Recommended Skeletal Muscle Relaxants for Acute Muscle Spasm in Adults
For acute muscle spasm in adults, cyclobenzaprine 5 mg three times daily for 7-14 days is the first-line skeletal muscle relaxant, with proven efficacy and a favorable safety profile when used short-term. 1, 2, 3
Standard Adult Dosing
Cyclobenzaprine (First-Line Agent)
- Starting dose: 5 mg three times daily 1, 2, 3
- Alternative dose: 10 mg three times daily if 5 mg is insufficient, though this increases sedation risk 2, 3
- Duration: 7-14 days maximum for acute conditions 1, 3
- Mechanism: Acts centrally at the brainstem level, not directly on skeletal muscle; reduces tonic somatic motor activity 2
- Efficacy: Significantly superior to placebo for muscle spasm, local pain, tenderness, and range of motion; onset of relief within 3-4 doses 3, 4
Tizanidine (Alternative Option)
- Starting dose: 2-4 mg three times daily 5
- Evidence: Demonstrated efficacy in 8 trials for acute low back pain 5
- Combination benefit: Adding tizanidine to NSAIDs or acetaminophen provides greater short-term pain relief than monotherapy 1, 5
- Monitoring required: Hepatotoxicity (generally reversible), hypotension, and sedation 5
Methocarbamol and Metaxalone
- Methocarbamol: Less sedating but limited effectiveness evidence; no specific dose adjustment guidelines provided 6
- Metaxalone: Less sedating but limited effectiveness evidence 6
- Key limitation: Neither has robust comparative efficacy data 6, 7
Elderly Patients (≥65 Years)
Avoid cyclobenzaprine entirely in elderly patients due to anticholinergic effects and fall risk; if a muscle relaxant is absolutely necessary, use baclofen starting at 5 mg three times daily. 8, 1
Baclofen (Preferred for Elderly)
- Starting dose: 5 mg three times daily 8, 1
- Titration: Increase weekly by small increments 8
- Maximum tolerated dose: 30-40 mg per day (elderly rarely tolerate higher doses) 8
- Critical warning: Never discontinue abruptly—requires slow tapering to avoid withdrawal symptoms including delirium, seizures, and CNS irritability 8, 1
Tizanidine (Alternative for Elderly)
- Starting dose: 2 mg three times daily 8
- Monitoring: Orthostatic hypotension, sedation, and drug-drug interactions 8
- Caution: Use with extreme caution in renal impairment 5
Agents to Avoid in Elderly
- Cyclobenzaprine: Structurally similar to tricyclic antidepressants with comparable adverse effects; listed in Beers Criteria as potentially inappropriate 8, 1
- Carisoprodol: Controlled substance with abuse potential; removed from European market 8
- Orphenadrine: Strong anticholinergic properties causing confusion, urinary retention, cardiovascular instability 8
Hepatic Impairment
In mild hepatic impairment, start cyclobenzaprine at 5 mg and titrate slowly; avoid cyclobenzaprine entirely in moderate-to-severe hepatic impairment. 2
- Pharmacokinetic data: AUC and Cmax approximately double in hepatic impairment compared to healthy controls 2
- Metaxalone: Contraindicated in significant hepatic dysfunction 8
- Methocarbamol: Elimination significantly impaired in liver disease 8
- Baclofen or tizanidine: Use with caution at lowest effective dose 1
Renal Impairment
Avoid methocarbamol and metaxalone in renal impairment; use baclofen or tizanidine with extreme caution at reduced doses. 8, 1
- Tizanidine: Use with extreme caution; requires dose adjustment though exact strategy not specified 5
- Baclofen: Use with caution at lowest effective dose 1
- Metaxalone: Contraindicated in significant renal dysfunction 8
- Methocarbamol: Elimination significantly impaired in kidney disease 8
Safety Considerations and Adverse Effects
Common Adverse Effects (All Agents)
- CNS effects: Sedation, drowsiness, dizziness (2-fold increase compared to placebo) 1, 5, 6
- Cyclobenzaprine-specific: Dry mouth (most frequent), anticholinergic effects 2, 3
- Tizanidine-specific: Dry mouth, hypotension, hepatotoxicity 5, 7
- Overall adverse event rate: 50% higher total adverse events with muscle relaxants versus placebo 1
Critical Pitfalls to Avoid
- Never use for chronic pain: No evidence of benefit beyond 2-3 weeks 1
- Fall risk: All muscle relaxants increase fall risk, particularly in elderly and frail patients 8, 1
- Abrupt discontinuation of baclofen: Risk of withdrawal syndrome with delirium and seizures 8, 1
- Combination with other CNS depressants: Increases sedation and fall risk 8
- Hepatotoxicity: Dantrolene and chlorzoxazone associated with rare serious hepatotoxicity 7
Drug Interactions
- Cyclobenzaprine metabolism: Mediated by CYP3A4, 1A2, and 2D6 2
- Combination with NSAIDs: Well tolerated but increases drowsiness 2
- No significant interaction: With aspirin, naproxen, or diflunisal regarding plasma levels 2
Pharmacokinetic Considerations
Cyclobenzaprine
- Bioavailability: 33-55% 2
- Half-life: 18 hours (range 8-37 hours) 2
- Steady state: Reached in 3-4 days with plasma concentrations 4-fold higher than single dose 2
- Metabolism: Extensive hepatic metabolism; excreted as glucuronides via kidney 2
- Protein binding: Highly bound to plasma proteins 2
Elderly-Specific Pharmacokinetics
- Cyclobenzaprine AUC: 1.7-fold higher in elderly (≥65 years) versus younger adults 2
- Elderly males: 2.4-fold increase in AUC 2
- Elderly females: 1.2-fold increase in AUC 2
Non-Pharmacological Alternatives
Consider non-pharmacological approaches first, particularly in elderly patients, before initiating muscle relaxant therapy. 8, 1
- Physical therapy and rest 1
- Topical analgesics: May provide relief with fewer systemic side effects in elderly 8, 1
- Scheduled acetaminophen: Effective for mild-to-moderate musculoskeletal pain in elderly 8
Combination Therapy
Adding cyclobenzaprine or tizanidine to NSAIDs or acetaminophen provides greater short-term pain relief than analgesic monotherapy, though this increases CNS adverse events. 1, 5