How to select pharmacologic treatments to manage recidivism risk in sex off enders Consider patient factors when choosing off -label hormonal and nonhormonal agents ® Dowden Healthex offenders Media traditionally are managed by the criminal justice system, but psychiatrists are fre- Squently called on to assess and treat these indi- CopyrightFor personalviduals. use Part only of the reason is the overlap of paraphilias (disorders of sexual preference) and sexual offending. Many sexual offenders do not meet DSM criteria for paraphilias,1 however, and individuals with paraphil- ias do not necessarily commit offenses or come into contact with the legal system. As clinicians, we may need to assess and treat a wide range of sexual issues, from persons with paraphilias who are self-referred and have no legal involvement, to recurrent sexual offenders who are at a high risk of repeat offending. Successfully managing sex offenders includes psychological and pharmacologic interven- 2009 © CORBIS / TIM PANNELL 2009 © CORBIS / tions and possibly incarceration and post-incarceration Bradley D. Booth, MD surveillance. This article focuses on pharmacologic in- Assistant professor terventions for male sexual offenders. Department of psychiatry Director of education Integrated Forensics Program University of Ottawa Reducing sexual drive Ottawa, ON, Canada Sex offending likely is the result of a complex inter- play of environment and psychological and biologic factors. The biology of sexual function provides nu- merous targets for pharmacologic intervention, in- cluding:2 • endocrine factors, such as testosterone • neurotransmitters, such as serotonin. The use of pharmacologic treatments for sex of- fenders is off-label, and evidence is limited. In general, Current Psychiatry 60 October 2009 pharmacologic treatments are geared toward reducing For mass reproduction, content licensing and permissions contact Dowden Health Media. 60_CPSY1009 60 9/15/09 2:00:24 PM Table 1 Pharmacologic treatment of male sex off enders: A risk-based approach Low-risk High-risk offenders offenders SSRI SSRI augmented Oral CPA,* 100 to IM CPA,* 100 to GNRH agonist: with finasteride, 500 mg/d, or oral 600 mg/week,† or IM leuprolide, 5 mg/d, MPA, 100 to 600 IM MPA, 100 to 7.5 mg/month; naltrexone, 100 mg/d 700 mg/week† IM goserelin, 3.6 to 200 mg/d, mg/month; or IM methylphenidate, triptorelin, 3.75 up to 1 mg/kg/d, mg/month oral MPA, 50 mg/d, or oral CPA,* 50 mg/d *Not available in the United States Clinical Point †Some authors suggest administering this dosage once every 2 weeks CPA: cyproterone acetate; GNRH: gonadotropin-releasing hormone; IM: intramuscular; MPA: medroxyprogesterone acetate; SSRI: selective serotonin reuptake inhibitor SSRIs may be more Source: References 3-5 appealing to patients than the ‘chemical sexual drive through nonhormonal or hor- increase in conventional sexual interests, castration’ of monal means (Table 1).3-5 although this may be related to placebo or hormonal treatments halo effects—patients may have reported an increase in conventional interests be- Nonhormonal treatments cause they noticed a decrease in paraphili- SSRIs. Selective serotonin reuptake inhibi- ac interests. Negative side effects included tors act by blocking serotonin reuptake in decreased sexual desires, delayed ejacula- the synaptic cleft. Soon after the fi rst SSRIs tion, decreased libido, and anorgasmia. were approved in 1988, reports appeared of Adi et al11 completed a more rigor- SSRIs interfering with sexual functioning.6 ous literature evaluation that included 9 This side effect quickly was exploited to as- studies with a total of 225 patients receiv- sist the treatment of sexual offenders.7 ing fl uoxetine, fl uvoxamine, sertraline, or The mechanism of action may include:8 paroxetine. Eight studies showed benefi ts; • direct effects, such as general inhibi- however, Adi noted that this preliminary tion of sexual activity, reduced impulsive- evidence was “far from conclusive.” ness, and an effect on the hypothesized “ob- SSRIs generally are well tolerated and sessive-compulsive” nature of paraphilias9 may be more appealing to patients than the • indirect reduction of testosterone. “chemical castration” of hormonal treat- A growing body of literature supports ments. Dosing is similar to that used in de- SSRIs’ effectiveness in treating paraphilias pression or obsessive-compulsive disorder. and sexual offenders. Greenberg7 reviewed Although most patients notice benefi cial case studies and open drug trials of nearly effects in 2 to 4 weeks, some notice the ef- 200 patients receiving fl uoxetine, fl uvox- fect nearly immediately. amine, or sertraline. Most studies showed 10 response rates of 50% to 90%. Positive ef- Naltrexone. An opioid antagonist thought ONLINE fects included decreases in: to affect the CNS processes of pleasure and ONLY • paraphiliac fantasies, urges, and sexu- pain, naltrexone has been used to treat Discuss this article at al acts alcohol dependence and pathologic gam- http://CurrentPsychiatry. • masturbation bling. A few case studies12-14 and 1 study of blogspot.com • hypersexual activity. 21 adolescent sex offenders15 have shown Some studies reported a preferential benefi ts in treating sexual offenders or para- Current Psychiatry decrease in paraphiliac interests with an philiacs. Benefi ts were seen at 50 mg/d, Vol. 8, No. 10 61 continued on page 68 61_CPSY1009 61 9/16/09 3:37:36 PM INVEGA® (paliperidone) Extended-Release Tablets continued from page 61 subjects and younger subjects, and other reported clinical experience has Table 2 not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. This drug is known to be substantially excreted by the kidney and clearance Common side eff ects of is decreased in patients with moderate to severe renal impairment [see antiandrogen therapy Clinical Pharmacology (12.3) in full PI], who should be given reduced doses. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal Depression function [see Dosage and Administration (2.5) in full PI]. Erectile dysfunction Renal Impairment: Dosing must be individualized according to the patient’s renal function status [see Dosage and Administration (2.5) in full PI]. Fatigue Hepatic Impairment: No dosage adjustment is required in patients with mild to moderate hepatic impairment. INVEGA® has not been studied in patients Gynecomastia with severe hepatic impairment. Hot flashes DRUG ABUSE AND DEPENDENCE ® Controlled Substance: INVEGA (paliperidone) is not a controlled substance. Hypertension Abuse: Paliperidone has not been systematically studied in animals or humans for its potential for abuse. It is not possible to predict the extent to which a Low libido CNS-active drug will be misused, diverted, and/or abused once marketed. Consequently, patients should be evaluated carefully for a history of drug Myalgia abuse, and such patients should be observed closely for signs of INVEGA® misuse or abuse (e.g., development of tolerance, increases in dose, Osteopenia drug-seeking behavior). Dependence: Paliperidone has not been systematically studied in animals or Osteoporosis humans for its potential for tolerance or physical dependence. Sweating OVERDOSAGE Human Experience: While experience with paliperidone overdose is limited, Thromboembolism among the few cases of overdose reported in pre-marketing trials, the highest estimated ingestion of INVEGA® was 405 mg. Observed signs and symptoms Weight gain included extrapyramidal symptoms and gait unsteadiness. Other potential signs and symptoms include those resulting from an exaggeration of paliperidone’s known pharmacological effects, i.e., drowsiness and somnolence, tachycardia and hypotension, and QT prolongation. with suggested dosing of 100 to 200 mg/d. Be- Paliperidone is the major active metabolite of risperidone. Overdose cause data are very limited, consider naltrexone experience reported with risperidone can be found in the OVERDOSAGE section of the risperidone package insert. only on an individual basis or as a possible adjunc- Management of Overdosage: There is no specific antidote to paliperidone, tive treatment. therefore, appropriate supportive measures should be instituted and close medical supervision and monitoring should continue until the patient recovers. Consideration should be given to the extended-release nature of the product Psychostimulants. Methylphenidate was added to when assessing treatment needs and recovery. Multiple drug involvement should also be considered. augment SSRI treatment in a study of 26 men with In case of acute overdose, establish and maintain an airway and ensure paraphilias or paraphilia-related disorders.16 Results adequate oxygenation and ventilation. Gastric lavage (after intubation if patient is unconscious) and administration of activated charcoal together with included further signifi cant decreases in total sexual a laxative should be considered. outlets (orgasms per week) and average time spent The possibility of obtundation, seizures, or dystonic reaction of the head and per day in paraphilia and paraphilia-related behav- neck following overdose may create a risk of aspiration with induced emesis. Cardiovascular monitoring should commence immediately, including ior. These gains appeared to be independent of the continuous electrocardiographic monitoring for possible arrhythmias.