Tricyclic antidepressants act to change the balance of naturally occurring chemicals in the brain that regulate the transmission of nerve impulses between cells. Trimipramine acts primarily to increase the concentration of norepinephrine and serotonin (both chemicals that stimulate nerve cells) and, to a lesser extent, to block the action of another brain chemical, acetylcholine. Trimipramine shares most of the properties of other tricyclic antidepressants, such as amitriptyline, amoxapine, clomipramine, desipramine, imipramine, nortriptyline, and protriptyline. Studies comparing trimipramine with these other drugs have shown that trimipramine is no more or less effective than other antidepressants of its type. Its choice for treatment is as much a function of physician preference as any other factor.
The therapeutic effects of trimipramine, like other antidepressants, appear slowly. Maximum benefit is often not evident for at least two weeks after starting the drug. People taking trimipramine should be aware of this and continue taking the drug as directed even if they do not see immediate improvement.
Recommended dosage
As with any antidepressant, trimipramine must be carefully adjusted by a physician to produce the desired therapeutic effect. Trimipramine is available as 25-mg, 50-mg, and 100-mg oral capsules. Therapy is usually started at 75 to 100 mg per day and gradually increased up to 200 mg daily as needed. Hospitalized patients with more severe depression may require 300 mg per day. Amounts up to 200 mg may be given as a single dose. In people over age 60 and in adolescents, the therapeutic dose should start at 50 mg per day and is rarely increased beyond 100 mg per day.
Precautions
Like all tricyclic antidepressants, trimipramine should be used cautiously and with close physician supervision in people, especially the elderly, who have benign prostatic hypertrophy, urinary retention, and glaucoma, especially angle-closure glaucoma (the most severe form). Before starting treatment, people with these conditions should discuss the relative risks and benefits of treatment with their doctors to help determine if trimipramine is the right antidepressant for them.
A common problem with tricyclic antidepressants is sedation (drowsiness, lack of physical and mental alertness).
This side effect is especially noticeable early in therapy. In most patients, sedation decreases or disappears entirely with time, but until then patients taking trimipramine should not perform hazardous activities requiring mental alertness or coordination. The sedative effect is increased when trimipramine is taken with other central nervous system depressants, such as alcoholic beverages, sleeping medications, other sedatives, or antihistamines. It may be dangerous to take trimipramine in combination with these substances. Trimipramine may increase the possibility of having seizures. Patients should tell their physician if they have a history of seizures, including seizures brought on by the abuse of drugs or alcohol. These people should use trimipramine only with caution and be closely monitored by their physician.
Trimipramine may increase heart rate and stress on the heart. It may be dangerous for people with cardiovascular disease, especially those who have recently had a heart attack, to take this drug or other antidepressants in the same pharmacological class. In rare cases where patients with cardiovascular disease must receive trimipramine, they should be monitored closely for cardiac rhythm disturbances and signs of cardiac stress or damage.
Side effects
Trimipramine shares side effects common to all tricyclic antidepressants. The most frequent of these are dry mouth, constipation, urinary retention, increased heart rate, sedation, irritability, dizziness, and decreased coordination. As with most side effects associated with tricyclic antidepressants, the intensity is highest at the beginning of therapy and tends to decrease with continued use.
Dry mouth, if severe to the point of causing difficulty speaking or swallowing, may be managed by dosage reduction or temporary discontinuation of the drug. Patients may also chew sugarless gum or suck on sugarless candy in order to increase the flow of saliva. Some artificial saliva products may give temporary relief.
Men with prostate enlargement who take trimipramine may be especially likely to have problems with urinary retention. Symptoms include having difficulty starting a urine flow and more difficulty than usual passing urine. In most cases, urinary retention is managed with dose reduction or by switching to another type of antidepressant. In extreme cases, patients may require treatment with bethanechol, a drug that reverses this particular side effect. People who think they may be experiencing any side effects from this or any other medication should tell their physicians.
Interactions
Dangerously high blood pressure has resulted from the combination of tricyclic antidepressants, such as trimipramine, and members of another class of antidepressants known as monoamine oxidase (MAO) inhibitors. Because of this, trimipramine should never be taken in combination with MAO inhibitors. Patient taking any MAO inhibitors, for example Nardil (phenelzinesulfate) or Parmate (tranylcypromine sulfate), should stop the MAO inhibitor then wait at least 14 days before starting trimipramine or any other tricyclic antidepressant. The same holds true when discontinuing trimipramine and starting an MAO inhibitor.
Trimipramine may decrease the blood pressure–lowering effects of clonidine. Patients who take both drugs should be monitored for loss of blood-pressure control and the dose of clonidine increased as needed.
American Society of Health-System Pharmacists. AHFS Drug Information 2002. Bethesda: American Society of Health-System Pharmacists, 2002.
DeVane, C. Lindsay, Pharm.D. "Drug Therapy for Mood Disorders." In Fundamentals of Monitoring Psychoactive Drug Therapy. Baltimore: Williams and Wilkins, 1990.
