Worst Pills, Best Pills

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Drug Profile

The information on this site is intended to supplement and enhance, not replace, the advice of a physician who is familiar with your medical history. Decisions about your health should always be made ONLY after detailed conversation with your doctor.

Limited Use [what does this mean?]
Generic drug name: desipramine (dess IP ra meen)
Brand name(s): NORPRAMIN
GENERIC: available FAMILY: Tricyclics
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: nortriptyline (nor TRIP ti leen)
Brand name(s): AVENTYL, PAMELOR
GENERIC: available FAMILY: Tricyclics
Find the drug label by searching at DailyMed.

Pregnancy and Breast-feeding Warnings [top]

No information is available from either animal or human studies. You should consult with your doctor if you are pregnant, thinking of becoming pregnant or if you are planning to nurse.

Safety Warnings For This Drug [top]


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 desipramine, nortriptyline 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.

Desipramine and nortriptyline 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]

Desipramine (NORPRAMIN) and nortriptyline (PAMELOR) are tricyclic antidepressants used to treat severe depression that is not caused by other drugs, alcohol or emotional losses (such as a death in the family). These two drugs produce fewer sedative effects and fewer harmful anticholinergic adverse effects (see box) than some other tricyclic antidepressants. We have designated desipramine and nortriptyline as Limited Use. For patients who need an antidepressant drug, we recommend trying one of...

Desipramine (NORPRAMIN) and nortriptyline (PAMELOR) are tricyclic antidepressants used to treat severe depression that is not caused by other drugs, alcohol or emotional losses (such as a death in the family). These two drugs produce fewer sedative effects and fewer harmful anticholinergic adverse effects (see box) than some other tricyclic antidepressants. We have designated desipramine and nortriptyline as Limited Use. 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.

Patients should not take these drugs for mild depression or anxiety, or as a sleeping pill.

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.

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 under the guidance of your doctor. Your doctor should monitor the level of the drug in your bloodstream, because there is a point at which a higher drug level produces less benefit. 

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 Food and Drug Administration (FDA) issued a public health advisory requiring manufacturers to add a black-box warning (see above) to the professional product labeling (package insert) of all antidepressants. A black-box warning is the strongest type of warning that the FDA can require. The FDA also requires that a Patient Medication Guide be given to patients receiving this drug advising them of the risk and precautions that can be taken.  

2007: The FDA announced May 2007 that it will 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 agency wants the new warnings to be black-box warnings 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.

2009: In October 2009, the FDA issued a public health advisory warning concerning risk associated with desipramine use.

The advisory included information that the death rate resulting from an overdose of desipramine is higher than the death rate resulting from an overdose of other tricyclic antidepressants.[4]

Before You Use This Drug [top]

Tell your doctor if you have or have had:

  •   allergies to drugs
  •   alcohol dependence
  •   asthma
  •   blood disorders
  •   heart or blood vessel disease
  •   epilepsy, seizures
  •   stomach or intestinal disease
  •   glaucoma
  •   kidney, liver, or thyroid problems
  •   manic-depressive illness, schizophrenia, or paranoia
  •   retention of urine or enlarged prostate
  •   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.
  • Do not smoke. Smoking may increase the drug’s effects on your heart.
  • 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. If the drug works, talk with your doctor about lowering the dose gradually.
  • 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 by 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 this drug.

How to Use This Drug [top]

  • If you miss a dose, use the following guidelines: If you are taking your drug more than once a day, take the missed dose as soon as you remember, but skip it if it is almost time for your next scheduled 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 other drugs, take them one to two hours before taking your antidepressant.
  • Capsules may be opened and the contents mixed with applesauce, jelly, or ketchup, then swallowed without chewing.
  • Do not store in the bathroom. Do not expose to heat, moisture, or strong light.

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:

ADRENALIN (also in bee sting kits), arbutamine, CELEXA, chlordiazepoxide, cimetidine, citalopram, COMTAN, CYTOMEL, diazepam, entacapone, epinephrine, flecainide, fluoxetine, guanethidine, halofantrine, IMDUR, INDERAL, INDERAL LA, ISMELIN, ISMO, ISORDIL, isosorbide, LIBRIUM, liothyronine, marijuana, MELLARIL, MERIDIA, nitroglycerin (sublingual), NITRO-BID, NITROSTAT, NORVIR, ORAP, paroxetine, PAXIL, phenothiazines, pirnozide, PRIFTIN, PRIMATENE MIST, propafenone, propranolol, PROZAC, quinidine, rifapentine, ritonavir, RYTHMOL, sertraline, sibutramine, SORBITRATE, TAGAMET, TAMBOCOR, thioridazine, tolazamide, TOLINASE, tramadol, TRANSDERM-NITRO, TRIOSTAT, ULTRACET, ULTRAM, VALIUM, 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
  •   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
  •   difficulty urinating
  •   shuffling walk
  •   slowed movements
  •   anxiety
  •   breast enlargement in both males and females
  •   hair loss
  •   unusual secretion of milk
  •   increased sensitivity to sunlight
  •   irritability
  •   muscle twitching
  •   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

Call your doctor if these symptoms continue:

  •   diarrhea
  •   dizziness
  •   dry mouth
  •   headache
  •   heartburn
  •   insomnia
  •   nausea or vomiting
  •   increased appetite for sweets
  •   unpleasant taste in mouth
  •   weight gain
  •   trouble sleeping

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

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

Signs of overdose:

  • confusion
  • severe drowsiness
  • fever
  • hallucinations
  • restlessness and agitation
  • seizures
  • shortness of breath, trouble breathing
  • unusually fast, slow, or 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
  •   pulse
  •   blood pressure
  •   glaucoma tests
  •   desipramine blood levels
  •   liver function tests
  •   kidney function tests
  •   heart function tests such as electrocardiogram (ECG, EKG)
  •   dental exams, at least twice yearly

last reviewed January 31, 2024