Drug Profile

The brand-name drug LIMBITROL contains two active ingredients: amitriptyline, a tricyclic antidepressant, and chlordiazepoxide, a benzodiazepine (tranquilizer or antianxiety drug). This combination drug is used to treat moderate-to-severe depression associated with moderate-to-severe anxiety. Public Citizen recommends against using LIMBITROL for three major reasons:

1. Combining an antidepressant with a benzodiazepine has not been shown to produce a more effective drug.[1]
2. Taking these two drugs together raises the risk of harmful adverse effects. Chlordiazepoxide might increase the harmful anticholinergic effects of amitriptyline (see box), and amitriptyline could increase the drowsiness caused by chlordiazepoxide.
3. The antidepressant in this combination, amitriptyline, has more 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?) and should not be used by older adults, either alone or in a combination such as this one.

A group of highly regarded drug-safety experts maintains a list of drugs they consider inappropriate for use in patients older than 65. This irrational combination product is among the 48 medications or classes of medication on that list.[2]

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.

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 recover from 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 a mental health professional, such as a therapist or psychiatrist. Antidepressant drugs should be reserved for major depression in which the patient does not respond to psychotherapy alone.

If you use Limbitrol, ask your doctor whether your treatment can be changed. Do not stop taking this drug suddenly. Your doctor may want to reduce your dose gradually over one or two months before you completely stop taking Limbitrol.

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.[3]

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

Regulatory actions surrounding amitriptyline and chlordiazepoxide

2004: In October, 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 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 agency wants the new warnings to be black-box warnings printed on the professional product labels for all antidepressants sold in the United States. The warning is an amendment to an existing black-box warning for children and adolescents.[4]

2016: The FDA required the addition of a black-box warning, the strongest warning used by the FDA, to the label of all opioid and benzodiazepine drugs stating that serious adverse effects — including respiratory depression, coma and death — have occurred when these medications are used together.

2023: The FDA updated the drug product label of Limbitrol to warn that the drug can cause sedation and withdrawal symptoms in newborns when used during late pregnancy. Breastfeeding is not recommended in nursing mothers using Limbitrol.[5]