ANTIDEPRESSANTS,TRICYCLIC (Systemic)

Some commonly used brand names are:

In the U.S.?

• Anafranil ³
• Asendin ²
• Aventyl ⁷
• Elavil ¹
• Endep ¹
• Norfranil ⁶
• Norpramin ⁴
• Pamelor ⁷
• Sinequan ⁵
• Surmontil ⁹
• Tipramine ⁶
• Tofranil ⁶
• Tofranil-PM ⁶
• Vivactil ⁸

In Canada?

• Anafranil ³
• Apo-Amitriptyline ¹
• Apo-Imipramine ⁶
• Apo-Trimip ⁹
• Asendin ²
• Aventyl ⁷
• Elavil ¹
• Impril ⁶
• Levate ¹
• Norpramin ⁴
• Novo-Doxepin ⁵
• Novopramine ⁶
• Novo-Tripramine ⁹
• Novotriptyn ¹
• Pertofrane ⁴
• Rhotrimine ⁹
• Sinequan ⁵
• Surmontil ⁹
• Tofranil ⁶
• Triadapin ⁵
• Triptil ⁸

Category

• Antibulimic?Amitriptyline; Clomipramine; Desipramine; Imipramine
• Anticataplectic?Clomipramine; Desipramine; Imipramine; Protriptyline
• Antidepressant?Amitriptyline; Amoxapine; Clomipramine; Desipramine; Doxepin; Imipramine; Nortriptyline; Protriptyline; Trimipramine
• Antienuretic?Amitriptyline; ImipramineHydrochloride
• Antinarcolepsy adjunct?Imipramine; Protriptyline
• Antineuralgic?Amitriptyline; Clomipramine; Desipramine; Doxepin; Imipramine; Nortriptyline; Trimipramine
• Antiobsessive-compulsive agent?Clomipramine
• Antipanic agent?Clomipramine; Desipramine; Doxepin; Imipramine; Nortriptyline
• Antipruritic?Doxepin
• Antiulceragent?Amitriptyline; Doxepin; Trimipramine

Description

Tricyclicantidepressants are used to relieve mental depression.

One form of this medicine (imipramine) is also used to treat enuresis (bedwetting)in children. Another form (clomipramine) is used to treat obsessive-compulsivedisorders. Tricyclic antidepressants may be used for other conditions as determinedby your doctor.

These medicines are available only with your doctor's prescription, inthe following dosage forms:

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 willdo. 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 orallergic reaction to any tricyclic antidepressant or to carbamazepine, maprotiline,or trazodone. Also tell your health care professional if you are allergicto 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 antidepressantsimmediately before delivery. Also, studies in animals have shown that sometricyclic antidepressants may cause unwanted effects in the fetus.

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

Children?Children are especially sensitive to the effectsof this medicine. This may increase the chance of side effects during treatment.However, side effects in children taking this medicine for bedwetting usuallydisappear upon continued use. The most common of these are nervousness, sleepingproblems, tiredness, and mild stomach upset. If these side effects continueor are bothersome, check with your doctor.

Antidepressants must be used with caution in children with depression.Studies have shown occurrences of children thinking about suicide or attemptingsuicide in clinical trials for this medicine. More study is needed to be sureantidepressants are safe and effective in children

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

Other medicines?Although certain medicines should not be usedtogether at all, in other cases 2 different medicines may be used togethereven if an interaction might occur. In these cases, your doctor may want tochange the dose, or other precautions may be necessary. When you are takinga tricyclic antidepressant, it is especially important that your health careprofessional 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 allergiesor
• Phenylephrine (e.g., Neo-Synephrine)?Using these medicineswith tricyclic antidepressants may increase the risk of serious effects onthe heart

• Antipsychotics (medicine for mental illness) or
• Clonidine (e.g., Catapres)?Using these medicines with tricyclicantidepressants may increase the CNS depressant effects and increase the chanceof serious side effects

• Antithyroid agents (medicine for overactive thyroid) or
• Cimetidine (e.g., Tagamet)?Using these medicines with tricyclicantidepressants may increase the chance of serious side effects

• Central nervous system (CNS) depressants (medicine that causes drowsiness)?Usingthese medicines with tricyclic antidepressants may increase the CNS depressanteffects

• Guanadrel (e.g., Hylorel) or
• Guanethidine (e.g., Ismelin)?Tricyclic antidepressants maykeep 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 maycause certain side effects to be more severe and occur more often

• Metrizamide?The risk of seizures may be increased

• Monoamine oxidase (MAO) inhibitor activity (isocarboxazid [e.g.,Marplan], isocarboxazid [e.g., Marplan], phenelzine [e.g., Nardil], procarbazine[e.g., Matulane], selegiline [e.g., Eldepryl], tranylcypromine [e.g., Parnate])?Takingtricyclic antidepressants while you are taking or within 2 weeks of takingMAO inhibitors may cause sudden high body temperature, extremely high bloodpressure, severe convulsions, and death; however, sometimes certain of thesemedicines may be used together under close supervision by your doctor

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

• Alcohol abuse (or history of)?Drinking alcohol may cause increasedCNS 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 conditionworse

• Kidney disease or
• Liver disease?Higher blood levels of tricyclic antidepressantsmay result, increasing the chance of side effects

• Overactive thyroid or
• Stomach or intestinal problems?Tricyclic antidepressants maycause an increased chance of serious side effects

Proper Use of This Medicine

To lessenstomach 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, to benefit your condition as much as possible. Do not take more ofit, do not take it more often, and do not take it for a longer time than yourdoctor ordered.

Sometimes this medicine must be taken for several weeksbefore you begin to feel better. Your doctor should check your progressat regular visits.

To use doxepin oral solution:

• This medicine is to be taken by mouth even though it comes in a dropperbottle. The amount you should take should be measured with the dropper providedwith your prescription and diluted just before you take each dose. Diluteeach dose with about one-half glass (4 ounces) of water, milk, citrus fruitjuice, tomato juice, or prune juice. Do not mix this medicine with grape juiceor 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 willbe different for different patients. Follow your doctor'sorders or the directions on the label. The following information includesonly the average doses of tricyclic antidepressants. If your dose is different, do not change it unless your doctor tellsyou to do so.

The number of capsules or tablets, or the amount of solution or syrup thatyou take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, andthe length of time you take the medicine depend on the medical problem forwhich 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 doseis usually not more than 150 mg a day, unless you are in the hospital. Somehospitalized 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 doseis 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 determinedby your doctor.
    • Older adults? At first, 25 mg at bedtime. Your doctor may increaseyour dose gradually as needed. However, the dose is usually not more than100 mg a day.
• For syrup dosage form:
  • For depression:
    • Adults?At first, 25 mg two to four times a day. Your doctormay 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 doseis 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 determinedby your doctor.
    • Older adults?At first, 10 mg three times a day, and 20 mg atbedtime. 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 determinedby 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 determinedby your doctor.
    • Older adults?At first, 25 mg two to three times a day. Yourdoctor 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 doctormay increase your dose gradually as needed. However, the dose is usually notmore than 250 mg a day, unless you are in the hospital. Some hospitalizedpatients may need higher doses.
    • Teenagers and children 10 years of age and over?At first, 25mg 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 determinedby your doctor.
    • Older adults?At first, 20 to 30 mg a day. Your doctor may increaseyour dose gradually as needed.

For desipramine
• For tablet dosage form:
  • For depression:
    • Adults?100 to 200 milligrams (mg) a day. Your doctor may increaseyour dose gradually as needed. However, the dose is usually not more than300 mg a day.
    • Teenagers?25 to 50 mg a day. Your doctor may increase yourdose gradually as needed. However, the dose is usually not more than 100 mga 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 yourdose gradually as needed. However, the dose is usually not more than 150 mga day.

For doxepin
• For capsule or solution dosage forms:
  • For depression:
    • Adults?At first, 25 milligrams (mg) three times a day. Yourdoctor may increase your dose gradually as needed. However, the dose is usuallynot more than 150 mg a day, unless you are in the hospital. Some hospitalizedpatients may need higher doses.
    • Children up to 12 years of age?Use and dose must be determinedby your doctor.
    • Older adults?At first, 25 to 50 mg a day. Your doctor may increaseyour 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 doseis usually not more than 200 mg a day, unless you are in the hospital. Somehospitalized patients may need higher doses.
    • Adolescents?25 to 50 mg a day. Your doctor may increase yourdose gradually as needed. However, the dose is usually not more than 100 mga 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 determinedby your doctor.
    • Older adults?At first, 25 mg at bedtime. Your doctor may increaseyour dose gradually as needed. However, the dose is usually not more than100 mg a day.
  • For bedwetting:
    • Children?25 mg once a day, taken one hour before bedtime. Yourdoctor 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 doctormay increase your dose gradually as needed. However, the dose is usually notmore than 200 mg a day, unless you are in the hospital. Some hospitalizedpatients may need higher doses.
    • Children up to 12 years of age?Use and dose must be determinedby your doctor.
• For injection dosage form:
  • For depression:
    • Adults?Dose must be determined by your doctor. It is injectedinto 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 determinedby your doctor.

For nortriptyline
• For capsule or solution dosage forms:
  • For depression:
    • Adults?25 milligrams (mg) three to four times a day. Your doctormay increase your dose gradually as needed. However, the dose is usually notmore than 150 mg a day.
    • Teenagers?25 to 50 mg a day. Your doctor may increase yourdose 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 yourdose gradually as needed.

For protriptyline
• For tablet dosage form:
  • For depression:
    • Adults?At first, 5 to 10 milligrams (mg) three to four timesa day. Your doctor may increase your dose gradually as needed. However, thedose is usually not more than 60 mg a day.
    • Teenagers?At first, 5 mg three times a day. Your doctor mayincrease your dose gradually as needed.
    • Children up to 12 years of age?Use and dose must be determinedby your doctor.
    • Older adults?At first, 5 mg three times a day. Your doctormay 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 mayincrease your dose as needed. However, the dose is usually not more than 200mg a day, unless you are hospitalized. Some hospitalized patients may needhigher doses.
    • Teenagers?At first, 50 mg a day. Your doctor may increase yourdose gradually as needed. However, the dose is usually not more than 100 mga day.
    • Children up to 12 years of age?Use and dose must be determinedby your doctor.
    • Older adults?At first, 50 mg a day. Your doctor may increaseyour dose gradually as needed. However, the dose is usually not more than100 mg a day.

Missed dose?If you miss a dose of this medicine and your dosingschedule is:

• One dose a day at bedtime?Do not take the missed dose in themorning 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, andgo 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 verydangerous 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 causethe medicine to break down.
• Keep the liquid form of this medicine from freezing.
• Do not keep outdated medicine or medicine no longer needed. Be surethat any discarded medicine is out of the reach of children.

Precautions While Using This Medicine

It isvery important that your doctor check your progress at regular visits to allowdosage 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 depressantsare 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, includingsome dental anesthetics. Check with your medical doctoror dentist before taking any of the above while you are taking this medicine.

Antidepressants may cause some people to be agitated, irritable or displayother abnormal behaviors. It may also cause some people to have suicidal thoughtsand tendencies or to become more depressed. If you or your caregiver noticeany of these adverse effects, tell your doctor right away.

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

Dizziness, lightheadedness, or fainting may occur,especially when you get up from a lying or sitting position. Getting up slowlymay help. If this problem continues or gets worse, check with your doctor.

This medicine may cause dryness of the mouth. For temporaryrelief, use sugarless gum or candy, melt bits of ice in your mouth, or usea saliva substitute. However, if your mouth continues to feel dry formore than 2 weeks, check with your medical doctor or dentist. Continuing drynessof the mouth may increase the chance of dental disease, including tooth decay,gum disease, and fungus infections.

Tricyclic antidepressants may cause your skin to be more sensitive to sunlightthan 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 10:00a.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 aboutthis, check with your health care professional.
• Apply a sun block lipstick that has an SPF of at least 15 to protectyour lips.
• Do not use a sunlamp or tanning bed or booth.

If you have a severe reaction from the sun, check withyour doctor.

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

Before having any kind of surgery, dental treatment,or emergency treatment, tell the medical doctor or dentist in charge thatyou are using this medicine. Taking tricyclic antidepressants togetherwith medicines used during surgery or dental or emergency treatments may increasethe risk of side effects.

For diabetic patients:

• This medicine may affect blood sugar levels. If you notice a changein 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 checkingwith your doctor. Your doctor may want you to reduce gradually theamount you are using before stopping completely. This may help prevent a possibleworsening of your condition and reduce the possibility of withdrawal symptomssuch as headache, nausea, and/or an overall feeling of discomfort.

The effects of this medicine may last for 3 to 7 daysafter you have stopped taking it. Therefore, all the precautions statedhere must be observed during this time.

For patients taking protriptyline:

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

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 mayneed medical attention.

Stop taking this medicineand get emergency help immediately if any of the following side effectsoccur:

Reported for amoxapine only?rare

Convulsions(seizures); difficult or fast breathing; fever with increased sweating; highor low (irregular) blood pressure; loss of bladdercontrol; muscle stiffness (severe); pale skin; unusual tiredness or weakness

Check with your doctor as soon as possible if any of the following sideeffects 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 armsand legs

Reported for amoxapine only (in addition to the above)?less common

Lipsmacking or puckering; puffing of cheeks; rapid or worm-like movements of tongue; uncontrolled chewing movements; uncontrolled movementsof hands, arms, or legs

Rare

Anxiety; breast enlargement in bothmales and females; hair loss; inappropriate secretion of milk?in females; increased sensitivity to sunlight; irritability; muscle twitching; red or brownish spotson skin; ringing, buzzing, or other unexplained soundsin 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 eyesor 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 notthere); 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 medicalattention. These side effects may go away during treatment as your body adjuststo the medicine. However, check with your doctor if any of the following sideeffects 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; weightgain

Less common

Diarrhea; heartburn; increased sweating; trouble in sleeping (more commonwith protriptyline, especially when taken late in the day); vomiting

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

Headache; irritability; nausea, vomiting, or diarrhea; restlessness; trouble in sleeping, withvivid dreams; unusual excitement

Reported for amoxapine only (in addition to the above)

Lip smacking or puckering; puffing ofcheeks; 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. Ifyou notice any other effects, check with your doctor.

Additional Information

Once a medicine has been approvedfor marketing for a certain use, experience may show that it is also usefulfor other medical problems. Although these uses are not included in productlabeling, tricyclic antidepressants are used in certain patients with thefollowing 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 continuingheadaches) (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)
• Nicotine dependence (as an aid to other smoking cessationn therapy)(nortriptyline)
• Panic disorder (clomipramine, desipramine, doxepin, nortriptyline,and trimipramine)
• Stomach ulcer (amitriptyline, doxepin, and trimipramine)
• Urinary incontinence (imipramine)

Other than the above information, there is no additional information relatingto proper use, precautions, or side effects for these uses.