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C UR REN T M EDIC A L RESE AR CH AN D O PI NI ON

VO L. 19 , NO . 2, 20 03, 114-12 4
2 0 0 3 L IB R AP HA R M LIM I TE D

ORIGINAL ARTICLE

The ELIXIR study: evaluation of


sexual dysfunction in 4557
depressed patients in France
Mireille Bonierbale1, Christophe Lanon1 and Jean Tignol2
Psychiatry Department, CHU Sainte Marguerite, 270, boulevard de Sainte
1

Marguerite, 13274 MARSEILLE Cedex 9, France


2
Psychiatry Department, Hpital Perrens, 33076 BORDEAUX Cedex, France

Address for correspondence: Dr Mireille Bonierbale, CHU Sainte Marguerite Pavillon X, 270, boule-
vard de Sainte Marguerite, 13274 Marseille Cedex 9, France. Tel. (+33)6.85.92.82.02; Fax
(+33)4.91.74.46.01; email mireille.bonierbale@wanadoo.fr
Key words: Antidepressants, SSRI Antidepressants, tricyclic ASEX Depression, major DSM-
IV Sexual dysfunction Tianeptine

SUMMARY

Objectives: This survey w as conducted in order to Frequency of sexual dysfunction w as som ew hat
determ ine the extent and nature of disorders of higher in patients treated w ith antidepressant s
sexual function in depressed patients treated in than in untreated patients (71% and 65%
the community in France. respectively). Treatm ent w ith tianeptine w as
Methods: Patients w ith DSM-IV major associated w ith a low er incidence of sexual
depressive episodes w ere included. The inclusion dysfunction than w as treatm ent w ith tricyclic
criteria stipulated that only patients with no antidepressant s or w ith selective serotonin
anteceden ts of sexual dysfunction could be reuptake inhibitors. Although in 39% of cases,
included. Inform ation on sexual function w as physicians managed the sexual problems
collected w ith a questionnaire w hich included encountered by changing the antidepressant
physician observations as w ell as the Arizona treatm ent, the most frequently adopted approach
Sexual Experience Scale. (42% of cases) w as to aw ait spontaneous
Results: Overall, 4557 patients w ere included in remission. Drug holidays or adjunctive therapy
the study. The prevalence of disorders of sexual were very rarely proposed.
function observed was 35% for spontaneously Conclusions: The prevalence of sexual
reported problems and 69% for problems dysfunction in patients w ith major depression is
identified by physician questioning. Impaired high. Antidepressant drugs appear to aggravate
sexual function in depressed patients is also such problem s, w ith certain classes of drug better
revealed by a high score on the Arizona Sexual tolerated than others. Sexual dysfunction in
Experience Scale (mean overall score of 21.4). depressed patients is often not optim ally treated.

Introduction be 9.1%1. It has been estimated that depressive


disorders may account for 10% of physician
Depression is a major public health problem with long- consultations in primary healthcare.
lasting consequences on quality of life, productivity and Morbidity of depression is not restricted to affective
lifestyle. A recent pan-European epidemiological study changes, but touches many aspects of psycho-
involving 80 000 subjects has estimated the prevalence physiological function. One of the most important of
of major depression in the French general population to these is sexual function, which has long been recognised

114 Paper 2299


as contributing to the clinical tableau in depression. For antidepressants causing sexual dysfunction with one of
example, in 1967, a loss of libido was described in 67% these newer drugs in cases where patients complain of
of depressed patients, compared to only 27% of sexual problems34.
euthymic subjects 2. The problems encountered are not Studies of sexual dysfunction in depression can be
restricted to libido, but cover all aspects of sexual complicated by difficulties in determining the relative
functioning3. More recently, a large population-based contribution of depression itself, of treatment, and of
study in Zurich showed that sexual problems could be underlying pre-existing sexual dysfunction14,35. Another
observed in 50% of patients, three times as frequently as confounding factor is that data collection from
in non-depressed subjects 4. These problems were also spontaneous patient self-report are likely to
more frequent in patients taking antidepressants than in underestimate the prevalence of dysfunction compared
untreated patients. Similar findings were obtained in an to data obtained from direct physician questioning11,15.
American population study of male ageing5, which We have therefore carried out a study of the
identified depression as a risk factor for erectile prevalence of sexual dysfunction in a large population
dysfunction, with a relative risk of 1.81. An American sample of patients consulting for major depression who
study on the prevalence of sexual dysfunction in the report no history of sexual dysfunction prior to the
general population showed this to be more frequent in current depressive episode. The study also compared
individuals with affective problems6. dysfunction rates obtained from patient self-reporting
In addition to problems of sexual function associated and by direct questioning by the physician and the
with morbidity, the use of antidepressant medication impact of different classes of antidepressants on sexual
itself can also aggravate or provoke sexual problems711. function. Collected data are also presented on how
The use of tricyclic antidepressants is associated with physicians managed sexual dysfunction.
loss of libido and erectile dysfunction12. These effects
can probably be explained by the anticholinergic
properties of these drugs, with perhaps a contribution
from their dopamine receptor antagonist properties on Methods
libido. Selective serotonin reuptake inhibitors (SSRIs),
on the other hand, can cause delayed ejaculation in The study was conducted in France between October
males 13 and anorgasmia in both sexes, as well as 2000 and April 2001. The investigators were general
impairment of libido and arousal1315. Indeed, the impact practitioners and community psychiatrists, distributed
of SSRIs on sexual function is perhaps the most in a demographically representative fashion across
deleterious side-effect of these drugs from the point of France, who were invited to consider the next five
view of the patients quality of life. It has been patients diagnosed with major depression seen in their
estimated that up to three-quarters of patients taking practice for inclusion in the study. Patients over the age
SSRIs may suffer from sexual problems 13,16,17. of 65, under 18 or with psychosis or dementia were not
Prospective studies have demonstrated the emergence considered for the study. Treatment of depression was
of dysorgasmia subsequent to initiation of SSRI freely chosen by the physician, and not influenced by
treatment in up to two-thirds of patients 18,19. the participation of the patient in the study.
A potential consequence of the impact of The data were collected during these routine
antidepressant therapy on sexual function may be poor consultations. The interviews, conducted during a single
compliance17,20, which is already poor for this class of consultation, consisted of three phases. During the first
drugs, particularly for tricyclic antidepressants 21,22. This phase, the physician questioned the patients in general
may be particularly problematic for patients needing terms about overall well-being or treatment side-effects.
maintenance treatment, because interruption of Patients spontaneously reporting sexual dysfunction
treatment may trigger recurrence of depression. were invited to answer a standard questionnaire
More recent drugs with different mechanisms of concerning sexual function. In the second phase, the
action may have less impact on sexual function. other patients were first asked directly by the physician
Moclobemide is a reversible monoamine oxidase if they had experienced sexual problems, and those that
inhibitor which has been shown to produce only a low admitted this were also invited to respond to the
incidence of sexual side-effects23,24. The same is true for questionnaire. Patients who gave their informed consent
bupropion 16,25,26, mirtazapine 27,28, nefazodone 19,30 and then replied to the questionnaire, which was filled in by
tianeptine 31. What these diverse drugs have in common the physician in their presence; this corresponded to the
is that they are relatively free of facilitatory activity at third phase of data collection.
central serotonergic synapses. Based on recent clinical The physician also reported on the questionnaire
studies26,32,33, guidelines produced by the American demographic data for all patients interviewed, regardless
Psychiatric Association recommend the substitution of of whether or not they described sexual dysfunction.

LIBRAPHARM LTD Curr Med Res Opin 2003; 19(2) Sexual Function in Depression Bonierbale et al. 115
These related to age, gender, marital status, number of completed a checklist of pharmacological (diuretics,
sexual partners, number of children, place of residence, antihypertensives, beta-blockers, others), medical
employment status and profession. In addition, the (diabetes, arterial hypertension, atherosclerosis, others)
physician used a symptom checklist of the DSM-IV or social (smoking, alcohol) risk factors for sexual
criteria for major depression 36 in order to ascertain the dysfunction.
diagnosis. Only patients fulfilling these criteria were The ASEX questionnaire on sexual functioning38 was
included in the study. completed to determine the severity of sexual
Depression severity was rated using the Montgomery dysfunction. This questionnaire had previously been
and sberg Depression Rating Scale (MADRS)37, and translated into French from the original American and
classified as mild (MADRS score between 15 and 20), validated by Pr. Y. Lecrubier (Psychiatry Department,
moderate (MADRS score between 21 and 26) and Hpital de la Piti-Salptrire, Paris). However,
severe (MADRS score > 26). The duration of the biometric validation of the French version of the
current depressive episode and whether the episode was questionnaire has not yet been published.
isolated or recurrent were noted. In the case of Physicians were expected to indicate what
recurrent depression, the date of the first depressive therapeutic strategy they intended to follow for each
episode was recorded. Any associated psychiatric patient taking an antidepressant drug with problems of
comorbidity was identified. The use of an sexual function. A checklist of five options was
antidepressant treatment and the duration of treatment proposed (dose reduction, change in medication,
were identified. The antidepressant used was treatment of the sexual dysfunction with an adjunctive
categorised according to its mechanism of action into pharmacotherapy, wait for spontaneous remission or
the following classes: tricyclic antidepressant drug holidays).
(amitriptyline, amox-apine, clomipramine, desipramine, All data were controlled, validated and analysed
desulepine, doxepine, imipramine, maprotiline or centrally by GECEM, 85/87 rue Gabriel Pri, 92120
trimipramine), SSRI (citalopram, fluoxetine, Montrouge, France, an independent contract research
fluvoxamine, paroxetine or sertraline), SNRI organisation specialising in clinical and epidemiological
(milnacipran or venlafaxine), tianeptine, monoamine studies. Subgroups were compared with the c2 test,
oxidase inhibitors (iproniazide, moclobemide, with a p-value of < 0.01 being considered as statistically
toloxatone) and miscellaneous (mian-serin, mirtazapine significant.
or viloxazine). The rationale behind this was to ensure
suitable sample size. Categories were identified that
would be expected to represent at least 10% of the
sample, based on known prescription rates of Results
antidepressants in France. All clinical data relating to the
depressive episode were entered into the questionnaire. The study included a total of 5048 patients, 4557 of
The sexual function interview was structured using whom (90.2%) yielded evaluable results. The remainder
the questionnaire; data were collected on the nature, corresponded to incomplete data sets or protocol
history and severity of the sexual function, as well as violations. Of those included, 2405 (53%) were
how physicians would treat dysfunction. It was noted recruited by general practitioners and 2005 (41%) by
whether the report of sexual dysfunction had been psychiatrists. The remaining 147 patients (3%) did not
spontaneous or elicited by the physician. Patients were identify themselves in the questionnaire.
first asked whether the identified sexual function The mean age of the subjects was 43.5 10.9 years;
predated the onset of the major depressive episode. the median age was 43 years; 57% of patients were
Those with a previous history of sexual dysfunction female. The age and gender distribution is presented in
prior to the current depressive episode were excluded Table 1. Of the patients, 61% were married and 81%
from the study and the interview stopped at this point. claimed to have a single sexual partner, the remainder
For the remainder, the nature of the sexual dysfunction claiming multiple partners. Around three-quarters
was attributed to one or more of the following (77%) had at least one child, two-thirds lived in an
categories: impaired libido/sexual appetite, retarded urban community. The characteristics of patients
orgasm, premature orgasm, erectile or lubrication recruited by general practitioners and psychiatrists were
difficulties, impaired frequency of sexual relations, essentially similar.
genital pain, loss of sensation and miscellaneous. The severity of the depression at the time of the
Whether the problem arose prior to, or subsequent interview was determined from the score on the
to, the start of antidepressant treatment was noted, as MADRS (Table 2). Overall, the subjects were divided
was the duration of the problem. Any known aetiology between mild (14%), moderate (52%) and severe (34%)
of the problem was indicated and the physician depressive episodes. However, the patients included by

116 Sexual Function in Depression LIBRAPHARM LTD Curr Med Res Opin 2003; 19(2)
Table 1. Demographic characteristics of the study subjects. Table 2. Clinical characteristics of the study subjects. Data
Data are given as absolute number of patients with the are given as absolute number of patients with the percentage
percentage in the category indicated in brackets. Where there in the category indicated in brackets. Where there were
were missing data, the total cohort number is indicated missing data, the total cohort number is indicated in brackets

Total Total
Age: (n = 4443) Severity: (n = 4472)
< 20 years 14 (0.3%) mild 638 (14.3%)
2030 years 451 (10.2%) moderate 2325 (52.0%)
3040 years 1168 (26.3%) severe 1509 (33.7%)
4050 years 1470 (33.1%) Duration: (n = 4535)
5060 years 997 (22.4%) < 2 weeks 207 (4.6%)
> 60 years 343 (7.7%) 2 weeks to 1 month 401 (8.8%)
Marital status: (n = 4508) 12 months 1312 (28.9%)
single 765 (17.0%) 26 months 1225 (27.0%)
married 2754 (61.1%) > 6 months 1390 (30.7%)
divorced 833 (18.5%) Previous depressive episodes: (n = 4514)
widowed 156 (3.5%) yes 1808 (40.1%)
Place of abode: (n = 4452) no 2706 (59.9%)
urban 3006 (67.5%)
suburban 976 (21.9%) Treated Tianeptine
rural 470 (10.6%) ( n = 2920) (n = 661)

Employment status: (n = 4516)


full-time employment 3150 (69.8%)
Tricyclic
retired 367 (8.1%) (n = 330)
unemployed 382 (8.5%)
other 617 (13.7%) Other
(n = 223)
SSRI MAOI
(n = 17)
psychiatrists tended to be more severely depressed than (n = 1332)
SNRI
(n = 310)
those included by general practitioners ( p < 0.01). Untreated
(n = 1637)
Most (60%) of the patients reported that this was their
first depressive episode. The length of the current Figure 1. Antidepressant treatment. Left: proportion of treated
and untreated patients. Right: class of antidepressant used.
depressive episode was variable, in the majority of cases
SSRI, selective serotonin reuptake inhibitor; SNRI, serotonin
over 2 months. At the time of the visit, 64% of patients and noradrenaline reuptake inhibitor; MAOI, monoamine
were already taking an antidepressant treatment, oxidase inhibitor. Note that for 53 individuals, the class of
predominantly an SSRI (Figure 1). The number of antidepressant was not recorded, so that the sum of the class
patients (17) taking a monoamine oxidase inhibitor was cohorts is less than the total number of treated patients
very low (< 1% of the sample), and these subjects were
combined with the other antidepressants group for When the physician actively searched for problems
subsequent analyses. Patients were less likely to be on with sexual function by direct questioning, the
treatment if their depressive episode was mild, or if it percentage of subjects reporting such problems rose to
was their first. The nature of the treatment also varied 69%, with only 1417 patients having no identified
with the severity of the depression (but not with its sexual dysfunction (Figure 2). Solicited complaints were
periodicity), with tricyclic antidepressants being over- again significantly more frequent ( p < 0.01) in those
represented in severely depressed patients, and groups identified in the analysis of spontaneous
tianeptine being over-represented in mildly depressed complaints (Table 3). The nature of the problems is
patients. presented in Figure 3. Problems of libido were the most
Thirty-five per cent of the subjects spontaneously frequently encountered, reported in over two-thirds of
complained of problems with sexual function to their the subjects. Again, the overall incidence of sexual
physician. Spontaneous complaints were significantly problems was higher in patients taking antidepressants
more frequent ( p < 0.01) in patients treated by than in untreated patients ( p < 0.001). There was a
psychiatrists, in males, in recurrent depression and in higher incidence of retarded orgasm in treated patients
treated versus untreated depression (Table 3). The compared to untreated patients (16.6% vs 8.2%;
prevalence of sexual dysfunction increased with the p < 0.001). However, the frequency of problems of
severity and duration of the depressive episode libido was similar in both treated and untreated patients
( p < 0.01). The relationship between severity and (Figure 4).
duration and prevalence was also observed in untreated When the incidence of sexual dysfunction was
patients. compared between classes of antidepressants, some

LIBRAPHARM LTD Curr Med Res Opin 2003; 19(2) Sexual Function in Depression Bonierbale et al. 117
Table 3. Sexual dysfunction and depression. Data are given as
absolute number of patients with the percentage in the
Patients interviewed
category reporting sexual dysfunction indicated in brackets.
4557 subjects
The statistical significance of differences observed within
categories is indicated (c2 test)

Spontaneous Elicited
No sexual problem
Physician: p < 0.01 p < 0.01 (1417 subjects 31.1%)
general practitioner 685 (28.7%) 1547 (64.3%)
psychiatrist 842 (42.2%) 1495 (74.6%)
Gender: p < 0.01 p < 0.01
male 891 (45.4%) 1479 (74.7%)
female 685 (26.8%) 1654 (64.4%) Elicited sexual problem
Severity: p < 0.01 p < 0.01 (3140 subjects 68.9%)
mild 176 (27.8%) 388 (60.8%)
moderate 801 (34.7%) 1581 (68.0%)
severe 574 (38.3%) 1115 (73.9%) Spontaneous report
Duration of episode: p < 0.01 p < 0.01 (1624 subjects 35.6%)
< 2 weeks 42 (20.6%) 90 (43.5%)
2 weeks to 1 month 104 (26.0%) 253 (63.1%)
12 months 415 (31.7%) 893 (68.1%)
26 months 446 (36.6%) 883 (72.1%)
> 6 months 583 (40.7%) 1008 (72.5%) Figure 2. Sexual problems in depression. Prevalence of sexual
Previous depressive episode: p < 0.01 p < 0.01 problems identified by spontaneous patient complaint or
no 881 (32.7%) 1818 (67.2%) elicited by physician questioning
yes 681 (37.8%) 1295 (71.6%)
Antidepressant treatment: p < 0.01 p < 0.01 Problem of libido
yes 1094 (38.3%) 2045 (71.2%) Delayed orgasm
no 466 (28.7%) 1063 (64.9%)
Premature orgasm
Length of treatment: NS p < 0.05
Erection
< 2 weeks 47 (28.0%) 101 (59.4%)
2 weeks to 1 month 179 (38.5%) 343 (73.6%) Lubrication
12 months 275 (39.3%) 519 (73.4%) Problem of frequency
26 months 279 (37.1%) 542 (71.6%) Genital pain
> 6 months 227 (43.2%) 376 (71.3%)
Loss of sensation
Others
differences emerged. Although the drug class versus
0 20 40 60 80 100
total sexual dysfunction effect ( p < 0.001) and the drug Subjects reporting sexual problems (%)
class versus individual sexual dysfunction effect
Figure 3. Prevalence of sexual problems according to gender.
( p < 0.005) were both statistically significant, these Prevalence of individual sexual problems in males (filled
inter-drug differences were quite modest. Overall, columns) and females (open columns)
problems were reported more frequently in patients
taking tricyclic antidepressants ( p < 0.005) or SSRIs function included neuroleptics (6.0%), antihyper-
( p < 0.001) compared to untreated patients, whereas in tensives (4.6%), beta-blockers (2.9%), fibrates (2.5%),
patients treated with tianeptine or the drugs in the diuretics (1.3%) and anti-androgens (0.2%).
other class, rates were similar (Table 4). Delayed Subjective experience of the patients sexual activity
orgasm was the only item significantly impacted was assessed using the ASEX questionnaire. The
( p < 0.001) by antidepressant treatment, and this was population evaluated corresponded to the 3140 subjects
observed with SSRIs, SNRIs and tricyclic for whom sexual problems had been detected during the
antidepressants (Table 4). physician interview. The depressed subjects scored
Patients were questioned about potential risk factors poorly on all dimensions of the scale (Table 5). The
for sexual dysfunction. The most frequently overall ASEX score was 21.4 {SD = 1.06} (on a scale
encountered were smoking (29% of subjects) and ranging from 5 to 30, where a high score corresponds to
regular alcohol consumption (15%). Comorbidities with perceived severity of sexual dysfunction). The median
an impact on sexual function included arterial severity scores were 4 on all items (somewhat weak sex
hypertension (6.5%), diabetes (2.0%), atherosclerosis/ drive, somewhat difficult arousal, erection/lubrication
coronary disease (1.2%), sleep apnoea, respiratory and orgasm, somewhat unsatisfying orgasm). Overall,
insufficiency, hepatic insufficiency, renal insufficiency ASEX scales were comparable in treated and untreated
and androgen deficiency (all < 1%). Concomitant patients (global scores of 21.4 {SD = 1.03} and 21.5
medications susceptible to interference with sexual {SD = 1.08} respectively). However, median scores in

118 Sexual Function in Depression LIBRAPHARM LTD Curr Med Res Opin 2003; 19(2)
orgasm item (Wilcoxon test, p < 0.01; c 2 test,
Libido
p < 0.005). When severity on this item was compared
Delayed orgasm between the different classes of antidepressants, a
*
Premature orgasm * median score of 5 was found for all classes except for
tianeptine-treated patients, who scored 4, like untreated
Erection/lubrication
patients.
Frequency
Finally, treatment strategies used by physicians for
Genital pain sexual dysfunction in their patients were assessed. They
Loss of sensation
were asked to choose one of five treatment options for
patients presenting with sexual dysfunction and under
0 20 40 60 80 100 treatment with an antidepressant. The most frequent
Subjects reporting sexual problems (%)
options chosen were to await remission (i.e. to do
nothing; 41.5%) and to change the antidepressant
treatment (39.3%), which account between them for
No drug
over 80% of responses (Table 6). There was a
Tricyclic statistically significant difference ( p < 0.01) in
approaches between general practitioners and
SSRI psychiatrists; the former tended to have a more active
approach than the psychiatrists, who were more likely
SNRI
to await spontaneous remission. The use of drug
Tianeptine holidays was very rare (4.0%).

Other

0 20 40 60 80 100
Discussion
Subjects reporting sexual problems (%)

Figure 4. Prevalence of sexual problems according to This study has evaluated the presence of disorders of
antidepressant treatment. Top: prevalence of individual sexual sexual function in 4557 depressed patients treated in
problems in treated (filled columns) and untreated (open
the community, either by a general practitioner or by a
columns) patients. The asterisk indicates a significant
difference between treated and untreated patients psychiatrist. As such, this has one of the largest sample
(p < 0.001). Bottom: prevalence of total sexual problems sizes for such a study in depression, comparable with
according to antidepressant drug treatment. Filled columns, general population studies of sexual function. The age
spontaneously reported problems; open columns, problems distribution of the patients evaluated is similar (gaussian
detected by patient questioning. SSRI, selective serotonin
with a peak in the fifth decade) to those observed in
reuptake inhibitor; SNRI, serotonin and noradrenaline
reuptake inhibitor
epidemiological studies of depression in the French
general population1. However, although there was a
the treated patients were higher on the ease of reaching female predominance in the subjects included, this did
orgasm and satisfaction with orgasm items (median not reach the sex ratio of 2 : 1 generally observed in
score = 5: very difficult, very unsatisfying). The depression. The reason for this difference is not clear.
distribution of severity grades was significantly different Since our data were analysed separately by sex, this non-
between the two groups only for the ease of reaching represenztivity should not bias the results obtained.

Table 4. Sexual dysfunction and antidepressant treatment. Number of patients reporting different sexual problems according to
antidepressant drug treatment. The figures in brackets refer to the percentage of patients taking the drug class who report the
problem. SSRI, selective serotonin reuptake inhibitor; SNRI, serotonin and noradrenaline reuptake inhibitor. Note that individual
subjects can report more than one sexual problem. *p < 0.001;**p < 0.05 compared to untreated patients

Untreated Treated Tricyclics SSRIs SNRIs Tianeptine Others


No dysfunction 574 (35.1%) 828 (28.8%) 81 (24.5%) 343 (25.8%) 82 (26.5%) 246 (37.2%) 76 (31.7%)
All problems 1063 (64.9%) 2045 (71.2%) 249 (75.5%)** 989 (74.2%)* 228 (73.5%) 415 (62.8%) 164 (66.3.%)
Libido 865 (52.8%) 1571 (54.7%) 197 (59.7%) 767 (57.6%) 176 (56.8%) 307 (46.4%) 124 (51.7%)
Delayed orgasm 134 (8.2%) 484 (16.6%)* 51 (15.9%)* 262 (19.7%)* 56 (18.1%)* 86 (13.0%) 29 (16.8%)
Premature orgasm 61 (3.7%) 64 (2.2%)* 13 (3.9%) 23 (1.7%) 7 (2.3%) 16 (2.4%) 5 (2.2%)
Erection/lubrication 396 (24.2%) 778 (27.1%) 102 (30.9%) 389 (29.2%) 86 (27.7%) 140 (21.2%) 61 (25.4%)
Frequency 480 (29.3%) 873 (30.4%) 100 (30.3%) 423 (31.8%) 96 (31.0%) 173 (26.2%) 81 (33.8%)
Genital pain 123 (7.5%) 223 (7.8%) 34 (10.3%) 92 (6.9%) 30 (9.7%) 47 (7.1%) 20 (8.6%)
Loss of sensation 170 (10.4%) 280 (9.7%) 37 (11.2%) 137 (10.3%) 30 (9.7%) 49 (7.4%) 27 (11.3%)
Others 1 (0.1%) 12 (0.4%) 1 (0.3%) 3 (0.2%) 2 (0.6%) 3 (0.5%) 3 (1.3%)

LIBRAPHARM LTD Curr Med Res Opin 2003; 19(2) Sexual Function in Depression Bonierbale et al. 119
Table 5. Distribution of ASEX severity scores. Data are presented as the percentage of patients in each severity grade.
The median severity grade for each item is indicated in bold

Item Untreated Treated Total


1. How strong is your sex drive?
1. Extremely strong 1.3% 1.1% 1.1%
2. Very strong 2.8% 3.5% 3.3%
3. Somewhat strong 9.0% 12.5% 11.4%
4. Somewhat weak 36.5% 36.9% 36.6%
5. Very weak 32.6% 27.7% 29.4%
6. Absent 17.8% 18.4% 18.2%
2. How easily are you sexually aroused?
1. Extremely easily 1.5% 1.3% 1.3%
2. Very easily 2.6% 5.3% 4.4%
3. Somewhat easily 10.5% 12.3% 11.8%
4. Somewhat difficult 42.6% 39.3% 40.3%
5. Very difficult 34.0% 31.5% 32.4%
6. Never 8.8% 10.4% 9.8%
3a. Can you easily get and keep an erection?
1. Extremely easily 2.7% 1.5% 1.9%
2. Very easily 4.5% 6.8% 6.0%
3. Somewhat easily 14.0% 13.4% 13.6%
4. Somewhat difficult 48.9% 44.4% 46.0%
5. Very difficult 27.6% 30.6% 29.6%
6. Never 2.3% 3.2% 2.9%
3b. How easily does your vagina become moist?
1. Extremely easily 0.8% 0.9% 0.8%
2. Very easily 4.4% 4.8% 4.7%
3. Somewhat easily 13.3% 13.2% 13.4%
4. Somewhat difficult 36.1% 42.4% 40.8%
5. Very difficult 37.7% 32.4% 34.1%
6. Never 5.6% 6.4% 6.1%
4. How easily can you reach an orgasm?
1. Extremely easily 3.2% 2.9% 3.1%
2. Very easily 4.2% 4.6% 4.6%
3. Somewhat easily 11.9% 8.9% 10.0%
4. Somewhat difficult 41.3% 33.9% 36.4%
5. Very difficult 25.8% 34.7% 31.5%
6. Never 13.6% 14.9% 14.4%
5. Are your orgasms satisfying?
1. Extremely satisfying 0.6% 2.1% 1.7%
2. Very satisfying 5.6% 7.3% 6.7%
3. Somewhat satisfying 14.1% 14.1% 14.3%
4. Somewhat unsatisfying 35.8% 30.1% 32.0%
5. Very unsatisfying 30.0% 31.9% 31.1%
6. Never achieve orgasm 13.9% 14.6% 14.3%

Table 6. Approaches to treatment. Treatment options chosen by general practitioners are compared to those chosen by
psychiatrists. Data are given as absolute number of patients with the percentage in the category indicated in brackets. It should
be noted that more than one treatment option could be proposed for individual patients. This was the case for 35 patients, so
that the sum of the options proposed are greater than 100%. Data were missing for 2729 patients

General practitioners Psychiatrists Total


Reduce antidepressant dose 59 (8.1%) 121 (12.6%) 180 (10.7%)
Change antidepressant class 325 (44.9%) 335 (35.0%) 660 (39.3%)
Adjunctive treatment 84 (11.6%) 26 (2.7%) 110 (6.5%)
Await a spontaneous remission 252 (34.8%) 446 (46.6%) 698 (41.5%)
Programme drug holidays 21 (2.9%) 46 (4.8%) 67 (4.0%)

120 Sexual Function in Depression LIBRAPHARM LTD Curr Med Res Opin 2003; 19(2)
The overall prevalence of disorders of sexual function Impaired sexual function in depressed patients is also
observed in our study is 69%. This figure can be revealed by the high scores that our patients obtain on
compared with a prevalence rate of around 33% or less the Arizona Sexual Experience Scale38. The mean overall
in females and 27% or less in males in a large general score was 21.4 and all dimensions of the scale were
population survey of 22 000 patients in France39. This impacted to a similar degree. This is the first time that
confirms the important impact of depression and the ASEX scale has been used in a survey in France, and
antidepressant treatment on sexual function described no normative data are available here. Nonetheless, in
in several recent studies 35,17. We observed that American samples, ASEX scores in the general
questioning of the patient by the physician elicited the population of 10.9 (males) and 13.5 (females) are
identification of sexual problems in twice as many obtained38. In the latter study, scores for psychiatric
patients as those identified by spontaneous reporting by patients were 17.2 (males) and 20.3 (females),
the patient. These compare well with the rates of 14% somewhat lower values than those found in our study.
and 58% for spontaneous and elicited reporting This discrepancy may be due to the fact that our study
described in a recent study in Spain17. The problem of reported ASEX values only for patients with a sexual
the inadequacy of spontaneous patient self-reporting for problem identified at physician interview. We have thus
identifying sexual problems indicates the importance of probably over-estimated the severity of sexual
the physician in revealing such dysfunction, which is dysfunction in the general population of depressed
deleterious for the patients quality of life and which can patients. This is a limitation inherent to the design of
be managed by appropriate treatment strategies10,34. the study, and needs to be addressed in a specific study.
There was a clear relationship between, on the one The most frequently encountered sexual dysfunction
hand, prevalence of sexual dysfunction and on the other was a problem of libido, reported in three-quarters of
hand, severity and duration of the depressive episode. the subjects. However, impairment in all aspects of
This appeared to be unrelated to the extent of sexual function was described. Delayed orgasm was
antidepressant treatment, since the relationship was reported in a quarter of the patients and difficulties in
observed in untreated patients. Also the correlation penile erection or vaginal lubrication in one-third of
between prevalence and duration of depression was them.
stronger than that between prevalence and length of A major handicap in attributing responsibility for
treatment. sexual dysfunction in depressed patients has been
There are certain intrinsic advantages and limitations identifying the contribution of pre-existing sexual
to the study design used here. The principal advantages dysfunction, depression, drug treatment and
are that it enables a large number of patients to be comorbidity. In our study, patients with sexual
included in the study, and that the naturalistic setting dysfunction previous to the current depressive episode
allows the data to reflect how depressed patients are were explicitly excluded from the study. Comorbidity
actually treated on a day-to-day basis in France. This is (e.g. cardiovascular disease) in our sample was low, and
in contrast with controlled randomised clinical studies, cannot explain the high rate of sexual dysfunction
where stringent inclusion and exclusion criteria may observed. The two principal determinants of sexual
limit the representativity of the sample, and where dysfunction thus seem to be depression itself and drug
rigorous follow-up may influence compliance and treatment, of which the former seems to be more
motivation of the patient. However, these advantages in important. The difference in reported rates of sexual
sample size and representativity must be traded off dysfunction in treated and untreated patients was rather
against potential data inaccuracy. In the case of drug low (71% and 65%, respectively). The overall
treatment, no information is available on the prevalence of sexual dysfunction in a recent Spanish
appropriateness of the dose or treatment duration, nor population study of treated depressed patients without
on patient compliance. An additional important antecedents of sexual dysfunction (59%) was quite
limitation of the design is that, due to its single- similar to that obtained in the present study, but this
interview approach, cross-sectional and retrospective study did not compare rates in untreated patients 40.
data collection, antecedents of sexual dysfunction are The relative contribution of iatrogenic sexual
identified uniquely by patient self-reporting, and are dysfunction in our sample is much lower than that
thus open to anamnestic error. The validity of the data reported in the literature 10,17. The impact of
obtained this way cannot easily be verified, nor has it antidepressant treatment seemed to be restricted to the
been verified in the study. Therefore, conclusions on the orgasm phase of the sexual response cycle, both
causality of the sexual problems observed should be according to physician interview and according to the
drawn with caution and indicate directions for future ASEX questionnaire. One explanation for this
prospective studies in order to confirm these difference may be the fact that our study explicitly
hypotheses. excluded patients with a previous history of sexual

LIBRAPHARM LTD Curr Med Res Opin 2003; 19(2) Sexual Function in Depression Bonierbale et al. 121
dysfunction; it is possible that patients with such associated with tianeptine was very similar to that
antecedents may be more vulnerable to antidepressant- observed in untreated patients, and rates of libido
triggered dysfunction than those without. Alternatively, problems and erectile/lubricative dysfunction were
it is possible that during the physician interview, somewhat lower than those seen in untreated patients.
depressed patients tended to have a de facto low opinion Mechanistically, tianeptine has an atypical action on
of their sexual function, which masked identification of serotonergic neurotransmission 42, and this may explain
treatment-emergent problems. This hypothesis could be the preservation of sexual function in patients treated
tested using a more rigorous questionnaire-based with this drug. Moreover, patients treated with
definition of sexual dysfunction than patient self- antidepressants in the Other class also presented a
reporting. Nonetheless, the observed absence of major lower rate of sexual problems. Although difficult to
differences in severity of sexual dysfunction measured interpret due to the heterogeneity of the sample, it
by the ASEX questionnaire is not in favour of this should be noted that this class included two
hypothesis. Finally, it may be more difficult to reveal antidepressants, mirtazapine and moclobemide, whose
differences between treated and untreated patients in use has previously been described to be associated with
population surveys than in clinical trials where patient a low risk of sexual problems23,27,30.
populations are more homogenous, better matched The final issue to be addressed in this study was how
between treatment options, where follow-up is more physicians managed the treatment of sexual
rigorous, and where the identification of treatment- dysfunction. In nearly half of the cases, spontaneous
emergent sexual dysfunction is an explicit goal. remission was passively awaited, in spite of these
A problem with most published studies (including our problems being distressing for the patients and in spite
own) is that they use cross-sectional data collection and of the existence of therapeutic strategies to alleviate
thus rely on accurate patient recall on previous history them, such as switching to another drug34 or initiating
of sexual dysfunction. The resolution of this issue will drug holidays43. Notably, the use of drug holidays or
require prospective studies where patients are followed adjunctive therapies in our population was extremely
from the onset of depression through the treatment limited. For drug switching, two of the three drugs
phase, such as those that have been performed with (bupropion and nefazodone) for which controlled
bupropion25,41. clinical trials have demonstrated utility in such
The large number of patients included in this study paradigms are not approved for the treatment of
made it possible to compare the impact of different depression in France. It may be that moclobemide and
classes of antidepressant drugs on sexual function. tianeptine could be used in drug switching strategies,
Nonetheless, given the naturalistic nature of the study, and clinical trials to address this would be useful.
the different treatment groups were unlikely to be These findings suggest that awareness amongst
balanced, and these results thus need to be interpreted community physicians (including psychiatrists) of sexual
with caution. Although our study revealed some dysfunction in depressed patients is low. Unlike in the
differences between drug classes, these were not as US, where the American Psychiatric Association has
marked as might have been expected from previous included treatment of sexual dysfunction in its practice
controlled clinical trials, or indeed the large general guidelines for depression 34, no such guidelines have been
population study of Montejo et al.40. The latter found proposed in France. It may be expected that American
much lower rates of sexual dysfunction in patients psychiatrists are more interventionist than their French
treated with mirtazapine, moclobemide, nefazodone or counterparts and that an educational programme to
amineptine than in those treated with SSRIs and SNRIs. incite physicians to look for and manage sexual
The reason for this poor discrimination between dysfunction in their depressed patients could usefully be
antidepressant classes in our study is not clear, but may initiated. Such a programme could help improve
relate to imbalance in terms of important determinants compliance on antidepressant medication and thus
of sexual dysfunction, such as severity. For example, reduce the risk of recurrence.
SSRIs were less often prescribed in severe depression
than tricyclics (33% of prescription compared to 44%).
Alternatively, the better discrimination of the Montejo
study may be due to the fact that the latter only Conclusion
included patients whose sexual dysfunction emerged
after initiation of antidepressant treatment. This large population survey reveals the high prevalence
The only apparent difference between antidepressant of problems of sexual function in patients with major
classes that emerged from our study was the relatively depression. These problems seem to be primarily due to
good tolerability on sexual function of tianeptine and depression itself, rather than to underlying sexual
the Other class. The overall rate of sexual dysfunction dysfunction, other comorbidities or iatrogenic effects.

122 Sexual Function in Depression LIBRAPHARM LTD Curr Med Res Opin 2003; 19(2)
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CrossRef links are available in the online published version of this paper:
http://www.cmrojournal.com
Paper CMRO-2299, Accepted for publication: 20 Dec 2002
DOI: 10.1185/030079902125001461

124 Sexual Function in Depression LIBRAPHARM LTD Curr Med Res Opin 2003; 19(2)