Depression with lack of energy or mild agitation
Obsessive Compulsive Disorders (OCD)
Panic attacks with or without Agoraphobia
Narcolepsy
chronic pain with or without organic disease, particular headache of the tension type
Enuresis (involuntary nightly urinating in sleep) in children / adolescents
Off label, sometimes antidepressants of this type have been found helpful in reducing relapses in cocaine addicts and to help repair cocaine-caused neurotransmitter imbalances and early brain damage. Further studies are needed for Clomipramine in this regard.

It may take 2 to 3 weeks before the full effects of this medication are noticed in all indications.

Contraindications

Concomitant therapy with an (irreversible) MAO-Inhibitor (e.g. Tranylcypromin, Phenelzin)
Acute intoxication with central depressants (alcohol, psychoactive drugs, narcotics)
States of confusion (caution), absolutely contraindicated in patients with coma and Delirium tremens
Patients with massive agitation or anxiety (give sedative drugs concomittantly)
Hypersensitivity/Allergy against Clomipramine or other related tricyclic compounds
Hypertrophy of the Prostate with urine retention (=difficulty in urinating)
Caution : Hypertrophy of the Prostate without urine retention
Preexisting closed angle glaucoma
Epilepsy and other conditions which lower the seizure-threshold (alcohol-withdrawal, active brain tumors)
Serious liver disease (elimination is decreased), if Clomipramine is given consider dose reduction
Serious kidney disease (elimination is decresed), if Clomipramine is given consider dose reduction
Severe hypotension, shock, serious cardiovascular dysfunction (postinfarctous states, heart insufficience, arrhythmias), avoid high oral doses or injections/infusions
Preexisting bone marrow depression (leukopenia, thrombopenia, anemia, pancytopenia), can be worsened by Clomipramine
Overfunction of the thyreoid gland makes the patient more sensitive to side-effects of Clomipramine. Cautious doses should be used and the overfunction should be treated.
Caution should be exerted when treating pediatric patients under 18 yrs. of age

Pharmacology

Clomipramine is the 3-chloro derivative of Imipramine. Clomipramine is a strong, but not completely selective Serotonic-Reuptake-Inhibitor (SRI), as the active main metabolite Desmethyclomipramine acts preferably as inhibitor of Noradrenaline-Reuptake. Other hydroxy-metabolites are also active. Alpha-1-Receptor blockage and beta-down-regulation as well as postsynaptic antagonism on H1 (histaminergic)-receptors have been noted. A blockade of Sodium-channels and NDMA-receptors might, as with other tricyclics, account for its effect in chronic pain, particular of the neuropathic type.

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Obsessive-compulsive disorder and clomipramine treatment
From American Family Physician, 7/1/89

Obsessive-Compulsive Disorder and Clomipramine Treatment

Until recently, obsessive-compulsive disorder was considered one of the most treatment-resistant psychiatric disorders. However, several recent studies have demonstrated that the tricyclic antidepressant clomipramine is an effective treatment. Other tricyclic antidepressants have not been consistently effective in the treatment of this disorder.

Data on the efficacy of clomipramine for obsessive-compulsive disorder are still accumulating. Pato and associates conducted a study to determine the appropriate duration of clomipramine therapy. The authors assessed 18 patients with obsessive-compulsive disorder who manifested sustained improvement while receiving clomipramine and who agreed to participate in a double-blind study. All of the patients were diagnosed as having obsessive-compulsive disorder at least three years previously. Thirteen of the patients also had a history of depression. All of the patients had been taking clomipramine, 100 to 300 mg daily, for five to 27 months and had experienced a definite improvement in their symptoms while taking the medication. The patients were regularly evaluated for symptoms, including the time devoted to compulsive rituals and obsessional thinking.

At the beginning of the study, all of the patients were given unmarked capsules and then switched to an identical looking capsule that contained a placebo. At the end of seven weeks of placebo administration, the patient and the psychiatrist evaluator were informed that the study was completed. The patient's clinical status was discussed and a decision was made about whether to reinitiate clomipramine.

Sixteen of the 18 patients who completed the study had a substantial recurrence of obsessive-compulsive symptoms during the placebo period. Progressive worsening of symptoms began at about four weeks after discountinuation of clomipramine. In addition, 11 patients also had a significant increase in depressive symptoms. Only one patient remained symptom-free at the six-month follow-up examination. Reinstitution of clomipramine therapy led to global improvement that was similar to the improvement that initially occurred with clomipramine.

The recurrence of obsessive-compulsive symptoms and depressive symptoms following discontinuation of clomipramine therapy is in contrast to the data on major depression. A significant number of patients do not have early recurrence of depression following discontinuation of tricyclic antidepressants.

Treatment duration before discontinuation of clomipramine was not related to the frequency or severity of obsessive-compulsive or depressive symptoms during the recurrence. These findings suggest that prolonged clomipramine therapy is needed in patients with obsessive-compulsive disorder. (American Journal of Psychiatry, December 1988, vol. 145, p. 1521.)

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