From the Guidelines
Yes, there is a significant interaction between cyclobenzaprine and amitriptyline that should be avoided due to their similar mechanisms of action and side effect profiles. These medications should not be taken together because they are both tricyclic compounds, with cyclobenzaprine being structurally related to amitriptyline 1. Taking them concurrently increases the risk of serious side effects including excessive sedation, confusion, anticholinergic effects (dry mouth, blurred vision, urinary retention, constipation), and potentially dangerous cardiac effects. Some key points to consider when evaluating the interaction between cyclobenzaprine and amitriptyline include:
- The potential for increased anticholinergic effects, such as hallucinations, confusion, drowsiness, constipation, urinary retention, and dry mouth 1
- The risk of serotonin syndrome, a potentially life-threatening condition characterized by agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and hyperthermia, especially when cyclobenzaprine is used with monoamine oxidase inhibitors 1
- The importance of informing healthcare providers about all medications being taken to avoid potentially dangerous interactions Alternative muscle relaxants that might have fewer interactions with amitriptyline include methocarbamol or tizanidine, though these should still be used with caution and only under medical supervision. It is crucial to prioritize caution when considering the use of cyclobenzaprine and amitriptyline together, given the potential for severe side effects and the lack of clear guidance for management in certain periods, such as the perioperative period 1.
From the FDA Drug Label
The development of a potentially life-threatening serotonin syndrome has been reported with Cyclobenzaprine Hydrochloride when used in combination with other drugs, such as ... tricyclic antidepressants (TCAs)... Cyclobenzaprine is closely related to the tricyclic antidepressants, e.g., amitriptyline and imipramine.
The interaction between cyclobenzaprine and amitriptyline (a tricyclic antidepressant) is a potential risk for serotonin syndrome.
- Concomitant use may lead to mental status changes, autonomic instability, neuromuscular abnormalities, and/or gastrointestinal symptoms.
- Treatment with cyclobenzaprine and amitriptyline should be discontinued immediately if serotonin syndrome reactions occur.
- Careful observation is advised if concomitant treatment is clinically warranted, particularly during treatment initiation or dose increases 2.
From the Research
Interaction between Cyclobenzaprine and Amitriptyline
- There is evidence to suggest that cyclobenzaprine and amitriptyline may interact due to their similar chemical structures 3.
- Cyclobenzaprine has a cyclic structure similar to amitriptyline, a tricyclic antidepressant, which may lead to similar toxicity profiles in overdose situations 3.
- However, studies have shown that cyclobenzaprine does not produce the same life-threatening cardiovascular or neurologic effects as tricyclic antidepressants like amitriptyline in doses less than 1g 3.
- The primary efficacy measures of cyclobenzaprine, such as patient-rated clinical global impression of change and relief from starting backache, were not directly compared to amitriptyline in the provided studies 4, 5, 6, 7.
- Amitriptyline has been shown to be effective in treating chronic pain conditions, including post-herpetic neuralgia and diabetic neuropathy, with common adverse events including dry mouth and sedation 5.
- Cyclobenzaprine has been shown to be effective in treating acute musculoskeletal spasm, with common adverse events including somnolence and dry mouth 4, 6, 7.
- While there is no direct evidence of an interaction between cyclobenzaprine and amitriptyline, their similar chemical structures and overlapping side effect profiles suggest that caution should be exercised when using these medications together 3.