Tricyclic Antidepressants (TCA) Overview

About Tricyclic Antidepressants
Tricyclic antidepressants (TCAs) are an old class of antidepressive drugs, much older than Prozac and other SSRIs. The first TCA imipramine was discovered back in the 1950s, when psychopharmacology was still a new science. The name "tricyclic" comes from their molecular structure which contains three rings of atoms.

The TCAs are effective antidepressants, but because they tend to cause more side effects than newer drugs, they are rarely used to treat depression any more. They are, however, still commonly used in the treatment of chronic pain, sleep disorders and some other conditions, usually in doses much smaller than would be used for depression.

The SSRIs are fairly selective for serotonin, as their name, selective serotonin reuptake inhibitors, implies. TCAs on the other hand are far from selective. They increase brain levels of serotonin, but also norepinephrine (noradrenaline). In addition they block histamine receptors, muscarinic acetylcholine receptors and alpha adrenergic receptors and have some other actions.

How TCAs work
Tricyclic antidepressants (TCAs) inhibit the reabsorption (reuptake) of serotonin and norepinephrine by brain cells. To a lesser extent, TCAs also inhibit reabsorption of dopamine. These antidepressants also block other cell receptors, which accounts for many of their side effects. TCAs are called tricyclic because of their chemical structure. They were among the earliest antidepressants developed and remained the first line of treatment for depression before newer antidepressants arrived.

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Antidepressants, in general, may also work by playing a neuroprotective role in how they relieve anxiety and depression. It's thought that antidepressants may increase the effects of brain receptors that help nerve cells keep sensitivity to glutamate — an organic compound of a nonessential amino acid — in check. This increased support of nerve cells lowers glutamate sensitivity, providing protection against the glutamate overwhelming and exciting key brain areas related to anxiety and depression.

Therapeutic effects of antidepressants may vary in people, due in part to each person's genetic makeup. It's thought that people's sensitivity to antidepressant effects, especially selective serotonin reuptake inhibitor effects, can vary depending on:
  • How each person's serotonin reuptake receptor function works
  • His or her alleles — the parts of chromosomes that determine inherited characteristics, such as height and hair color, which combine to make each person unique

Antidepressant medications are often the first treatment choice for adults with moderate or severe depression, sometimes along with psychotherapy. Although antidepressants may not cure depression, they can help you achieve remission — the disappearance or nearly complete reduction of depression symptoms.

TCA and Clinical Depression
For many years the TCAs were the first choice for pharmacological treatment of clinical depression. Although they are still considered to be highly effective, they have been increasingly replaced by the SSRIs and other newer antidepressants. Notably, however, a recent Cochrane review of the efficacy of the SSRIs concluded that they were only slightly more effective than placebo for the treatment of people with depression. Other indications of SSRIs were not tested. Newer antidepressants are thought to have fewer and less intense side effects and are also thought to be less likely to result in injury or death if used in a suicide attempt, as the doses required for clinical treatment and potentially lethal overdose are far wider in comparison.

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Nonetheless, the TCAs are still occasionally used for treatment-resistant depression that has failed to respond to therapy with newer antidepressants. They are not considered addictive and are somewhat preferable to the monoamine oxidase inhibitors (MAOIs). The side effects of the TCAs usually come to prominence before the therapeutic benefits against depression and/or anxiety do, and for this reason, they may potentially be somewhat dangerous, as volition can be increased, possibly giving the patient a greater desire to attempt or commit suicide.

TCAs approved to treat depression
Here are the TCAs approved by the Food and Drug Administration specifically to treat depression, with their generic, or chemical, names followed by available brand names in parentheses:
  • Amitriptyline
  • Amoxapine
  • Desipramine (Norpramin)
  • Doxepin (Sinequan)
  • Imipramine (Tofranil, Tofranil-PM)
  • Nortriptyline (Pamelor)
  • Protriptyline (Vivactil)
  • Trimipramine (Surmontil)
Some of these medications come in forms that must be injected or as oral solutions that must be mixed with liquids, such as water or juice.
Some of these medications may also be used to treat conditions other than depression.

Side effects of TCA
The most common side effects of tricyclic antidepressants, and ways to deal with them are as follows:
  • Dry mouth -it is helpful to drink sips of water; chew sugarless gum; brush teeth daily. Or use saliva substitutes, which come in liquid and tablet forms and are available without a prescription.
  • Constipation -bran cereals, prunes, fruit, and vegetables should be in the diet.
  • Bladder problems -emptying the bladder completely may be difficult, and the urine stream may not be as strong as usual. Older men with enlarged prostate conditions may be at particular risk for this problem. The doctor should be notified if there is any pain.
  • Sexual problems -sexual functioning may be impaired; if this is worrisome, it should be discussed with the doctor.
  • Blurred vision -this is usually temporary and will not necessitate new glasses. Glaucoma patients should report any change in vision to the doctor.
  • Dizziness -rising from the bed or chair slowly is helpful.
  • Drowsiness as a daytime problem - this usually passes soon. A person who feels drowsy or sedated should not drive or operate heavy equipment. The more sedating antidepressants are generally taken at bedtime to help sleep and to minimize daytime drowsiness.
  • Increased heart rate -pulse rate is often elevated. Older patients should have an electrocardiogram (EKG) before beginning tricyclic treatment.
  • Increased sensitivity to sunlight. Even brief exposure to sun can cause severe sunburn or a rash. While being treated with this tricyclic antidepressants, avoid being in direct sunlight, especially between 10A.M. and 3 P.M.; wear a hat and tightly woven clothing that covers the arms and legs; use a sunscreen with a skin protection factor (SPF) of at least 15; protect the lips with a sun block lipstick; and do not use tanning beds, tanning booths, or sunlamps.
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Special conditions
People with certain medical conditions or who are taking certain other medicines can have problems if they take tricyclic antidepressants. Before taking these drugs, be sure to let the physician know about any of these conditions:
-        ALLERGIES. Anyone who has had unusual reactions to tricyclic antidepressants or to carbamazepine (Tegretol), maprotiline (Ludiomil), ortrazodone (Desyrel) in the past should let his or her physician know before taking tricyclic antidepressants. The physician should also be told about anyallergies to foods, dyes, preservatives, or other substances.
-        PREGNANCY. Problems have been reported in babies whose mothers took tricyclic antidepressants just before delivery. Women who are pregnant or who may become pregnant should check with their physicians about the safety of using tricyclic antidepressants.
-        BREASTFEEDING. Tricyclic antidepressants pass into breast milk and may cause drowsiness in nursing babies whose mothers take the drugs. Women who are breastfeeding should check with their physicians before using tricyclic antidepressants.
-        DIABETES. Tricyclic antidepressants may affect blood sugar levels. Diabetic patients who notice changes in blood or urine test results while taking this medicine should check with their physicians

Suicidal feelings and TCAs
In some cases, antidepressants may be associated with worsening symptoms of depression or suicidal thoughts or behavior in those ages 18 to 24. These symptoms likely occur in the first one to two months of treatment or when you change your dosage. Be sure to talk to your doctor about any changes in your symptoms. You may need more careful monitoring when beginning treatment or changing dosage, or you may need to stop the medication if your symptoms worsen. Adults age 65 and older taking antidepressants have a decreased risk of suicidal thoughts.

Work with your doctor or a mental health provider to nix your irritability, sadness or guilt and boost your mood with tricyclics. Feel good again.

Recommended dosage
The recommended dosage depends on many factors, including the patient's age, weight, general health and symptoms. The type of tricyclic antidepressant and its strength also must be considered. Check with the physician who prescribed the drug or the pharmacist who filled the prescription for the correct dosage.

Always take tricyclic antidepressants exactly as directed. Never take larger or more frequent doses, and do not take the drug for longer than directed. Do not stop taking the medicine just because it does not seem to be working. Several weeks may be needed for its effects to be felt. Visit the physician as often as recommended so that the physician can check to see if the drug is working and to note for side effects.

Do not stop taking this medicine suddenly after taking it for several weeks or more. Gradually tapering the dose may be necessary to reduce the chance of withdrawal symptoms.

Taking this medicine with food may prevent upset stomach.

Sources and Additional Information:


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