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Tricyclic antidepressants



About Tricyclic antidepressants

Tricyclic antidepressants are type of medication used to treat clinical depression. These drugs may also be used to treat other conditions, such as bedwetting (enuresis), obsessive-compulsive disorder (OCD) and some chronic pain conditions. They are usually taken for at least six to 12 months before the patient tapers off usage of the drug.

From the 1960s to the 1980s, tricyclic antidepressants were the first choice of medications used for treating depression. These drugs work by inhibiting the reabsorption of three neurotransmitters associated with depression, serotonin, norepinephrine and dopamine (to a lesser extent), and increasing the levels of these chemicals in the brain.

Today, there are many different types of antidepressants available. Although tricyclics are just as effective as newer antidepressants, they tend to cause more side effects in patients and may be more likely to cause lethal overdoses. However, tricyclics still may be the best choice for some patients, especially individuals who have failed to respond to other types of antidepressants.

Tricyclic antidepressants are available in syrup, pill and injectable forms. They should be taken as directed by a physician. In most cases, patients will be instructed to take the drug with food. It may take several weeks after therapy starts before a patient begins to experience the benefit of these medications.


Types and differences

There are various types of tricyclic antidepressants. They include:

Generic NameBrand Name(s)


Elavil, Endep






Norpramin, Pertofrane


Sinequan, Adapin






Pamelor, Aventyl








Conditions treated with tricyclic antidepressants

Traditionally, tricyclic antidepressants were used to treat clinical depression, and they are still used for that purpose. However, these drugs are also used to treat other mental health disorders. For example, imipramine has been used to treat bedwetting (enuresis) and clomipramine has been used to treat obsessive-compulsive disorder (OCD).

In addition, tricyclic antidepressants are frequently used to help manage chronic pain conditions, even in patients who are not depressed. They are particularly effective in reducing the burning pain associated with nerve damage that occurs with diabetes, shingles or strokes. They may also help prevent migraines and fibromyalgia, a condition characterized by widespread pain in the joints, muscles, tendons and other soft tissues. The painkilling mechanism of tricyclic antidepressants is not fully understood.

Conditions of concern

Patients should notify their physician if they have ever had an allergic reaction to a tricyclic antidepressant. They should also report allergies to substances such as foods, preservatives or dyes.

Patients with pre-existing heart disease and individuals older than 40 should have an electrocardiogram (test that records electrical activity of the heart) performed before beginning treatment with tricyclic antidepressants. These drugs also should not be used by patients with bundle branch block (a type of heart disorder) or during the acute recovery period after myocardial infarction (heart attack).

Tricyclic antidepressants can affect a patient’s blood sugar levels, which is a concern for people with conditions such as diabetes. However, the drugs are often considered a first-line treatment for diabetic neuropathy (nerve pain). Patients with diabetic neuropathy should discuss any concerns they may have about tricyclic antidepressants with their physician.

Other medical conditions that may be of concern to patients considering using tricyclic antidepressants include:

  • Alcohol abuse
  • Asthma
  • Bipolar disorder
  • Blood disorders
  • Convulsions (seizures)
  • Difficulty urinating
  • Enlarged prostate
  • Heart disease
  • High blood pressure (hypertension)
  • Kidney or liver disease
  • Overactive thyroid
  • Stomach or intestinal problems
  • Glaucoma (disease that damages the optic nerve) or increased eye pressure
Side effects

Potential side effects

Use of tricyclic antidepressants may result in many side effects. These commonly include dry mouth, blurred vision and constipation. Some patients may experience drowsiness while taking tricyclic antidepressants. These medications may also cause a patient’s skin to be more sensitive to sunlight, and even brief exposures can result in skin rash, itching, redness or other discoloration, or severe sunburn. This is particularly true for patients with fair skin.

Dryness of the mouth may occur due to decreased salivary secretion. If dry mouth lasts for more than two weeks, patients should see their physician or dentist, as long-term dryness of the mouth can increase the risk of dental diseases. Patients may also experience lightheadedness or fainting, particularly if they rise quickly from a lying or sitting position.

Other side effects may include:

  • Agitation or irritability
  • Anxiety
  • Blurred vision
  • Constipation
  • Dry skin
  • Sweating
  • Weight gain
  • Elevated heart rate
  • Agranulocytosis (acute blood disorder)
  • Hepatitis (inflammation of the liver caused by infectious or toxic agents)
  • Orthostatic hypotension (sudden drop in blood pressure after a person rises)
  • Sexual dysfunction

Other potentially serious side effects of tricyclic antidepressants include dizziness and falls (particularly in the elderly), seizures, cardiac arrhythmias (abnormal rate of muscle contractions in the heart), mania or hypomania, glaucoma, urinary retention, low or high white blood cell count, fever, sudden high fever with jaundice, priapism (condition marked by persistent erections), swollen lymph nodes and respiratory distress.

Patients should be aware that a physician may need to adjust the dosage or change medications to achieve the best results with minimal side effects. Patients should not stop taking tricyclic antidepressants unless they are instructed to do so by a physician. Failure to gradually and carefully reduce the amount of medication taken before quitting can lead to withdrawal symptoms such as headache, nausea and an overall feeling of discomfort.

In addition, the U.S. Food and Drug Administration (FDA) has advised that antidepressants may increase the risk of suicidal thinking in some patients and all people being treated with them should be monitored closely for unusual changes in behavior. For more information, see antidepressants.


Drug or other interactions

Patients using tricyclic antidepressants should consult their physician before taking any additional prescriptions, over-the-counter medications, nutritional supplements or herbal medications. Certain medications may interact poorly with tricyclic antidepressants. For example, use of central nervous system (CNS) depressants such as antihistamines, hay fever and cold medicines, sedatives and tranquilizers may result in increased drowsiness. Use of tricyclic antidepressants within two weeks of taking monoamine oxidase inhibitor (MAOI) medications can cause sudden high body temperature, extreme rise in blood pressure, severe convulsions and death.

The effect of many tricyclic antidepressants is reduced when the patient is a heavy smoker or uses barbiturates (medications that suppress the central nervous system). The affected medications include: amitriptyline, amoxapine, desipramine, doxepin, imipramine, nortriptyline and trimipramine.

Patients should inform their physician before taking certain types of medications such as:

  • Amphetamines
  • Anticonvulsants
  • Antihypertensives
  • Antipsychotics
  • Antithyroid medications
  • Appetite suppressants
  • Asthma medications
  • Central nervous system depressants
  • Cold, sinus or hay fever medications
  • Selective serotonin reuptake inhibitors (SSRIs), another form of antidepressant medication

In addition, certain specific drugs may interact poorly with tricyclic antidepressants, causing moderate to severe side effects. These medications include:

  • Bupropion (antidepressant)
  • Cimetidine (antiulcer, heartburn medication)
  • Ephedrine (asthma medication, nasal decongestant)
  • Isoproterenol (asthma medication)
  • Metoclopramide (antinausea medication)
  • Pemoline (epilepsy medication)
  • Phenylephrine (medication to narrow blood vessels)
  • Promethazine (antinausea medication and antihistamine)
  • Propoxyphene (painkiller)
  • Trimeprazine (antihistamine)

Lifestyle considerations

Some patients may experience drowsiness while taking tricyclic antidepressants. Patients who experience this symptom should not drive, use machinery or perform any other tasks that require a high level of alertness. Some patients may benefit from taking the medication in the evening before bed to avoid daytime drowsiness.

Patients who take tricyclic antidepressants may find that their skin has an increased sensitivity to the sun. To lower the risk of rash or sunburn, patients should:

  • Stay out of direct sunlight, particularly during the hours of 10 a.m. and 3 p.m.
  • Use sunscreen and lip balm with a sun protection factor (SPF) of at least 15
  • Wear protective clothing, including a hat
  • Avoid use of sun lamps or tanning beds

Tricyclic antidepressants often cause dry mouth. Patients can reduce this side effect by drinking water, sucking on ice cubes, chewing gum or talking to their physician about using synthetic saliva, which is available at pharmacies. Stool softeners (also available at pharmacies) can help with constipation, as can a diet rich in bran cereals, prunes, fruit and vegetables. Patients who avoid dehydration and add salt to their diet may lower the risk of orthostatic hypotension (sudden drop in blood pressure after a person rises). Standing up gradually and holding onto something can also help prevent orthostatic hypotension.

How to use

Pregnancy use issues

Studies have not been performed in pregnant women using tricyclic antidepressants. Nonetheless, there have been reports that women who take these drugs shortly before delivery have given birth to babies who experience muscle spasms and heart, breathing and urinary problems. In addition, studies on animals have shown a link between tricyclic antidepressants and unwanted effects in the fetus.

Tricyclic antidepressants can pass into breast milk, and some may cause drowsiness in a nursing baby. Women who are or may become pregnant should discuss the risks and benefits of tricyclic antidepressants with the physician.

Child use issues

Children are especially sensitive to the effects of this medication and may have an increased risk of suffering side effects such as nervousness, sleeping problems, tiredness and mild stomach upset. These unwanted effects tend to disappear over time in children who take tricyclic antidepressants to prevent bedwetting.

Antidepressants must be used with great caution in children, as the U.S. Food and Drug Administration (FDA) issued a warning about a possible link between antidepressants and increased risk of thoughts of suicide or suicide attempts.

Elderly use issues

Elderly patients are often more sensitive to the effects of these drugs and may be at greater risk of experiencing side effects such as drowsiness, dizziness, confusion, vision problems, dry mouth, constipation and problems urinating.

Symptoms of medication overdose

Overdose of tricyclic antidepressants can cause lethal toxicity. For example, tricyclics taken at high doses can cause life-threatening arrhythmias (irregular heartbeats). Major complications associated with an overdose of tricyclics include neuropsychiatric impairment, hypotension (low blood pressure) and seizures.

Tricyclics have significant anticholinergic activity, meaning they inhibit or block the action of the neurotransmitter acetylcholine. Anticholinergic overdose can lead to symptoms such as agitation, hallucinations, arrythmias, severe hypertension (high blood pressure) and seizures. A condition called anticholinergic delirium may also occur. Symptoms include hot and dry skin, dry mucous membranes, dilated pupils and tachycardia (rapid heartbeat). This is a dangerous condition that requires immediate medical care.

Questions for your doctor

Patients may wish to ask their doctor the following questions related to tricyclic antidepressants:
  1. Are tricyclic antidepressants a good option for treating my condition?
  2. I’ve heard that they can have significant side effects – why should I use tricyclic antidepressants instead of an alternative medication?
  3. Which tricyclic antidepressant is most appropriate for me?
  4. Which medical conditions may prevent me from using tricyclic antidepressants?
  5. Which prescription drugs interact poorly with tricyclic antidepressants?
  6. Are there any over-the-counter drugs I should avoid while taking tricyclic antidepressants?
  7. Are there things I can do to minimize side effects associated with tricyclic antidepressants?
  8. For how long will I have to take tricyclic antidepressants?
  9. How soon can I expect to notice a reduction in symptoms?
  10. What should I do if I accidentally miss a dose of this medication?

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