NEUROPSYCHOPHARMACOLOGY 1994-VOL.11, NO.1 21 Imipramine and Sexual Dysfunction during the Long-term Treatment of Recurrent Depression Jordan F. Karp, B.A., Ellen Frank, Ph.D., Angela Ritenour, B.S., Ann McEachran, M.S., and David J. Kupfer, M.D. Ninety patients in the maintenance therapy phase of the Rating Scale for Depression and the SeL-90. Logistic Pittsburgh Study of Maintenance Therapies in Recurrent regression analysis revealed no relationship between Depression (Frank et al., 1990) were studied to determine treatment with active imipramine and sexual functioning possible relationships between the type of therapy for the total group, or for females alone. Analysis of (imipramine versus no drug) and the level of sexual males alone revealed a decreased interest in sex among functioning. The level of sexual functioning was those treated with imipramine, but no significant determined by a composite subscale score of the Social differences in frequency or problems. The implications for Adjustment Scale which assessed (1) current level of maintenance pharmacotherapy and the costibenefit ratio enjoyment and interest in sex; (2) change in interest; (3) of unacceptable side effects versus drug efficacy are current frequency of sexual intercourse; (4) change in discussed. lNeuropsychopharmacology 11:21-27, frequency; and (5) pain and/or difficulty reaching 1994J orgasm. Loss of libido was assessed by both the Hamilton KEY WORDS: Imipramine; Sexual dysfunctions; mon reason for drug discontinuation or noncompliance, Maintenance; Depression; Tricyclics the number of controlled studies of the effects of an­ tidepressant medication on sexual function is limited. Research examining the side-effectsof antidepressants Kolodny et al. (1979) state that approximately 5% has effectively documented the potential negative of depressed patients treated with tricyclics experience effectssuch agents may have on patients sufferingfrom a paradoxicalsexual response involving a continued dis­ acute major depression (Jefferson 1975; Cassem 1982; ruption of sexual function despite clinical amelioration Rabkin et al. 1985; Pollack and Rosenbaum 1987; Frank of other symptoms of depression. A comprehensive re­ et al. 1990). It would appear, however, that those en­ view of the sexual side effectsof psychiatric drugs (Se­ rolled in long-term maintenance therapy may ex­ graves 1988) documents 33 case reports of sexual im­ perience fewer such effects,at least in the area of weight pairment due to antidepressant agents. Most of these gain(Frank et al. 1992). Despite anecdotal evidence sug­ descriptions (22 out of 33 patients) are men experienc­ gesting that sexual side effectsare frequent and a com- ing erectile dysfunction and ejaculatory failure as a re­ sult of tricyclic medications (Greenberg 1965; Simpson et al. 1965; Gross 1982; Schwarcz 1982; Yassa 1982; From the University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania. Nininger 1987; Price and Grunhaus 1990). Address reprint requests to: Ellen Frank, Ph.D., Professor of A double-blind study conducted by Harrison et al. Psychiatry and Psychology. Western Psychiatric Institute and Clinic, (1985, 1986) examined the effects of imipramine and 3811 O'Hara Street, Pittsburgh, Pennsylvania 15213 Received November 11, 1993; revised February 1, 1994; accepted phenelzine on sexual function. Both drugs decreased February 28, 1994. the frequency of masturbation, and phenelzine de- © 1994 American College of Neuropsychopharmacology Published by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 0893-133X/94/$7.00 22 J.F. Karp et al. NEUROPSYCHOPHARMACOLOGY 1994-VOL. 11, NO.1 creased the number of sexual thoughts. Kowalski and mg in comparison to those assigned to placebo or to colleagues (1985) examined the effectsof amitriptyline non pill conditions. and mianserin on nocturnal penile tumescence. The results suggest that both compounds decrease the mag­ nitude and the frequency of nocturnal erections. It should be noted, however, that the sample used was METHODS a nonpsychiatric population. Only one placebo-controlled clinical trial has been The patients included in the present report were receiv­ identifIedthat specifIcallyevaluates the effectof a tricy­ ing treatment in the Pittsburgh Study of Maintenance clic (clomipramine) on the sexual functioning of women Therapies in Recurrent Depression (Frank et al. 1990). (Monteiro et al. 1987). The population studied were all Allsubjects were between ages 21 and 65, and entered seeking treatment for symptoms of obsessive-compul­ the program in their third or greater episode of definite sive disorder, and not depression. Twenty-nine per­ major depressive disorder, according to Research Di­ cent of the women in the clomipramine treatment group agnostic Criteria (RDC) (Spitzer et al. 1978). In addi­ reported both decreased interest in sex (attributing to tion, all patients were required to have had at least one diffIculty achieving orgasm) and problems with lubri­ other major depressive episode during the prior 2.5 cation. Forty-three percent described reduced sexual years, one additional lifetime major depressive episode, sensation, and 71% were anorgasmic. The generaliza­ and at least a 10-week period of remission between the tion of these findings for women being treated with index episode and the immediately previous episode. depression is questionable because the neurological and These criteria for patient selection were utilized to yield affectivedifferences between obsessive-compulsive dis­ a study group at high risk for recurrence. All previous order and major depression are marked. episodes must have required psychiatric treatment or Several case reports have documented sexual dys­ must have resulted in significant functionalimpai rment. function in depressed women, due not to their affec­ Patients with a recent history of nonaffectiveAxis I psy­ tive illness, but due to their treatment with tricyclics. chiatric disorder were excluded, as were those who had Price et al. (1986) describe a patient experiencing anor­ significantmedical histories. Patients meeting fullRDC gasmia from treatment with imipramine. Quirk and for borderline or antisocial personality disorder were Einarson (1982) report that two women (ages 24 and also excluded from the study, although patients with 30) both having depression and features of obses­ other Axis IIdisorders were not. Following a minimum sive-compulsive disorder became completely anorgas­ two-week drug-free wash-out period, each patient un­ mic upon treatment with clomipramine. Riley and Riley derwent a comprehensive independent assessment to (1986) similarly describe two depressed women who reevaluate the severityof depression. A Raskin Severity became anorgasmic due to treatment with clomipra­ of Depression score (Raskin et al. 1969) of seven or mine, and one woman who experienced similar side greater, and a Hamilton Rating Scale for Depression effectsresulting from treatment with imipramine. Sov­ (HRSD) score (Hamilton 1960) of 15 or greater con­ ner (1983) and Shen (1982) report anorgasmia in de­ stituted the severity criteriafor inclusion in this protocol. pressed women due to treatment with imipramine and Allsubjects then received the same short-term treat­ amoxapine, respectively. Sovner (1984) also reported ment regimen consisting of a combination of imipra­ that nortriptyline, an antidepressant which affects mine hydrochloride (150 mg to 300 mg) and interper­ serotonergic activity, produced anorgasmia. sonal psychotherapy (IPT) (KIerman et al. 1984). These potential negative side-effects of treatment Treatment sessions were scheduled weekly for 12 with tricyclics may increase the wariness of men and weeks, then biweekly for 8 weeks, and then monthly. women experiencing depression with regard to the At whatever point in thisshort-term treatment regimen efficacy of these medications, and this may diminish the patient maintained an HRSD score of less than or the adherence to prescribed treatment regimens. This equal to five for three consecutive weeks, a second bio­ increased wariness may also reduce the willingness of logical and psychosocial evaluation was completed. Pa­ a patient to continue treatment with maintenance phar­ tients then continued to receive combined treatment macotherapy, even though this has been found to for an additional 17 weeks, during which both HRSD signifIcantlyreduce the chance of recurrence (Frank et and Raskin scores, and imipramine dosages were re­ al. 1990; Kupfer et al. 1992; Frank et al. 1993). There­ quired to remain stable. A third evaluation was then fore, a better understanding of the impact of main­ conducted. After that, patients were randomly assigned tenance tricyclic therapy on sexual function is clearly to one of the five maintenance treatments: (1) a main­ warranted. The present report focuses on ongoing sex­ tenance form of IPT (IPT-M; Frank 1991) offeredalone; ual difficultiesin patients randomly assigned to main­ (2) IPT-M with active imipramine therapy continued at tenance treatment with imipramine in the range of 200 the acute treatment dosage; (3) IPT-Mwith placebo; (4) NEUROPSYCHOPHARMACOLOGY 1994- VOL. 11, NO. 1 Imipramine and Sexual Dysfunction 23 Table 1. Demographic and lllness-History Characteristics Total Group (n = 90) Drug No-Drug KW, Variable Mean SO Mean SO p Value Gender 35F/9M 36F/I0M Age at entry 38.93 11.18 40.67 11.42 0.49, NS Duration of index episode (weeks) 22.89 18.20 21.26