertraline vs. placebo in the treatment of compulsive sexual behaviour, saying that the requisites for review of such a biological study were beyond its expertise.

Nevertheless, continuing efforts to evaluate the pharmacological treatment of these disorders continue. Uncontrolled open-label studies have suggested that androgen reduction treatment has been effective in reducing sexual offending (Rosler and Witztum 1998, 2009). Their reports concerned 100 males treated with triptorelin, a long-acting agonist analogue of gonadotropin-releasing hormone analogue, together with supportive psychotherapy followed for up to 15 years; as long as patients continued with pharmacological treatment, no recidivism was detected. Recently (Landgren et al. 2020) reported on a randomised clinical trial of dagarelix, a gonadotropin-releasing hormone antagonist that reduces testosterone. This was found to reduce the risk score of committing sexual abuse in men with paedophilic disorder 2 weeks after the initial injection. This study was considered to be a milestone (Briken 2020). Both studies, however, relied on outcome measures with very limited validation, especially given the reliance on self-report from a forensic population where such a report can be unreliable.

There is a desperate need for valid outcome measures to assess the effect of treatment targeting sexual behaviour. Recent advances in medical technology involving wearables, if validated for patterns of sexual behaviour, might offer some solution (Yetisen et al. 2018). Further study and validation of current instruments offer another path.

One can anticipate that the future will bring more interest and support for pharmacological studies and that research design can result in the ethical conduct of such studies. Child sexual abuse (CSA) is an expensive matter; a recent study estimated the annual economic burden of CSA in the United States to be $9.3 billion (Letourneau et al. 2018). In the U.S., some support has been provided by the Centres for Disease Control and Prevention and the National Institute of Mental Health (Wainberg et al. 2006). The United States Institute of Justice just published a monograph on conducting randomised controlled trials in state prisons (Bucklen 2020). A recent Swedish study investigated the efficacy of methylphenidate in the treatment of attention deficit hyperactivity disorder and drug relapse in criminal offenders with substance dependence released to the community (Konstenius et al. 2014). A Canadian study (Gallo et al. 2019) reported on a long-term outcome study on depot-leuprolide acetate administration using officially recorded recidivism as the primary dependent measures. Such studies suggest that the field is innovating and advancing and that there will be increasing scientific interest in and support for the pharmacological treatment of paraphilic disorders.

Statement of interest

None to declare.

Acknowledgements

None.