BRIEF REPORTS

Selective Serotonin Reuptake Inhibitor-Induced

Sexual Dysfunction: Efficacy of a Drug Holiday

Anthony J. Rothschild, M.D.

Objective: The purpose ofthis study was to evaluate whether weekend drug holidays would
improve sexual functioning in recovered depressed patients with selective serotonin reuptake
inhibitor (SSRI)-induced sexual dysfunction. Method: Thirty outpatients who reported wors-
ening ofsexual functioning during SSRI treatment were instructed to discontinue their SSRIs
after the Thursday morning dose and to restart the SSRIs (at their previous dosage) on Sunday
at 12:00 noon for four weekends. Results: Significant improvement in sexual functioning was
reported by the patients taking sertraline and paroxetine but not by those taking fluoxetine.
There were no statistically significant increases in mean Hamilton depression scores after
discontinuation of the SSRIs; two patients had increases in scores from the 4-8 range to the
1 0-1 4 range. Conclusions: For some patients taking sertraline and paroxetine who experience
sexual dysfunction side effects, brief drug holidays may allow for significant improvement in
sexual functioning without a significant return of depressive symptoms.
(AmJ Psychiatry 1995; 152:1514-1516)

N umenous
controlled
case reports
studies
and the results
have documented
of a few
sexual dys-
fects the discontinuation
sive syndrome.
of the SSRI had on the depres-

function in association with almost all antidepressants,

including the selective senotonin reuptake inhibitors
(SSRIs) (1, 2). Sexual dysfunction may contribute to METHOD
noncompliance with treatment regimens (1, 2) and sig-
nificantly impair the patient’s quality of life (3). The Over an 18-month period, outpatients in an office-based private
frequency of sexual dysfunction in depressed patients practice within a private psychiatric hospital who reported worsening
of sexual functioning during SSRI treatment were asked to participate
prior to initiation of phanmacotherapy or after SSRI
in the study. Patients were included in the study if they 1 ) were be-
treatment is unclear; estimates of SSRI sexual dysfunc- tween the ages of I 8 and 70 years, 2) met the DSM-III-R criteria for
tion range from 9% to 24% (1). Several strategies have major depression (unipolar), 3) had responded to treatment with an
been suggested for treating SSRI-induced sexual dys- SSRI, with a posttneatment Hamilton Depression Rating Scale (10)
score of 10 or less, 4) had orgasm failure and/on delay while taking
function, including the addition of cyproheptadine (4),
the SSRI that had not been present before SSRI treatment or before
yohimbine (5, 6), or amantadine (7), a switch to an- the depressive episode, 5) indicated that the sexual dysfunction was
other antidepressant such as bupnopion (8), or delaying of sufficient magnitude that if it was not connected they would choose
the intake of the antidepressant until after coitus (9). not to continue taking the SSRI, 6) were in a stable relationship (6
The purpose of this study was to ascertain whether brief months) with the same partner, and 7) were willing and able to en-
gage in sexual activity on four consecutive weekends. Patients were
weekend drug holidays would improve sexual function-
excluded from the study if they I ) had a clinical history of alcohol on
ing in patients with sexual dysfunction from either flu- substance abuse in the past year, 2) had sexual dysfunction associated
oxetine, paroxetine, on sertraline and to assess what ef- with an etiology other than SSRI treatment, 3) had a diagnosis of
hypoactive sexual disorder, paraphilia, pedophilia, or any other sex-
ual disorder, 4) were currently taking systemic sex hormones (except
Presented in part at the 33rd annual meeting of the American Col- for birth control pills), 5) were female and were pregnant or lactating
lege of Neuropsychopharmacology, San Juan, Puerto Rico, Dec. 12- or did not agree to use birth control, 6) had received any new medi-
16, 1994, and the 148th annual meeting of the American Psychiatric cations within the past 4 weeks, 7) were actively suicidal, or 8) had a
Association, Miami, May 20-25, 1995. Received Nov. 16, 1994; re- previous history of suicide attempts.
visions received Feb. 9 and May 22, 1995; accepted July 19, 1995. Patients considered appropriate for the study gave written informed
From the Department of Psychiatry, Harvard Medical School, Boston, consent and were instructed to take their total daily SSRI doses in the
and the Mood and Anxiety Disorders Program, McLean Hospital. morning but to discontinue the SSRIs after the Thursday morning
Address reprint requests to Dr. Rothschild, McLean Hospital, I IS dose and to restart the SSRIs (at their previous dosage) on Sunday at
Mill St., Belmont, MA 02178. 12:00 noon. Patients were instructed to have sexual relations between
Supported in part by NIMH grant MH-47457 and grants from the Thursday evening and Monday morning and were uniformly told
Poitras Charitable Foundation and the Ruth Rothstein Greif Fund. that they might expect to see some improvement in sexual functioning.
The author thanks Ms. Suzanne Brewster, Dr. Jacqueline Samson, This procedure was followed for four consecutive weekends.
and Dr. Whitney Wykoff for assistance in analysis of the data and Dr. Ratings of depression and sexual functioning were performed in
Andrew Satlin for his critique of the manuscript. person on Thursday and by telephone on Monday morning. For the

1514 Am J Psychiatry 1 52:1 0, October 1995

 BRIEF REPORTS

TABLE 1. Patients Taking Selective Serotonin Reuptake Inhibitors Who Reported “Much” or “Very Much” Improved Sexual Functioning for at
Least 50% of Four Weekend Drug Holidays
Patients Patients Patients
Taking Taking Taking
Sentraline Paroxetine Fluoxetine
(N=1O) (N=lO) (N=1O) . .
Pairwise Comparisons
Measure N % N % N % (Fisher’s exact test, one-tailed)

Orgasm function 6a 60 5h so i io Sentraline versus paroxetine, n.s.

Sertraline versus fluoxetine, p=O.O3
Paroxetine versus fluoxetine, p=O.O7
Sexual satisfaction 5h 5h 0 0 Sentraline versus paroxetine, n.s.
Sentraline versus fluoxetine, p=O.O2
Paroxetine versus fluoxetine, p=O.O2
Libido 5h 5b 0 0 Sertnaline versus paroxetine, n.s.
Sertraline versus fluoxetine, p=O.O2
Paroxetine versus fluoxetine, p=O.O2

Impnovement in three of five women and three of five men.

hlmprovement in two of five women and three of five men.
Clmprovement in none of six women and one of four men.

initial ratings of depression and evaluation of sexual functioning, pa- no significant differences among the three groups in
tients were asked to rate their experience for the previous 2 weeks.
duration of SSRI treatment (fluoxetine: mean=14.6
For subsequent ratings, patients were asked to comment on their ex-
penience since the last rating.
months, SD=S; paroxetine: mean=17.7 months, SD=4;
Depression was evaluated with the Hamilton depression scale (10) sentraline: mean=13.8 months, SD=6; F=0.09, df=2, 27)
by one rater well trained in its use. Sexual functioning was evaluated on in duration of sexual dysfunction (fluoxetine: mean=
with a 7-point Likert rating scale (1=very much improved, 7=very 12.5 months, SD=S; paroxetine: mean=12.S months, SD=
much worse) to assess changes in orgasm function, libido, and satis-
4; sertraline: mean=1 1.8 months, SD=6; F=0.07, df=2,
faction with overall sexual functioning. The test-retest reliability of
this scale was examined in a separate group of 20 (10 female, 10 27). There were no significant differences among the three
male) successfully treated depressed patients by administering the test groups in concomitant medications that were being taken;
in the morning and again later in the afternoon and asking about one patient in each group was taking a low dose (<1.5
sexual functioning for the past 3 days. The correlations between
mg/day) of borazepam.
morning and afternoon ratings were as follows: orgasm function,
r=O.90; libido, r=O.99; sexual satisfaction, r=O.94.
The proportions ofpatients reporting “much” or “very
All analyses were performed with the use of SPSS-X software ( I I). much” improved sexual functioning for at least half of
Data from all four drug holidays were used in the analyses. For com- the weekends are shown in table 1. Sexual dysfunction
panisons of Hamilton depression scores before and after SSRI discon- returned in all patients after they restarted their SSRIs.
tinuation, data from the four drug holidays were grouped together.
Group comparisons of continuous data (age, length of time taking an
ANOVA revealed no significant differences in mean
SSRI, duration of sexual dysfunction, baseline and final Hamilton Hamilton depression scores before discontinuation of
depression scores) were achieved with the use of one-way analysis of the antidepnessants among patients taking the three SSRIs
variance (ANOVA). For group comparisons of categorical data (sex- (fluoxetine: mean=4.8, SD= 1 .7; sertraline: mean=4.S,
ual functioning, gender) the nonparametnic Fisher’s exact test was
SD=1.4; paroxetine: mean=4.7, SD=1.9; F=0.07, df=2,
used. To assess changes in Hamilton depression scores before and
after discontinuation of the SSRIs, the Wilcoxon matched-pairs
27). After discontinuation of the SSRIs, there continued
signed rank test was used. to be no significant difference in Hamilton depression
scores among the three groups (fluoxetine: mean=4.7,
SD=1.S; sentnaline: mean=S.2, SD=2.8; paroxetine:
RESULTS mean=S.S, SD=2.8; F=0.22, df=2, 27). For each individ-
ual SSRI, a Wilcoxon matched-pairs signed rank test com-
Thirty outpatients (16 women and 14 men) whose paring Hamilton depression scores before and after the
mean age was 42 years (SD=6)-10 taking fluoxetine, 10 drug holidays did not reveal any significant changes (flu-
taking panoxetine, and 10 taking sertraline-began and oxetine: z=-O.06; sertraline: z=-1 .2; panoxetine: z=-O.77).
completed the four drug holidays. There were no sig- The Hamilton depression scores of one patient in the ser-
nificant differences in the ages of the patients taking the traline group and one patient in the paroxetine group
three SSRIs (fluoxetine: mean=42 years, SD=7; panoxe- consistently rose from the 4-8 range to the I 0-1 4 range
tine: mean=44 years, SD=7; sentraline: mean=41 years, (without change in the Hamilton depression scale suicidal
SD=S; F=0.47, df=2, 27). There were also no significant ideation rating) each time the SSRI was discontinued.
differences in the number of women and men taking each
SSRI (fluoxetine: six women, four men; paroxetine: five
women, five men; sentraline: five women, five men). The DISCUSSION
mean doses of SSRI upon entry into the study were flu-
oxetine, 24 mg/day (SD=7); panoxetine, 26 mg/day The different rates of improvement in sexual func-
(SD=7); and sertraline, 60 mg/day (SD=21). There were tioning of the paroxetine and sertraline patients com-

Am J Psychiatry 1 52: 1 0, October 1995 1515

BRIEF REPORTS

pared with the fluoxetine patients is presumably due to strategy for SSRI-induced sexual dysfunction, how fne-
the shorter half-lives of paroxetine and sertnaline. Al- quently they can be implemented, and whether there
though a placebo effect in this open clinical trial cannot are any long-term negative consequences (e.g., lessen-
be ruled out, the lack of improvement in the patients ing of the therapeutic effect). These questions are cur-
who discontinued fluoxetine and the repeated improve- rently being studied in our facility.
ment after repeated implementation of drug holidays in
the panoxetine and sertnaline patients argues against a
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1516 Am J Psychiatry 152:10, October 1995