Cyclobenzaprine Side Effects
Cyclobenzaprine commonly causes drowsiness (29-38%), dry mouth (21-32%), and fatigue (6%), with these adverse effects being dose-dependent and more pronounced at higher doses. 1
Common Side Effects
- Drowsiness/Sedation: Occurs in 29% of patients at 5mg dose and 38% at 10mg dose 1
- Dry Mouth: Affects 21% of patients at 5mg dose and 32% at 10mg dose 1
- Fatigue: Reported by 6% of patients 1
- Headache: Occurs in approximately 5% of patients 1
- Dizziness: Reported in 11% of patients in clinical trials, 3% in surveillance programs 1
Less Common Side Effects (1-3% incidence)
- Abdominal pain
- Acid regurgitation
- Constipation
- Diarrhea
- Nausea
- Irritability
- Decreased mental acuity
- Nervousness
- Upper respiratory infection
- Pharyngitis 1
Serious Adverse Effects
Cardiovascular Effects
Cyclobenzaprine is structurally related to tricyclic antidepressants and may cause:
- Tachycardia
- Arrhythmias
- Prolonged conduction time
- Hypotension
- Palpitations 1
Neurological/Psychiatric Effects
- Seizures
- Ataxia
- Tremors
- Disorientation
- Anxiety
- Agitation
- Hallucinations
- Confusion 1
Serotonin Syndrome
Potentially life-threatening when combined with:
- SSRIs
- SNRIs
- Tricyclic antidepressants
- Tramadol
- Bupropion
- MAO inhibitors (contraindicated) 1
Signs of serotonin syndrome include:
- Mental status changes
- Autonomic instability
- Neuromuscular abnormalities
- Gastrointestinal symptoms 1
Dose-Related Side Effects
The incidence of side effects is dose-dependent, with higher doses causing more adverse effects. A 5mg TID regimen has been shown to be as effective as 10mg TID but with fewer sedative effects 2. In overdose cases, cyclobenzaprine does not typically produce life-threatening cardiovascular or neurologic effects at doses less than 1g 3.
Mechanism of Side Effects
Recent research has identified that cyclobenzaprine is a potent non-competitive antagonist of histamine H1 receptors, which likely explains its significant sedative effects 4. The anticholinergic side effects (dry mouth, constipation, blurred vision) are related to its structural similarity to tricyclic antidepressants 5, 6.
Special Considerations
- Elderly patients: Should start with lower doses (5mg) due to increased risk of side effects 7
- Liver impairment: Use with caution as metabolism is primarily hepatic 7
- Drug interactions: Avoid concomitant use with MAO inhibitors and use caution with other serotonergic medications 1
- Fibromyalgia patients: The European League Against Rheumatism (EULAR) gives only a weak recommendation for cyclobenzaprine use in fibromyalgia, noting that 85% of patients experience side effects and 29% discontinue treatment due to adverse events 8
Duration and Discontinuation
- Short-term use (≤21 days) is recommended whenever possible 7
- Abrupt discontinuation after prolonged use may cause withdrawal symptoms including malaise, nausea, and headache 7
- Tapering is recommended over 2-3 weeks to prevent withdrawal symptoms 7
When prescribing cyclobenzaprine, the benefits must be weighed against these potential side effects, particularly in elderly patients or those with pre-existing conditions that may increase sensitivity to anticholinergic or sedative effects.