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Clomipramine

Brands and Forms

  • Anafranil
    • capsule: 25mg, 50mg, 75mg

Uses of Clomipramine

Clomipramine can be used for treating Obsessive-Compulsive Disorder and other Anxiety Disorders, as well as Major Depressive Disorder, Dysthymia, and Body Dysmorphic Disorder. It is also used at times for alleviating neuropathic pain.

How Clomipramine Works

Clomipramine is a Tricyclic Antidepressant. It boosts serotonin actions in the central nervous system and also increases norepinephrine neurotransmission. It also has anticholingergic properties that are responsible for many of the side-effects.

Cautions when Using Clomipramine

Clomipramine can induce Manic or Mixed Episodes and Rapid Cycling in people with Bipolar Disorder.

Children and adolescents who use antidepressants like Clomipramine may develop self-injurious or suicidal behaviors (for more information, see here).

Use caution in people with a known seizure disorder, heart disease, urinary retention, or hyperthyroidism.

Tricyclic Antidepressants such as Clomipramine have been shown to increase the risk of cardiovascular disease [ref]. Furthermore, because of the risk of cardiac arrhythmias and other cardiovascular side-effects, the risk/benefit ratio may not justify the use of this medication in individuals with heart disease.

Long-term use of Clomipramine may increase the risk of osteoporosis and bone fractures in individuals over age 50.

Clomipramine should not be used during or within 14 days following the administration of an MAOI, because a hypertensive crisis may result.

Dosing of Clomipramine

The usual therapeutic range of Clomipramine is 100-200mg/day, though some individuals will require up to 250mg/day. Doses of 300mg/day or more have a significant risk of causing seizures.

Clomipramine is usually given once daily at bedtime, as it can be quite sedating, but it can also be given twice a day.

Initial dose is usually 25mg/day, and it can be increased over 2 weeks to 100mg/day. At that point, it is generally recommended to wait at least 4 weeks to see if therapeutic effects occur before increasing the dose further.

When wanting to stop this medication, the dose should be decreased gradually over a period of 6-8 weeks. A sudden cessation of the medication can result in a discontinuation syndrome.

Onset of action

Therapeutic effects for Depression are not expected before 2-4 weeks at a dose of 100mg/day, and for OCD the onset of therapeutic action can take 6-12 weeks. If no significant effects are seen for Depression after 6-8 weeks of use, including at least 2 weeks at a dose above 100mg/day, then the medication may not work at all. If no significant effects are seen for OCD after 12 weeks of use, then the medication may not work at all.

Kidney impairment

Use with caution.

Liver impairment

Use with caution.

Side-effects of Clomipramine

Below is a list of most of the reported side-effects of Clomipramine. Most of these side-effects occur in only a minority of individuals, and many also resolve with time while the medication is continued.

Cardiovascular: postural hypotension; palpitation, rapid heart rate; fainting; QTc prologation; stroke; heart block; congestive heart failure.

Central Nervous System: dizziness; somnolence; tremor; headache; insomnia; decreased libido; myoclonus; increased appetite; impaired memory; paresthesia; twitching; impaired coordination; hypertonia; abnormal dreaming; confusion; migraine; speech disorder; yawning; weakness; paresis; abnormal thinking; vertigo; confusion; seizures (rare at doses below 300mg/day).

Dermatologic: excessive sweating; itchiness; rash; abnormal skin odor; acne; dermatitis; dry skin; urticaria; hair loss (rare).

Endocrine/Metabolic: abnormal breast milk secretion; breast enlargement in men and women; breast pain.

Eyes, Ears, Nose and Throat: dry mouth; abnormal vision; pharyngitis; rhinitis; tinnitus; otitis media; abnormal lacrimation; anisocoria; acute angle glaucoma; blepharospasm; laryngitis; mydriasis; ocular allergy; vestibular disorder; conjunctivitis.

Gastrointestinal: constipation; nausea; dyspepsia; diarrhea; appetite loss or increase; weight gain; abdominal pain; vomiting; flatulence; tooth disorder; dysphagia; eructation; bad breath; elevated liver enzymes; gastrointestinal obstruction (rare).

Genitourinary: ejaculation failure; impotence; dysmenorrhea; urinary retention; urinary tract infection; micturition frequency; cystitis; dysuria; vaginitis; amenorrhea.

Hematologic: increases bleeding time (thins the blood); anemia; leucopenia; pancytopenia; thrombocytopenia.

Muskuloskeletal: risk of osteoporosis and bone fractures with long-term use.

Psychiatric: anxiety; agitation; apathy; irritability; worsening depression; depersonalization; suicidal thoughts; self-injurious behaviors among children and adolescents; can induce Manic or Mixed Episodes and Rapid Cycling in people with Bipolar Disorder.

Respiratory: bronchospasm; coughing; sinusitis; dyspnea; epistaxis.

Common side-effects of Clomipramine

Dizziness, sedation/fatigue, tremor, headache, blurred vision, constipation, urinary retention, ejaculation failure; impotence; increased appetite, weight gain, dry mouth, nausea, diarrhea, heartburn, unusual taste in mouth, weakness, anxiety, restlessness, sweating, sexual dysfunction.

Rare but serious side-effects of note of Clomipramine

  • Children and adolescents who use antidepressants like Clomipramine may develop self-injurious or suicidal behaviors (for more information, see here).
  • Seizures
  • QTc prolongation, which can lead to serious heart arrhythmias
  • Heart attack and stroke
  • Acute angle glaucoma
  • Intestinal obstruction

Clompiramine discontinuation syndrome

Individuals who suddenly stop using Clomipramine after taking the medication at moderate or high doses over a significant period of time are at risk of developing a discontinuation syndrome, which can include the following symptoms: dizziness, electric shock-like sensations, sweating, nausea, insomnia, tremor, anxiety, restlessness, agitation, depressed mood, irritability, confusion, lethargy, and vertigo. These symptoms usually start anywhere from one day to one week after the medication was stopped, and can persists for days or even weeks.

This syndrome can be treated by restarting the medication at its prior dose. It can be prevented by decreasing the dose gradually over a period of 6-8 weeks when wanting to stop the medication. In rare cases, individuals may experience the discontinuation syndrome even when the medication is being tapered gradually; in such cases, an extremely slow and gradual taper will be necessary.

Clomipramine overdose

Agitation, cessation of urination, unsteadiness, abnormal movements, cardiac dysrhythmias, CNS depression including coma, convulsions, cyanosis, delirium, drowsiness, ECG changes (particularly in QRS axis or width), hyperactivity reflexes, hyperpyrexia, muscle rigidity, mydriasis, oliguria, rare cardiac arrest, respiratory depression, restlessness, severe hypotension, severe perspiration, shock, signs of CHF, stupor, tachycardia, and vomiting. Can be fatal.

Clomipramine and pregnancy

Category C: some animal studies show adverse effects at very high doses, but no controlled human studies have been done; should only be used in pregnancy if clearly needed and if benefits outweigh potential risks. For further information, see the section on treating Depression in pregnancy.

Medical Monitoring for Clomipramine

Monitor blood counts (CBC with differential), body mass index; blood sugars (in patients with diabetes), electrocardiogram, and liver function tests as needed.

Drug Interactions with Clomipramine

  • Caution should be used when combining Clomipramine with other drugs that have anticholinergic properties.
  • Clomipramine blood concentrations can be increased by Fluoxetine, Paroxetine, Bupropion, Duloxetine, Fluvoxamine, Cimetidine, Methylphenidate, Haloperidol, and phenothiazines.
  • Clomipramine should not be used during or within 14 days following the administration of an MAOI, because a hypertensive crisis may result.
  • QTc prolongation and serious cardiac arrhythmias can occur if Clomipramine is combined with beta-blockers, calcium channel blockers, clonidine, digitalis, diuretics, stimulant laxatives, IV amphotericin B, glucocorticoids.
  • Combination with other serotonergic medications, including SSRI medications, can precipitate a serotonin syndrome.