Tricyclic antidepressants —such as amitriptyline, desipramine (Norpramin), doxepin, imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil)—are named for their chemical structure: a chain of three rings. Tricyclics (or TCAs) raise brain concentrations of the neurotransmitters norepinephrine, serotonin, and, to a lesser extent, dopamine by blocking reabsorption of these chemical messengers by the nerve cells that release them. Tricyclics are used mainly to treat moderate to severe depression and have proven less effective for chronic low-grade depression. About 60% of people who take tricyclics experience significant improvement within four to six weeks. Each of the tricyclic drugs is believed to be equally effective, but side effects may differ.

When a person begins tricyclic therapy, he or she is given a small dose and carefully monitored for side effects. The dose is often raised over several weeks because a gradual increase may be less likely to lead to side effects. Side effects also tend to diminish with continued use. For older people, dosages are usually 30 to 50% lower than usual. When the proper dosage is established, tricyclics can be taken at bedtime so that any resulting drowsiness occurs before sleep rather than during the day.

Although a positive response to tricyclics typically appears within four to six weeks, doctors recommend taking the medication for six to eight weeks at a full dosage to assess the effects. During this time, blood tests may be ordered to make sure that the drug level is high enough to exert a therapeutic effect but not so high as to be toxic (nortriptyline's optimal blood level is the one most accurately known). If a person's depression does not improve while taking a tricyclic, it may be that the drug is not effective for that person or that he or she is not taking the drug as prescribed. About one third of people stop taking tricyclics because of side effects, and about two thirds of older people miss 25 to 50% of their doses. Poor compliance leads to fluctuating blood levels of the drug and, consequently, a poor response. Therefore, it is important to tell your doctor about unpleasant side effects instead of just stopping your medication.

Tricyclics Side Effects

The most prominent side effects of tricyclics are postural hypotension (dizziness on standing due to a drop in blood pressure), drowsiness, weakness, headache, dry mouth, blurred vision, constipation, nausea, and difficulty urinating. Many of these side effects can be managed, however. Drowsiness can be remedied by taking the dose before bedtime (if your doctor approves). Postural hypotension, which can lead to falls and broken bones in older people, can be reduced by standing up slowly after sitting or lying down and waiting 30 seconds before trying to walk. Pilocarpine (Pilocar) eyedrops may alleviate blurred vision. Chewing sugar-free gum or candy will help dry mouth. (Be sure to mention dry mouth to your dentist —a lack of saliva can lead to an increase in cavities and oral infections.) Bethanechol (Duvoid, Urabeth, Urecholine) may be prescribed to counteract problems with urination. And constipation can be managed by consuming foods high in fiber and drinking at least eight glasses of water or juice a day. Amitriptyline and Tofranil are more likely than other tricyclics to cause side effects in older people.

People Who Should Not Take Tricyclics

Tricyclics are not given to people with closed-angle glaucoma (a form of glaucoma characterized by a rapid increase in pressure within the eye) and should be used with caution in men who have symptoms of benign prostatic hyperplasia (an enlarged prostate), as they may lose the ability to urinate. This medical emergency must be treated with catheterization.

Tricyclic Drug Interactions to Avoid

Tricyclics can also magnify the depressive effects of alcohol and benzodiazepines. The combination of tricyclics with antihistamines can lead to severe constipation, impacted stools, or difficulty urinating, particularly in older adults. In addition, tricyclics (and SSRIs) should not be mixed with the drug selegiline (Eldepryl), which is used to treat Parkinson’s disease. Although rare, an interaction between these drugs may cause high fever, tremors, agitation, restlessness, or, in some cases, death. Other symptoms resulting from such drug combinations may include fainting, profuse sweating, seizures, behavioral changes, and stiffened muscles.

Tricyclics and Heart Disease

Tricyclics are not currently recommended for use in most people with coronary heart disease (CHD) because they can cause life-threatening ventricular fibrillation (abnormal rhythm in the heart's lower chambers) in these individuals. Despite the heart risks of tricyclics, they are still used to treat depression because they are sometimes the only effective antidepressants for severely depressed older people.

An older person with mild to moderate depression and severe CHD may first be given a medication from another drug class (an SSRI, such as Luvox, Celexa, Lexapro, Prozac, Paxil, or Zoloft, or the dopamine reuptake inhibitor Wellbutrin). If the individual does not respond to these drugs, a tricyclic would then be tried. Because the risk of ventricular fibrillation from tricyclics increases with the severity of CHD, the doctor must weigh the severity of the depression against the potential danger to the heart.

Publication Review By: Karen L. Swartz, M.D.

Published: 03 Mar 2011

Last Modified: 22 Jun 2011