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A Comparison of Treatment of with Three Serotonin Reuptake Inhibitors: A Retrospective Study

David M. Greenberg, MMed, John M. W. Bradford, MB, Susan Curry, BA, and Annice O'Rourke

Treatment of the paraphilic disorders using behavioral, cognitive, pharmacologi- cal, and social interventions has been shown to have limited success with poorly motivated or noncompliant patients. Researchers have speculated on the role of the serotonergic system in the paraphilic disorders. Recent anecdotal studies have reported successful results with the selective serotonin reuptake inhibitors (SSRls) in the treatment of the paraphilic disorders. This retrospective study evaluates and compares the effectiveness of three SSRls in a group of paraphilics (N = 58). The individual effectiveness of fluvoxamine, fluoxetine, and sertraline were examined and compared. Results found that the severity of fantasies de- creased and that there were no significant differences in the reported efficacy between fluvoxamine, fluoxetine, and sertraline. Although double blind placebo crossover studies are still needed to assess the efficacy of these agents, this study further supports the growing body of literature on the potential use of these drugs in the treatment of the paraphilias.

The DSM-IV defines the essential fea- that occur over a period of at least 6 tures of paraphilic disorders as being "re- months" (p 522-3).' Paraphilic behavior current, intense sexually arousing sexual is ~~suallychronic in its course. and the urges, or behaviors involving (1) non hu- underlying often endures man objects, (2) the suffering or humili- throughout the adult life of a paraphiliac. ation of oneself or one's partner. or (3) Due to the immediate gratification this children or other non consenting persons behavior brings to these individuals and the often poor internal controls for para- -- - Drs. Greeribcrg and Bradford are affiliated with the philic behavior, people with paraphilias Sexual Behaviours Clinic, Royal Ottawa Hospital, and the Department of , University of Ottawa, are often viewed as resistant to change.' Ottawa, Canada. Ms. Cur-ry is also affiliated with the Successful cognitive and behavioral treat- Sexual Behaviours Clinic. Royal Ottawa Hospital, and Ms. O'Rourke with Carleton University. Ottawa, Can- ments require that the client be motivated ada. Address correspondence to Dr. D. M. Greenberg. to change and exercise self-control over Royal Ottawa Hospital, 1145 Carling Ave., Ottawa. Canada. their paraphilic behavior. Anti-androgen

Bull Am Acad Psychiatry Law, Vol. 24, No. 4, 1996 525 Greenberg et a/. such as cyproterone acetate sults by suggesting that serotonin re- (CPA) and medroxyprogesterone acetate uptake inhibitors (SSRIs) in the treatment (MPA) reduce paraphilic behavior of paraphilic disorders may be an alterna- through the global suppression of conven- tive pharmacological inte~vention.'~-~" tional and paraphilic sexual fantasies, These case studies have reported fewer preoccupations. and urges.'-' However, adverse effects and encouraging clinical potential adverse side effects, such as the efficacy as compared with traditional reduction in conventional , methods of treatment and management of impotence, impaired . weight this group of patients. gain, gynecomastia, and fatigue, cause Exhibitionism has been reported to many patients to decline this kind of treat- have been successfully treated with flu- m~nt.~.8-9 Their use with adolescents is oxetine. Zohar et a1.I8 reported a also limited for similar seasons.1° Conse- case in which the patient was treated un- quently, these medications are often re- der a partial single-blind condition (pa- served for the more serious sexual of- tient was blind to placebo) with fluvox- fender. amine, desipsamine, and a placebo that The role of serotonin in the treatment resembled the fluvoxamine (ABACA). of major affective disorders has received The impulse to expose himself and the considerable attention over the past 20 behavior itself were eliminated with flu- years. Serotonin reuptake inhibitors have voxamine, without affecting his sexual been used with encouraging results in desire. Treatment with desipramine and several placebo-controlled drug tri- the placebo resulted in the return of the I-'" This new group of drugs has also unwanted paraphilic impulses and behav- been successful in the treatment of anxi- ior. Fluoxetine has been reported to suc- ety disorders, including obsessive-con- cessfully treat both voyeurisn~and cross- pulsive disorder (OCD) and panic disor- dre~sing~('-~'as well as fetishism.22 ders, as well as eating dis~rders.l~-'~ ~afka~~treated 12 men with para- Although the paraphilias are not classi- philias or so-called nonparaphilic sexual fied as OCDs, paraphilics often describe addictions (e.g., compulsive masturba- symptoms that are compulsive in na- tion) with either fluoxetine or imipra- t~re.'~~'~Apart from the direct raised se- mine.2' Their results showed a substantial rotonin effect that serotonin reuptake in- and sustained improvement (i.e., decrease hibition may have on sexual behavior, in the frequency and intensity of uncon- plasma prolactin levels in rodents, nonhu- ventional sexual behaviors, fantasies, and man primates, and humans have also been urges) in all but one patient. Kafka and shown to increase following serotonergic ~rentk~~~also reported successful treat- stimulation. It has been hypothesized that ment results of 10 paraphilics (sexual these neurotransmitter changes are asso- masochists, sadists. exhibitionists, - ciated with inhibition of sexual behavior. teurs, etc.) and 10 nonparaphiliac sexual Recent literature on the treatment of addictions (e.g., compulsive masturba- sexual disorders has shown promising re- tion) with fluoxetine in an open drug trial.

526 Bull Am Acad Psychiatry Law, Vol. 24, No. 4, 1996 Treatment of Paraphilic Disorders

From their study. they concluded that ilu- mean dose of 131 mg of sertraline was oxetine reduced the unconventional or de- reported to be effective in providing viant sexual desire and behavior while symptomatic relief of paraphilic fanta- preserving normative sexual arousal. sies, urges, and drives: results showed Perilstein and his associates" treated a that pedophiles were able to maintain pedophile, an exhibitionist. and a voyeur1 conventional sexual relations with adult frotteur with fluoxetine. All three patients partners. reported improvements (decrease in Our retrospective study reviews the de- deviant fantasies and urges) during the gree and severity of paraphilic fantasies treatment, and that improvement was of a group of paraphilic patients at the sustained for three to six months of sexual behaviors clinic of a university follow-up. Stein et a1." reviewed the teaching hospital who were treated with records of five patients with paraphilias, selective serotonin reuptake inhibitors. five with nonparaphilic sexual addictions, There have been no comparative studies and three with sexual thoughts or rituals of the efficacy of the different SSRls (tlu- that met the criteria for obsessive-com- voxamine, fluoxetine, and sertraline) in pulsive disorders, all of whom were the literature on the treatment of the para- treated with either fluoxetine. clomipra- philias. In this present study. comparisons mine. or fluvoxamine. Their results indi- were made between fluoxetine. fluvox- cated that these medications were most anline. and sertraline to determine effective in treating the sexual obsessions whether one of them is more effective in and compulsions and that the paraphilics reducing paraphilic fantasies. responded less to the medications. ~afka'~reported treating 14 men with Method paraphilias and 12 with -related Procedure In our 12-week retrospec- disorders (e.g.. dependence. tive study, the subjects were treated with compulsive ) with sertr a I'~ne one of the SSRIs. Demographic informa- and fluoxetine. He reported some success tion, type. and dosage of SSRIs pre- with the efficacy of these SSRIs in reduc- scribed (fluvoxamine HCL, fluoxetine ing deviant sexual fantasies and behaviors HCL, or sertraline HCL) was extracted while maintaining normative sexual from the medical charts at baseline and arousal. symptoms were also weeks 4. 8. and 12 by one of the authors assessed and found to be unrelated to the (A.O'R.). Information on the paraphilias clinical in~proven~entof paraphilic symp- being treated and the comorbid DSM- toms. In an open-label. dose-titrated study 111-R diagnoses were also collected from using sertraline to treat pedophiles. Brad- the records. The type of adjunct psycho- ford et a/.'' reported using a variety of social treatment(s) were recorded for each measures including penile plethysmogra- subject. Severity of illness and global im- phy. a decrease in pedophilic fantasies. provement were scored using the Clinical urges, and arousal to pedophilia symp- Global Impression Frequency toms. In their group of 21 pedophiles, a and severity of sexual fantasies were also

Bull Am Acad Psychiatry Law, Vol. 24, No. 4, 1996 527 Greenberg et a/. scored. The severity level of these fanta- study been planned, and for this reason sies. which was rated on a five-point scale there are areas that are not as complete as (0 = no fantasies; 1 = mild, occasional, we would have liked. not too disturbing. easily able to stop: 2 = Seventeen (29.3%) of the subjects re- moderate. frequent, disturbing. less able ceived treatment with fluoxetine. 25 to stop: 3 = severe. very disturbing. very (43.1%) with sertraline. and 16 (27.6%) frequent, rarely able to stop; and 4 = with fluvoxamine. Seventy-nine percent extreme. almost constant, very disturbing, of the patients also received concurrent unable to stop). psychosocial treatment. such as covert Subjects Ninety-four patients who sensitization (n = 32). n~asturbatorysati- were treated at the Sexual Behaviours ation (11 = 13), (n = 19). or Clinic (Royal Ottawa Hospital) between in the relapse prevention group (n = 16) 1991 and 1995 with SSRIs made up the or the group (n = 4). Thirty-six study population. Those patients who had percent of the patients received only one previously been treated for their para- psychosocial treatment and 43 percent re- philia (n = 15) were excluded to rule out ceived two or more types of psychosocial confounding results. Nine subjects did treatment. The typeis) of psychosocial not return for follow-up. Patients who treatment(s) received did not differ were taking CPA concomitantly (n = 6) among the three SSRI groups. were excluded, as were those patients The sample ranged in age from 17 to 72 showing symptoms of (n = 5). years. with a mean age of 35.7 years. One subject was excluded because he was There were no differences between the alone in taking paroxetine. The final sanl- three SSRI groups. The mean education ple size was 58. level was 12.2 years. with a range of 3 to Patients were included in the popula- 21 years. There were no educational dif- tion if they had been treated for paraphilia ferences between the three SRI groups: with an SSRI and came to more than one 56.9 percent of the patients were single: follow-up visit. were male. had not re- 25.8 percent were married or living com- ceived any previous treatment for their mon-law: and 17.2 percent were sepa- paraphilia, and signed a consent form al- rated or divorced. There were no differ- lowing their data to be used for research ences between the groups on marital purposes. An alpha level of at least .05 status. was assumed to declare significance. The mean number of paraphilias per patient was 1.6. The majority of the sam- Results ple were diagnosed as pedophiles As this is a retrospective study, there (74.1%). Atypical paraphilia (24.1 %). ex- are invariably some data missing. Some hibitionism (13.8%), and sexual sadism patients missed a monthly appointment (1 2.1 %) were also common diagnoses and therefore missed one of their fol- (Fig. 1). There were no differences be- low-up visits in this study. The data col- tween the three SSRI groups in the num- lected were not as particular as if the ber of paraphilias. The most common

528 Bull Am Acad Psychiatry Law, Vol. 24, No. 4, 1996 Treatment of Paraphilic Disorders

Percent Table 1 Most Common Adverse Effects N 8 Delayed ejaculation 8 Headaches 7 Drowsiness 6 Reduced sex drive 4 Diarrhea 3 Nausea 3 Blurred vision 2 Figure 1. Paraphilias concurrent psychiatric illness was person- week 4 (six at the 4-week visit, six at the ality disorder (3 1 .0%), followed by de- 8-week visit, and five inore at the 12- pression (27.6%), alcohol abuse or depen- week visit). There was not a significant dence (17.2%), and adjustment disorders relationship between adverse effects and (15.5%) (Fig. 2). withdrawal from the treatment. Table 2 There were no differences found in the lists the reasons for exclusion from the number of adverse effects in the three study after week 4. The compliance rate SSRI groups during weeks 4, 8. and 12; was reported as excellent, with only five 40.4 percent reported one or more ad- patients showing questionable noncom- verse effects at week 4, 30 percent at pliance (missing one or more dosages be- week 8, and 23.1 percent at week 12. tween follow-up visits) at the 4-week Compliance was not significantly af- visit, four patients at the 8-week visit, and fected by adverse effects at any week. six patients at the 12-week visit. Table 1 shows the frequency of the most Most patients when rated on a scale of common adverse effects reported. severity of illness were found to be mod- During the course of the treatment, data erately ill (46.6%) or markedly ill collection for 17 patients was stopped and (29.3%) at baseline. There were no dif- they were excluded from the study after

Table 2 Percent Excluded from Study After Week 4 Reason N Discontinued (AMA) Treated with CPA Side effects-discontinued SSRl Felt better-discontinued SSRl Incarcerated-lost to follow-up Discharged to home province- lost to follow-up Changed SSRl Unknown Figure 2. Concurrent psychiatric illness

Bull Am Acad Psychiatry Law, Vol. 24, No. 4, 1996 529 Greenberg et a/.

severily 5

Baseline Week 4 Week 8 Week 12 Figure 3. Global Improvement Scale Figure 4. Severity of fantasy ferences between the three SSRI groups in frequency). A zero rating indicated no on the Global Improvement Scale. When change (Fig. 5). The Wilcoxon matched the three groups were combined. there pairs signed-ranks test showed a signifi- was a significant improvement on the cant decrease in fantasy levels when com- Global ln~provementScale from baseline paring baseline with week 4 (Z = -4.54, to week 4 (r = 7.96: df = 5 1 : 17 < .00 1 ). two-tailed p < .001) and from week 4 to from week 4 to week 8 (r = 4.3 1 : df = 35: week 8 (Z = 2.02, two-tailed y < .05). 17 < .001). and from week 8 to week 12 Fantasy level did not differ from week 8 (t = 2.76; df = 29: p < .05) (Fig. 3.). to week 12. Forty-four (75.9%) of the patients at baseline admitted to having paraphilic Conclusion fantasies. By week 4. 30 (57.7%) of the This study did not find a difference patients admitted having paraphilic fanta- among fluoxetine, sertraline, and fluvox- sies. 23 patients (57.5%) by week 8, and amine in reducing paraphilic fantasies. 12 patients (30.8%) by week 12. There Furthermore. among the three SSRIs was no significant difference in the fan- tasy severity anlong the thsee SSRI groups at baseline, week 4, week 8, or week 12. Paired-samples t tests showed a significant decrease in the fantasy sever- ity from baseline to week 4 (t = 6.77: dj = 39: y < .001) and from week 4 to week 8 (r = 2.40: rlf = 3 1: y < .05). Fantasy severity did not differ fsom week I 8 to week 12 (Fig. 4). At the three fol- Baseline Week 4 Week 8 Week 12 low-up visits, fantasy frequency level5 -1 = decrease 0 = no change were assessed by rating them fsom - 1 I = increasc (decreasing in fi-equency) to I (increasing Figure 5. Mean fantasy level.

530 Bull Am Acad Psychiatry Law, Vol. 24, No. 4, 1996 Treatment of Paraphilic Disorders there was no significant relationship be- Therefore, it could be argued that these tween the reported adverse effects and effects are merely side effects of the med- withdrawal of subjects from the treat- ications. However, Bradford and col- ment. Serotonin reuptake inhibitors ap- leaguesz7 have used both self-report and pear to be effective in reducing paraphilic penile plethysrnography measures to sug- fantasies with a variety of paraphilias. gest that there is a differential treatment The greatest decrease in paraphilic fanta- response of paraphilic symptoms as com- sies occurred over the baseline to four- pared with conventional adult sexuality.'7 week period, followed by the four- to It can be hypothesized, therefore. that the eight-week period. paraphilic disorders are part of an OCD This was a retrospective study with no spectsum and possibly have a similar un- random assignment or control groups. derlying pathophysiology. Further dou- Furthermore, not all subjects wese seen ble-blind placebo-contsolled study is exactly once a month and the subjects' needed to clarify the efficacy of the self-report fantasies were rated on scales SSRIs in treating the paraphilic disorders. by the authors. There is a possibility, Finally, these agents should be seen as an therefore. of differences between the adjunct therapy in a broad base of exist- three groups. Despite these limitations, ing treatment modalities. rather than a our results do show that a significant irn- panacea for these disordcrs. provement was realized in decreasing paraphiliac fantasies. An open trial study with a larger sample size would be desir- References able as a follow-up for reducing the miss- American Psychiatric Association: Diagnostic ing data inherent in a retrospective study. and Statistical Manual of Mental Disorders (ed 3 rev). Washington, DC: APA, 1994 A study of conventional sexual fantasies, George WH, Marlatt GA: Introduction to re- urges, and behaviors would reveal impol-- lapse prevention with sex offenders, in Re- tant data on the benefits of SSRIs; these lapse Prevention with Sex Offenders. edited hy Laws OR. New York: Guilfol-d Press, 1989 were examined in this study, but the data McConaghy N, Blaszczynski A. Kidson W: collected were insufficient to run any Treatment of sex offenders with imaginal de- sensitization andlor medroxyprogestero~ie. meaningful statistical analysis. Although Acra I'sychiatr Scand 77: 199-206, 1988 this study lacks strict scientific rigor. it Stermac L, Hucker S: Combining cognitive- contributes to the beginning of a small behavioral therapy and pharmacotlierapy in the treatment of pedophilic incest offenders. body of literature supporting the use of Bchav Sci Law 6:257-66, 1988 fluvoxamine, fluoxetine. and sertraline in Cooper AJ, Sandli~~S, Losztyn S, Cer~iovsky Z: A double-blind placebo controlled trial of the treatment of the pasaphilias. ~ncdroxyprogestero~~eacetate a~idcyproterone Some clinicians have been sceptical acetate with scvcn pedophiles. Can J Psychi- about the efficacy of treating the para- atry 37:687-93, 1992 Meyer WJ, Cole C, and Emory E: Depo philic disorders with SSRIs. Adverse sex- provers treatment for sex offending behavior: ual dysfunction effects such as impotence an evaluation of outcome. Bull Am Acad Psy- chiatry Law 20:249-59, I992 and delayed ejaculation are widely re- Bradford JMW, Pawlak A: Double-blind pla- ported in people using these agents.'" cebo crossover study of cyproterone acetate in

Bull Am Acad Psychiatry Law, Vol. 24, No. 4, Greenberg et a/.

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Bull Am Acad Psychiatry Law, Vol. 24, No. 4, 1996