Clomipramine Hydrochloride , ANAFRANIL®

Brand name


Drug Class

1. Tricyclic anti-depressant

2. Anti-Obsessional


  • Tablets 10 mg, 25 mg and 50 mg


  • Obsessive Compulsive Disorder
  • Major Depressive Disorder


  • Inhibits norepinephrine and serotonin uptake into central nerve terminals >>> blocking the membrane-pump of neurons
  • Weak antihistamine
  • Potentiates the effect of norepinephrine and other drugs acting on the central nervous system


  • Absorption: Completely orally >>> Peak plasma levels >>> 2 hours >>> Plasma half-life ~ 21 hours.
  • Distribution: binding to serum proteins is very high -96 to 97%-
  • Metabolism: Hydroxylation, Demethylation and N-oxidation.
  • Excretion: 2/3 Urine, 1/3 Feces.


1. Depression:


  • Initial Dosage: 25mg/day >>> 150 mg by the end of two weeks (Gradual increase) >>> over a period of several weeks to 200 mg (Gradual Increase)
  • Maintenance dose: lowest effective level
  • Max Dose: 300 mg/day


Elderly And Debilitated Patients:

  • Initial Dosage: 20 to 30 mg daily (Divided suggested) >>> very gradual increments, depending on tolerance and response
  • Maintenance dose: lowest effective level

2. Obsessive Compulsive Disorders:


  • Initial Dosage: 25 mg/day >>> 100 or 150 mg by the end of 2 weeks (Gradual Increase) >>> over a period of several weeks to 200 mg (Gradual Increase)
  • Maintenance dose: lowest effective level
  • Max Dose: 250 mg/day

Children And Adolescents:

  • Aged 10 to 17 years>>> Initial Dose: 25 mg per day >>> Increase within 3 to 4 day intervals >>> in 2 weeks, titrate up to 100-150 mg per day or 3 mg/kg
  • Maintenance dose: Lowest effective dose
  • Max Dose: 200 mg/day

Elderly And Debilitated Patients:

  • Initial Dose: 20-30 mg/day >>> very gradual increments, depending on tolerance and response
  • Maintenance dose: Lowest effective dose

Drug Interactions

1. Major Depressive Disorder: (MDD)

2. Obsessive Compulsive Disorder: (OCD)

3. Alcoholic beverages

4. CNS depressants, eg:

  • Barbiturates
  • Benzodiazepines
  • General anaesthetics

5. Guanethidine

6. Bethanidine

7. Clonidine

8. Reserpine

9. Alpha-methyldopa

10. Isoprinosine

11. Ephedrine

12. Phenylephrine

13. Noradrenaline

14. Adrenaline

15. Amphetamine (methylphenidate)

16. Selective serotonin reuptake inhibitors (SSRIs)

17. Enzyme inhibitor medications such as: Cimetidine

18. Enzyme inducer Medications: Barbiturates, Carbamazepine, Phenytoin, Nicotine & Oral contraceptives.

19. Neuroleptic agents: (e.g., phenothiazines and butyrophenones, thioridazine )

20. Alprazolam

21. Disulfiram

Adverse Effects

Frequent: (> 10 %)

  • Mild sedation
  • Mania
  • Somnolence
  • Tremor
  • Sexual Dysfunction: (Libido change, Impotence, Ejaculation Failure)
  • Urinary Retention
  • Blurred Vision
  • Dyspepsia
  • Dry Mouth, Nausea, Vomiting, Constipation

< 10%:

  • Orthostatic Hypotension
  • Suicidal thoughts/ Ideation
  • Myocardial Infarction
  • Thrombocytopenia & Agranulocytosis: (Bone Marrow Failure)


  • Hypersensitivity to medication.
  • Monoamine oxidase inhibitor (MAOIs).
  • Acute recovery phase following myocardial infarction.
  • Acute congestive heart failure.
  • Liver or kidney
  • Blood dyscrasias.
  • Narrow angle Glaucoma
  • Paralytic ileus
  • Pheochromocytoma
  • Neuroblastoma

Pregnancy and Breastfeeding

  • Pregnancy: Category C
  • Lactation: Do not use in nursing mother


1. Mild sedative effect >>> Alleviating the anxiety accompanying depression >>> difficulty in concentrating and thinking >>> Avoid Driving! Using complex machineries, swimming, climbing.

2. Persistent increase in the frequency of shifts into stage I sleep >>> produces marked reduction or suppression of rapid eye movement sleep

3. Elderly patients require lower doses of ANAFRANIL.

4. Practically concentration-independent within the therapeutic range. (Low Therapeutic index)

5. Should not be given in conjunction with monoamine oxidase inhibitor >>> Caution for Serotonin Syndrome: Hypertensive crises, hyperactivity, hyperpyrexia, spasticity, severe convulsions / coma / death >>> Wait for least 14 days!

6. Anti- Cholinergic effects : Do not use in Glaucoma & urinary retention (prostatic hypertrophy) >>> aggravated condition >>> atropine-like effects.

7. Seizures: extreme caution in patients with a history of convulsive disorders/ predisposing factors: brain damage, alcoholism, drugs lower the seizure threshold.

8. Cardiovascular: particularly in high doses, sinus tachycardia, changes in conduction time (AV block 1-2-3) + arrhythmias (premature ventricular contractions, ST-T wave changes = Most common) >>> Use with caution!

  •  Check the patient’s blood pressure before stating Clomipramine
  • Do regular ECGs & Blood pressure. (Postural Hypotension > Diminish the dose)
  • QTc prolongation & Torsades de points at supra-therapeutic doses
  • Hyperthyroid patients/ patients receiving thyroid medication: Transient cardiac arrhythmias.
  • Caution in concomitant use with: Guanethidine, Bethanidine, Clonidine, Reserpine /alpha-methyldopa.
  • Potentiate the cardiovascular effects of noradrenaline / adrenaline, amphetamine, nasal drops & sympathomimetic, local anaestheticsg. >>> Isoprenaline, Ephedrine, Phenylephrine.

9.  Paralytic ileus: Ederly & hospitalized patients >>> Use with caution!

10. Tumors of the adrenal medulla: Pheochromocytoma, Neuroblastoma >>> Use with caution!

11. Suicidal abuse risk: Prescribe ANAFRANIL for the smallest possible quantity of the drug consistent with good patient management.

12. Psychosis, Mania-Hypomania:

Patients treated with TCAs >>> May Occur:

  • Activation of latent schizophrenia/
  • Aggravation of existing psychotic manifestations
  • Over-stimulation of agitated patients
  • In predisposed & elderly patients >>> Provoke delirium. (Especially with night use)

13. Hepatic Changes: elevations in SGOT and SGPT >>> Caution is considered!

14. Hematologic Changes: bone marrow depression with agranulocytosis >>> Use with caution in hematologic disorder patients!

15. Withdrawal Symptoms: Do not do abrupt discontinuation! >>> Taper gradually

16. Metabolic Effects: Tricyclic antidepressants have been associated with porphyrinogenicity in susceptible patients.

17. Renal Function: monitor renal function during long-term therapy (BUN, Cr)

18. Dental Effects: Lengthy treatment >>> increased incidence of dental caries.

19. Decreased lacrimation: may cause damage to the corneal epithelium in patients with contact lenses.

20. Endocrine Effects: ANAFRANIL elevates prolactin levels

21. ANAFRANIL has not been studied in patients under 10 y/o

22. Diuretics: Concomitant use may lead to hypokalemia

23. Co-medication with Selective serotonin reuptake inhibitors (SSRIs) may lead to additive effects on the serotonergic system. >>> Caution!

24. ANAFRANIL should be discontinued prior to elective surgery.

25. Concomitant treatment with neuroleptic agents: (e.g., phenothiazines and butyrophenones) >>> Enzyme inhibitor effect >>> increased plasma concentrations of ANAFRANIL >>> lowered convulsion threshold.

26. Lower the dosage of ANAFRANIL if administered concomitantly with Alprazolam or Disulfiram.

27. Tricyclic antidepressants may potentiate the anticoagulant effect of Coumarin drugs (eg: Warfarin) by inhibiting hepatic metabolism of these drugs. Careful monitoring of Protrombine time + INR.

28. Over-dosage: (General treatment overview):

  • Symptoms: drowsiness, stupor, ataxia, vomiting, cyanosis, restlessness, muscle rigidity, athetoid and choreiform movements, & convulsions, Cardiac Shock, Coma.
  • Admit to hospital without delay > Gastric lavage up to 12 hours> Heart Monitoring > activated charcoal > peritoneal dialysis and hemodialysis.
  • Goal: insure maintenance of the vital functions


This document is prepared by the “Mental Health for All” team. This document is provided for information purposes only and does not necessarily represent endorsement by or an official position of the Essentials of Medicine. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient’s medical history.

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