Clomipramine (Dosage)

Clomipramine is an antidepressant used in the treatment of depression, phobias, anxiety and obsessive-compulsive syndrome, among others. Differences in drug response may be mediated by the presence of polymorphisms in the CYP2D6 and CYP2C19 genes.

Clomipramine is a tricyclic antidepressant (TCA). It is indicated in the treatment of depression, phobias, panic attacks, obsessive syndromes, nocturnal enuresis and certain types of narcolepsy, although currently its therapeutic use is usually mainly the treatment of pain

ACTION MECHANISM

Clomipramine inhibits the neuronal reuptake of noradrenaline, norepinephrine and serotonin released in synaptic cleft.

Clomipramine is a potent tricyclic with less stimulating effect than imipramine. It has an intermediate sedative effect between that of amitriptyline and imipramine, although with more side effects than the latter.

It is an especially useful drug with extensive experience of use in obsessive disorders; in children, it is very useful in attention deficit disorder with/without hyperactivity.

CONTRAINDICATIONS

Clomipramine is contraindicated in cases of hypersensitivity or cross-sensitivity to tricyclic dibenzodiazepine antidepressants (clomipramine, desipramine, imipramine, nortriptyline and trimipramine). Clomipramine is also contraindicated in combination with MAOIs, or in the 14-day period before or after treatment with MAOIs.

PRECAUTIONS

Precautions should be taken when clomipramine is prescribed in patients with epilepsy and with predisposing factors to epilepsy, in patients with cardiovascular disorders, cardiovascular insufficiency, conduction disorders or arrhythmias.

Caution in patients with a history of elevated intraocular pressure, angle-closure glaucoma, urinary retention, severe hepatic failure and adrenal medulla tumors.

Attention should be paid when prescribing clomipramine to patients with cyclical affective disorders, schizophrenia, hypotension, hyperthyroidism, hematologic alterations and cranial brain trauma.

Caution with the elderly and in patients with chronic constipation (risk of paralytic ileus).

Extreme caution should be exercised when prescribing clomipramine to patients at risk of suicide.

Dental checks should be performed in prolonged treatments with clomipramine.

If clomipramine is combined with selective serotonin reuptake inhibitors (SSRIs) or diuretics, there exists risk of hypokalemia.

Avoid sudden interruption of treatment. Clomipramine is not recommended in children and adolescents.

Caution should be exercised if clomipramine is ingested concomitantly with drugs that prolong the cardiac QT interval or other serotonergic drugs.

Risk of anaphylactic shock if clomipramine is given intravenously.

SIDE EFFECTS

Dizziness, fatigue, tiredness, increased appetite, confusion, disorientation, hallucinations (especially in the elderly and patients with Parkinson's disease), states of anxiety, agitation, sleep disorders, mania, hypomania, aggression, loss of memory and concentration, depersonalization, aggravation of depression, insomnia, nightmares, yawning; tremor, headache, myoclonus; delirium, language disorders, paresthesia, muscle weakness, muscle hypertonia; dry mouth, sweating, constipation, disorders of visual accommodation, blurred vision, urination disorders, hot flushes, mydriasis; sinus tachycardia, palpitations, postural hypotension, changes in the electrocardiogram clinically irrelevant in patients with normal cardiac status; nausea, vomiting, abdominal disorders, diarrhea, anorexia; elevation of transaminases, skin itching, urticaria; weight gain, disorders of libido and potency, galactorrhea, increase in breast size; taste disorders, tinnitus.

After abrupt withdrawal or dose reduction: nausea, vomiting, abdominal pain, diarrhea, insomnia, headache, nervousness, anxiety

PHARMACOLOGIC INTERACTIONS

Clomipramine decreases the antihypertensive effect of: guanethidine, betenidine, reserpine, clonidine and alphamethyldopa.

Clomipramine potentiates the cardiovascular effect of: adrenaline, noradrenaline, isoprenaline, ephedrine, phenylephrine.

Clomipramine potentiates the effect of: alcohol, barbiturates, benzodiazepines, general anesthetics, phenothiazine, antiparkinsonians, antihistamines, atropine, biperiden.

Clomipramine potentiates the action and toxicity of coumarin.

The action of clomipramine may be diminished by: barbiturates, carbamazepine, phenytoin, nicotine, oral contraceptives.

Clomipramine should not be used with quinidine.

There is a possibility of cardiac toxicity if clomipramine is taken with thyroid preparations.

The plasma concentrations of clomipramine are increased with: cimetidine, methylphenidate, estrogens.

The comedication of clomipramine with SSRIs (selective serotonin reuptake inhibitors) can lead to additive effects in the serotonin system.

BRAND NAME

  • Anafranil ®

Genes analyzed

CYP2C19 CYP2D6

Bibliography

Hicks JK, Swen JJ, Thorn CF, et al.Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants. Clin Pharmacol Ther, 2013; 93(5):402-8.

Hicks JK, Sangkuhl K, Swen JJ, et al.Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther. 2017 Jul;102(1):37-44.

Yokono A, Morita S, Someya T, et al.The effect of CYP2C19 and CYP2D6 genotypes on the metabolism of clomipramine in Japanese psychiatric patients. J Clin Psychopharmacol. 2001 Dec;21(6):549-55.

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