Drug Profile

Amitriptyline (generic only) is a tricyclic antidepressant used to treat depression. We have designated this drug as Do Not Use because it has more harmful adverse effects than any other drug in its family (see Adverse Effects of Antidepressants table in Depression: When are Drugs Called For And Which Ones Should You Use?). A group of highly regarded drug safety experts maintains a list of drugs they consider inappropriate for use in patients over 65. Amitriptyline is among the 48 medications or classes of medication on that list.[1] 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. If symptoms do not improve sufficiently with use of an SSRI and remain severe, further treatment with other antidepressants is warranted.

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.

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 its 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 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 (or package inserts) 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.