Clomipramine

Clomipramine is used to treat people with obsessive-compulsive disorder (a condition that causes repeated unwanted thoughts and the need to perform certain behaviors over and over). Clomipramine is in a group of medications called tricyclic antidepressants. It works by increasing the amount of serotonin, a natural substance in the brain that is needed to maintain mental balance.

Keep all appointments with your doctor.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Mechanism of Action

Parent drug may affect serotonin uptake; active metabolite may may affect norepinephrine uptake

Pharmacokinetics

Peak Plasma Time: 2-6 hr

Concentration: 56-154 ng/mL

Half-Life: 32 hr (parent drug), 69 hr (metabolite)

Excretion: Urine (60%); feces (32%)

Steady-state therpaeutic plasma concentration: 100-250 ng/mL (parent drug), 230-550 ng/mL (metabolite)

Bioavailability: 50%

Protein Bound: 97-98%

Vd: 17 L/kg

Metabolism: Hepatic CYP2D6

Metabolites: Desmethylclomipramine

Dialyzable: No

Tell your doctor if yo are pregnant or plan to become pregnant. 

The FDA categorizes medication based on safety for use during pregnancy. Five categories - A, B, C, D, and X - are used to classify the possibel risks to an unborn baby when a medication is taken during pregnancy.

Clomipramine falls into category C. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

Take clomipramine exactly as prescribed.

Clomipramine comes in oral capsule form and it is taken 1 to 3 times a day. At the beginning of treatment, take clomipramine with food.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take 2 doses of clomipramine at the same time.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• other medications you are taking
• how you respond to this medication
• your weight
• your age

The initial recommended dose of clomipramine is 25 mg daily. The dose should be gradually increased, as tolerated, to approximately 100 mg daily during the first 2 weeks. The maximum recommended dose of clomipramine is 250 mg daily.

Initially, the medication should be divided into 3 doses and taken with meals. After the dose has been increased, the total daily dose may be given once daily, at bedtime.

Suicidality and Antidepressant Drugs

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of clomipramine hydrochloride or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Clomipramine hydrochloride is not approved for use in pediatric patients except for patients with obsessive compulsive disorder (OCD).

Avoid drinking alcohol. It can cause dangerous side effects when taken together with clomipramine.

This medicine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Usual Adult Dose for Obsessive Compulsive Disorder:

Initial dose: 25 mg orally once a day at bedtime
Maintenance dose: 100 mg orally per day
Maximum dose: 250 mg per day

Comments:
-The dose should be increased gradually, as tolerated, to 100 mg during the first 2 weeks. After the initial titration, the dose may be increased gradually over the next several weeks, up to a maximum of 250 mg per day.
-During initial titration, this drug should be given in divided doses with meals to reduce gastrointestinal side effects.
-During maintenance, the total daily dose may be given once a day at bedtime to minimize daytime sedation.
-Dosage adjustments should be made to maintain the patient on the lowest effective dosage.

Use: Treatment of obsessions and compulsions in patients with Obsessive-Compulsive Disorder (OCD)

Usual Pediatric Dose for Obsessive Compulsive Disorder:

10 to 17 years:
Initial dose: 25 mg orally once a day at bedtime
Maintenance dose: May increase to 3 mg/kg or 100 mg orally per day, whichever is the smaller dose
Maximum dose: 3 mg/kg/day or 200 mg orally per day, whichever is the smaller dose

Comments:
-During initial titration, this drug should be given in divided doses with meals to reduce gastrointestinal side effects.
-After titration, the total daily dose may be given once a day at bedtime to minimize daytime sedation.
-Dosage adjustments should be made to maintain the patient on the lowest effective dosage.

Use: Treatment of obsessions and compulsions in patients with Obsessive-Compulsive Disorder (OCD)

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Major depressive disorder

Data from randomized, double-blind studies supports the use of clomipramine in the treatment of major depressive disorder [DUAG 1986], [DUAG 1990], [DUAG 1999], [Lépine 2000], [Zohar 2003]. Additional trials may be necessary to further define the role of clomipramine in this condition.

According to the American Psychiatric Association treatment guidelines, clomipramine is effective and recommended for the management of major depressive disorder. Although the WFSBP treatment guidelines also recommend clomipramine, particularly for patients with severe depression or concomitant obsessive-compulsive disorder, the guidelines recommend prescribing a limited supply for severely depressed patients at risk of overdose.

Panic disorder

Data from randomized, double-blind, placebo-controlled studies supports the use of clomipramine in the management of panic disorder with or without agoraphobia to decrease severity of anxiety and phobias, as well as severity and frequency of panic attacks. Additional trials may be necessary to further define the role of clomipramine in this condition.

Based on the American Psychiatric Association guidelines for the treatment of panic disorder, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and benzodiazepines all have roughly comparable efficacy in the treatment of panic disorder, but SSRIs are likely to have the most favorable balance of efficacy and adverse effects for most patients. Based on the Canadian Psychiatric Association guidelines for the management of anxiety disorders, TCAs like clomipramine are second-line choices for panic disorder. Based on the World Federation of the Societies of Biological Psychiatry guidelines for the management of anxiety disorders, TCAs are recommended in panic disorder in patients who have not responded to SSRIs or SNRIs.

Hypersensitivity to clomipramine, other tricyclic agents, or any component of the formulation; use of MAO inhibitors intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing either clomipramine or the MAO inhibitor); initiation of clomipramine in a patient receiving linezolid or intravenous methylene blue; use in a patient during the acute recovery phase of MI

Obsessive-compulsive disorder (OCD), treatment: Children ≥10 years and Adolescents: Oral:

Initial: 25 mg daily; gradually increase as tolerated over the first 2 weeks to 3 mg/kg/day or 100 mg daily (whichever is less) in divided doses

Maintenance: After the initial titration, wait 2 to 3 weeks between dosing adjustments to assess tolerability and effectiveness. May further increase over next several weeks up to maximum of 3 mg/kg/day or 200 mg/day (whichever is less); after titration, may give as a single once daily dose at bedtime

Discontinuation of therapy: Refer to adult dosing.

MAO inhibitor recommendations: Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Use with caution in patients with hepatic impairment.

Applies to clomipramine: oral capsule

Nervous system

Very common (10% or more): Somnolence (up to 54%), tremor (up to 54%), dizziness (up to 54%), headache (up to 52%), nervousness (up to 18%), myoclonus (up to 13%)
Common (1% to 10%): Paraesthesia, twitching, hypertonia, confusion, speech disorder, migraine, paresis, taste perversion, abnormal thinking, vertigo
Uncommon (0.1% to 1%): Abnormal coordination, abnormal EEG, abnormal gait, ataxia, coma, convulsions, dyskinesia, dysphonia, encephalopathy, euphoria, extrapyramidal disorder, hyperkinesia, hypokinesia, neuralgia, sensory disturbance, somnambulism, stimulation
Rare (less than 0.1%): Cerebral hemorrhage, anticholinergic syndrome, aphasia, apraxia, cholinergic syndrome, choreoathetosis, generalized spasm, hemiparesis, hyperesthesia, hyperreflexia, hypoesthesia, indecisiveness, neuropathy, nystagmus, oculomotor nerve paralysis, stupor
Frequency not reported: Neuroleptic malignant syndrome[Ref]

Cardiovascular

Common (1% to 10%): Flushing, chest pain, postural hypotension, palpitation, tachycardia, syncope
Uncommon (0.1% to 1%): Abnormal ECG, arrhythmia, bradycardia, cardiac arrest, extrasystoles, pallor, increased blood pressure
Rare (less than 0.1%): Cyanosis, aneurysm, atrial flutter, bundle branch block, cardiac failure, heart block, myocardial infarction, myocardial ischemia, peripheral ischemia, thrombophlebitis, vasospasm, ventricular tachycardia[Ref]

Psychiatric

Very common (10% or more): Insomnia (up to 25%)
Common (1% to 10%): Anxiety, memory impairment, impaired concentration, depression, sleep disorder, psychosomatic disorder, abnormal dreaming, agitation, depersonalization, irritability, emotional lability, panic reaction, aggressive reaction
Uncommon (0.1% to 1%): Delirium, delusion, apathy, euphoria, catalepsy, illusion, impaired impulse control, mutism, oculogyric crisis, hallucinations, hostility, hypnagogic hallucinations, manic reaction, paranoia, phobic disorder, suicidal ideation, suicide attempt, psychosis
Rare (less than 0.1%): Withdrawal syndrome, schizophrenic reaction[Ref]

Gastrointestinal

Very common (10% or more): Dry mouth (up to 84%), constipation (up to 47%), nausea (up to 33%), dyspepsia (up to 22%), diarrhea (up to 13%), abdominal pain (up to 11%)
Common (1% to 10%): Vomiting, flatulence, tooth disorder, gastrointestinal disorder, dysphagia, esophagitis, eructation, ulcerative stomatitis, halitosis
Uncommon (0.1% to 1%): Blood in stool, teeth-grinding, colitis, duodenitis, gastric ulcer, gastritis, gastroesophageal reflux, gingivitis, glossitis, hemorrhoids, increased saliva, irritable bowel syndrome, peptic ulcer, rectal hemorrhage, tongue ulceration, tooth caries
Rare (less than 0.1%): Cheilitis, chronic enteritis, discolored feces, gastric dilatation, gingival bleeding, hiccup, intestinal obstruction, oral/pharyngeal edema, paralytic ileus, salivary gland enlargement[Ref]

General

The most commonly reported side effects were somnolence, tremor, dizziness, headache, dry mouth, constipation, and nausea.[Ref]

Genitourinary

Very common (10% or more): Libido change (up to 21%), micturition disorder (up to 14%), dysmenorrhea (up to 12%)
Common (1% to 10%): Urinary tract infection, micturition frequency, urinary retention, dysuria, cystitis, lactation (nonpuerperal), menstrual disorder, vaginitis, leukorrhea, breast enlargement, breast pain, amenorrhea, ejaculation failure, impotence
Uncommon (0.1% to 1%): Endometriosis, epididymitis, hematuria, nocturia, oliguria, ovarian cyst, perineal pain, polyuria, prostatic disorder, urethral disorder, urinary incontinence, uterine hemorrhage, vaginal hemorrhage
Rare (less than 0.1%): Albuminuria, anorgasmy, breast engorgement, breast fibroadenosis, cervical dysplasia, endometrial hyperplasia, premature ejaculation, pyelonephritis, pyuria, uterine inflammation, vulvar disorder[Ref]

Hematologic

Common (1% to 10%): Purpura, anemia
Uncommon (0.1% to 1%): Lymphadenopathy
Rare (less than 0.1%): Leukemoid reaction, lymphoma-like disorder, marrow depression
Very rare (less than 0.01%): Leucopenia, agranulocytosis, thrombocytopenia, eosinophilia[Ref]

Endocrine

Common (1% to 10%): Hot flushes, galactorrhea
Uncommon (0.1% to 1%): Hypothyroidism
Rare (less than 0.1%): Goiter, gynecomastia, hyperthyroidism
Very rare (less than 0.01%): SIADH (inappropriate antidiuretic hormone secretion syndrome)
Frequency not reported: Increased blood prolactin[Ref]

Hepatic

Uncommon (0.1% to 1%): Abnormal hepatic function, hepatitis[Ref]

Dermatologic

Very common (10% or more): Increased sweating (up to 29%)
Common (1% to 10%): Rash, pruritus, dermatitis, acne, dry skin, urticaria, abnormal skin odor[Ref]

Other

Very common (10% or more): Fatigue (up to 39%)
Common (1% to 10%): Fever, pain, local edema, chills, otitis media, asthenia, tinnitus, vestibular disorder
Uncommon (0.1% to 1%): Malaise, deafness, earache, foreign body sensation, hyperacusis, parosmia
Rare (less than 0.1%): Dependent edema, labyrinth disorder[Ref]

Metabolic

Very common (10% or more): Weight increase (up to 18%), anorexia (up to 12%), increased appetite (up to 11%)
Common (1% to 10%): Weight decrease, thirst, decreased appetite
Uncommon (0.1%): Dehydration, diabetes mellitus, gout, hypercholesterolemia, hyperglycemia, hyperuricemia, hypokalemia
Rare (less than 0.1%): Fat intolerance, glycosuria[Ref]

Hypersensitivity

Common (1% to 10%): Allergy
Very rare (less than 0.01%): Anaphylactic and anaphylactoid reactions[Ref]

Respiratory

Very common (10% or more): Pharyngitis (up to 14%), rhinitis (up to 12%)
Common (1% to 10%): Yawning, sinusitis, coughing, bronchospasm, epistaxis, dyspnea, laryngitis
Uncommon (0.1% to 1%): Bronchitis, hyperventilation, increased sputum, pneumonia
Rare (less than 1%): Hemoptysis, hypoventilation, laryngismus
Very rare (less than 0.01%): Pneumonitis[Ref]

Ocular

Very common (10% or more): Abnormal vision (up to 18%)
Common (1% to 10%): Abnormal lacrimation, mydriasis, conjunctivitis, anisocoria, blepharospasm, ocular allergy
Uncommon (0.1% to 1%): Abnormal accomodation, diplopia, eye pain, photophobia, scleritis
Rare (less than 0.1%): Blepharitis, chromatopsia, conjunctival hemorrhage, exophthalmos, glaucoma, keratitis, night blindness, retinal disorder, strabismus, visual field defect
Postmarketing reports: Angle-closure glaucoma[Ref]

Musculoskeletal

Very common (10% or more): Myalgia (13%)
Common (1% to 10%): Back pain, arthralgia, muscle weakness
Uncommon (0.1% to 1%): Arthrosis
Rare (less than 0.1%): Dystonia, exostosis, myopathy, myositis, polyarteritis nodosa, torticollis
Frequency nor reported: Rhabdomyolysis[Ref]

Immunologic

Uncommon (0.1% to 1%): Increased susceptibility to infection[Ref]

Renal

Uncommon (0.1% to 1%): Renal calculus, renal pain
Rare (less than 0.1%): Renal cyst[Ref]

Some side effects of clomipramine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.