Clomipramine

Products

Clomipramine is commercially available as sustained-release tablets and coated tablets (Anafranil). It has been approved in many countries since 1966 (originally Geigy, later Novartis). The injection and infusion preparations are no longer marketed.

Structure and properties

Clomipramine (C19H23ClN2, Mr = 314.9 g/mol) is present in drugs as clomipramine hydrochloride, a white to pale yellow crystalline powder that is readily soluble in water. It belongs structurally to the dibenzazepines and to the tricyclic antidepressants. It is a chlorinated imipramine.

Effects

Clomipramine (ATC N06AA04) has antidepressant, antiobsessive, depressant, alpha-1-adrenolytic, anticholinergic, antihistamine, and antiserotonergic properties. It inhibits the reuptake of norepinephrine and serotonin into the presynaptic neuron. The active metabolite desmethylclomipramine is formed by CYP2D6. The mean half-life is 21 hours for clomipramine and 36 hours for desmethylclomipramine.

Indications

Medical indications include:

  • Depression
  • Phobias, panic attacks
  • Obsessive-compulsive disorders
  • Cataplexy in narcolepsy
  • Chronic pain
  • Enuresis nocturna (bedwetting)

Dosage

According to the professional information. The dose is adjusted individually and built up gradually. Discontinuation is gradual.

Contraindications

  • Hypersensitivity, including to related agents.
  • Therapy with antiarrhythmic agents such as quinidine and propafenone, which are potent CYP2D6 inhibitors
  • Combination with MAO inhibitors
  • Fresh myocardial infarction
  • Congenital prolonged QT syndrome
  • Acute intoxication with central depressant drugs or alcohol.
  • Acute urinary retention
  • Acute delirium
  • Untreated narrow-angle glaucoma
  • Prostate enlargement with residual urine formation
  • Pyloric stenosis
  • Paralytic ileus

For complete precautions, see the drug label.

Interactions

Clomipramine is a substrate of CYP450 isozymes. These include CYP3A4, CYP2C19, CYP1A2, and CYP2D6. It has a high potential for interaction, for example, with MAO inhibitors, serotonergic drugs, sympathomimetics, and anticholinergics.

Adverse effects

The most common possible adverse effects include:

  • Dry mouth, sweating, voiding dysfunction.
  • Increased appetite, weight gain.
  • Sleepiness, fatigue, inner restlessness.
  • Dizziness, tremor, headache, myoclonia.
  • Accommodative disorders, blurred vision.
  • Constipation

Clomipramine may prolong the QT interval.