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treatment & management

Drug Profiles:
Tricyclic Antidepressants

CAUTION: Federal law prohibits dispensing without prescription.

Description:
Tricyclic antidepressants are used to relieve clinical depression. They are also being used, with some success, as Migraine preventives for some patients. Another form (clomipramine) is used to treat obsessive-compulsive disorders. Tricyclic antidepressants may be used for other conditions as determined by your doctor.

In addition to their use as a Migraine preventive, Migraineurs may find these medications useful for clinical (chemical) depression. Migraine and depression are now being considered comorbid diseases, they appear to have a definite link Ń 47% of Migraineurs experience clinical depression as opposed to just 17% of the general population. Talk to you doctor about ruling out if you my also be suffering from clinical depression, and work with her/him on an appropriate treatment.

   
Oral
  • Amitriptyline
    • Syrup (Canada)
    • Tablets (U.S. and Canada)
  • Amoxapine
    • Tablets (U.S. and Canada)
  • Clomipramine
    • Capsules (U.S.)
    • Tablets (Canada)
  • Desipramine
    • Tablets (U.S. and Canada)
  • Doxepin
    • Capsules (U.S. and Canada)
    • Oral solution (U.S.)
  • Imipramine
    • Capsules (U.S.)
    • Tablets (U.S. and Canada)
  • Nortriptyline
    • Capsules (U.S. and Canada)
    • Oral solution (U.S.)
  • Protriptyline
    • Tablets (U.S. and Canada)
  • Trimipramine
    • Capsules (U.S. and Canada)
    • Tablets (Canada)

Parenteral

  • Amitriptyline
    • Injection (U.S.)
  • Imipramine
    • Injection (U.S.)

Before Using This Medicine
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For tricyclic antidepressants, the following should be considered:

Allergies-
Tell your doctor if you have ever had any unusual or allergic reaction to any tricyclic antidepressant or to carbamazepine, maprotiline, or trazodone. Also tell your health care professional if you are allergic to any other substances, such as foods, preservatives, or dyes.

Pregnancy-
Studies have not been done in pregnant women. However, there have been reports of newborns suffering from muscle spasms and heart, breathing, and urinary problems when their mothers had taken tricyclic antidepressants immediately before delivery. Also, studies in animals have shown that some tricyclic antidepressants may cause unwanted effects in the fetus.

Breast-feeding-
Tricyclic antidepressants pass into the breast milk. Doxepin has been reported to cause drowsiness in the nursing baby.

Children-
Children are especially sensitive to the effects of this medicine. This may increase the chance of side effects during treatment. However, side effects in children taking this medicine for bedwetting usually disappear upon continued use. The most common of these are nervousness, sleeping problems, tiredness, and mild stomach upset. If these side effects continue or are bothersome, check with your doctor.

Older adults-
Drowsiness, dizziness, confusion, vision problems, dryness of mouth, constipation, and problems in urinating are more likely to occur in elderly patients, who are usually more sensitive than younger adults to the effects of tricyclic antidepressants.

Other medicines-
Although certain medicines should not be used together at all, in other cases 2 different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking a tricyclic antidepressant, it is especially important that your health care professional know if you are taking any of the following:

  • Amphetamines or
  • Appetite suppressants (diet pills) or
  • Ephedrine or
  • Epinephrine (e.g., Adrenalin) or
  • Isoproterenol (e.g., Isuprel) or
  • Medicine for asthma or other breathing problems or
  • Medicine for colds, sinus problems, or hay fever or other allergies or
  • Phenylephrine (e.g., Neo-Synephrine)—Using these medicines with tricyclic antidepressants may increase the risk of serious effects on the heart
  • Antipsychotics (medicine for mental illness) or
  • Clonidine (e.g., Catapres)—Using these medicines with tricyclic antidepressants may increase the CNS depressant effects and increase the chance of serious side effects
  • Antithyroid agents (medicine for overactive thyroid) or
  • Cimetidine (e.g., Tagamet)—Using these medicines with tricyclic antidepressants may increase the chance of serious side effects
  • Central nervous system (CNS) depressants (medicine that causes drowsiness)—Using these medicines with tricyclic antidepressants may increase the CNS depressant effects
  • Guanadrel (e.g., Hylorel) or
  • Guanethidine (e.g., Ismelin)—Tricyclic antidepressants may keep these medicines from working as well
  • Methyldopa (e.g., Aldomet) or
  • Metoclopramide (e.g., Reglan) or
  • Metyrosine (e.g., Demser) or
  • Pemoline (e.g., Cylert) or
  • Pimozide (e.g., Orap) or
  • Promethazine (e.g., Phenergan) or
  • Rauwolfia alkaloids (alseroxylon [e.g., Rauwiloid], deserpidine [e.g., Harmonyl], rauwolfia serpentina [e.g., Raudixin], reserpine [e.g., Serpasil]) or
  • Trimeprazine (e.g., Temaril)—Tricyclic antidepressants may cause certain side effects to be more severe and occur more often
  • Metrizamide—The risk of seizures may be increased
  • Monoamine oxidase (MAO) inhibitors (furazolidone [e.g., Furoxone], isocarboxazid [e.g., Marplan], phenelzine [e.g., Nardil], procarbazine [e.g., Matulane], selegiline [e.g., Eldepryl], tranylcypromine [e.g., Parnate])—Taking tricyclic antidepressants while you are taking or within 2 weeks of taking MAO inhibitors may cause sudden high body temperature, extremely high blood pressure, severe convulsions, and death; however, sometimes certain of these medicines may be used together under close supervision by your doctor

Other medical problems-
The presence of other medical problems may affect the use of tricyclic antidepressants. Make sure you tell your doctor if you have any other medical problems, especially:

  • Alcohol abuse (or history of)—Drinking alcohol may cause increased CNS depressant effects
  • Asthma or
  • Bipolar disorder (manic-depressive illness) or
  • Blood disorders or
  • Convulsions (seizures) or
  • Difficult urination or
  • Enlarged prostate or
  • Glaucoma or increased eye pressure or
  • Heart disease or
  • High blood pressure (hypertension) or
  • Schizophrenia—Tricyclic antidepressants may make the condition worse
  • Kidney disease or
  • Liver disease—Higher blood levels of tricyclic antidepressants may result, increasing the chance of side effects
  • Overactive thyroid or
  • Stomach or intestinal problems—Tricyclic antidepressants may cause an increased chance of serious side effects

Proper Use of This Medicine
To lessen stomach upset, take this medicine with food, even for a daily bedtime dose, unless your doctor has told you to take it on an empty stomach.

Take this medicine only as directed by your doctor

Sometimes this medicine must be taken for several weeks before you begin to feel better

To use doxepin oral solution:

  • This medicine is to be taken by mouth even though it comes in a dropper bottle. The amount you should take should be measured with the dropper provided with your prescription and diluted just before you take each dose. Dilute each dose with about one-half glass (4 ounces) of water, milk, citrus fruit juice, tomato juice, or prune juice. Do not mix this medicine with grape juice or carbonated beverages since these may decrease the medicine's effectiveness.
  • Doxepin oral solution must be mixed immediately before you take it. Do not prepare it ahead of time.

Dosing-
The dose of tricyclic antidepressants will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of tricyclic antidepressants. If your dose is different, do not change it unless your doctor tells you to do so.

The number of capsules or tablets, or the amount of solution or syrup that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are taking tricyclic antidepressants.

For amitriptyline

  • For tablet dosage form:
    • For depression:
      • Adults—At first, 25 milligrams (mg) two to four times a day. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 150 mg a day, unless you are in the hospital. Some hospitalized patients may need higher doses.
      • Teenagers—At first, 10 mg three times a day, and 20 mg at bedtime. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 100 mg a day.
      • Children 6 to 12 years of age—10 to 30 mg a day.
      • Children up to 6 years of age—Use and dose must be determined by your doctor.
      • Older adults— At first, 25 mg at bedtime. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 100 mg a day.
  • For syrup dosage form:
    • For depression:
      • Adults—At first, 25 mg two to four times a day. Your doctor may increase your dose gradually as needed.
      • Teenagers—At first, 10 mg three times a day, and 20 mg at bedtime. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 100 mg a day.
      • Children 6 to 12 years of age—10 to 30 mg a day.
      • Children up to 6 years of age—Use and dose must be determined by your doctor.
      • Older adults—At first, 10 mg three times a day, and 20 mg at bedtime. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 100 mg a day.
  • For injection dosage form:
    • For depression:
      • Adults—20 to 30 mg four times a day, injected into a muscle.
      • Children up to 12 years of age—Use and dose must be determined by your doctor.

For amoxapine

  • For tablet dosage form:
    • For depression:
      • Adults—At first, 50 milligrams (mg) two to three times a day. Your doctor may increase your dose gradually as needed.
      • Children up to 16 years of age—Use and dose must be determined by your doctor.
      • Older adults—At first, 25 mg two to three times a day. Your doctor may increase your dose gradually as needed.

For clomipramine

  • For capsule or tablet dosage forms:
    • For obsessive-compulsive disorders:
      • Adults—At first, 25 milligrams (mg) once a day. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 250 mg a day, unless you are in the hospital. Some hospitalized patients may need higher doses.
      • Teenagers and children 10 years of age and over—At first, 25 mg once a day. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 200 mg a day.
      • Children up to 10 years of age—Use and dose must be determined by your doctor.
      • Older adults—At first, 20 to 30 mg a day. Your doctor may increase your dose gradually as needed.

For desipramine

  • For tablet dosage form:
    • For depression:
      • Adults—100 to 200 milligrams (mg) a day. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 300 mg a day.
      • Teenagers—25 to 50 mg a day. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 100 mg a day.
      • Children 6 to 12 years of age—10 to 30 mg a day.
      • Older adults—25 to 50 mg a day. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 150 mg a day.

For doxepin

  • For capsule or solution dosage forms:
    • For depression:
      • Adults—At first, 25 milligrams (mg) three times a day. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 150 mg a day, unless you are in the hospital. Some hospitalized patients may need higher doses.
      • Children up to 12 years of age—Use and dose must be determined by your doctor.
      • Older adults—At first, 25 to 50 mg a day. Your doctor may increase your dose gradually as needed.

For imipramine

  • For tablet dosage form:
    • For depression:
      • Adults—25 to 50 milligrams (mg) three to four times a day. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 200 mg a day, unless you are in the hospital. Some hospitalized patients may need higher doses.
      • Adolescents—25 to 50 mg a day. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 100 mg a day.
      • Children 6 to 12 years of age—10 to 30 mg a day.
      • Children up to 6 years of age—Use and dose must be determined by your doctor.
      • Older adults—At first, 25 mg at bedtime. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 100 mg a day.
    • For bedwetting:
      • Children—25 mg once a day, taken one hour before bedtime. Your doctor may increase the dose as needed, based on the child's age.
  • For capsule dosage form:
    • For depression:
      • Adults—At first, 75 mg a day taken at bedtime. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 200 mg a day, unless you are in the hospital. Some hospitalized patients may need higher doses.
      • Children up to 12 years of age—Use and dose must be determined by your doctor.
  • For injection dosage form:
    • For depression:
      • Adults—Dose must be determined by your doctor. It is injected into a muscle. The dose is usually not more than 300 mg a day.
      • Children up to 12 years of age—Use and dose must be determined by your doctor.

For nortriptyline

  • For capsule or solution dosage forms:
    • For depression:
      • Adults—25 milligrams (mg) three to four times a day. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 150 mg a day.
      • Teenagers—25 to 50 mg a day. Your doctor may increase your dose gradually as needed.
      • Children 6 to 12 years of age—10 to 20 mg a day.
      • Older adults—30 to 50 mg a day. Your doctor may increase your dose gradually as needed.

For protriptyline

  • For tablet dosage form:
    • For depression:
      • Adults—At first, 5 to 10 milligrams (mg) three to four times a day. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 60 mg a day.
      • Teenagers—At first, 5 mg three times a day. Your doctor may increase your dose gradually as needed.
      • Children up to 12 years of age—Use and dose must be determined by your doctor.
      • Older adults—At first, 5 mg three times a day. Your doctor may increase your dose gradually as needed.

For trimipramine

  • For capsule or tablet dosage forms:
    • For depression:
      • Adults—At first, 75 milligrams (mg) a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 200 mg a day, unless you are hospitalized. Some hospitalized patients may need higher doses.
      • Teenagers—At first, 50 mg a day. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 100 mg a day.
      • Children up to 12 years of age—Use and dose must be determined by your doctor.
      • Older adults—At first, 50 mg a day. Your doctor may increase your dose gradually as needed. However, the dose is usually not more than 100 mg a day.

Missed dose-
If you miss a dose of this medicine and your dosing schedule is:

  • One dose a day at bedtime—Do not take the missed dose in the morning since it may cause disturbing side effects during waking hours. Instead, check with your doctor.
  • More than one dose a day—Take the missed dose as soon as possible. However, if it is almost time for your next dose, skip the missed dose, and go back to your regular dosing schedule. Do not double doses.

If you have any questions about this, check with your doctor.

Storage-
To store this medicine:

  • Keep out of the reach of children. Overdose of this medicine is very dangerous in young children.
  • Store away from heat and direct light.
  • Do not store the tablet or capsule form of this medicine in the bathroom, near the kitchen sink, or in other damp places. Heat or moisture may cause the medicine to break down.
  • Keep the liquid form of this medicine from freezing.
  • Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of the reach of children.

Precautions While Using This Medicine
It is very important that your doctor check your progress at regular visits to allow dosage adjustments and to help reduce side effects.

This medicine will add to the effects of alcohol and other CNS depressants (medicines that make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; barbiturates; medicine for seizures; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your medical doctor or dentist before taking any of the above while you are taking this medicine .

This medicine may cause some people to become drowsy. If this occurs, do not drive, use machines, or do anything else that could be dangerous if you are not alert.

Dizziness, lightheadedness, or fainting may occur

This medicine may cause dryness of the mouth. For temporary relief, use sugarless gum or candy, melt bits of ice in your mouth, or use a saliva substitute

Tricyclic antidepressants may cause your skin to be more sensitive to sunlight than it is normally. Exposure to sunlight, even for brief periods of time, may cause a skin rash, itching, redness or other discoloration of the skin, or a severe sunburn. When you begin taking this medicine:

  • Stay out of direct sunlight, especially between the hours of 10:00 a.m. and 3:00 p.m., if possible.
  • Wear protective clothing, including a hat. Also, wear sunglasses.
  • Apply a sun block product that has a skin protection factor (SPF) of at least 15. Some patients may require a product with a higher SPF number, especially if they have a fair complexion. If you have any questions about this, check with your health care professional.
  • Apply a sun block lipstick that has an SPF of at least 15 to protect your lips.
  • Do not use a sunlamp or tanning bed or booth.

If you have a severe reaction from the sun, check with your doctor

Before you have any medical tests, tell the medical doctor in charge that you are taking this medicine. The results of the metyrapone test may be affected by this medicine.

Before having any kind of surgery, dental treatment, or emergency treatment, tell the medical doctor or dentist in charge that you are using this medicine

For diabetic patients

  • This medicine may affect blood sugar levels. If you notice a change in the results of your blood or urine sugar tests or if you have any questions, check with your doctor.

Do not stop taking this medicine without first checking with your doctor

The effects of this medicine may last for 3 to 7 days after you have stopped taking it

For patients taking protriptyline

  • If taken late in the day, protriptyline may interfere with nighttime sleep.

Side Effects of This Medicine
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Stop taking this medicine and get emergency help immediately if any of the following side effects occur:

  • Reported for amoxapine only--rare
    • Convulsions (seizures);  difficult or fast breathing;  fever with increased sweating;  high or low (irregular) blood pressure;  loss of bladder control;  muscle stiffness (severe);  pale skin;  unusual tiredness or weakness  
  • Check with your doctor as soon as possible if any of the following side effects occur:
    • Less common:
      Blurred vision;  confusion or delirium  constipation (especially in the elderly); decreased sexual ability (more common with amoxapine and clomipramine); difficulty in speaking or swallowing; eye pain;  fainting; fast or irregular heartbeat (pounding, racing, skipping);  hallucinations; loss of balance control; mask-like face; nervousness or restlessness; problems in urinating; shakiness or trembling;  shuffling walk; slowed movements; stiffness of arms and legs 
  • Reported for amoxapine only (in addition to the above)
    • less common: Lip smacking or puckering; puffing of cheeks; rapid or worm-like movements of tongue; uncontrolled chewing movements;  uncontrolled movements of hands, arms, or legs 
    • Rare: Anxiety; breast enlargement in both males and females; hair loss; inappropriate secretion of milk—in females; increased sensitivity to sunlight; irritability; muscle twitching; red or brownish spots on skin; ringing, buzzing, or other unexplained sounds in the ears; seizures (more common with clomipramine); skin rash and itching; sore throat and fever; swelling of face and tongue; swelling of testicles (more common with amoxapine); trouble with teeth or gums (more common with clomipramine); weakness; yellow eyes or skin 
  • Symptoms of acute overdose: Confusion; convulsions (seizures); disturbed concentration; drowsiness (severe); enlarged pupils; fast, slow, or irregular heartbeat; fever; hallucinations (seeing, hearing, or feeling things that are not there); restlessness and agitation; shortness of breath or troubled breathing; unusual tiredness or weakness (severe); vomiting  

Other side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. However, check with your doctor if any of the following side effects continue or are bothersome:

  • More common: Dizziness; drowsiness; dryness of mouth; headache;  increased appetite (may include craving for sweets); nausea; tiredness or weakness (mild); unpleasant taste; weight gain 
  • Less common: Diarrhea; heartburn; increased sweating; trouble in sleeping (more common with protriptyline, especially when taken late in the day); vomiting 

Certain side effects of this medicine may occur after you have stopped taking it. Check with your doctor if you notice any of the following effects:

  • Headache; irritability; nausea, vomiting, or diarrhea; restlessness; trouble in sleeping, with vivid dreams; unusual excitement 
  • Reported for amoxapine only (in addition to the above): Lip smacking or puckering; puffing of cheeks; rapid or worm-like movements of the tongue; uncontrolled chewing movements; uncontrolled movements of arms or legs 

Other side effects not listed above also may occur in some patients. If you notice any other effects, check with your doctor.

Additional Information:
Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, tricyclic antidepressants are used in certain patients with the following medical conditions:

  • Attention deficit hyperactivity disorder (hyperactivity in children) (desipramine, imipramine, and protriptyline)
  • Bulimia (uncontrolled eating, followed by vomiting) (amitriptyline, clomipramine, desipramine, and imipramine)
  • Cocaine withdrawal (desipramine and imipramine)
  • Headache prevention (for certain types of frequent or continuing headaches) (most tricyclic antidepressants)
  • Itching with hives due to cold temperature exposure (doxepin)
  • Narcolepsy (extreme tendency to fall asleep suddenly) (clomipramine, desipramine, imipramine, and protriptyline)
  • Neurogenic pain (a type of continuing pain) (amitriptyline, clomipramine, desipramine, doxepin, imipramine, nortriptyline, and trimipramine)
  • Panic disorder (clomipramine, desipramine, doxepin, nortriptyline, and trimipramine)
  • Stomach ulcer (amitriptyline, doxepin, and trimipramine)
  • Urinary incontinence (imipramine)

 

Some commonly used brand names are:

In the U.S.-

  • Anafranil
  • Asendin
  • Aventyl
  • Elavil
  • Endep
  • Norfranil
  • Norpramin
  • Pamelor
  • Sinequan
  • Surmontil
  • Tipramine
  • Tofranil
  • Tofranil-PM
  • Vivactil

In Canada-

  • Anafranil
  • Apo-Amitriptyline
  • Apo-Imipramine
  • Apo-Trimip
  • Asendin
  • Aventyl
  • Elavil
  • Impril
  • Levate
  • Norpramin
  • Novo-Doxepi
  • Novopramine
  • Novo-Tripramine
  • Novotriptyn
  • Pertofrane
  • Rhotrimine
  • Sinequan
  • Surmontil
  • Tofranil
  • Triadapin
  • Triptil
 
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Information offered at this Web site by either a lay person or a health professional should not be interpreted as giving a diagnosis or a treatment recommendation. These can only be provided by a physician who has had an opportunity to interact with a patient in person and at length, with access to the patient's previous records and appropriate follow-up.