Article on Clomipramine

(for Gale Encyclopedia of Mental Disorders)

 

Definition

Clomipramine is an antidepressant drug used primarily to alleviate obsessions and compulsions in patients with obsessive-compulsive disorder. Clomipramine is also used in the treatment of depressive disorders and in a number of other psychiatric and medical conditions. In the United States, the drug has also been known by the brand name, Anafranil.

Purpose

 

Clomipramine is principally used in the treatment of the obsessions and compulsions of obsessive-compulsive disorder (OCD), when these symptoms greatly disrupt the patient's daily activities. Obsessions are repetitive thoughts and impulses, and compulsions are repetitive behaviors. Patients with OCD find these experiences inappropriate, distressing, and time-consuming.

 

Clomipramine may also be used in the treatment of depressive disorders, especially when associated with obsessions and compulsions, in panic disorder, pain management, sleep attacks (narcolepsy and cataplexy), and anorexia nervosa. The drug may help to reduce compulsive behaviors in a variety of disorders with such symptoms, including trichotillomania (hair-pulling), onychophagia (nail-biting), Tourette's disorder (tics and vocalizations), and childhood autism.

Description

 

Clomipramine is one of the tricyclic antidepressants, so-called because of the three-ring chemical structure common to these drugs. In the 1940s and 1950s, pharmaceutical researchers synthesized a number of new compounds for possible medical use as antihistamines and sedatives. After testing in animal experiments, a few of these substances were selected for human study. One potential drug, a tricyclic compound called imipramine, was not useful in calming agitation, but it had a striking effect in improving the mood of certain patients with depression.

Since the discovery of imipramine, many other tricyclic antidepressants have been developed for somewhat differing pharmacological activities and side effect profiles. Within this group of drugs, clomipramine is exceptionally potent in affecting levels of serotonin in the brain. In this action, it is similar to serotonin-selective antidepressant drugs, like fluoxetine (Prozac), which act specifically on serotonin levels and are effective in OCD. Serotonin is a messenger chemical (neurotransmitter) involved in transmitting signals between nerve cells. The effects on serotonin neurotransmission of clomipramine and serotonin-selective antidepressants are thought to be related to the improvement the drugs produce in depression and OCD.

Recommended dosage

For adults, clomipramine is administered in dosages up to a maximum of 250 mg per day. Starting with a dose of 25 mg, the dose is increased during the first two weeks to 100 mg per day. If needed, it is further increased gradually over the next several weeks to the maximum. The initial dose is low to avoid side effects, and it is increased slowly to permit the patient to develop tolerance or adapt to side effects that may occur.

 

Geriatric patients, children, and adolescents are more sensitive to the side effects and toxicities of tricyclic antidepressants. The maximum daily dose is usually lower for geriatric patients than adults. For children and adolescents, the maximum recommended daily dose is the lesser of 100 mg or 3 mg per kg of body weight.

 

Precautions

 

Epileptic seizures are the most important risk associated with clomipramine. Among patients taking the drug for six months or more, more than 1% may experience seizures. The risk of seizure increases with larger doses, and seizures have been reported to occur following abrupt discontinuation of the medication. Caution is required if the patient has a history of epilepsy or some other condition associated with seizures, such as brain damage or alcoholism.

 

Clomipramine and other tricyclic antidepressants may cause drowsiness.  Activities requiring alertness, such as driving, may be impaired. Dizziness or lightheadedness may occur on arising due to sudden decreases in blood pressure.  Fainting may occur.  Some patients may experience difficulty urinating, especially men with prostate enlargement. Glaucoma may be aggravated. Sensitivity to ultraviolet light may be increased, and sunburns may occur more easily.

 

Tricyclics antidepressants, including clomipramine, should be used with caution in patients with heart disease, because of the possibility of adverse effects on heart rhythm. Adverse effects on the heart occur frequently when tricyclics are taken in overdose. Only small quantities of these drugs should be given to patients who may be suicidal.

 

Tricyclic antidepressants may cause dry mouth due to decreased saliva, possibly contributing to the development of tooth decay, gum disease, and mouth infections. Patients should avoid sweets, sugary beverages, and chewing gum containing sugar.