Brand name: Anafranil
Clomipramine
Brand name: Anafranil |
|
Antidepressant - Antiobsessional
Clomipramine is a tricyclic agent with both antidepressant and antiobsessional properties. Like other tricyclics, clomipramine inhibits norepinephrine and serotonin uptake into central nerve terminals, possibly by blocking the membrane-pump of neurons, thereby increasing the concentration of transmitter monoamines at receptor sites. Clomipramine is presumed to influence depression and obsessive and compulsive behaviour through its effects on serotonergic neurotransmission. The actual neurochemical mechanism is unknown, but clomipramine's capacity to inhibit serotonin reuptake is thought to be important. Clomipramine appears to have a mild sedative effect which may be helpful in alleviating the anxiety component often accompanying depression.
As with other tricyclic compounds, clomipramine possesses anticholinergic properties which are responsible for some of its side effects. It also has weak antihistamine and antiserotonin properties, lowers the convulsive threshold, potentiates the effect of norepinephrine and other drugs acting on the CNS, has a quinidine-like effect on the heart and may impair cardiac conduction.
The action of clomipramine on the human EEG is one of desynchronization. It causes a persistent increase in the frequency of shifts into stage I sleep and produces marked reduction or suppression of rapid eye movement sleep (REM or paradoxical sleep) with partial recovery within 3 to 4 weeks and a rebound after drug withdrawal which appears to last approximately the same time. In normal human volunteers tricyclic antidepressants tend to produce a sedative effect accompanied by atropine-like symptoms and may produce some difficulty in concentrating and thinking.
Absorption is rapid and complete after oral administration in man. Plasma levels usually peak 2 hours after dosage but much individual variation occurs. The plasma half-life after a single oral dose is approximately 21 hours. After 28 days of oral administration to patients in a daily dosage of 75 mg, plasma concentrations of clomipramine ranged from 17 to 70 ng/mL (mean=35.7 ng/mL). The concentration of the active metabolite, desmethylclomipramine, was about twice as high.
Binding to serum proteins at 96 to 97% is very high and is practically concentration-independent within the therapeutic range. Clomipramine has a volume of distribution of approximately 12 L/kg bodyweight.
Clomipramine is extensively metabolized in the body with hydroxylation, demethylation and N-oxidation being the quantitatively more important routes of metabolism.
Owing to the lower clearance of clomipramine in plasma, elderly patients require lower doses of clomipramine than patients in younger age groups.
As expected, the metabolites of clomipramine are quite similar to those of imipramine, all retaining the benzazepine structure. Two-thirds of clomipramine is excreted in the form of water-soluble conjugates in the urine and approximately one-third in the feces. After a 25 mg radiolabelled dose of clomipramine in 2 subjects, the urinary recoveries of clomipramine and desmethylclomipramine were about 2% and 0.5% of the total radioactivity, respectively.
For the treatment of depression. Clomipramine also appears to have a mild sedative effect which may be helpful in alleviating the anxiety component often accompanying depression.
For the treatment of obsessions and compulsions in patients with obsessive compulsive disorder (OCD). The obsessions and compulsions must cause marked distress, be time-consuming, or significantly interfere with social or occupational functioning.
The effectiveness of clomipramine for long-term use (i.e. for more than 10 weeks) has not been systematically evaluated in placebo-controlled trials. The physician who elects to use clomipramine for extended periods should periodically re-evaluate the long term usefulness of the drug for the individual patient.
Patients who have known hypersensitivity to the drug or have known hypersensitivity to tricyclic antidepressants belonging to the dibenzazepine group.
Clomipramine should not be given in conjunction with or within 14 days of treatment with a MAO inhibitor. Hypertensive crises, hyperactivity, hyperpyrexia, spasticity, severe convulsions or coma, and death have been reported in patients receiving such combinations.
It is contraindicated during the acute recovery phase following myocardial infarction and in the presence of acute congestive heart failure.
Clomipramine is contraindicated in patients with existing liver or kidney damage and should not be administered to patients with a history of blood dyscrasias.
Clomipramine is contraindicated in patients with glaucoma, as the condition may be aggravated due to the atropine-like effects of the drug.
Seizures:
Tricyclic agents are known to lower the convulsive threshold and clomipramine
should, therefore, be used with extreme caution in patients with a history
of convulsive disorders and other predisposing factors, e.g., brain damage
of varying etiology, alcoholism, and concomitant use with other drugs
that lower the seizure threshold. Total daily doses should not exceed
the recommended total daily dose (see Dosage). Concurrent administration
of ECT and clomipramine may be hazardous and such treatment should be
limited to patints for whom it is essential. Physicians should discuss
with patients the risk of taking clomipramine while engaging in activities
in which a sudden loss of consciousness could result in serious injury
to the patient or others e.g. the operation of complex machinery, driving,
swimming, or climbing.
Cardiovascular:
Tricyclic antidepressants, particularly in high doses, have been reported
to produce sinus tachycardia, changes in conduction time and arrhythmias.
A few instances of unexpected death have been reported in patients with
cardiovascular disorders. Myocardial infarction and stroke have also been
reported with drugs of this class. Therefore, clomipramine should be administered
with extreme caution to patients with a history of cardiovascular disease,
especially those who have a history of conduction disorders, those with
circulatory lability and elderly patients. It also has a hypotensive action
which may be detrimental in these circumstances. In such cases, treatment
should be initiated at low doses with progressive increases only if required
and tolerated, and the patients should be under close surveillance at
all dosage levels. Monitoring of cardiac function and the ECG is indicated
in such patients.
Use in Concomitant Illness:
Caution should be observed in prescribing clomipramine in hyperthyroid
patients or in patients receiving thyroid medication conjointly. Transient
cardiac arrhythmias have occurred in rare instances in patients who have
been receiving other tricyclic compounds concomitantly with thyroid medication.
Because of its anticholinergic properties, clomipramine should be used with caution in patients with increased intraocular pressure or a history of urinary retention, particularly in the presence of prostatic hypertrophy.
Particularly in the elderly and in hospitalized patients the tricyclic antidepressants may give rise to paralytic ileus and, therefore, appropriate measures should be taken if constipation occurs.
Caution is called for when employing clomipramine in patients with tumours of the adrenal medulla (e.g. pheochromocytoma, neuroblastoma) in whom the drug may provoke hypertensive crisis.
Clomipramine should be kept in a safe place, well out of the reach of children.
Pregnancy:
Safe use in pregnant women has not been established. Withdrawal symptoms
including tremors, convulsions, and respiratory depression have been reported
in neonates whose mothers received tricyclic antidepressants during the
third trimester of pregnancy. Therefore, it should not be administered
to women of childbearing potential, or during pregnancy, unless, in the
opinion of the physician, the expected benefit to the patient outweighs
the potential risk to the fetus.
Lactation:
Since clomipramine passes into breast milk, nursing mothers receiving it
should not breast-feed their infants.
Suicide:
The possibility of a suicide attempt is inherent in depression with or
without obsessive-compulsive disorder. These patients should be carefully
supervised during treatment with clomipramine, and hospitalization or
concomitant electroconvulsive therapy may be required. To minimize the
risk of an intentional overdose by a depressed patient, prescriptions
for clomipramine should be written for the smallest possible quantity
of the drug consistent with good patient management.
Psychosis, Mania-Hypomania, and other
Neuropsychiatric Phenomena:
In patients treated with tricyclic antidepressants, activation of latent
schizophrenia or aggravation of existing psychotic manifestations in schizophrenic
patients may occur; patients with manic-depressive tendencies may experience
hypomanic or manic shifts; and hyperactive or agitated patients may become
over-stimulated. A reduction in dose or discontinuation of clomipramine
should be considered under these circumstances.
In predisposed and elderly patients, tricyclic antidepressants may, particularly at night, provoke pharmacogenic (delirious) psychoses which disappear without treatment within a few days of withdrawing the drug.
Since clomipramine may produce sedation, particularly during the initial phase of therapy, patients should be cautioned about the danger of engaging in activities requiring mental alertness, judgement and physical coordination.
Cardiovascular:
Before initiating treatment, it is advisable to check the patient's blood
pressure, because individuals with hypotension or a labile circulation
may react to the drug with a fall in blood pressure. Regular measurements
of blood pressure should be performed in susceptible patients. Postural
hypotension may be controlled by reducing the dosage or administering
circulatory stimulants.
ECG abnormalities have been observed in patients treated with clomipramine. The most common ECG changes were premature ventricular contractions (PVCs), ST-T wave changes, and abnormalities in intraventricular conduction. These changes were rarely associated with significant clinical symptoms. Nevertheless, caution is necessary in treating patients with heart diseases, as well as elderly subjects. In these patients cardiac function should be monitored and ECG examinations performed during long-term therapy. Gradual dose titration is also recommended.
Hepatic Changes:
Clomipramine has occasionally been associated with elevations in AST (SGOT)
and ALT (SGPT) of potential clinical significance (i.e. values greater
than 3 times the upper limit of normal). In the majority of cases, these
enzyme elevations were not associated with other clinical findings suggestive
of hepatic injury.
Isolated cases of obstructive jaundice have been reported. Caution is indicated in treating patients with known liver disease, and periodic monitoring of hepatic function is recommended in such patients.
Hematologic Changes:
Isolated cases of bone marrow depression with agranulocytosis have been
reported. Leukocyte and differential blood cell counts are recommended
in patients receiving treatment with clomipramine over prolonged periods,
and should be performed for patients who develop fever, an influenzal
infection, or sore throat. In the event of an allergic skin reaction,
clomipramine should be withdrawn.
CNS:
More than 30 cases of hyperthermia have been recorded by nondomestic post-marketing
surveillance systems. Most cases occurred when clomipramine was used in
combination with other drugs. When clomipramine and a neuroleptic were
used concomitantly, the cases were sometimes considered to be examples
of a neuroleptic malignant syndrome.
Withdrawal Symptoms:
A variety of withdrawal symptoms have been reported in association with
abrupt discontinuation of clomipramine, including dizziness, nausea, vomiting,
headache, malaise, sleep disturbance, hyperthermia and irritability. In
addition, such patients may experience a worsening of psychiatric status.
While the withdrawal effects of clomipramine have not been systematically
evaluated in controlled trials, they are well known with closely related
tricyclic antidepressants, and it is recommended that the dosage be tapered
gradually and the patient monitored carefully during discontinuation.
Metabolic Effects:
Tricyclic antidepressants have been associated with porphyrinogenicity
in susceptible patients.
Renal Function:
It is also advisable to monitor renal function during long-term therapy
with tricyclic antidepressants.
Dental Effects:
Lengthy treatment with tricyclic antidepressants can lead to an increased
incidence of dental caries.
Endocrine Effects:
As with certain other psychotherapeutic drugs, clomipramine elevates prolactin
levels. Tissue culture experiments indicate that approximately one-third
of human breast cancers are prolactin dependent in vitro, a factor of
potential importance if the prescription of clomipramine is contemplated
in a patient with a previously detected breast cancer. Although disturbances
such as galactorrhea, amenorrhea, gynecomastia, and impotence have been
reported, the clinical significance of elevated serum prolactin levels
is unknown for most patients. An increase in mammary neoplasms has been
found in rodents after chronic administration of neuroleptic drugs. Neither
clinical studies nor epidemiologic studies conducted to date, however,
have shown an association between chronic administration of these drugs
and mammary tumorigenesis: The available evidence is considered too limited
to be conclusive at this time.
Children:
As clomipramine has not been studied in patients under 10 years of age,
specific recommendations for use in this age group cannot be provided.
The long-term effects of clomipramine on childhood growth and development
have not been determined.
Drug Interactions:
Patients should be warned that, while taking clomipramine, their responses
to alcoholic beverages, other CNS depressants (e.g. barbiturates, benzodiazepines
or general anesthetics) or anticholinergic agents (e.g. atropine, biperiden,
levodopa) may be exaggerated. When tricyclic antidepressants are given
in combinations with anticholinergics or neuroleptics with an anticholinergic
action, hyperexcitation states or delirium may occur, as well as attacks
of glaucoma. Tricyclic antidepressants should not be employed in combination
with anti-arrhythmic agents of the quinidine type.
Since clomipramine may diminish or abolish the antihypertensive effects of guanethidine, clonidine, reserpine, methyldopa, patients requiring concomitant treatment for hypertension should be given antihypertensives of a different type (e.g. diuretics, beta-blockers).
Clomipramine may potentiate the cardiovascular effects of noradrenaline or adrenaline, amphetamine, as well as nasal drops and local anesthetics containing sympathomimetics.
Methylphenidate and fluoxetine may increase the activity and plasma concentrations of tricyclic antidepressants.
Caution should be exercised if clomipramine is administered together with cimetidine since cimetidine has been shown to inhibit the metabolism of several tricyclic antidepressants and clinically significant increases in plasma levels of clomipramine may occur.
Substances which activate the hepatic mono-oxygenase enzyme system (e.g. barbiturates, phenytoin, nicotine) may lower plasma concentrations of tricyclic antidepressants and so reduce their antidepressive effects.
Clomipramine should not be administered for a period of at least 14 days after the discontinuation of treatment with MAO-inhibitors due to the potential for severe interactions (see Contraindications). The same caution should also be observed when administering an MAO-inhibitor after previous treatment with clomipramine.
Clomipramine should be discontinued prior to elective surgery, for as long as clinically feasible, since little is known about the interaction between clomipramine and general anesthetics.
Concomitant administration of clomipramine and phenytoin may lead to elevated serum phenytoin concentration. If necessary, the phenytoin dosage should be adjusted accordingly.
Neuroleptic agents (e.g. phenothiazines and butyrophenones) may increase the plasma concentration of clomipramine. No such effects are known to occur in combination with diazepam but it might be necessary to lower the dosage of clomipramine if administered concomitantly with alprazolam or disulfiram.
If administered concomitantly with estrogens, the dose of clomipramine should be reduced since steroid hormones inhibit the metabolism of clomipramine.
Because clomipramine is highly bound to serum proteins, the administration of clomipramine to patients taking other drugs that are highly bound to protein (i.e. warfarin, digoxin) may cause an increase in plasma concentrations of these drugs, potentially resulting in adverse effects. Conversely, adverse reactions may result from the displacement of protein bound clomipramine by other highly bound drugs.
Teratology:
No teratogenic effects were observed in rats and mice at doses up to 20
times the maximum daily human dose. Slight nonspecific fetotoxic effects
were seen in the offspring of pregnant mice given doses 10 times the maximum
daily human dose. Slight nonspecific embryotoxicity was observed in rats
given doses 5 to 10 times the maximum daily human dose.
Animal Toxicology:
As with tricyclic compounds, clomipramine has been associated with changes
in testicular and lung tissue in long-term animal toxicology studies.
In 1 and 2 year studies in rats, a dose 4 times the maximum daily human
dose was associated with phospholipidosis in the lungs and changes in
the testes (atrophy, aspermatogenesis, and calcification). In a 1 year
toxicity study in dogs, testicular atrophy was detected in animals receiving
10 times the maximum recommended daily human dose.
The most commonly observed adverse events associated with the use of clomipramine and not seen at an equivalent incidence among placebo-treated patients were gastrointestinal complaints, including dry mouth, constipation, nausea, dyspepsia, and anorexia; nervous system complaints, including somnolence, tremor, dizziness, nervousness and myoclonus; genitourinary complaints including changed libido, ejaculatory failure, impotence and micturition disorder; and other miscellaneous complaints, including fatigue, sweating, increased appetite, weight gain, and visual changes.
The tabulations that follow list adverse reactions that have also been observed with clomipramine; these are categorized by organ system and listed in order of decreasing frequency.
Neurological:
Extrapyramidal effects such as ataxia, also headache, delirium, speech
disorders, muscle weakness, muscle hypertonia, tinnitus, paresthesias
of the extremities, convulsions, EEG changes, hyperpyrexia. Peripheral
neuropathy has been reported with other tricyclic antidepressants.
Behavioral:
Drowsiness, fatigue, restlessness, confusion accompanied by disorientation
(particularly in geriatric patients and patients suffering from Parkinson's
disease), anxiety states, agitation, sleep disturbances, insomnia, nightmares,
aggravated depression, hypomania or manic episodes, disturbed concentration,
visual hallucinations, impaired memory, aggressiveness, yawning, depersonalization,
activation of latent psychosis, delusions.
Autonomic:
Difficulty with accommodation, slurred speech, urinary retention, hot flushes,
mydriasis, glaucoma, paralytic ileus.
Cardiovascular:
Hypotension, particularly orthostatic hypotension with associated vertigo,
sinus tachycardia, palpitations. A quinidine-like effect and other reversible
ECG changes in patients with normal cardiac status (such as flattening
or inversion of T-waves, depressed S-T segments). Arrhythmias, hypertension,
conduction disorders (e.g. widening of QRS complex, PQ changes, bundle-branch
block), syncope.
Fibrillation, myocardial infarction, stroke and unexpected death in patients with cardiovascular disorders have been reported with tricyclic antidepressants.
Hematologic:
Leukopenia, agranulocytosis, thrombocytopenia, eosinophilia and purpura.
One case of pancytopenia has been reported.
Gastrointestinal:
Vomiting, abdominal pain, diarrhea, taste perversion, elevated transaminases,
obstructive jaundice, hepatitis with or without jaundice.
Endocrine:
Weight loss, breast enlargement and galactorrhea in the female, inappropriate
antidiuretic hormone (ADH) secretion syndrome, gynecomastia in the male,
changes in blood sugar levels, increase in prolactin levels, menstrual
irregularity.
Allergic or Toxic:
Allergic skin reactions (skin rash, urticaria), photosensitization, pruritus,
edema, drug fever.
Withdrawal Symptoms:
Abrupt cessation of treatment with tricyclic antidepressants after prolonged
administration may occasionally produce nausea, vomiting, abdominal pain,
diarrhea, insomnia, nervousness, anxiety, headache and malaise. These
symptoms are not indicative of addiction.
Since children may be more sensitive than adults to acute overdosage with tricyclic antidepressants, and since fatalities in children have been reported, effort should be made to avoid potential overdose particularly in this age group.
Symptoms:
These may vary in severity depending on various factors such as the amount
of drug absorbed, the interval between drug ingestion and start of treatment,
and the age of the patient. Accidental ingestion in children should be
regarded as serious and potentially fatal.
The first signs and symptoms of overdosage with tricyclic antidepressants generally take the form of severe anticholinergic reactions which set in about 1/2 to 2 hours after the drug has been taken.
Symptoms may include drowsiness, stupor, ataxia, vomiting, cyanosis, restlessness, agitation, delirium, severe perspiration, hyperactive reflexes, muscle rigidity, athetoid and choreiform movements, and convulsions. Hyperpyrexia, mydriasis, bowel and bladder paralysis, and respiratory depression may occur.
Hypotension and initial hypertension may occur. However, the usual finding is increasing hypotension which may lead eventually to shock. Serious cardiovascular disturbances are frequently present, including tachycardia, cardiac arrhythmias (flutter, atriofibrillation, ventricular premature beats and ventricular tachycardia) as well as impaired myocardial conduction, atrio-ventricular and intraventricular block, ECG abnormalities (such as widened QRS complexes and marked S-T shifts and signs of congestive heart failure) and cardiac arrest. Coma may ensue.
Treatment:
Patients in whom overdosage is suspected should be admitted to hospital
without delay. No specific antidote is available and treatment is essentially
symptomatic and supportive. Gastric lavage or aspiration should be performed
promptly and is recommended up to 12 hours or even more after the overdose,
since the anticholinergic effect of the drug may delay gastric emptying.
Administration of activated charcoal may help to reduce absorption of
the drug. As clomipramine is largely protein bound, forced diuresis, peritoneal
dialysis and hemodialysis are unlikely to be of value.
Treatment should be designed to insure maintenance of the vital functions. An open airway should be maintained in comatose patients and assisted ventilation instituted, if necessary, but respiratory stimulants should not be used. Hyperpyrexia should be controlled by external measures, such as ice packs and cooling sponge baths. Acidosis may be treated by cautious administration of sodium bicarbonate. Adequate renal function should be maintained.
ECG monitoring in an intensive care unit is recommended in all patients, particularly in the presence of ECG abnormalities, and should be maintained for several days after the cardiac rhythm has returned to normal. Unexpected deaths attributed to cardiac arrhythmias have been reported several days following an apparent recovery from tricyclic antidepressant overdose. Correction of hypoxia and acidosis, if present, may be beneficial. Correction of metabolic acidosis and low potassium concentrations by means of bicarbonate i.v. and potassium substitution may also be effective for treatment of arrhythmias. If bradyarrhythmia or AV-block occur, consider temporary insertion of a cardiac pacemaker. Because of its effect on cardiac conduction, digitalis should be used only with caution. If rapid digitalization is required for the treatment of congestive heart failure, special care should be exercised in using the drug.
External stimulation should be minimized to reduce the tendency to convulsions. If convulsions occur, anticonvulsants (preferably i.v. diazepam) should be administered. Barbiturates may intensify respiratory depression, particularly in children, and aggravate hypotension and coma. Paraldehyde may be used in some children to counteract muscular hypertonus and convulsions with less likelihood of causing respiratory depression. If the patient fails to respond rapidly to anticonvulsants, artificial ventilation should be instituted. Prompt control of convulsions is essential since they aggravate hypoxia and acidosis and may thereby precipitate cardiac arrhythmias and arrest.
Shock should be treated with supportive measures, such as i.v. fluids, plasma expanders and oxygen. The use of corticosteroids in shock is controversial and may be contraindicated in tricyclic antidepressant overdose. Hypotension usually responds to elevation of the foot of the bed. Pressor agents (but not epinephrine) should be given cautiously, if indicated. In the event of reduced myocardial function, consider recourse to treatment with dopamine or dobutamine by i.v. drip.
Physostigmine i.v. has been used in the treatment of tricyclic-induced anticholinergic toxicity. Its use is controversial and should be reserved for life-threatening situations. Physostigmine is not innocuous and carries the risk of inducing seizures, bronchospasm, hypertension and severe arrhythmias. It should not be used routinely or to reverse coma. However, it may be indicated in the treatment of seizures or combative hallucinations. It should not be used in patients who are acidemic or who have conduction defects.
Adults:
A test dose of 0.5 mg i.v. is given initially. Give 1 to 2 mg slowly i.v.
(over 2 minutes). If no clinical changes or cholinergic signs occur within
15 to 30 minutes, an additional 1 to 2 mg may be cautiously administered.
Repeat doses of 1 to 2 mg i.v. every 30 minutes up to 2 hours. As the
CNS effects of physostigmine wear off rapidly, it is important to monitor
the patient continuously.
Physostigmine is the only drug of this class that may be used. Neostigmine should not be used as it does not have any cholinergic effects.
If symptoms of cholinergic toxicity develop, physostigmine should be discontinued. Deaths by deliberate or accidental overdosage have occurred with this class of drugs. Since the propensity for suicide is high in depressed patients, a suicide attempt by other means may occur during the recovery phase. The possibility of simultaneous ingestion of other drugs should also be considered.
Dosage should be individualized according to the requirements of each patient. Treatment should be initiated at the lowest recommended dose and increased gradually, noting carefully the clinical response and any evidence of intolerance. During the initial dose titration phase, the total daily dose of clomipramine should be divided and served with meals to reduce gastrointestinal side-effects.
Owing to the long elimination half-lives of clomipramine and its active metabolite, desmethylclomipramine, steady-state plasma levels may not be achieved until 2 to 3 weeks after a dosage adjustment. It may thus be advisable to wait 2 to 3 weeks after the initial dose titration phase, before attempting further dosage adjustments. It should be kept in mind that a lag in therapeutic response usually occurs at the onset of therapy, lasting from several days to a few weeks. Increasing the dosage does not normally shorten this latent period and may increase the incidence of side effects.
Depression:
Initial Dosage:
Adults:
Clomipramine therapy should be initiated at daily doses of 25 mg. Dosage
may be increased by 25 mg increments, as tolerated, at 3 to 4 day intervals
up to a total daily dose of 150 mg by the end of 2 weeks. Thereafter,
the dose may be gradually increased over a period of several weeks to
200 mg. Doses in excess of 200 mg daily are not recommended for outpatients.
Occasionally, in more severely depressed hospitalized patients, dosages
up to 300 mg daily may be required.
Elderly and Debilitated Patients:
In general, lower dosages are recommended for these patients. Initially,
20 to 30 mg daily in divided doses is suggested, with very gradual increments,
depending on tolerance and response. Blood pressure and cardiac rhythm
should be checked frequently, particularly in patients who have unstable
cardiovascular function.
Maintenance Dosage:
Dosage during maintenance therapy should be kept at the lowest effective
level. To minimize daytime sedation during maintenance treatment, the
total daily dosage may be given as a single dose at bedtime. Medication
should be continued for the expected duration of the depressive episode
in order to minimize the possibility of relapse following clinical improvement.
Obsessive Compulsive Disorders:
Initial Dosage:
Adults:
Clomipramine therapy in adult obsessive compulsive patients should be initiated
at daily doses of 25 mg. Dosage may be increased by 25 mg increments,
as tolerated, at 3 to 4 day intervals up to a total daily dose of 100
or 150 mg by the end of 2 weeks. Thereafter, the dose may be gradually
increased over a period of several weeks to 200 mg. Doses in excess of
200 mg/day are not generally recommended for outpatients. However, in
the treatment of severe cases of Obsessive Compulsive Disorder, daily
doses of up to 250 mg may be required.
Children and Adolescents:
In children aged 10 to 17 years, an initial dose of 25 mg/day is recommended.
Dosage may be increased by 25 mg increments, as tolerated, at 3 to 4 day
intervals. By the end of 2 weeks, patients may be titrated up to 100 to
150 mg/day or 3 mg/kg, whichever is lower. Thereafter, the dose may be
gradually increased to 200 mg or 3 mg/kg whichever is lower. A total daily
dose above 200 mg should not be used in children or adolescents.
Elderly and Debilitated Patients:
In general, lower dosages are recommended for these patients. Initially,
20 to 30 mg daily in divided doses is suggested, with very gradual increments,
depending on tolerance and response. Blood pressure and cardiac rhythm
should be checked frequently, particularly in patients who have unstable
cardiovascular function.
Maintenance Dosage (Adults, Children,
and Adolescents):
Double blind extension phase studies of clomipramine therapy in patients
with Obsessive Compulsive Disorder have followed patients for up to 52
weeks. Although placebo enrolment in these studies was inadequate to permit
a controlled comparison, data do suggest that clomipramine therapy can
be continued for up to a year without loss of efficacy.
Dosage adjustments may be made during maintenance therapy with the objective of maintaining the patient at the lowest effective dose. To minimize daytime sedation during maintenance treatment, the total daily dosage may be given as a single dose at bedtime. If symptoms recur, the dosage should be increased until the symptoms are controlled. Patients should be reassessed periodically to determine the need for continued treatment. To avoid withdrawal symptoms upon discontinuation of therapy, a gradual decrease in dosage and careful patient monitoring are recommended.
10 mg:
Each sugar-coated, cream-colored, triangular tablet, with GEIGY printed
on one side and identification code DK on the other side, contains: Clomipramine
HCl 10 mg. Also contains lactose. Energy: 1.3 kJ (0.3 kcal).
25 mg:
Each sugar-coated, cream-colored, round tablet, with GEIGY printed on one
side and identification code FH on the other side, contains: Clomipramine
HCl 25 mg. Also contains lactose. Energy: 0.8 kJ (0.19 kcal).
50 mg:
Each film-coated, white, round, slightly biconvex, beveled-edge tablet,
with GEIGY printed on one side and identification code LP on the other
side, contains: Clomipramine HCl 50 mg. Also contains lactose. Energy:
0.96 kJ (0.23 kcal).
The research information is available separately on Internet Mental Health.
Note: This information is from a Canadian monograph. There can be differences in indications, dosage forms and warnings for this drug in other countries.
Internet Mental Health (www.mentalhealth.com) copyright © 1995-2009 by Phillip W. Long, M.D.