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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Clomipramine therapy in obsessive-compulsive disorder - Tips from Other Journals
From American Family Physician, 2/1/92

Obsessive-compulsive disorder is characterized by recurrent obsessions (persistent ideas, thoughts, impulses or images) or compulsions (repetitive behaviors), or both. Lifetime prevalence rates in the United State range from 1.2 to 2.4 percent of the population. The disorder can be a distressing and time-consuming illness that interferes with daily living. Members of the Clomipramine Collaborative Study Group conducted two randomized, placebo-controlled trials to evaluate the therapeutic efficacy and safety of clomipramine hydrochloride in the treatment of obsessive-compulsive disorder. Clomipramine is a tripcyclic antidepressant drug with serotonergic properties.

The first study included 239 patients who had at least a two-year history of obsessive-compulsive disorder. A total of 209 patients completed the treatment protocol. The second study included 281 patients who had at least a one-year history of obssessive-compulsive disorder. A total of 255 patients completed the treatment.

The studies were double-blind parallel trials. After two-to four-week washout period, all of the patients entered a two-week, single-blind placebo period. After the single-blind placebo period, patients in both studies were randomized to receive either clomipramine or palcebo during a 10-week, dougble-blind period.

In both studies, a minimum dosage of 100 mg per day was required for continuation in the trial beyong the third week of treatment. Clomipramine was administered in increasing doses to a maximum of 300 mg daily. For most patients, the maximum dosage was between 150 mg and 250 mg daily. Treatment success was measured by standardized assessment scales, patient's self-ratings of therapeutic change and blinded physician evaluations. The patients were seen weekly during the study period.

At the end of 10 weeks, improvement on the assessment scales was significantly greater in the clomipramine groups than in the control groups. In addition, 55 percent of the patients receiving clomipramine considered themselves "very much" or "much" improved, compared with 10 percent of the control patients. Finally, physician evaluations also revealed significant improvements in patients receiving clomipramine treatment. Many patients taking clomipramine reported side effects typical of tricyclic antidepressant drugs, including dry mouth, dizziness, tremor, fatigue, somnolence and constipation.

The authors conclude that clomipramine is an effective treatment for obsessive-compulsive disorder and is generally well tolerated. (Archives of General Psychiatry, August 1991, vol. 48, p. 730.)

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