Drugs Aging 2008; 25 (7): 541-549

LEADING ARTICLE 1170-229X/08/0007-0541/$48.00/0

© 2008 Adis Data Information BV. All rights reserved.

Drug-Induced Urinary Incontinence

Peter Tsakiris,1 Matthias Oelke1 and Martin C. Michel2
1 Department of Urology, Academic Medical Center, University of Amsterdam, Amsterdam,
the Netherlands
2 Department of Pharmacology and Pharmacotherapy, Academic Medical Center, University of
Amsterdam, Amsterdam, the Netherlands

Abstract Physiological urinary continence depends on many factors that are potentially
vulnerable to adverse drug effects, which may lead to incontinence. In principle,
drugs could cause incontinence by lowering bladder outlet resistance and/or by
increasing intravesical pressure, which disrupts the normal pressure relationship
between the bladder and urethra and leads to urinary leakage; other possibilities
include disturbances of central nervous control of voiding or an overproduction of
urine. While many drug groups could theoretically induce urinary incontinence
based upon pathophysiological considerations, evidence demonstrating a cause-
effect relationship between drug usage and incontinence is sparse. Drug classes in
which induction of incontinence has been proposed include α1-adrenoceptor
antagonists, antipsychotics, benzodiazepines, antidepressants and hormone
replacement therapy in postmenopausal women. However, other drug classes are
not innocent in terms of causing urinary incontinence and physicians are well
advised to closely monitor patients for the occurrence of incontinence after new
prescriptions and/or major dosage changes.

While the kidneys produce urine continuously, has a major adverse effect on the quality of life of
voiding is a discontinuous event occurring only a afflicted patients and their caregivers.[4]
few times per day in healthy humans. This necessi- Several diseases can cause bladder dysfunction
tates that the bladder be able to store urine for and eventually urinary incontinence, but in many
several hours. To accomplish this, the bladder needs
cases the specific cause of incontinence remains
to be able to increase compliance whereas the mus-
unclear. On the other hand, urinary incontinence
culature of the bladder outflow tract must be able to
may also be iatrogenic, i.e. an adverse effect of
contract to generate resistance. Disturbances of this
storage function of the bladder can lead to urinary medical treatment. Numerous medications have
incontinence, which can occur in multiple forms been proposed as plausible causes of drug-induced
including stress urinary incontinence, urgency urin- urinary incontinence (table I). However, surprising-
ary incontinence, overflow urinary incontinence and ly few studies have actually provided direct evi-
mixed forms. The combined prevalence of all forms dence for a cause-effect relationship. Against this
of urinary incontinence is high.[1,2] Hence, urinary background, this article summarizes the key mech-
incontinence has a major socioeconomic impact; for anisms involved in maintaining urinary continence,
example, it is a leading cause of nursing home which are also potential mechanisms for drug-in-
admissions.[3] Moreover, urinary incontinence also duced urinary incontinence. We then review the
542 Tsakiris et al.

Table I. Drugs potentially associated with urinary incontinence based upon their mechanism of action
Mechanism of urinary incontinence Drugs Type of evidence
Decreased urethral pressure (stress incontinence) α-Adrenoceptor antagonists Weak
Antipsychotics Weak
Benzodiazepines Weak
Detrusor overactivity (urgency incontinence) Direct parasympathomimetics Theoretical
Indirect parasympathomimetics Theoretical
Antidepressants Equivocal
Serotonin 5-HT4 receptor agonists Theoretical
Hormone replacement Equivocal
Incomplete bladder emptying (overflow incontinence) Anticholinergics Theoretical
Antiparkinsonism agents Theoretical
β-Adrenoceptor antagonists Theoretical
Excessive urine production (urgency incontinence) Diuretics Equivocal

existing data with regard to specifically proven striated muscle in the distal urethra and pelvic floor,
cases of drug-induced urinary incontinence. which contract and thereby contribute to increased
bladder outlet resistance. When afferent signalling
1. Mechanisms Involved in to the brain exceeds a certain threshold and the
Urinary Continence higher brain centres indicate that it is a socially
acceptable time to void, efferent signalling switches
Several comprehensive articles have reviewed to the pontine micturition centre. This stops efferent
the neurophysiological mechanisms mediating urin- sympathetic and somatic outflow and activates para-
ary continence.[5,6] In this regard it needs to be sympathetic outflow via the pelvic nerves. These
emphasized that almost all of the underlying work release acetylcholine, which acts on muscarinic re-
was performed in experimental animals and conclu- ceptors (under physiological conditions mostly the
sions regarding the human situation are largely M3 subtype, but under some pathological conditions
based upon extrapolation from these animal studies. the more numerous M2 receptors may also contrib-
Briefly, the urinary bladder senses its degree of ute) in detrusor smooth muscle cells to cause con-
filling by means of distension, and the urothelium is traction. The specific mechanisms involved in the
likely to play a major role in this process. This leads regulation of continence within the CNS remain
to excitation of afferent Aδ-fibres (under pathologi- elusive, but many transmitters, including dopamine,
cal conditions C fibres may also be involved) that serotonin and endorphins, have been implicated.
relay the information via the spinal cord to the
pontine storage centre and other parts of the brain. 2. General Considerations on
This triggers an efferent impulse to enhance urine Drug-Induced Incontinence
storage, which involves activation of the sympathet-
ic innervation of the lower urinary tract (hypogastric Stress urinary incontinence, urgency urinary in-
nerves). These release norepinephrine to stimulate continence and overflow urinary incontinence may
β3-adrenoceptors in the detrusor and α1-adre- involve distinct dysfunctions in the aforementioned
noceptors in the bladder neck and proximal urethra. control of voiding. Stress incontinence occurs large-
The former mediate smooth muscle relaxation and ly in women and is characterized by insufficient
hence increase bladder compliance; the latter media- bladder outlet resistance. Plausible ways for drugs to
te smooth muscle contraction and hence increase induce stress urinary incontinence include ant-
bladder outlet resistance. Concomitantly, the somat- agonism of α1-adrenoceptors or nicotinic receptors.
ic pudendal and sacral nerves are activated. They Urgency incontinence affects both genders and is
release acetylcholine to act on nicotinic receptors in characterized by involuntary detrusor contractions

© 2008 Adis Data Information BV. All rights reserved. Drugs Aging 2008; 25 (7)
Drug-Induced Urinary Incontinence 543

during the storage phase of the micturition cycle. rence during medication may be under-reported.
Plausible ways for drugs to cause urgency urinary Thirdly, some physicians may consider urinary in-
incontinence include antagonism of β3-adre- continence an inevitable consequence of aging and
noceptors and agonism of muscarinic receptors. may not attribute treatment-emerging urinary incon-
Overflow incontinence affects largely men. Para- tinence to prescribed drugs. This is particularly im-
doxically, it is characterized by an overfilling of the portant because drug usage and aging are statistical-
bladder due to an inability to expel urine. This may ly associated. Fourthly, it may often be difficult to
be caused by weak detrusor activity or bladder outlet determine whether urinary incontinence results from
obstruction. When this overfilling of the bladder treatment or is associated with the underlying dis-
reaches a critical degree, it eventually causes urinary ease for which the treatment has been prescribed.
incontinence despite a poor ability of the bladder to Fifthly, most studies of drug-induced urinary incon-
expel urine. A plausible way for drugs to cause tinence have not carefully documented continence
overflow urinary incontinence is by antagonism of status prior to drug exposure and, if anything, rely
muscarinic receptors. upon disappearance of incontinence after withdraw-
al of the suspected medication. In the absence of
Among these forms of urinary incontinence,
pre-treatment data this cannot be considered conclu-
stress incontinence occurs most frequently and over-
sive evidence. Finally, continence status depends
flow incontinence least frequently. Of note, the
not only on lower urinary tract function but also on
abovementioned plausible causes refer to a drug
environmental factors, physical functioning, cogni-
effect on efferent mechanisms in lower urinary tract
tive status, psychological distress, mobility, manual
tissues. Drug-induced urinary incontinence based
dexterity, motivational factors and medical condi-
upon effects on the afferent part of the innervation
tions,[7-9] and the many possible combinations of
and/or central nervous processing of the information
these factors create problems in terms of defining
appears equally possible, but little specific know-
homogeneous study groups. Therefore, sections 3–8
ledge exists in this regard. Moreover, it is important
focus largely on specific drugs and drug groups for
to understand that overproduction of urine by the
which evidence is available.
kidneys may also lead to urinary incontinence, and
diuretics are a plausible cause of such overproduc-
3. Adrenoceptor Antagonists
tion. While this is unlikely to occur in people with a
healthy lower urinary tract, overproduction of urine α-Adrenoceptor antagonists have been widely
may manifest clinically as incontinence in the con- used in the treatment of arterial hypertension. Al-
text of pre-existing (perhaps subclinical) impair- though they are no longer considered to be a first-
ment of lower urinary tract function. Finally, one line treatment for this condition, they continue to be
should not forget that continence also requires a used in combination therapy of hypertensive pa-
certain level of cognitive capabilities and hence tients. Perhaps more importantly, they are also used
impairment thereof can also lead to urinary inconti- to treat voiding dysfunction of elderly men, which
nence.[7-9] is usually attributed to an enlarged prostate. As a
Apart from this pathophysiological information, result of their effect on lower urinary tract function,
other factors need to be considered when examining α-adrenoceptor antagonists have also been used
the limited information on drug-induced urinary in- in patients with neuropathic bladder dysfunction.
continence. First, as the prevalence of urinary incon- Finally, many antidepressant and antipsychotic
tinence is high,[1,2] minor additional iatrogenic ef- drugs exhibit considerable α1-adrenoceptor ant-
fects may be difficult to detect, particularly if they agonism in therapeutic doses.
are not directly linked to any of the abovementioned The non-selective and irreversible α-adre-
mechanisms. Secondly, patients may be ashamed to noceptor antagonist phenoxybenzamine has been
report urinary incontinence, and hence its occur- reported to induce stress urinary incontinence in

© 2008 Adis Data Information BV. All rights reserved. Drugs Aging 2008; 25 (7)
544 Tsakiris et al.

several patients (mostly children) with neurogenic noceptors, a subtype for which clinically used β-
bladder dysfunction receiving long-term treat- adrenoceptor antagonists have little affinity.[21]
ment.[10] Occurrence of urinary incontinence with
use of selective α1-adrenoceptor antagonists such as 4. Antipsychotics
prazosin has been described in case reports.[11-17] A
cause-effect relationship is made plausible by Interpretation of reports connecting use of anti-
urodynamic studies demonstrating that prazosin psychotics to urinary incontinence has been compli-
reduces urethral pressure and functional urethral cated by the fact that psychosis itself has been
length.[18] Nevertheless, studies systemically inves- described as a cause of urinary incontinence.[22]
tigating the association between α1-adrenoceptor Antipsychotics are antagonists at dopamine recep-
antagonist use and urinary incontinence are sparse. tors and/or, in the case of the ‘atypical’ agents,
serotonin receptors; however, many antipsychotics,
One study investigated 49 women receiving α- particularly the low-potency drugs, also act on nu-
adrenoceptor antagonists for arterial hypertension merous other receptor types, particularly α1-adre-
(prazosin n = 4, doxazosin n = 40 and terazosin noceptors and muscarinic receptors. This complex
n = 5) and a control group of women matched for situation regarding the molecular target of antipsy-
age and parity.[19] At least some degree of urinary chotics makes it difficult to generalize findings for
incontinence was reported in 20 of the patients re- specific drugs to the overall class. Nevertheless, it
ceiving α-adrenoceptor antagonists (40.8%), where- has been proposed that both central dopamine block-
as only eight (16.3%) of the control patients had this ade and peripheral α-blockade causing urethral re-
symptom (p < 0.02, relative risk [RR] 2.5). With- laxation may play a role in the development of
drawal of the drug in 18 of the patients with urinary urinary incontinence.[23,24]
incontinence reduced the number of incontinent Urinary incontinence has been reported in several
women to six (14%), supporting a causal effect. cases in patients treated with thioridazine.[23,25] Day-
However, the type of urinary incontinence induced time incontinence and nocturnal enuresis have been
by α1-adrenoceptor antagonists was not mentioned found in response to treatment with various antipsy-
in this study. In another report, the same researchers chotics including chlorpromazine and haloperi-
assessed possible confounding variables in these dol.[26,27]
patients and found an association between α-adre-
Clozapine is an atypical, antipsychotic drug indi-
noceptor antagonists and loop diuretics,[20] which
cated for the management of severely ill schizo-
theoretically can also induce urinary incontinence. phrenic patients who do not respond adequately to
While adjustment for the use of loop diuretics re- standard antipsychotic drug treatment; in therapeu-
duced the RR of urinary incontinence during α- tic doses, clozapine also has pronounced antagonist
adrenoceptor antagonist use to 1.96, the patient pop- effects at α1-adrenoceptors and muscarinic recep-
ulation was too small to show a statistically signif- tors.[28] One study reported that 17 of 57 patients
icant difference. In conclusion, the overall data raise (30%) with schizophrenia or schizoaffective disor-
the possibility that use of α1-adrenoceptor antagon- der treated with clozapine developed urinary incon-
ists may lead to urinary incontinence, and patho- tinence, although this required diaper use in only
physiological considerations suggest that this may two patients.[29] A comparison between those pa-
be largely stress incontinence. However, existing tients who developed urinary incontinence and those
studies are insufficient to allow reliable conclusions who did not showed that urinary incontinence was
to be drawn. associated with female gender and concomitant
While β-adrenoceptor antagonists could theoreti- treatment with typical antipsychotic drugs. Based
cally interfere with the storage function of the urin- upon effective treatment of the urinary incontinence
ary bladder, this is unlikely to be of clinical rele- with the α1-adrenoceptor agonist ephedrine, the in-
vance because this function is promoted by β3-adre- vestigators postulated that the α1-adrenoceptor ant-

© 2008 Adis Data Information BV. All rights reserved. Drugs Aging 2008; 25 (7)
Drug-Induced Urinary Incontinence 545

agonist component of clozapine may have been re- 5. Benzodiazepines

sponsible for the occurrence of urinary inconti-
Based upon their effects on GABAA receptors in
nence. In a larger study investigating the incidence
the CNS, benzodiazepines can cause relaxation of
of clozapine-induced urinary incontinence, 27 of 61 striated muscle. The risk of urinary incontinence
patients (44%) developed urinary incontinence at associated with use of oxidative or non-oxidative
some time during treatment.[30] In 15 of these pa- benzodiazepines was estimated in an observational
tients (25%), urinary incontinence persisted. The study of elderly people.[36] In a sample of 4583
investigators found no statistically significant differ- nursing home residents, urinary incontinence was
ences in age, gender, clozapine dose or concurrent recorded in 33% of patients and approximately 8%
treatment with other antipsychotics between the in- of patients were benzodiazepine users. There was a
continence and non-incontinence groups. Nocturnal greater prevalence of benzodiazepine users among
urinary incontinence also developed in 5 of 12 pa- incontinent patients compared with continent pa-
tients (42%) during clozapine treatment. This preva- tients (10.7% vs 7.5%, respectively; p < 0.001).
lence rate is especially remarkable because 80% of Overall, users of benzodiazepines had a nearly 45%
the affected patients were embarrassed and reluctant greater risk of urinary incontinence (adjusted odds
ratio 1.44). However, limitations of this study in-
to report this adverse event to staff, indicating a
cluded a lack of documentation of the type of urin-
possible underestimation of urinary incontinence in
ary incontinence or the dosage and schedule of
this group.[31] However, nocturia is notoriously diffi-
benzodiazepine use. It should also be noted that
cult to understand because of its multi-factorial these results were obtained in nursing home re-
pathophysiology, and there is insufficient character- sidents and cannot necessarily be extrapolated to
ization of clozapine-associated nocturnal inconti- community-dwelling elderly individuals. Finally,
nence in the literature. the statistical association observed in this study does
Drug-induced urinary incontinence has also been not necessarily prove a cause-effect relationship be-
observed with use of newer antipsychotic agents. In cause use of benzodiazepines may have been asso-
a study including 68 patients treated with risper- ciated with other factors with potential influence on
idone, the investigators found that 28% of patients the continence status of these patients.
reported at least transient urinary incontinence after
6. Antidepressants
initiation of treatment whereas only 13% had such
symptoms prior to risperidone.[32] Induction of urin- While most antidepressants are inhibitors of neu-
ary incontinence by olanzapine has also been sug- ronal norepinephrine and/or serotonin uptake, many
gested in case reports.[33,34] Interestingly, data in of them, particularly those of the tricyclic group,
experimental animals demonstrated that olanzapine also exhibit pronounced antagonism of adrenergic,
has greater maximal effects than risperidone on sev- cholinergic or histaminergic receptors at therapeutic
doses.[37] Newer antidepressants, particularly from
eral voiding parameters and decreases the activity of
the selective serotonin reuptake inhibitor (SSRI)
the external urethral sphincter.[35] Thus, the overall
group, appear to be largely free of direct antagonist
data make it likely that antipsychotics as a class can effects on transmitter receptors.[37] Similar to the
induce urinary incontinence, but these data are not situation with antipsychotic agents, this makes gen-
sufficient to allow a reliable and clinically relevant eralized statements regarding the entire class of anti-
differentiation between members of this class with depressants difficult to make.
regard to urinary incontinence. Moreover, it remains Case reports have described drug-induced urin-
unclear in most reported studies whether inconti- ary incontinence with use of venlafaxine,[38,39] an
nence was indeed drug induced or may have been agent that inhibits both norepinephrine and seroto-
present prior to treatment with antipsychotics. nin uptake but has no relevant direct effects on

© 2008 Adis Data Information BV. All rights reserved. Drugs Aging 2008; 25 (7)
546 Tsakiris et al.

neurotransmitter receptors. Recently, the results of a women (sample sizes ranging from 16 to 1525
large retrospective follow-up investigating a poss- women). A subanalysis of 15 trials compared 374
ible association between use of SSRIs and the occur- women randomized to estrogen with 344 women
rence of urinary incontinence were reported.[40] randomized to placebo; the combined subjective
Within a database of approximately 450 000 pa- cure and improvement rates were higher in women
tients, a total of 13 531 patients were identified as receiving estrogen for both urgency incontinence
first-time users of an SSRI. Compared with non- (35/61 vs 16/58 taking placebo; RR 2.09; 95% CI
exposure, the incidence density ratio for urinary 1.3, 3.34) and stress urinary incontinence (46/107 vs
incontinence during SSRI exposure was 1.75 (95% 29/109 taking placebo; RR 1.62; 95% CI 1.15, 2.28).
CI 1.56, 1.97). Compared with baseline, SSRI use The authors concluded that therapy with estrogens is
caused 14 extra cases of urinary incontinence per associated with greater subjective cure and/or im-
1000 patients treated per year. After adjustment for provement of urinary incontinence than placebo.
co-morbidities and co-medications, the RR for urin- However, the odds ratio for cure was only 1.61 (95%
ary incontinence due to SSRI use was 1.61 (95% CI CI 1.04, 2.49), and many of the underlying studies
1.42, 1.82). In addition, the investigators showed were small (typically <30 patients per arm).
that users of sertraline are at the highest risk of
Moreover, recent studies have shown that es-
developing urinary incontinence (adjusted RR 1.72;
trogen alone or in combination with progestin can
95% CI 1.10, 2.78). As with the benzodiazepine
induce urinary incontinence.[45,46] One study includ-
association study[36] (see section 5), it remains to be
ed 39 436 postmenopausal health participants from
determined whether use of SSRIs was indeed a
cause of urinary incontinence or merely an indicator the Nurses’ Health Study cohort who had reported
of other causative factors. In this regard it is impor- no leakage of urine in 1996 and were followed up
tant to note that both venlafaxine and duloxetine, for 4 years to identify new cases of urinary inconti-
which are dual norepinephrine and serotonin uptake nence.[45] The investigators identified 5060 cases of
inhibitors without relevant direct effects on neuro- occasional urinary incontinence (leaking urine one
transmitters, exhibited continence-promoting effects to three times per month) and 2495 cases of frequent
in cats.[41] More importantly, duloxetine has been incontinence (leaking at least weekly). Their results
shown in a review of several placebo-controlled demonstrated that the risk of urinary incontinence
studies to be effective in the treatment of stress was elevated among women taking hormone re-
urinary incontinence, possibly via an effect on placement treatment compared with women who
Onuf’s nucleus in the lower spinal cord.[42] How- had never taken hormone replacement treatment
ever, it remains to be established whether antide- (oral estrogen: RR 1.54, transdermal estrogen: RR
pressants can indeed induce urinary incontinence in 1.68, oral estrogen with progestin: RR 1.34). Upon
hitherto continent people. cessation of treatment, the RR decreased to 1.14. In
a large, randomized, double-blind, placebo-control-
7. Hormone Replacement Therapy led clinical trial, 27 347 postmenopausal women
were randomized based on hysterectomy status to
Based upon pathophysiological considerations it active treatment or placebo in estrogen plus proges-
had been assumed that estrogen substitution, alone tin or estrogen-alone trials.[46] In this study, hormone
or in combination with progestin (progestogen), replacement increased the incidence of all types of
may be beneficial for incontinent postmenopausal urinary incontinence at 1 year among women who
women.[43] Numerous studies have addressed this were continent at baseline. More specifically, the
question, and a systematic meta-analysis of these investigators reported that the risk was highest for
has been presented by the Cochrane Collabora- stress incontinence (estrogen alone: RR 2.15, es-
tion.[44] This meta-analysis involved 28 trials of trogen plus progestin: RR 1.87), followed by mixed
various hormone preparations with a total of 2926 incontinence (estrogen alone: RR 1.79, estrogen

© 2008 Adis Data Information BV. All rights reserved. Drugs Aging 2008; 25 (7)
Drug-Induced Urinary Incontinence 547

plus progestin: RR 1.49). The risk of developing continence was more prevalent in those taking diur-
urgency incontinence with estrogen-only treatment etics than those not taking diuretics (85% vs 25%,
was double that for combination treatment with es- respectively; p = 0.009). The authors hypothesized
trogen plus progestin (RR 1.32 vs RR 1.15, respec- that diuretics can cause large, sudden effluxes of
tively). The investigators’ explanation for the great- urine into the bladder that might trigger involuntary
er risk of hormone replacement-induced stress in- detrusor contractions. In another study of 130 com-
continence was based on the findings of a munity-dwelling women with urinary incontinence,
randomized, placebo-controlled clinical trial of es- 45 of these women took diuretics and 85 did not.[49]
trogen-alone treatment, which showed a significant These groups were compared with regard to clinical
decrease in total periurethral collagen, consequent and urodynamic characteristics, severity of urinary
damage to periurethral connective tissue and asso- incontinence and frequency of diurnal and nocturnal
ciated ineffective urethral closure.[47] Thus, some micturition. Urodynamic assessment revealed es-
data suggest that hormone replacement treatment sentially no significant differences between groups
may have a beneficial effect in incontinent postmen- other than for volume voided during uroflowmetry;
opausal women. On the other hand, large studies patients receiving diuretics voided significantly
demonstrate that the risk of becoming incontinent is smaller volumes than patients not taking such drugs.
increased by hormone replacement therapy. While In addition, patients taking diuretics had significant-
treatment of incontinence with estrogens and emer- ly more incontinent episodes and diurnal urinary
gence of incontinence upon treatment with estrogen frequency. A study of 38 continent and 76 inconti-
in continent women are not directly comparable, the nent female nursing home patients found no statisti-
overall risk-benefit ratio of hormone replacement cally significant difference between groups in the
therapy in postmenopausal women makes its use at use of diuretics.[50] Thus, the presently available data
best a second-line choice for treatment of urinary do not unequivocally support the idea that use of
incontinence. In this regard it should also be noted diuretics is associated with a major risk of urinary
that effects on continence were reported from secon- incontinence.
dary post hoc analyses which, by definition, provide
limited evidence. Induction of urinary incontinence
in previously continent women should be consid- 9. Conclusions and
ered a possible adverse effect of hormone replace- Practical Recommendations
ment therapy.
While various drug classes could plausibly be
8. Diuretics accused of causing urinary incontinence, convincing
evidence that this is the case has been provided only
Diuretics are frequently used in the general elder- for hormone replacement therapy in previously con-
ly population. An epidemiological survey of 1956 tinent women. In general, this appears to reflect a
people aged ≥60 years revealed that 24.6% of men lack of carefully performed, adequately powered
and 36.9% of women were current users of a diuretic studies rather than convincing data about an absence
medication.[48] While use of diuretics, particularly of urinary incontinence as an adverse effect of
loop diuretics, will increase urine output and hence medical treatment. This absence of evidence should,
may plausibly increase the volume of urine the therefore, not be misinterpreted as evidence for ab-
bladder is required to hold, only limited data are sence of urinary incontinence. Any physician is well
available on diuretic-induced urinary incontinence. advised to actively inquire of the patient whether
In a study of predominantly male patients, use of urinary incontinence has developed after initiation
diuretics had no overall effect on continence status of new treatments or major dosage changes. If the
in either gender.[48] However, within the group of type of urinary incontinence reported matches what
men with proven detrusor overactivity, urinary in- a given drug could plausibly induce, an attempt at

© 2008 Adis Data Information BV. All rights reserved. Drugs Aging 2008; 25 (7)
548 Tsakiris et al.

withdrawal of the possibly causative medication 17. Dwyer PL, Teele JS. Prazosin: a neglected cause of stress
incontinence. Obstet Gynaecol 1992; 79: 117-21
may be warranted. 18. Donker PJ, Ivanovici F, Noach EL. Analyses of the urethral
pressure profile by means of electromyography and the admin-
istration of drugs. Br J Urol 1972; 44: 180-93
Acknowledgements 19. Marshall HJ, Beevers DG. Alpha-adrenergic blockade and urin-
ary incontinence. J Hypertens 1993; 11: 1152-3
No sources of funding were used to assist in the prepara- 20. Marshall HJ, Beevers DG. α-Adrenoceptor blocking drugs and
tion of this article. Professor Martin Michel has acted as a female urinary incontinence: prevalence and reversibility. Br J
consultant and/or received honoraria from Astellas, Boeh- Clin Pharmacol 1996; 42: 507-9
ringer, Elbion, Pfizer, Bayer and Eli Lilly, and has received 21. Vrydag W, Michel MC. Tools to study β3-adrenoceptors.
grants from Astellas, Boehringer and Pfizer. The other au- Naunyn-Schmiedebergs Arch Pharmacol 2007; 374: 385-98
thors have no conflicts of interest that are directly relevant to 22. Berrios GE. Temporary urinary incontinence in the acute psy-
the content of this article. chiatric patient without delusion or dementia. Br J Psychiatr
1986; 149: 224-7
23. Van Putten T, Malkin MD, Weiss MS. Phenothiazine-induced
stress incontinence. J Urol 1973; 104: 625-6
References 24. Ambrosini PJ. A pharmacologic paradigm for urinary inconti-
1. Anger JT, Saigal CS, Stothers L, et al. The prevalence of urinary
nence and enuresis. J Clin Psychopharmacol 1984; 4: 247-53
incontinence among community dwelling men: results from
the National Health and Nutrition Examination Survey. J Urol 25. Renshaw DC. Thioridazine and incontinence. JAMA 1971; 218:
2006 Nov; 176: 2103-8 738
2. Anger JT, Saigal CS, Litwin MS, et al. The prevalence of 26. Ambrosini PJ, Nurnberg HG. Enuresis and incontinence occur-
urinary incontinence among community dwelling adult ring with neuroleptics. Am J Psychol 1980; 137: 1278-9
women: results from the National Health and Nutrition Exam- 27. Nurnberg HG, Ambrosini PJ. Urinary incontinence in patients
ination Survey. J Urol 2006; 175: 601-4 receiving neuroleptics. J Clin Psychol 1979; 40: 271-4
3. Morrison A, Levy R. Fraction of nursing home admissions 28. Clozaril (clozapine). In: The Physicians’ Desk Reference. 53rd
attributable to urinary incontinence. Value Health 2006; 9: ed. Montvale (NJ): Medical Economics, 1999: 2004-8
272-4 29. Fuller MA, Borovicka MC, Jaskiw GE, et al. Clozapine-induced
4. Saadoun K, Ringa V, Fritel X, et al. Negative impact of urinary urinary incontinence: incidence and treatment with ephedrine.
incontinence on quality of life, a cross-sectional study among J Clin Psychiatr 1996; 57: 514-8
women aged 49-61 years enrolled in the GAZEL cohort. 30. Lin CC, Bai YM, Chen JY, et al. A retrospective study of
Neurourol Urodyn 2006; 25: 696-702 clozapine and urinary incontinence in Chinese in-patients.
5. Michel MC, Oelke M, Peters SLM. The neuro-urological con- Acta Psychiatr Scand 1999; 100: 158-61
nection. Eur Urol Suppl 2005; 4: 18-28 31. Warner JP, Harvey CA, Barnes TR. Clozapine and urinary
6. Bannowsky A, Juenemann KP. Innervation and function of the incontinence. Int Clin Psychopharmacol 1994; 9: 207-9
female urinary bladder and urethra. EAU Update Series 2003; 32. Vokas CS, Steele VM, Norris JI, et al. Incidence of risperidone
1: 120-7 induced incontinence [abstract]. Schizophr Res 1997; 24: 267
7. Resnick NM. Urinary incontinence in the elderly. Lancet 1995; 33. Vernon L, Fuller M, Hattab H, et al. Olanzapine-induced urinary
346: 94-9 incontinence: treatment with ephedrine. J Clin Psychiatry
8. Resnick NM, Baumann M, Scott M. Risk factors for inconti- 2000; 61: 601-2
nence in nursing home: a multivariate study. Neurourol 34. Sagar R, Varghese ST, Balhara YP. Olanzapine-induced double
Urodyn 1988; 7: 274-6 incontinence. Indian J Med Sci 2005; 59: 163-4
9. Scientific Committee of the First International Consultation on 35. Vera PL, Miranda-Sousa A, Nadelhaft I. Effects of two atypical
Incontinence. Assessment and treatment of urinary inconti- neuroleptics, olanzapine and risperidone, on the function of the
nence. Lancet 2000; 355: 2153-8 urinary bladder and the external urethral sphincter in anesthe-
10. Harrison NW, Whitfield HN, Williams DI. The place of alpha- tized rats. BMC Pharmacol 2001; 1: 4
blocking drugs in the treatment of children with neuropathic 36. Landi F, Cesari M, Russo A, et al. Benzodiazepines and the risk
bladders. Urol Int 1977; 32: 224-31 of urinary incontinence in frail older persons living in the
11. Mathew TH, McEwan J, Rohan A. Urinary incontinence secon- community. Clin Pharmacol Ther 2002; 72: 729-34
dary to prazosin. Med J Aust 1988; 148: 305-6 37. Andersson KE. Treatment of overactive bladder: other drug
12. Wall LL, Addison WA. Prazosin induced stress incontinence. mechanisms. Urology 2000; 55: 51-7
Obstet Gynaecol 1990; 75: 558-60 38. Votolato NA, Stern S, Caputo RM. Serotonergic antidepressants
13. Menefee SA, Chesson R, Wall LL. Stress urinary incontinence and urinary incontinence. Int Urogynecol J Pelvic Floor Dys-
due to prescription medications: alpha-blockers and angioten- funct 2000; 11: 386-8
sin converting enzyme inhibitors. Obstet Gynecol 1998; 91: 39. Cavanaugh GL, Martin RE, Stenson MA, et al. Venlafaxine and
853-4 urinary incontinence: possible association [letter]. Ann
14. Thien T, Delaere KP, Debruyne FM, et al. Urinary incontinence Pharmacother 1997; 31: 372
caused by prazosin. BMJ 1978; 1: 622-3 40. Movig KL, Leufkens HG, Belitser SV, et al. Selective serotonin
15. Kiruluta GH, Mercer AR, Winsor GM. Prazosin as cause of reuptake inhibitor-induced urinary incontinence. Pharma-
urinary incontinence. Urology 1981; 18: 618-9 coepidemiol Drug Saf 2002; 11: 271-9
16. Srinivasan V, Blackford HN. Genuine stress incontinence in- 41. Katofiasc MA, Nissen J, Audia JE, et al. Comparison of the
duced by prazosin. Br J Urol 1993; 72: 510 effects of serotonin selective, norepinephrine selective, and

© 2008 Adis Data Information BV. All rights reserved. Drugs Aging 2008; 25 (7)
Drug-Induced Urinary Incontinence 549

dual serotonin and norepinephrine reuptake inhibitors on lower 48. Diokno AC, Brown MD, Herzog AR. Relationship between use
urinary tract function in cats. Life Sci 2002; 71: 1227-36 of diuretics and continence status in the elderly. Urology 1991;
42. Michel MC, Oelke M. Duloxetine in the treatment of stress 38: 39-42
urinary incontinence. Womens Health 2005; 1: 345-8
43. Griebling TL, Nygaard IE. The role of estrogen replacement 49. Fantl JA, Wyman JF, Wilson M, et al. Diuretics and urinary
therapy in the management of urinary incontinence and urinary incontinence in community-dwelling women. Neurourol
tract infection in postmenopausal women. Endocrinol Metab Urodyn 1990; 9: 25-34
Clin North Am 1997; 26: 347-60
44. Moehrer B, Hextall A, Jackson S. Oestrogens for urinary incon- 50. Ouslander JG, Uman GC, Urman HN, et al. Incontinence among
tinence in women. Cochrane Database Syst Rev 2003; (2): nursing home patients: clinical functional correlates. J Am
CD001405 Geriatr Soc 1987; 35: 324-30
45. Grodstein F, Lifford K, Resnick NM, et al. Postmenopausal
hormone therapy and risk of developing urinary incontinence.
Obstet Gynecol 2004; 103: 254-60
Correspondence: Professor Martin C. Michel, Department of
46. Hendrix SL, Cochrane BB, Nygaard IE, et al. Effects of es-
trogen with and without progestin on urinary incontinence. Pharmacology and Pharmacotherapy, Academic Medical
JAMA 2005; 293: 935-48 Center, Meibergdreef 15, 1105 AZ, Amsterdam, the
47. Jackson S, James M, Abrams P. The effect of oestradiol on
vaginal collagen metabolism in postmenopausal women with Netherlands.
genuine stress incontinence. BJOG 2002; 109: 339-44 E-mail: m.c.michel@amc.nl

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