FORMULARY FORUM
CWMIPRAMINE: A TRICYCLIC ANTIDEPRESSANT EFFECTIVE IN
OBSESSIVE COMPULSIVE DISORDER
Michael W. Kellyand Carol W. Myers
ABSTRACT: Clomipramine hydrochloride, a chlorinated analog of
imipramine, is a widely used antidepressant recently approved for use
in the u.s. for the treatment of obsessive-compulsive disorder (OCD),
a potentially incapacitating affliction. Its primary pharmacologic action
is blockade of the reuptake of the neurotransmitter serotonin. Its
metabolite, desmethylclomipramine, is a potent norepinephrine
reuptake inhibitor. Significant first-pass metabolism reduces oral
bioavailability to <62 percent. The drug is widely distributed
throughout the body (volume of distribution 9-25 Ukg) and is 90-98
percent protein-bound. Clomipramine follows first-order elimination
pharmacokinetics, with a plasma half-life of 20-24 hours. Recent
double-blind controlled clinical trials have demonstrated the drug's
effectiveness in the treatment ofOCD. Response is most often
associated with doses> 75 rng/d, with 250 mg the maximum
recommended daily dose. Relapse upon withdrawal is frequently
reported. The adverse effect profile of clomipramine is similar to other
tricyclic antidepressants, with anticholinergic, cardiovascular, sexual,
and central nervous system effects the most prominent.
Dlep Ann Pharmacother 1990;24:739-44.
CLOMIPRAMINE HYDROCHLORIDE, a tricyclic antidepressant
(TCA), has been available in Europe and Canada for many
years. Although similar to other tricyclics, clomipramine
appears unique in its ability to relieve the condition known
as obsessive-compulsive disorder (OCD).
Pharmacology
Clomipramine differs from imipramine only by a 3-chlo-
rine substitution (Figure 1).1 The precise mechanism of
action of clomipramine, like all TCAs, is unclear. The anti-
depressant effect possibly relates to the ability ofthe drug to
increase synaptic availability of monoamine neurotransmit-
ters in the brain by blocking their reuptake at the presynap-
tic membrane.' Recent evidence suggests that the long-
term administration of these compounds may also alter the
MICHAEL W. KELLY, Phann.D., M.S., is an Assistant Professor ofPhannacy Prac-
tice, Southwestern Oklahoma State University: andCAROL W. MYERS, Phann.D., is
an Assistant Professor, Departments of Phannacy Practice and Psychiatry, Schools of
Pharmacy andMedicine, University of Pillsburgh. Reprints: Michael W. Kelly,
Phann.D., M.S., Department ofPhannacy, Baptist Medical Center of Oklahoma, 3300
N.W. Expressway, Oklahoma City, OK 73112.
This article is approved for continuing education credit.
DICP, The Annals of Pharmacotherapy
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V:OCI
I
CHlCHzCHZNCCH) lz
, HC1
Figure I. Graphic formula ofclomipramine.
sensitivity of adrenergic and serotonergic neuroreceptors, a
factor that may contribute to the antidepressant activity. 3
Clomipramine's primary pharmacologic effect is upon the
reuptake of the neurotransmitter serotonin, whereas its
major metabolite, desmethylclomipramine, is a potent nor-
epinephrine uptake inhibitor.4
The mechanism by which clomipramine relieves OCD is
less clear. Because of its pronounced potency in blocking
synaptosomal reuptake of serotonin coupled with its unique
activity in the treatment ofOCD, a serotonin hypothesis has
been developed to explain the pathogenesis of the con-
dition. The hypothesis postulates that a dysregulation of
serotonin is responsible for the disorder and that clomipra-
mine exerts its activity by correcting this imbalance. This,
however, remains unproven. S
Clomipramine binds with varying affinity to a variety of
neuroreceptors in the brain and periphery. These include
alpha- and alphaj-adrenoceptors, as well as opiate, his-
taminergic, and cholinergic receptors. 3 Activity at these
receptors may result in clinically significant therapeutic and
adverse effects.
Pharmacokinetics
ABSORPTION AND DISTRIBUTION
Despite being well absorbed orally, systemic bioavaila-
bility of clomipramine is estimated to range between 36 and
62 percent, with a significant hepatic first-pass effect. 6,7
Both clomipramine and desmethylclomipramine are highly
lipophilic and are widely distributed throughout the body
with the volume of distribution (Vd ) estimated to be 9-25
L'kg." Protein binding is extensive; clomipramine is
90-98 percent bound and desmethyIclomipramine is
92-98 percent bound. 8
• 1990 July/August, Volume 24 • 739
 METABOLISM AND ELIMINATION
Clomipramine undergoes extensive metabolism, with
less than three percent of a radio labeled dose excreted
unchanged in the urine." A major route of transformation
is N-demethylation to yield desmethylclomipramine. In
addition, both clomipramine and desmethylclomipramine
undergo hydroxylation." All three metabolites have been
shown in vitro to be effective inhibitors of serotonin reup-
take. Upon repeated dosing, these metabolites accumulate
to a significant degree, making interpretation of blood con-
centrations difficult, and may help to explain some of the
observed interpatient variability in response to c1omipra-
mine." The decline in plasma concentration of clomipra-
mine and its metabolites is best described by first-order
pharmacokinetics using a two-compartment open model. 11
Mean clomipramine plasma half-life when administered
orally has ranged from 20 to 24 hours, and that of its metab-
olite has ranged from 37 to 50 hours.":"
Clinit:alStudies
OBSESSIVE-COMPULSIVE DISORDER
OCD, classified in the revised third edition of the Amer-
ican Psychiatric Association's Diagnostic and Statistical
Manual ofMental Disorders (DSM-III-R) as an anxiety
disorder." is characterized by obsessions or compulsions
that cause significant distress or interfere with a person's
ability to function in a normal fashion. Obsessions are
recurrent thoughts, images, impulses, or ideas that are con-
sidered intrusive or senseless. The person realizes the
thoughts are from his own mind and attempts to ignore or
suppress them. Compulsions are repetitive and purposeful
behaviors that are performed according to certain rules or in
a stereotyped fashion and serve to lessen discomfort or pre-
vent some dreaded event. The person is aware that this
behavior is unreasonable. Two common presentations of
the disorder are obsessions of contamination coupled with
cleaning compulsions, and obsessive doubt leading to com-
pulsive checking.
Once considered rare, recent findings suggest that OCD
may be fairly common. A survey of three U.S. commu-
nities found lifetime prevalence of OCD to be in the range
of 1.9-3.0 percent." Another study of the same subjects
examining six-month prevalence rates found the condition
to be the fourth most common psychiatric disorder in
women 25-64 years 01d.14 OCD usually begins in adoles-
cence or early adulthood, but may begin in childhood. It
appears to afflict both sexes equally. Of all psychiatric dis-
orders, the condition is considered one of the most resistant
to treatment and may result in considerable chronic impair-
ment of an individual's ability to function. Nevertheless,
studies of the natural course of OCD indicate that up to 40
percent of patients may follow a fluctuating or phasic
course, complicating assessment of treatment response. IS
The effectiveness of clomipramine in patients with OCD
was reported as early as 1967. 16 Following this observa-
tion, the drug was studied in several uncontrolled trials with
generally favorable results. 1'021 Since then, a number of
double-blind clinical trials comparing clomipramine with
either placebo or other antidepressant drugs have been per-
formed (Table 1). Clomipramine significantly improved
symptoms of OCD in a variety of both observed and self-
740 • DICP, The Annals of Pharmacotherapy •
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reported obsession/compulsion rating scales used in the
studies, whereas placebo,22-26 nortriptyline hydrochlor-
ide,26 amitriptyline hydrochloride ,27 clorgiline.P and de-
sipramine hydrochloride did not.:" In a study comparing
clomipramine with its structural analog, imipramine, patients
showed partial improvements with both drugs, but clomipra-
mine was deemed somewhat superior. 30 Clomipramine
therapy was effective in children as well as adults. 25
Response rates to clomipramine in these trials were vari-
able, with 43-75 percent of patients exhibiting moderate to
marked improvement. By comparison, a 1989 multicenter
trial demonstrated a virtual absence of placebo response. 31
Doses associated with clinical response were 75-300 mg/d.
Time-to-treatment effect was generally 5-6 weeks, with
some patients exhibiting initial improvements as late as 10
weeks and others showing continuing improvements after
12 weeks of therapy. Relapse was likely to occur upon dis-
continuation of the drug with improvement following
reinstitution.
Two studies used behavior therapy22.23 and one used psy-
chotherapy" as concurrent treatment. Although psycho-
therapy has not been shown to be effective in treating OCD,
behavior therapy, particularly exposure and response pre-
vention, has demonstrated positive results with lasting im-
provement in as many as 70 percent of patients. 32.33 Despite
the addition of these interventions, clomipramine per-
formed significantly better than either placebo or active
drug.
Because these early studies have suffered from small
sample size, two large, multicenter clinical trials have re-
cently been performed to evaluate the safety and efficacy of
clomipramine." One of these studies, Protocol 59, was a
fully randomized trial in 262 nondepressed patients scoring
:516 on the Hamilton Depression Rating Scale (HDRS).
Protocol 61 involved 313 subjects and was a stratified trial
with randomization into two groups: those with HDRS
scores of :516 and those with scores of 17-21. Following a
two-week placebo run-in, subjects with a primary DSM-III
diagnosis of OCD and clinically significant disability were
randomized to receive double-blind treatment with either
clomipramine or placebo for ten weeks. Clomipramine was
initiated at 25 mg/d and gradually increased to a dose of
100-300 mg/d based upon therapeutic effect and toler-
ability. Response to treatment was evaluated weekly with
the National Institute of Mental Health Global Obsessive
Compulsive Scale, Physician Global Rating Scale, Patient
Global Self-Rating Scale (PGSRS) and the Yale-Brown
Obsessive Compulsive Scale (Y-BOCS), with the Y-BOCS
being the principal outcome measure. Both trials included
a one-year double-blind extension.
In Protocol 59 patients, statistically significant (p<0.05)
differences in mean PGSRS and Y-BOCS scores were ob-
served between the two treatment groups at week 2 and at
each subsequent week of treatment. At the end of ten weeks
of treatment, those receiving placebo were essentially un-
changed, with a five percent reduction in mean Y-BOCS
score. In contrast, clomipramine treated patients demon-
strated a 38 percent reduction in mean Y-BOCS score.
Similar results were obtained in patients participating in
Protocol 61. Patients with HDRS scores of :516 who re-
ceived clomipramine demonstrated a consistent decline in
the mean Y-BOCS score resulting in a 45 percent reduction
from baseline over the ten weeks of treatment. There was a
1990 July/August, Volume 24
 Clomipramine

corresponding four percent reduction in the placebo-treated Adverse Effects

group. Between-group comparisons of mean PGSRS and
Y-BOCS scores at week 2 and each subsequent week of treat-
ment indicated a significant (p<0.05) difference favoring
clomipramine over placebo. The small subgroup (n = 18)of
patients scoring 17-21 on the HDRS received similar bene-
fit from clomipramine."
Continuing therapeutic benefit was observed in patients
receiving clomipramine during the one-year double-blind
extension phase of the trials;" In both protocols, mean Y-
BOCS scores remained virtually unchanged during the
period.
DEPRESSION AND OTHER USES
Potential usefulness of clomipramine as an antidepres-
sant has been widely recognized for over 20 years." Dou-
ble-blind clinical trials have found clomipramine to be
superior to placebo and equally effective compared with
imipramine;" amitriptyline;" and doxepin hydrochlor-
ide" for the treatment of depression. Clomipramine has
also been used successfully in the treatment of cataplexy,"
premature ejaculation." pain," panic disorder.? and tri-
chotillomania."
The adverse effect profile of clomipramine is similar to
other TCAs. The majority of adverse effects are unwanted
pharmacologic effects, and true toxic events are rare. 44
Common anticholinergic effects include dry mouth and
mild to moderate constipation. Sedation, blurred vision,
and urinary retention occur less frequently. A significant
increase in sweating has also been reported. 45 Gastroin-
testinal adverse effects are frequently encountered at initia-
tion of clomipramine therapy and can lead to early with-
drawal." Of these, nausea and vomiting are most com-
mon, but disturbances of appetite and taste, epigastric dis-
tress, and diarrhea have also occurred.
The major cardiovascular adverse effect of clomipra-
mine is orthostatic hypotension. The reported incidence of
this effect varies from 0 to 16percent. 47 Other cardiovascu-
lar events noted during treatment with clomipramine
include syncope, palpitations, and tachycardia. Most cases
were mild and did not require treatment or drug discon-
tinuation.
Central nervous system adverse effects include tremor,
myoclonus, ataxia, rigidity, dizziness, sedation, and head-
ache. Seizures have been reported in 0.7 percent of approx-

Table 1. Summary of Clomipramine Drug Trials in Obsessive-Compulsive Disorder

PATIENT DATA CLOMIPRAMINE
REF STUDY DESIGN (n) DOSAGE RESULTS COMMENTS

22 double-blind, placebo-
controlled, 8-wk active drug
period
23 double-blind, placebo-
crossover, 4-wk active drug
period
24 double-blind. placebo-
controlled, 8-wk active drug
period
25 double-blind, placebo-
crossover, 5-wk active drug
period
26 double-blind, placebo-
controlled comparison with
NTP (50-150 mg/d) 6-wk
active drug period
27 double-blind comparison
with AMT 75-300 mg/d,
4-wk active drug period
28 double-blind, placebo-
controlled comparison with
CGL 30 mg/d, 6-wk active
drug period
29 double-blind, placebo-
controlled comparison with
DIP 50-300 rng/d, 6-wk
active drug period
30 double-blind, comparison
with IMI 50-300 mg/d,
12-wk active drug period
chronic, handicapping OCD
of 2: I Y duration (40)
severe OCD without
primary or secondary
depression (14)
OCD with at least one
unsuccessful treatment (12)
patients 10-18 Y with severe
OCD (19)
OCD of 2: I Y duration, at
least I unsuccessful
treatment (24)
treatment-resistant OCD of
>2 y duration (20)
OCD of > I Y duration, pri-
mary depression excluded
(23)
OCD of > I Y duration, low
baseline depression (10)
OCD of > 1 Y duration (23)
10-225 mg/d CMP superior to PLB by
flexible patient rating (p<0.05)
75 rng/d CMP superior to PLB for
fixed obsessive thoughts but not
compulsions
50-300 mg/d CMP superior to PLB by
flexible OCNS rating (p<0.05); no
difference in HDRS ratings
up to 3 mg/kg/d CMP superior to PLB by
to a maximum of OCRS, LOI, NIMH-OC
200 mg/d flexible ratings (p<0.05); anxiety
and depression unchanged
50-150 mg/d CMP superior to placebo by
flexible LOI ratings (p<0.05), NTP
not different from CMP or
PLB
75-300 rng/d number and severity of OCD
flexible symptoms decreased;
anxiety and depression
improved on CMP but not
AMT
50-300 mg/d CMP superior to CGL and
flexible PLB by CPRS-OC, NIMH
Global, and Compulsive
Checklist ratings (p<0.05)
50-300 mg/d CMP superior to DIP by
flexible NIMH-OC and CPRS-OC
ratings (p<0.05)
50-300 mg/d partial improvement with
flexible both drugs; CMP superior
by SRONS and GEE ratings
(p<0.05)
maximum CMP effect at
week 10
low dose, short-active drug
period
CMP activity in OCD inde-
pendent of antidepressant
effect
not all subjects benefitted;
full recovery not obtained;
relapse upon withdrawal
50% response rate, 5 wk to
effect, relapse upon
withdrawal
both drugs safe in doses
administered
no carryover effect
observed; relapse upon
withdrawal
effects seen at 4 and 6 wk
baseline severity greater in
IMI group

AMT = amitriptyline; CGL = c1orgiline; CMP = clomipramine; CPRS-OC = Comprehensive Psychopathological Rating Scale-Obsessive Compulsive
Scale; DIP = desipramine; GEE = Global Evaluation of Efficacy; HDRS = Hamilton Depression Rating Scale; IMI = imipramine; LOI = Leyton Obsession-
al Inventory; NIMH-OC = National Institute of Mental Health-Obsessive Compulsive Scale; NTP = nortriptyline; OCD = obsessive-compulsive disorder;
OCNS = Obsessive Compulsive Neurotic Scale; OCRS = Obsessive Compulsive Rating Scale; PLB = placebo; SRONS = Self-Rating Obsessional Neu-
rotic Scale.

DICP, The Annals of Pharmacotherapy • 1990 July/August, Volume 24 • 741

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imately 3000 patients treated with clomipramine in clinical
trials in the U.S. 48 Generally, seizures are more often
associated with doses>300 mg/d and intravenous adminis-
tration. Seizures have also been reported following with-
drawal from clomipramine in patients" as well as in neo-
nates born to mothers treated with the drug throughout
pregnancy. SO,5\ Mania has been noted to develop in sev-
eral patients treated with clomipramine for depressive
symptoms. 52
A characteristic of clomipramine that may be particu-
larly troublesome to some patients is a high incidence of
sexual dysfunction. The drug has been associated with
changes in libido in both sexes, delayed ejaculation, partial
or total anorgasmia, and, in some instances, orgasm while
yawning.":" Normal sexual functioning returns within a
few days of discontinuing therapy.
Elevations of serum prolactin have occurred following
single or multiple doses of clomipramine. 55 Doses within
the therapeutic range may cause uncomfortable breast en-
gorgement, lactation, and irregular or absent menstrua-
tion. 56 Weight gain is also a potential problem. Although
rare, blood dyscrasias have been observed with the use of
clomipramine, specifically one case each of agranulocyto-
sis" and pancytopenia. 58 Both patients recovered with-
out complications.
Table 2 presents a summary of the most frequently
observed adverse effects in 520 subjects receiving double-
blind therapy with clomipramine or placebo for the treat-
ment of OCD. 34 Given the frequency of occurrence of
these untoward effects, it is not surprising that dropout rates
due to adverse effects have been as high as 28 percent in
therapeutic trials. Even though adverse effects are fre-
quently encountered and may prove troublesome, the sever-
ity and intractable nature of OCD often justifies the use of
the drug.
DRUG INTERACTIONS
Particular care should be exercised when clomipramine
is given to patients who have previously received mono-
amine oxidase inhibitors (MAOI). A serious neurotoxic
reaction occurred in three of six patients started on clomip-
ramine 100 mg/d despite a one-month washout from the
investigational MAOI clorgiline.P The reaction consisted
of hyperreflexia, tremor, rigidity, and clonus in the lower
extremities within 30 minutes of taking clomipramine. Car-
diac irritability was also observed. 59 Symptoms resolved
in 24 hours and the patients were able to tolerate clomipra-
mine at a lower dose when it was reinitiated six weeks later.
In a separate case, clomipramine therapy was started
Table 2. Adverse Effects of Clomipramine and Placebo
CLOMIPRAMINE PLACEBO
ADVERSE EFFECT (%)
Dry mouth 80.4
Dizziness 52.7
Tremor 53.1
Headache 45.4
Fatigue 38.8
Somnolence 49.2
Constipation 44.6
Nausea 28.8
Increased sweating 23.5
Ejaculation failure 17.7
742 • DICP, The Annals of Pharmacotherapy • 1990 July/August, Volume 24
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immediately after the discontinuation of the nonspecific
MAOI phenelzine sulfate." Within one hour, the patient,
who had no prior history of seizure disorder, developed sta-
tus epilepticus that required intravenous diazepam and phe-
nytom to control. These cases illustrate the need to wait a
sufficient length of time for monoamine oxidase enzymes
to recover before starting clomipramine therapy in those
previously treated with MAOIs. If in doubt as to whether
enough time has elapsed, clomipramine should be initiated
at a low dose and the patient monitored closely.
Dosing
Clomipramine is effective for the treatment of OCD
when given orally in doses of 75-300 mg/d. 22 ,26 ,28 Similar
doses are effective in the treatment of depression. 36-38 How-
ever, because the risk of seizure increases with increasing
dose, the manufacturer recommends a 250 mg/d maximum
dose. The pediatric daily dose may be titrated as tolerated
to a maximum of 3 mg/kg or 200 109, whichever is smaller.
Many authors have attempted to correlate the steady
state plasma concentrations of clomipramine and des-
methylclomipramine to antiobsessional response. 25,28,6\.62
Although sample sizes are small and conclusions tentative,
therapeutic response is most often associated with serum
clomipramine concentrations of >318 nmollL. Desmethyl-
clomipramine serum concentrations are not predictive of
OCD response. In light of these findings, dosage adjust-
ment in nonresponsive patients may best be made on the
basis of serum concentration measurements, where avail-
able. Case reports suggest that nonresponsive patients may
also benefit from the addition of lithium to clomipramine
therapy. 63 The serotonin precursor tryptophan has also
been used to augment the effect of clomipramine, but its
use cannot be recommended until safety issues have been
resolved. 63 ,64
Summary and Recommendations
Although similar to other TCAs in most respects, clo-
mipramine has demonstrated a unique antiobsessional
activity separate from its antidepressant activity. When
administered for OCD, the drug should be given for a six-
week therapeutic trial. In nonresponsive individuals, blood
concentration monitoring and/or lithium augmentation may
be considered. Patients should be alerted to potential ad-
verse effects. Relapse upon discontinuation is frequently
reported, but remission of symptoms is likely with reinsti-
tution of clomipramine.
Prior to the release of clomipramine, no drug has had
approval for use in the treatment of OCD. The reported
1.9-3.0 percent prevalence of the condition suggests that a
sizable patient population exists for this agent. Although
nonpharmacologic approaches remain the treatment of first
(%)
choice in OCD, many patients will fail to benefit from these
and clomipramine will offer their first real option. As a
16.9 result, clomipramine will be a useful formulary addition.e>
12.7
1.5
41.2
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EXTRACTO
Clomipramina, un ana logo de imipramina usado comunmente como
antidepresivo, ha sido recientemente aprobado en los Estados
Unidos para el tratamiento del desorden obsesivo-compulsivo. Su
acci6n farmacol6gica primordial es la de bloquear la recaptaci6n de
serotonina mientras que su metabolito, desmetiJclomipramina, es
un potente inhibidor de la recaptaci6n de norepinefrina. La
biodisponibilidad oral es reducida significativamente a menos del
62 por ciento por medio de metabolismo de primer paso. La droga
es ampliamente distribuida a traves del cuerpo con un volumen de
distribuci6n de 9-25 Ukg y es 90-98 por ciento enlazada a
protefnas. Clomipramina exhibe una eliminaci6n de primer orden
con una vida media de 20-24 horas. Estudios clfnicos recientes,
doble-ciegos y controlados, han demostrado que la droga es
efectiva en el tratamiento del desorden obsesivo-compulsivo, un
desorden potencialmente incapacitante. La respuesta es usual mente
asociada con una dosis sobre 75 mg/d y la dosis maxima
recomendada es de 250 mg/d. Frecuentemente se ha reportado
Pharmacoepidemiology, An Introduction, Second Edition
Edited by A.G. Hartzema, PhD, MSPH, M.S. Porta, MD, MPH, H.H. Tilson, MD, MPH, DrPH
The long-awaited expanded second edition contains 20
chapters that provide in-depth discussions of method-
ologic considerations (i.e.,causality assessment), the sta-
tistical analyses used, and the implications of and stan-
dards for pharmacoepidemiologic research. A complete
annotated bibliography of selected studies is included.
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relapso al descontinuar el medicamento. EI perfil de efectos
adversos de clomipramina es similar al de otros antidepresivos
tricfclicos, siendo los efectos anticolinergicos, cardiovasculares,
sexuales, y del sistema nervioso central los mas prominentes.
ANNETTE PEREZ
RESUME
La clomipramine, un derive chlore de l'imipramine, est utilisee
depuis longtemps comme antidepresseur, Recernment, la FDA
americaine en a approuve l'utilisation dans Ie traitement des
troubles obsessionnels-compulsifs.
Ce medicament agit en bloquant la recaptation de la serotonine,
augmentant ainsi la disponibilite de ce neurotransmetteur au
cerveau. Son metabolite actif, la demethylclomipramine, est un
inhibiteur puissant de la recaptation de la norepinephrine. Une
hypothese impliquant la serotonine dans la pathologie des troubles
obsessionels-compulsifs justifie l'utilisation de la clomipramine,
bien que cette hypothese ne soit pas encore demontree.
La biodisponibilite de la clomipramine par voie orale varie de 36
a 62 pourcent. Ceci est attribuable a un effet important de premier
passage hepatique. Le medicament possede un grand volume de
distribution (Vd 9-25 Llkg) et est fortement lie aux proteines
(90-98 pourcent). L'elirnination de la clomipramine se fait selon
un modele pharmacocinetique d'ordre premier, et sa demi-vie est
de 20 a 24 heures.
Des etudes cliniques recentes, comparatives ou avec temoin, et a
double-insu, ont demontre l'efficacite de cet antidepresseur dans Ie
traitement des troubles obsessionnels-compulsifs. On note
generalement une reponse a des doses quotidiennes superieures a
75 mg, et pouvant aller jusqu'a la dose maximale de 250 mg par
jour. On a rapporte frequemment une reapparition des troubles
obsessionnels-compulsifs a l'arret de la therapie.
Le profil des effets secondaires de la clomipramine se compare a
celui des autres antidepresseurs tricycliques: effets anticholin-
ergiques, cardiovasculaires, troubles de la fonction sexuelle et
reactions indesirables au niveau du systerne nerveux central,
principalement.
JoELLE SAINT-PIERRE
Reserve copies, paperbound or hardbound
(circle one) of Pharmacoepidemiology, An Introduction,
Second Edition. Enclosed is $
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