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The Relationship Between Depression
and Erectile Dysfunction
Stuart N. Seidman, MD, and Steven P. Roose, MD
Address
Department of Psychiatry, College of Physicians and Surgeons of
Columbia University, 1051 Riverside Drive, Unit 98, New York, NY
10032, USA.
E-mail: sns5@columbia.edu
E-mail: spr2@columbia.edu
Current Psychiatry Reports 2000, 2:201–205
Current Science Inc. ISSN 1523-3812
Copyright © 2000 by Current Science Inc.
Introduction
Erectile dysfunction (ED) is a common disorder of aging
men with a prevalence of 5% in men 40 years of age, increas-
ing to 15% to 25% at age 65 years and older [1,2]. Unipolar
depressive disorders, such as major depressive disorder
(MDD) and milder depressive syndromes (
eg,
dysthymia)
affect 10% to 20% of men. Among elderly men, milder
depressive syndromes appear to be more common.
Although comorbidity between ED and depressive
illness is apparently high, the causal relationship is
unclear. ED and the psychosocial distress that often
accompanies it may trigger the development of depressive
illness in vulnerable individuals; depression may induce
ED (
eg,
a subgroup of men with MDD develop a reversible
loss of nocturnal penile tumescence while depressed)
[3–6]; a third factor, such as substance abuse or medical
illness, may cause both conditions; or these conditions
may be etiologically unrelated and are comorbid simply
because of their high prevalence, particularly in older men.
Depression in Men
The lifetime prevalence of MDD in young adult men
(15–54 years) is 12.7%, and the female-to-male adjusted
odds ratio is 1.57 [7]. Among older men, MDD appears to
be less common but may be replaced by milder depressive
syndromes [8]. In an on-site expansion of the Epidemio-
logic Catchment Area study that focused on the psychiatric
status of community-dwelling elderly individuals, 465
men older than age 60 were interviewed [9]. Of these men,
18% had some degree of depression. Notably, among the
depressed men, MDD was rare (2.4%), milder depressive
syndromes were more common, and significant, isolated
dysphoria was most common (73%).
Male Sexual Function and Dysfunction
Sexual function can be divided into four overlapping
phases: 1) drive; 2) arousal, marked by erection in men;
3) release, marked by orgasm and ejaculation; and
4) resolution, which involves some degree of refractori-
ness. Normal sexual function is a biopsychosocial process.
Sexual dysfunction may be biologic, psychologic, or social
in origin, but virtually always affects all three. In clinical
practice, the most commonly encountered male sexual
dysfunctions are hypoactive sexual desire disorder, prema-
ture ejaculation, and ED. In the fourth edition of the
Diag-
nostic and Statistical Manual of Mental Disorders
(DSM-IV),
these diagnoses are strikingly dependent on clinical judg-
ment and do not include frequency or duration criteria
[10]. This article focuses on ED and explores physiologic
factors contributing to its development, the relationship
between ED and depression, and current treatments.
Erectile dysfunction
Erectile dysfunction is defined as the inability to obtain and
maintain an erection sufficient for satisfactory intercourse or
other sexual expression. It is a para-aging phenomenon that
affects more than half of all men between the ages of 40 and
70 years [1,11]. ED is associated with, and presumably
exacerbated by, poor health and is more common among
men who smoke and those with diabetes, heart disease,
hypertension, and hyperlipidemia [1,12].
Normal sexual function is a biopsychosocial process; sexual
dysfunction almost always has organic and psychologic
components, and it requires multidisciplinary, goal-directed
evaluation and treatment. Factors such as aging, declining
testosterone levels, medical illness, certain medications,
and comorbid depressive illness can contribute to sexual
dysfunction. Erectile dysfunction (ED) is the most common
male sexual dysfunction encountered in the clinical setting.
Comorbidity between ED and depressive illness is high,
but the causal relationship is unclear, and likely bidirec-
tional. In this article, we review the existing literature
on the relationship between depression and ED.
202 Sexual Dysfunction
Factor Contributing to Changes in Sexual
Function
Age
The change in sexual function with age is multidimen-
sional and variable [11,12]. Important determinants
include availability and health of a partner, relationship
dynamics, fear of performance failure, chronic illness,
substance and medication use, neuropathy and vascular
insufficiency, and depression.
Age-associated changes in male sexual response
include reduced libido; reduced number and frequency of
morning erections; reduced penile sensitivity; reduced
arousal, including an increase in the time needed to
achieve erection and difficulty maintaining an erection;
prolonged plateau phase; reduced ejaculatory volume and
force of expulsion; and prolonged refractory period
(Table 1). The normative decline in testosterone level may
be associated with a reduction in libido and mood,
although this is not well established [13•].
Medications and substance use
Many medications and substances have been reported to
induce sexual dysfunction, particularly tobacco, antihyper-
tensives, anti-ulcer drugs, alcohol, anxiolytics, mood
stabilizers, antipsychotics, and antidepressants [1,14].
Depression itself is associated with decreased libido,
diminished erectile function, and decreased sexual activity
(see below) [3,4]. Sexual dysfunction as a symptom of
depression, coupled with the paucity of controlled data
regarding the effects of medications on sexual function,
makes interpretation of data regarding antidepressant-
induced sexual dysfunction difficult.
Most antidepressants are associated with sexual side
effects. Antidepressants may cause sexual side effects in the
drive phase (
eg,
decreased libido, although this is difficult
to distinguish from the decrease in sexual satisfaction
associated with pervasive anhedonia), the arousal phase
(
eg,
erectile dysfunction, although the relationship to pre-
existing organic factors and to major depression compli-
cates this association), and the release phase (
eg,
delayed
orgasm or anorgasmia). With serotonergic medications
such as selective serotonin reuptake inhibitors, orgasmic
delay appears to be most common, followed by decreased
libido and then arousal difficulties [15]. Painful ejacula-
tion occurs in some men taking tricyclic antidepressants
[16]. In comparing classes of antidepressants, sexual
dysfunction is reported most often with serotonin
reuptake inhibitors, somewhat less frequently with
monoamine oxidase inhibitors, and even less frequently
with tricyclic antidepressants [14].
Strategies for treating antidepressant-induced sexual
dysfunction include decreasing the dose, waiting, adding
an “antidote,” or switching, although none of these
treatments has well-established efficacy.
Disease
Determining the impact of medical illness on sexual
function is complicated by the effects of age and relation-
ship dynamics. Reduced libido and loss of spontaneous or
fantasy-related erectile function are clearly associated with
hypogonadism [13•]. ED is more common among men
with diabetes, heart disease, hypertension, and hyper-
lipidemia [1,12].
Comorbid Depression and Erectile
Dysfunction
Erectile function in men with major depressive
disorder
Loss of libido is a classic symptom of melancholic MDD
and has played a prominent role in psychodynamic and
other anecdotal descriptions of depressive illness. System-
atically collected data confirm that MDD is frequently
associated with decreased libido, diminished erectile func-
tion, and decreased sexual activity [3,4].
In some men, the presence of MDD is associated with a
reversible impairment in sexual neurophysiology, leading
to ED. Steiger
et al
. [17] assessed several parameters of
nocturnal penile tumescence (NPT) in 25 men with an
acute episode of depression compared with nondepressed
control subjects. Although no statistically significant differ-
ences in NPT parameters were found between the
depressed group and the control subjects, there was a
complete lack of NPT in four of 25 depressed men that was
reversed after antidepressant therapy.
In contrast, Thase
et al
. [3] demonstrated a significant
reduction in NPT time and decreased penile rigidity in 34
depressed men compared with nondepressed control
Table 1. Expected changes in sexual function in aging men
Function Change
Desire Variably reduced, depending on testosterone level, desire of partner, length of time in relationship, baseline
libido
Erection Increased time to achieve erection, difficult to maintain; nocturnal penile tumescence time decreases from
age 13, “use or lose” principle
Ejaculation Reduced volume of ejaculate, reduced force of expulsion, period of ejaculatory inevitability not as evident
Refractory period Prolonged
The Relationship Between Depression and Erectile Dysfunction • Seidman and Roose 203
subjects. NPT time was reduced by at least one standard
deviation below the control mean in 40% of depressed
men and was comparable to that in a group of 14 non-
depressed men with a diagnosis of ED due to organic
causes. These findings were confirmed in a repeat study
with a new group of 51 men with major depression [18].
Together, the results of these studies support the conclusion
that erectile function as assessed by NPT is impaired or
absent in some, but not all, depressed men, suggesting a
neurophysiologic link between depression and ED.
Depressive symptoms among men with erectile
dysfunction
The link between ED and depression among men who
present with ED has not been systematically studied in
clinical settings. There is, however, suggestive evidence
from a large epidemiologic sample as well as from a sexual
dysfunction clinic.
The Massachusetts Male Aging Study was a cross-
sectional, community-based random-sample survey of
health and aging in men aged 40 to 70 years. It was
conducted in 11 randomly selected towns in the Boston area
between 1987 and 1989, and had a response rate of 76%
(
n
= 1290). Based on the subjects’ responses to nine
questions that were highly correlated with biologic
measures of erectile response, levels of ED were graded as nil
(48%), minimal (17%), moderate (25%), or complete
(10%) [1]. Depression and anger were highly correlated with
ED. Using the Center for Epidemiologic Studies Depression
Scale cutoff of 16 (which is correlated with MDD), all men
with this degree of depressive symptomatology had some
(
ie,
minimal, moderate, or complete) ED [19••]. Maximal
level of anger (either suppression or expression, as defined
by Spielberger’s anger scales) was associated with approxi-
mately 75% overall ED, double the ED prevalence among
men who reported minimal anger [1].
Two large studies describing psychiatric diagnoses and
symptoms among men presenting to the Johns Hopkins
Sexual Behaviors Consultation Unit from 1976 to 1979
(
n
= 199) and from 1984 to 1986 (
n
= 223) revealed that
approximately one third had a comorbid psychiatric diag-
nosis (mostly affective, anxiety, or personality disorders)
[20,21]. Men with ED had high levels of depressive, somatic,
and anxious symptoms and scored very high on measures of
overall psychological distress (
eg,
using one well-validated
instrument that measures such distress, these men scored in
the 92nd percentile of the normative population).
Finally, multiple studies have demonstrated a strong
positive correlation between ED and reduced quality of
life, impaired social and occupational functioning, and
substance abuse [22]. Successful treatment of ED appears
to reverse much of this morbidity [23].
Treatment of Erectile Dysfunction
Until the recent introduction of effective oral agents, the
only nonsurgical ED treatments with proven efficacy were
penile self-injection therapy and vacuum device therapy.
Penile self-injection therapy is an effective nonsurgical
treatment [24] that involves the injection of vasodilator
medications into the penis using a small needle. After the
initial test injections in the urologist’s office, patients
receive instructions in the self-injection technique. Once
they have learned the proper technique and reached the
satisfactory dose of the medication, patients receive
medication and supplies for home injections. Follow-up is
conducted through periodic visits to ensure compliance
and to supply additional medication. The most commonly
utilized injectable medication is alprostadil, which is
available as a ready-to-use kit under the brand name
Caverject (Pharmacia and Upjohn, Peapack, NJ). Many
men and their partners find these methods unacceptable.
Follow-up studies of patients for whom injection therapy
was effective determined that about half of the patients
had discontinued treatment [25,26]. The urethral supposi-
tory is a minimally invasive pharmacologic therapy for ED.
A small pellet of alprostadil, preloaded in a sterile applica-
tor, is inserted into the urethra prior to sexual intercourse.
In March 1998, the US Food and Drug Administration
(FDA) approved the first “on-demand” oral medication for
the treatment of ED, sildenafil (Viagra; Pfizer, New York,
NY). Sildenafil is a competitive inhibitor of cyclic GMP–
specific phosphodiesterase type 5 (PDE5), the predomi-
nant isozyme causing the breakdown of cyclic GMP in the
human corpus cavernosum. After sexual stimulation,
neurogenically mediated release of nitric oxide induces the
formation of cyclic GMP by guanylate cyclase within the
corpus cavernosum smooth muscle. Sildenafil amplifies
the effect of sexual stimulation by retarding the degrada-
tion of cyclic GMP by PDE5. It is not effective in the
absence of sexual stimulation. Sildenafil has demonstrated
significant efficacy in ED associated with primarily
psychogenic, primarily organic, and mixed etiologies in
worldwide clinical trials [27]. The most frequently
reported adverse events are headache, facial flushing, and
indigestion. The only absolute contraindication to the
administration of sildenafil is the concomitant use of
organic nitrates in any form at any time. This class of drugs
may precipitate hypotension and syncope in the presence
of sildenafil [28]. Additionally, drugs that are potent inhib-
itors of the subclasses of hepatic P450 enzymes that metab-
olize sildenafil (CYP3A4 and CYP2C9), such as cimetidine,
erythromycin, and protease inhibitors, may result in an
increase in serum levels of sildenafil. However, these
increases do not appear to be associated with an increase
in the type or severity of adverse events seen when sildena-
fil is administered alone.
In April 2000, the FDA approved a second oral medi-
cation for the treatment of nonorganic ED, apomorphine
(Uprima; TAP Pharmaceuticals, Deerfield, IL). Apomor-
204 Sexual Dysfunction
phine is a centrally acting dopamine agonist. It has been
available since 1869 and has been utilized parenterally as an
emetic agent and as an anti-Parkinsonian drug. Uprima is a
novel sublingual formulation of apomorphine that is
rapidly absorbed following sublingual administration, with
clinical effects within 20 to 45 min in the presence of sexual
stimulation. In multicenter double-blind clinical trials,
more than 1000 patients with ED with no major organic
component were randomized to placebo or apomorphine 2,
4, or 6 mg. Global efficacy was as follows: apomorphine 2
mg, 44% to 46%; apomorphine 4 mg, 52% to 58%;
apomorphine 6 mg, 60%; and placebo 31% to 38%
(
P
< 0.001 for all apomorphine doses compared with
placebo). The primary side effects were nausea, syncope, and
sedation (Reproductive Health Drugs Advisory Committee,
FDA Briefing Package. Uprima, April 10, 2000).
Treatment of erectile dysfunction in depressed men
Shabsigh
et al
. [29] conducted a study of 120 men who
presented to a urologic clinic with ED, benign prostate
hyperplasia, or both, and who completed self-report
depression symptom inventories, the Primary Care Evalua-
tion of Mental Disorders Survey (PRIME-MD) and the Beck
Depression Inventory (BDI). Criteria for the diagnosis of
“depression” were a BDI score of greater than 15 and four
or more depressive symptoms from the PRIME-MD.
Overall, depression was more commonly reported by men
with ED (55%) than those with only benign prostate
hyperplasia (21%). A total of 15 patients in the ED group
who did not experience depression and 18 patients with
ED and depression were treated for their ED with either
penile intracavernosal injection or a vacuum device. All 15
(100%) patients in the ED-only group continued treatment
and were satisfied with the outcome. In contrast, only 7 of
18 (38.9%) who had ED and depression continued
treatment [29].
In a retrospective analysis of patients who took part in
the placebo-controlled prerelease sildenafil clinical trials,
134 men were diagnosed with depression [30]. Of those who
received sildenafil, 76% responded positively to the global
efficacy question (“Did the treatment improve your erec-
tions?”), compared with 18% of those who received placebo.
We recently conducted a placebo-controlled, parallel-
group, double-blind study of 50 to 100 mg of sildenafil or
placebo in 146 men with ED and comorbid subthreshold
MDD. Patients were older than 18 years, were in stable
heterosexual relationship, and had been experiencing ED
for over 6 months. Subthreshold MDD was diagnosed as a
score of at least 12 on the 24-item Hamilton Rating Scale
for Depression (HAM-D) and two to four DSM-IV major
depressive episode criteria, with at least one being
depressed mood or loss of interest or pleasure in most
activities all day or every day for 2 weeks. The standard
diagnosis of MDD involves five major depressive episode
criteria, and such patients were excluded. Follow-up
HAM-D, BDI, and Clinical Global Impression scores were
assessed at week 12 [31].
Men with ED and depression were treated for 12 weeks
with sildenafil or placebo. An “ED responder” was defined
by a score of greater than 22 on the erectile function domain
(range 1–30) of the International Index of Erectile Function,
as well as affirmative responses to two questions regarding
improvement in erections and ability to have intercourse:
1) Did the treatment improve your erections? and 2) Did the
treatment improve your ability to have sexual
intercourse? Among the responders, 83% were treated with
sildenafil and 17% received placebo (
P
< 0.0001). Moreover,
depressive symptoms decreased significantly in ED respond-
ers: the mean HAM-D score among ED-responders
decreased from 16.8 to 7.0; among ED-nonresponders, it
decreased from 16.8 to 13.6. Although the majority of men
who were ED responders were in the sildenafil treatment
group, even among the small number of ED responders
treated with placebo, there were similar improvements in
their depression scores [31].
Conclusions
Erectile dysfunction is a multifactorial condition.
Precipitating factors include cardiovascular disease,
diabetes, smoking, relationship problems, anxiety, and
depression. It is a common disorder that becomes more
prevalent with age, but it is not an inevitable consequence
of aging. More studies are needed to fully understand the
complex relationship between ED and depression and to
determine the most appropriate treatment for men with
both disorders.
References and Recommended Reading
Recently published papers of particular interest have been
highlighted as:
• Of importance
•• Of major importance
1. Feldman HA, Goldstein I, Hatzichristou G,
et al.
:
Impotence
and its medical and psychosocial correlates: results of the
Massachusetts Male Aging Study.
J Urol
1994,
151:
73–80.
2. NIH Consensus Panel on Impotence:
Impotence.
JAMA
1993,
270:
83–90.
3. Thase ME, Reynolds CF, Jennings R,
et al.
:
Nocturnal penile
tumescence is diminished in depressed men.
Biol Psychiatry
1988,
24:
33–46.
4. Reynolds CF III, Frank E, Thase ME,
et al.
:
Assessment of sexual
function in depressed, impotent, and healthy men: factor
analysis of a brief sexual function questionnaire for men.
Psychiatry Res
1988,
24:
231–250.
5. Roose SP, Glassman AH, Walsh BT, Cullen K:
Reversible
loss of nocturnal penile tumescence during depression:
a preliminary report.
Neuropsychobiology
1982,
8:
284–288.
6. Mathew RJ, Weinman ML:
Sexual dysfunctions in depression.
Arch Sex Behav
1982,
11:
323–328.
7. Blazer DG, Kessler RC, McGonagle KA, Swartz MS:
The prevalence and distribution of major depression
in a national community sample: the National Comorbidity
Survey.
Am J Psychiatry
1994,
151:
979–986.
The Relationship Between Depression and Erectile Dysfunction • Seidman and Roose 205
8. Devanand DP, Nobler MS, Singer T,
et al.
:
Is dysthymia a
different disorder in the elderly?
Am J Psychiatry
1994,
151:
1592–1599.
9. Blazer DG, Hughes DC, George LK:
The epidemiology
of depression in an elderly community population.
Gerontologist
1987,
27:
281–287.
10. American Psychiatric Association:
Diagnostic and Statistical
Manual of Mental Disorders:
edn 4, revised. Washington, DC:
American Psychiatric Association; 1994:100–102.
11. Seidman SN, Rieder RO:
Sexual behavior through the life
cycle: an empirical approach.
In
American Psychiatric Press
Review of Psychiatry,
vol 14. Edited by Oldham J, Riba M.
Washington, DC: American Psychiatric Press; 1995:639–676.
12. Mulligan T, Retchin SM, Chinchilli VM,
et al.
:
The role
of aging and chronic disease in sexual dysfunction.
J Am Geriatr Soc
1988,
36:
520–524.
13.• Seidman SN, Walsh BT:
Testosterone and depression in aging
men.
Am J Geriatr Psychiatry
1999,
7:
18–33.
This paper reviews the relationship between major depressive
disorder and testosterone level, as well as treatment with exogenous
testosterone.
14. Gitlin MJ:
Psychotropic medications and their effects on
sexual function: diagnosis, biology, and treatment
approaches.
J Clin Psychiatry
1994,
55:
406–413.
15. Ashton AK, Hamer R, Rosen RC:
Serotonin reuptake inhibitor-
induced sexual dysfunction and its treatment: a large-
scale retrospective study of 596 psychiatric outpatients.
J Sex Marital Ther
1997,
23:
165–175.
16. Balon R, Yeragani VK, Pohl R,
et al.
:
Sexual dysfunction during
antidepressant treatment.
J Clin Psychiatry
1993,
54:
209–212.
17. Steiger A, Holsboer F, Bunkert O:
Studies of nocturnal penile
tumescence and sleep electroencephalogram in patients
with major depression and in normal controls.
Acta Psychiatr
Scand
1993,
87:
358–363.
18. Thase ME, Reynolds CF III, Jennings RJ,
et al.
:
Diminished
nocturnal penile tumescence in depression: a replication
study.
Biol Psychiatry
1992,
31:
1136–1142.
19.•• Araujo AB, Durante R, Feldman HA,
et al.
:
The relationship
between depressive symptoms and male erectile dysfunction:
cross-sectional results from the Massachusetts Male Aging
Study.
Psychosom Med
1998,
60:
458–465.
This paper establishes the strong epidemiologic relationship between
ED (using reliable criteria) and depression (using CES-D cutoff > 16).
20. Derogatis LR, Meyer JK, King KM:
Psychopathology in
individuals with sexual dysfunction.
Am J Psychiatry
1981,
138:
757–763.
21. Fagan PJ, Schmidt CW, Wise TN,
et al.
:
Sexual dysfunction
and dual psychiatric diagnoses.
Comp Psychiatry
1988,
29:
278–284.
22. Jonler M, Moon T, Brannan W,
et al.
:
The effect of age,
ethnicity and geographical location on impotence and
quality of life.
Br J Urol
1995,
75:
651–655.
23. Willke RJ, Glick HA, McCarron TJ,
et al.
:
Quality of life
effects of alprostadil therapy for erectile dysfunction.
J Urol
1997,
157:
2124–2128.
24. Padma-Nathan H, Hellstrom WJG, Kaiser FE,
et al.
:
Treatment of men with erectile dysfunction with
transurethral alprostadil.
N Engl J Med
1997,
336:
1–7.
25. Althof SE, Turner LA, Levine SB,
et al.
:
Through the eyes of
women: the sexual and psychological responses of women
to their partner’s treatment with self-injection or external
vacuum therapy.
J Urol
1992,
147:
1024–1027.
26. van Driel MF, Mooibroek JJ, van de Wiel HBM,
et al.
:
Intracavernous pharmacotherapy: psychological, sexological
and medical aspects.
Int J Impot Res
1991,
3:
95–104.
27. Steers W, for the Sildenafil Study Group:
Meta-analysis of
the efficacy of sildenafil (VIAGRA) in the treatment of
severe erectile dysfunction.
J Urol
1998,
159(suppl):
238.
28. Morales A, Gingell JC, Collins M,
et al.
:
Clinical safety of
oral sildenafil citrate (Viagra) in the treatment of erectile
dysfunction.
Int J Impot Res
1998,
10:
69–74.
29. Shabsigh R, Klein LT, Seidman S,
et al.
:
Increased incidence
of depressive symptoms in men with erectile dysfunction.
Urology
1998,
52:
848–852.
30. Price D:
Sildenafil citrate (Viagra) efficacy in the treatment
of erectile dysfunction in patients with common concomi-
tant conditions.
Int J Clin Pract
1999,
102(suppl):
S21–S23.
31. Seidman S, Rosen R, Roose SP,
et al.
:
Sildenafil citrate for
erectile dysfunction and depression.
XI World Congress of
Psychiatry,
Hamburg, Germany, August, 1999.
