International Journal of Impotence Research (1998) 10, 181±184 ß 1998 Stockton Press All rights reserved 0955-9930/98 $12.00 http://www.stockton-press.co.uk/ijir Treatment of premature ejaculation with hydrochloride

CG McMahon

St. Luke's Hospital Complex, Sydney, Australia

Purpose: To evaluate the ef®cacy of sertraline hydrochloride in the treatment of premature ejaculation (P.E.). Materials and Method: Forty-six normally potent men, aged 22 to 63 years (mean 42 years) with premature ejaculation were treated with oral sertraline in a dose ranging study. All men were either married or in a stable relationship. The mean ejaculatory interval was 1 minute (range 0± 5 min). All men were started on Sertraline 25 mg daily and were increased to 50 mg after 3 weeks and 100 mg after a further 3 weeks. None of the men received any formal psychosexual therapy. Results: With a dose of 25 mg, the mean ejaculatory interval increased to 7.6 min (range 0±20 min). With a dose of 50 mg, the mean ejaculatory interval increased to 13.1 min (range 7 min± anejaculation) with 4 men experiencing anejaculation. With a dose of 100 mg, the mean ejaculatory interval increased to 16.4 min (range 7 min±anejaculation), 10 men experiencing anejaculation. With a dose of 25 mg, 1 man described transient dizziness. With a dose of 50 mg, 1 man described some drowsiness and anorexia and 1 man experienced minor dyspepsia. With a dose of 100 mg, 2 men described erectile dysfunction and reduced libido, 2 men described transient drowsiness and anorexia, 2 men experienced minor dyspepsia and 2 men described feelings of anxiety. Conclusion: Sertraline appears to be a useful agent in the pharmacological treatment of premature ejaculation.

Keywords: premature ejaculation; sertraline; selective re-uptake inhibitors

Introduction Although the `cornerstone' of treatment is short term directive sex therapy, premature ejaculation may also be treated pharmacologically with a variety Premature ejaculation (PE) is the most common of different . These medications either male sexual disorder, affecting perhaps as many as act centrally or locally to retard the psychoneurolo- 75% of men at some stage in their sexual lives. The gical control of ejaculation and subsequent orgasm. Diagnostic and Statistical Manual of Psychiatry It is well established that major tranquillisers such (DSM-IV) de®nes premature ejaculation as `ejacula- as the phenothiazine, thioridazine, will retard tion that occurs before the individual wishes ejaculation signi®cantly and will, in a signi®cant because of recurrent and persistent lack of reason- percentage of men result in failure to ejaculate.2 able voluntary control of ejaculation and orgasm Although these agents can be used to treat PE their during sexual activity ...'.1 ef®cacy is unfortunately counteracted by the high Premature ejaculation is invariably psychogenic incidence of adverse side effects including drowsi- and can be due to performance anxiety, fear or ness, tardive dyskinesia and other extrapyramidal psychological trauma. Men with premature ejacula- adverse effects. The is tion progress very rapidly from excitement to often associated with delayed or absent ejaculation orgasm which is often experienced as minimally with an incidence of up to 94%3,4 and has been pleasurable. They appear to have a hypersensitive reported as useful in the treatment of PE.5,6 ejaculatory re¯ex. The fact that anxiety plays a role The selective serotonin re-uptake inhibitors in this process however, is attested by the frequent (SSRIs) are primarily indicated in the treatment of situational nature of the problem and the almost depression and are often associated with a variety of universal experience of good ejaculatory control sexual adverse reactions including delayed ejacula- during solitary masturbation. tion. The side effect pro®le differs between different SSRIs, ¯uoxetine tending to effect ejaculation, orgasm and sexual desire, all of which are restored slowly after withdrawal of the drug, whereas sertra- Received 15 May 1997; revised=accepted 28 December 1997 line and tend to affect ejaculation more. Treatment of premature ejaculation CG McMahon 182 This paper reports the results of a prospective Results open label dose ranging study of the ef®cacy of sertraline hydrochloride (Zoloft1, P®zer) in treat- ment of PE. The mean age of the 46 men studied was 42 y (range 22±63 y). The mean pre-treatment ejaculatory la- tency time was 1.0 min with a range of ejaculation occurring from during foreplay or at intromission to 5 min after intromission. The pre-treatment fre- Materials and methods quency of intercourse was 0.6 times=week. Thirty- six men (78%) had primary premature ejaculation, the remaining 10 men (22%) describing secondary Forty-six normally potent men, aged 22±63 y (mean premature ejaculation with previous acceptable 42 y) suffering from PE were enrolled in a prospec- ejaculatory control. Of the 36 men with primary tive dose ranging study to assess the ef®cacy and premature ejaculation, 6 men (17%) had severe tolerance of sertraline hydrochloride (Zoloft1) in the primary premature ejaculation and had never management of PE. All of the study group were achieved intravaginal ejaculation. heterosexual, had no other sexual disorders and In treatment phase 1 (25 mg sertraline=d), the were either married or in a stable relationship. mean ejaculatory latency time of the 46 enrolled Premature ejaculation was regarded as ejaculation men was 7.6 min (range 0±20 min). In treatment that occurred earlier than either the man or his phase 2 (50 mg sertraline=d) the mean ejaculatory partner wished. As no attempt was made to enrol latency time of the 46 enrolled men was 13.1 min men using accepted average ejaculatory latency time (range 7 min anejaculation). Four men were unable intervals, several men had ejaculatory latency inter- to ejaculate after prolonged intercourse with 50 mg vals that would be regarded as acceptable by normal sertraline=d and declined to enrol in treatment standards. Men with erectile dysfunction, reduced phase 3. In treatment phase 3 (100 mg sertraline=d) sexual desire, inhibited male orgasm, chronic the mean ejaculatory latency time of the 42 men psychiatric or physical illness, alcohol or substance enrolled was 16.4 min (range 7 min anejaculation). abuse and the use of psychotropic were Ten men were unable to ejaculate after prolonged excluded from the trial. Men were asked not to use intercourse with 100 mg sertraline=d (Table 1). The condoms, topical penile anaesthetic creams or mean pre-treatment ejaculatory latency time of the sprays. None of the men received any formal 14 men who experienced anejaculation was 1.9 min psychosexual counselling. (range 0±5 min). The study comprised three consecutive treatment The mean frequency of intercourse after three phases each separated by a three week washout weeks of treatment was 1.6 times=week in treatment period. In treatment phase I, men received 25 mg phase 1 (25 mg sertraline=d), 2.1 times=week in sertraline daily for three weeks. Following comple- treatment phase 2 (50 mg sertraline=d) and 2.2 tion of phase 1 and the subsequent drug washout times=week in treatment phase 3 (100 mg period, men were enrolled in treatment phase 2 and sertraline=d). The mean frequency of intercourse received 50 mg sertraline daily for a further three after three weeks of treatment was signi®cantly weeks. Following completion of phase 2 and the superior to the pre-treatment mean frequency with subsequent drug washout period, men were enrolled all doses of sertraline (p < 0.001). There was no in treatment phase 3 and received 100 mg sertraline statistical difference between the mean frequency of daily for the ®nal three weeks. intercourse with differing doses of sertraline. Men were supplied with an ejaculation diary and Intravaginal ejaculation was achieved for the ®rst were asked to record their frequency of coitus, time in each of the cohort of six men with severe quality of erection and orgasm, and to measure and primary premature ejaculation who had never record their ejaculatory latency time using a stop- achieved intravaginal ejaculation. Intravaginal ejac- watch. Men were required to attempt coitus on at ulation occurred in four of the six men with 25 mg least two occasions each week. Results were ana- sertraline=d and in all men with 50 mg and 100 mg lysed using standard statistical methods. sertraline=d. The mean age of this group of six men

Table 1 Results of dose ranging study of sertraline hydrochloride (25, 50 and 100 mg) in the treatment of premature ejaculation

Mean ejaculatory interval Ejaculatory interval range Dose (min) (min) Men with anejaculation Frequency of intercourse

Pre-treatment 1.0 0±5 Ð 0.6 25 mg 7.6 0±20 0 1.6 50 mg 13.1 7±anejac. 4 2.1 100 mg 16.4 7±anejac. 10 2.2 Treatment of premature ejaculation CG McMahon 183 was 26.9 years (range 23±32 years). All men in this logical control of ejaculation and subsequent or- cohort were either married or were involved in a gasm. Animal studies have shown that the central long term stable relationship. One man in this cohort neurotransmitter serotonin has an inhibitory effect developed anejaculation with 100 mg sertraline=d. on sexual function, while is generally Sertraline was, in general, well tolerated. Most stimulatory.7 Sexual effects can occur through any side effects were minor and none prompted with- shift in this serotonin-dopamine balance by an drawal from the study, apart from the anejaculation increase or decrease in either or both neurotrans- experienced by four and 10 men in treatment phase mitter. The serotonin re-uptake inhibitors (SSRI) 2 and 3 respectively. With 25 mg sertraline=d, one should reduce sexual excitement and have a man described transient dizziness. With a dose of bene®cial effect on premature ejaculation. 50 mg sertraline=d, one man described some minor There have been multiple reports in the literature drowsiness and anorexia and one man experienced regarding the sexual adverse effects of antidepres- minor dyspepsia. With a dose of 100 mg sertraline=d, sant and their potential use as treatment for two men described erectile dysfunction and reduced PE. Deveaugh-Geiss et al3 in a multicentre study libido, two men described transient drowsiness and reported failure of ejaculation in 42% of 520 men anorexia, two men experienced minor dyspepsia treated for depression with 200 mg clomipramine=d. and two men described feelings of anxiety (Table 2). Monteiro et al 4 reported a double blind study which showed even greater sexual dysfunction in de- pressed men treated with clomipramine among 17 Discussion men, ejaculation was delayed in only three and absent in 17. Girgis et al 5 and Althof and Seftel6 reported success in the actual treatment of PE with Many men decline or fail to complete a trial of clomipramine. psychosexual counselling for a variety of reasons. Patterson8 noted retarded or absent ejaculation in Men may decline treatment with psychosexual 45 out of 60 male men treated with 20 mg=d ¯uoxetine counselling as a result of their non-acceptance of for depression. Kara et al 9 in a double blind placebo counselling as a valid treatment due to incorrectly controlled study of ¯uoxetine demonstrated a seven assumed social stigma associated with attending a fold increase in the ejaculatory interval which was psychiatrist or psychologist. Some men may be noted as early as one week after initiation of treatment. unable or not prepared to devote the time required Crenshaw10 reported a dose related improvement in to attend several counselling sessions. Other men ejaculatory control in 46 men with ¯uoxetine treat- may demand a quicker response than psychosexual ment of PE. He noted that some men maintained counselling is reported to offer. Optimal results with improved ejaculatory control after withdrawal of psychosexual counselling are highly dependant on ¯uoxetine after 3±6 months of treatment. Both the cooperation of the sexual partner of the man in Waldinger et al 11 and Ludovico et al 12 reported attending and actively participating in the counsel- signi®cant improvement in ejaculatory control with ling sessions. Many men do not have a current paroxetine. Swartz13 and Mendels14 have demon- sexual partner or may have a non-compliant sexual strated a consistently bene®cial effect of sertraline in partner. Clearly, a signi®cant treatment `hiatus' the treatment of premature ejaculation. exists in the management of PE which may be ®lled Sertraline has a relatively long half life of 26 h by alternate non-counselling treatment methods. allowing once daily dosing and promptly achieves Delayed ejaculation is a common side effect of peak plasma levels within 4±6 h. It undergoes many psychotropic and antidepressant drugs which extensive ®rst pass metabolism to the less active act centrally or locally to retard the psychoneuro- desmethylsertraline and its only contraindication, apart from known hypersensitivity, is the concur- rent use of monoamine oxidase inhibitors. In Table 2 Incidence of side effects in a dose ranging study of addition to its selective serotonin inhibitory prop- sertraline hydrochloride (25, 50 and 100 mg) in the treatment of erty, sertraline also appears to inhibit excitatory premature ejaculation responses through blocking dopamine receptors and effecting amino acid sigma receptors, and by down 25 mg 50 mg 100 mg 15 Adverse effect sertraline sertraline sertraline regulating central b-adrenergic receptors. The most common side effects are sexual and gastrointestinal Anorexia 1 2 but a very occasional man will experience the Anejaculation 4 10 agitation and tremor seen with ¯uoxetine. Anxiety 2 Dizziness 1 This study demonstrates that sertraline prolongs Drowsiness 1 2 the ejaculatory interval in a direct dose related Dyspepsia 1 2 fashion and increases the frequency of intercourse. Erectile Dysfunction 2 The occurrence of anejaculation, the most common Reduced Libido 2 adverse effect of sertraline, is also dose related. 1=46 (2%) 6=46 (13%) 18=42 (43%) Anejaculation was not observed with 25 mg Treatment of premature ejaculation CG McMahon 184 sertraline=d but did occur with dose escalation from occurrence of other sexual adverse effects of erectile 25 mg to 50 or 100 mg sertraline=d. Delayed ejacula- dysfunction and diminished libido was dose re- tion and as a consequence, improved ejaculatory lated, occurring only with 100 mg sertraline=d. control, appears to occur within 1±2 weeks of initiating treatment. This acute effect is due to sertraline's direct blocking effect on central seroto- Conclusions nergic re-uptake and cannot be attributed to a decrease in psychopathology since none of the men were clinically depressed. Furthermore, the Sertraline appears to be a useful and reasonably well antidepressant effect of sertraline has not been tolerated oral treatment for premature ejaculation reported to occur within 1±2 weeks. As a signi®cant with improved ejaculatory control usually occurring improvement in ejaculatory control was observed at within 1±2 weeks and subsequent increased fre- doses as low as 25 mg and as anejaculation occurred qency of intercourse. There appears to be a direct in 10 out of 42 (24%) of men at a dose of 100 mg, it dose related increase in ejaculatory latency time seems reasonable to suggest that sertraline treatment which may result in anejaculation in some men with of PE be initiated at a dose of 25 mg and that the doses of 50 mg or higher. clinician should expect a satisfactory therapeutic response in most men with a dose of 25±50 mg. 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