Worst Pills, Best Pills

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Drug Profile

Do NOT stop taking this or any drug without the advice of your physician. Some drugs can cause severe adverse effects when they are stopped suddenly.

Do Not Use [what does this mean?]
Generic drug name: amoxapine (a MOX a peen)
Brand name(s):
GENERIC: available FAMILY: Tricyclics
Find the drug label by searching at DailyMed.

Do Not Use [what does this mean?]
Generic drug name: doxepin (DOX e pin)
Brand name(s): SILENOR, SINEQUAN
GENERIC: available FAMILY: Tricyclics
Find the drug label by searching at DailyMed.

Do Not Use [what does this mean?]
Generic drug name: imipramine (im IP ra meen)
Brand name(s): TOFRANIL, TOFRANIL PM
GENERIC: available FAMILY: Tricyclics
Find the drug label by searching at DailyMed.

Pregnancy and Breast-feeding Warnings [top]

Pregnancy Warning

There have been clinical reports of congenital malformations associated with the use of imipramine. Do not use during pregnancy. Amoxapine and doxepin have not been adequately tested but can be assumed to pose similar risks.

Breast-feeding Warning

Data suggest that imipramine is excreted in milk. There is a report of trouble breathing and drowsiness in a nursing infant whose mother is taking doxepin, another drug in this group. Because the possibility exists that the drugs can harm the child, mothers taking these drugs should not nurse.

Safety Warnings For This Drug [top]

FDA BLACK BOX WARNING

Suicidality and Antidepressant Drugs

Compared with placebo, antidepressants increased the risk of suicidal thinking and behavior (suicidality) in children, adolescents and young adults in short-term studies of major depressive disorder and other psychiatric disorders. Anyone considering the use of amoxapine (generic only), doxepin, imipramine or any other antidepressant in a child, adolescent or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared with placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber.

Amoxapine, doxepin and imipramine are not approved for use in pediatric patients.

Anticholinergic Effects

Warning: Special Mental and Physical Adverse Effects

Older adults are especially sensitive to the harmful anticholinergic effects of these drugs. Drugs in this family should not be used unless absolutely necessary.

Mental Effects: confusion, delirium, short-term memory problems, disorientation and impaired attention

Physical Effects: dry mouth, constipation, difficulty urinating (especially for a man with an enlarged prostate), blurred vision, decreased sweating with increased body temperature, sexual dysfunction and worsening of glaucoma

Facts About This Drug [top]

The drugs discussed in this profile are known as tricyclic antidepressants. They are used to treat severe depression that is not caused by other drugs, alcohol or emotional losses (such as a death in the family). We have designated amoxapine, doxepin (SILENOR) and imipramine (TOFRANIL) as Do Not Use because they have more harmful adverse effects (see Adverse Effects of Antidepressants table in Depression: When are Drugs Called For And Which Ones Should You Use?) than the newer SSRIs and...

The drugs discussed in this profile are known as tricyclic antidepressants. They are used to treat severe depression that is not caused by other drugs, alcohol or emotional losses (such as a death in the family). We have designated amoxapine, doxepin (SILENOR) and imipramine (TOFRANIL) as Do Not Use because they have more harmful adverse effects (see Adverse Effects of Antidepressants table in Depression: When are Drugs Called For And Which Ones Should You Use?) than the newer SSRIs and certain other tricyclic antidepressants. For patients who need an antidepressant drug, we recommend trying one of the newer selective serotonin reuptake inhibitors (SSRIs) (for example, fluoxetine [PROZAC, SARAFEM, SELFEMRA]) first, as these are the safest antidepressants. If symptoms do not improve sufficiently with use of an SSRI and remain severe, further treatment with other antidepressants is warranted.

Don’t overdose
Patients over 60 generally need to take one-third to one-half the dose of antidepressants  -used by younger adults. If the initial dose is not enough and needs to be increased, this should be done very slowly.

Amoxapine can cause tardive dyskinesia—uncontrolled movements of the jaws, tongue, and lips—a side effect also seen with antipsychotic drugs. Doxepin (SINEQUAN) has especially strong sedative effects. 

The length of time it takes an antidepressant to work can overlap with the time of spontaneous recovery, especially if the depression is situational (if it is caused by a death or other external circumstances). Most people lift themselves out of depression with friends, spiritual resources, or activities such as exercise, work, reading, play, art, and travel. If depression is not overcome by these measures, seek help from mental health professionals, such as therapists or psychiatrists. Antidepressant drugs should be reserved for major depression in which the patient does not respond to psychotherapy alone.

Studies say…

A major meta-analysis commissioned by the U.S. Department of Health and Human Services failed to show any significant difference in effectiveness between tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs), a newer class of antidepressants.

The side effects of new and old antidepressants are different—except for withdrawal symptoms, which are common to both tricyclic antidepressants and SSRIs. But patients are simply trading off one group of side effects for another when deciding between the two types of antidepressants.

There does not appear to be any difference in the proportion of people who can tolerate either of these two groups of antidepressants. In terms of side effects, large-scale meta-analyses found no significant difference between the SSRIs and tricyclic antidepressants in overall discontinuation rates of use of these drugs by patients.[1] (Drug discontinuation rates can be used to compare adverse reactions between drugs.)

In 2015, a study published in JAMA Internal Medicine showed that strong anticholinergic drugs were associated with an increased risk of dementia in older adults. The study also showed that higher doses and longer use of these drugs are associated with higher risk of dementia.[2]

Refer to the August 2015 issue of Worst Pills, Best Pills News for examples of strong anticholinergic drugs.

Regulatory actions surrounding tricyclic antidepressants

2004: In October 2004, the FDA issued a public health advisory requiring manufacturers to add a black-box warning (see above) to its professional product labeling (package insert) of all antidepressants. A black-box warning is the strongest type of warning that the FDA can require.

2007: The FDA announced in May 2007 that it would require new warnings concerning the increased risk of suicidal thoughts and behavior in young adults ages 18 to 24 during the first one to two months of treatment with antidepressants. The black-box warnings are printed on the professional product labels for all antidepressants sold in the U.S. The warning is an amendment to an existing black-box warning for children and adolescents.[3] 

The FDA-approved professional product labeling for antidepressant drugs sold in the United States carries the following statement:

Suicide: The possibility of a suicide attempt is inherent in major depressive disorder and may persist until significant remission occurs. Close supervision of high-risk patients should accompany initial drug therapy. Prescriptions for Drug X should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Before You Use This Drug [top]

Tell your doctor if you have or have had:

  • allergies to drugs
  • alcohol dependence
  • asthma
  • bipolar disorder (manic-depressive illness) or schizophrenia
  • blood disorders
  • convulsions (seizures)
  • difficulty urinating or enlarged prostate
  • glaucoma
  • heart or blood vessel disease
  • high blood pressure
  • kidney or liver problems
  • overactive thyroid
  • stomach or intestinal disorders
  • pregnancy or are breast-feeding

Tell your doctor about any other drugs you take, including aspirin, herbs, vitamins, and other nonprescription products.

Ask your doctor to check your blood pressure, once while you are lying down and once after you have been standing up for at least two minutes, and to do an electrocardiogram.

When You Use This Drug [top]

  • Do not stop taking this drug suddenly. Your doctor must give you a schedule to lower your dose gradually, to prevent withdrawal symptoms such as headache, mood change, nausea, vomiting, diarrhea, and trouble sleeping and vivid dreams.
  • Until you know how you react to this drug, do not drive or perform other activities requiring alertness. These drugs may cause blurred vision and drowsiness.
  • It may take several weeks before you can tell that these drugs are working. Do not take more drug than prescribed. If the drug works, talk with your doctor about gradually lowering the dose.
  • Do not smoke. Smoking may increase the drug’s effects on your heart.
  • Do not drink alcohol or use other drugs that can cause drowsiness.
  • You may feel dizzy when rising from a lying or sitting position. When getting out of bed, hang your legs over the side of the bed for a few minutes, then get up slowly.
  • When getting up from a chair, stay beside the chair until you are sure that you are not dizzy.
  • Check with your doctor before taking any other drugs, prescription or nonprescription. These drugs frequently interact with other drugs.
  • The effects of these drugs may last for up to a week after you stop taking them. Avoid alcohol and heed all other warnings for this time period.
  • If you plan to have any surgery, including dental, tell your doctor that you take one of these drugs.
  • Avoid unprotected exposure to sun.

How to Use This Drug [top]

  • If you miss a dose, use the following guidelines: If you are taking more than one dose a day of one of these drugs, take the missed dose as soon as you remember, but skip it if it is almost time for the next dose. If you are taking your drug only once a day at bedtime, and you go to sleep without taking that dose, do not take it in the morning. Instead, call your doctor. Do not take double doses.
  • Do not share your medication with others.
  • Take the drug at the same time(s) each day.
  • Take with food.
  • If you are taking any other drugs, take them one to two hours before you take your antidepressant.
  • Capsules may be opened and the contents mixed with applesauce, jelly, or ketchup, then swallowed without chewing.
  • Store at room temperature. Do not store in the bathroom. Do not expose to heat, moisture, or strong light. Keep out of reach of children.

Interactions with Other Drugs [top]

The following drugs, biologics (e.g., vaccines, therapeutic antibodies), or foods are listed in Evaluations of Drug Interactions 2003 as causing “highly clinically significant” or “clinically significant” interactions when used together with any of the drugs in this section. In some sections with multiple drugs, the interaction may have been reported for one but not all drugs in this section, but we include the interaction because the drugs in this section are similar to one another. We have also included potentially serious interactions listed in the drug’s FDA-approved professional package insert or in published medical journal articles. There may be other drugs, especially those in the families of drugs listed below, that also will react with this drug to cause severe adverse effects. Make sure to tell your doctor and pharmacist the drugs you are taking and tell them if you are taking any of these interacting drugs:

The depressant effects of alcohol, barbiturates, and central nervous system (CNS) depressants may be enhanced with the use of these drugs.

ADRENALIN (also in bee sting kits), arbutamine, CELEXA, cimetidine, citalopram, COMTAN, CYTOMEL, entacapone, epinephrine, flecainide, fluoxetine, guanethidine, IMDUR, ISMELIN, ISMO, ISORDIL, isosorbide, liothyronine, MELLARIL, MERIDIA, nitroglycerin (sublingual), NITROBID, NITRO-DUR, NITROSTAT, NORVIR, paroxetine, PAXIL, PRIMATENE MIST, propafenone, PROZAC, quinidine, ritonavir, RYTHMOL, sertraline, sibutramine, SORBITRATE, TAGAMET, TAMBOCOR, thioridazine, tolazamide, TOLINASE, tramadol, TRANSDERM-NITRO, TRIOSTAT, ULTRACET, ULTRAM, ZOLOFT.

You should wait at least 14 days after stopping one of these drugs and starting one of these MAO inhibitors: deprenyl, ELDEPRYL, furazolidone, FUROXONE, isocarboxazid, MARPLAN, MATULANE, NARDIL, PARNATE, phenelzine, procarbazine, selegiline, tranylcypromine.

Adverse Effects [top]

Call your doctor immediately if you experience:

  • irregular blood pressure
  • nervousness or restlessness
  • loss of bladder control
  • severe muscle stiffness
  • pale skin
  • blurred vision
  • constipation
  • confusion, delirium, or hallucinations
  • decreased sexual ability
  • difficulty in speaking or swallowing
  • eye pain
  • fainting
  • loss of balance control
  • masklike face
  • difficulty urinating
  • shakiness or trembling
  • shuffling walk
  • slowed movements
  • stiffness of arms and legs
  • anxiety
  • breast enlargement in both males and females
  • hair loss
  • inappropriate secretion of milk
  • increased sensitivity to sunlight
  • irritability
  • twitching muscle
  • red or brownish spots on skin
  • ringing or buzzing in the ears
  • skin rash and itching
  • sore throat and fever
  • swelling of face and tongue
  • swelling of testicles
  • trouble with teeth or gums
  • yellow skin or eyes

For tricyclic antidepressants:

Call your doctor if these symptoms continue:

  • diarrhea
  • dizziness
  • dry mouth
  • drowsiness
  • headache
  • heartburn
  • insomnia
  • nausea or vomiting
  • increased appetite (may include craving for sweets)
  • unpleasant taste in mouth
  • weight gain
  • trouble sleeping

For amoxapine only (in addition to above):

Signs of neuroleptic malignant syndrome:

  • convulsions
  • difficult breathing
  • fast heartbeat or irregular pulse
  • fever
  • irregular blood pressure
  • increased sweating
  • loss of control of urination
  • severe muscle stiffness
  • unusual tiredness or weakness

Call your doctor if these symptoms continue after you stop taking the drug:

  • headache
  • irritability
  • nausea and vomiting
  • diarrhea
  • restlessness or unusual excitement
  • insomnia

For amoxapine only (in addition to above):

Signs of tardive dyskinesia:

  • lip smacking or puckering, puffing of cheeks
  • rapid or wormlike movements of tongue
  • uncontrolled movements of arms, legs, or mouth

Signs of overdose:

  • confusion
  • severe drowsiness
  • fever
  • hallucinations
  • restlessness and agitation
  • seizures
  • breathing difficulty
  • irregular heartbeat
  • unusual tiredness
  • weakness
  • vomiting
  • enlarged pupils

If you suspect an overdose call this number to contact your poison control center: (800) 222-1222.

Periodic Tests[top]

Ask your doctor which of these tests should be done periodically while you are taking this drug:

  • complete blood count
  • blood pressure
  • pulse
  • glaucoma tests
  • liver function tests
  • kidney function tests
  • heart function tests such as electrocardiogram (ECG, EKG)
  • dental exams (at least twice yearly)
  • plasma tricyclic determinations

last reviewed January 31, 2021