Drug Profile

Cyclobenzaprine was approved for marketing by the FDA in August 1977. This drug is approved, in addition to rest and physical therapy, for relief of muscle spasm associated with acute, painful musculoskeletal conditions.[1] Cyclobenzaprine is very close in chemical structure to the tricyclic antidepressant amitriptyline (ELAVIL) and may cause some of the same adverse effects and dangerous drug interactions.

Cyclobenzaprine has not been shown to be any more effective than painkillers or anti-inflammatory drugs such as aspirin for relieving the pain of local muscle spasm.[2]

A systematic analysis of clinical trials in which cyclobenzaprine was used to manage low back pain found that the drug was more effective than a placebo. However, the authors of the analysis commented: “Studies comparing the relative value of acetaminophen, nonsteroidal anti-inflammatory drugs, and cyclobenzaprine individually and in combination for the treatment of back pain are needed.”[3]

Cyclobenzaprine must not be used with the family of antidepressants known as monoamine oxidase (MAO) inhibitors or within 14 days after stopping an MAO inhibitor. Seizure resulting from a high fever and deaths have occurred in patients receiving cyclobenzaprine (or structurally similar tricyclic antidepressants) and MAO inhibitor drugs.

The risk of seizure is enhanced when cyclobenzaprine is taken with the pain reliever tramadol (ULTRAM) or tramadol and acetaminophen (ULTRACET). Both are listed as Do Not Use drugs.

Cyclobenzaprine, especially when used with alcohol or other central nervous system (CNS) depressants, can impair mental or physical abilities, or both, required for the performance of hazardous tasks, such as operating machinery or driving a motor vehicle. In the elderly, the frequency and severity of adverse events associated with the use of cyclobenzaprine, with or without the use of other drugs, are increased.

In 1999 cyclobenzaprine’s manufacturer applied to the FDA to market the drug over the counter in a five-milligram strength. The advisory committee reviewing the studies submitted by the company found that “the efficacy of 5- mg Flexeril had not been established ... and that ... by day 7 about 70 percent of back spasm was resolved—including those on placebo.”[4]

Remarkably, in 2003 the FDA approved cyclobenzaprine in the 5-milligram strength as a prescription drug. The new strength is being promoted as less sedating. Although this is undoubtedly true, sedation may still be the way this drug works.

In 2013, the FDA issued an advisory concerning the use of cyclobenzaprine at the same time as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil or MAO inhibitors. The advisory referred to reports of potentially life-threatening serotonin syndrome when cyclobenzaprine is used in combination with these drugs. Serotonin syndrome may include one or more of the following symptoms: excitement, restlessness, loss of consciousness, confusion, disorientation, anxiety, agitation, weakness, tremor, incoordination, shivering, sweating, vomiting and rapid heartbeat.