What are the recommended first-line and second-line treatments for muscle spasms using Skeletal Muscle Relaxants (SMR)?

Skeletal Muscle Relaxants for Muscle Spasms: First-Line and Second-Line Treatment Recommendations

For acute muscle spasms associated with musculoskeletal conditions, cyclobenzaprine is the recommended first-line skeletal muscle relaxant, with acetaminophen or NSAIDs as the preferred initial pharmacologic approach before any muscle relaxant. 1

First-Line Treatment Strategy

Initial Pharmacologic Approach (Before Muscle Relaxants)

• Acetaminophen and NSAIDs are the recommended first-line agents for musculoskeletal pain and muscle spasm, with acetaminophen having fewer side effects than NSAIDs 1
• Acetaminophen dosing typically uses 4 g/day, though lower doses are recommended for patients with liver disease 1
• NSAIDs are equally effective as muscle relaxants for acute low back pain and have fewer adverse effects 2
• COX-2 NSAIDs carry decreased gastrointestinal risk but increased cardiovascular risk compared to traditional NSAIDs 1

First-Line Skeletal Muscle Relaxant

When a muscle relaxant is indicated, cyclobenzaprine is the preferred agent based on the most extensive clinical trial evidence and consistent efficacy data 1, 3

• Cyclobenzaprine has been evaluated in the most clinical trials and has consistently demonstrated effectiveness for acute muscle spasm 3
• Skeletal muscle relaxants are moderately superior to placebo for short-term (2-4 days) pain relief in acute low back pain, with relative risk of 0.80 for not achieving pain relief 1
• Cyclobenzaprine demonstrated superiority over diazepam in three studies for muscle spasm, local pain, tenderness, and limitation of motion 4
• Dosing: Cyclobenzaprine 5 mg three times daily is effective and better tolerated than 10 mg three times daily, with statistically significant superiority over placebo at day 3-4 and day 8 4
• Extended-release cyclobenzaprine 15-30 mg once daily is effective after 4 days of treatment and associated with less daytime drowsiness than immediate-release formulations 5

Duration of Therapy

• Limit skeletal muscle relaxant use to 2-3 weeks maximum for acute musculoskeletal conditions 2, 3
• All efficacy trials were 2 weeks or less in duration, with the exception of a single 3-week trial 1

Second-Line Treatment Options

Alternative Muscle Relaxants

When cyclobenzaprine is contraindicated or not tolerated:

• Methocarbamol or metaxalone are preferred alternatives over carisoprodol, as they have similar efficacy without controlled substance classification 2
• Tizanidine has fair evidence of efficacy for acute musculoskeletal conditions and may provide perioperative benefits 1, 2
• Metaxalone has the fewest reports of side effects and no reports of major safety issues 6

Combination Therapy

• Cyclobenzaprine combined with naproxen provides greater objective improvement in muscle spasm, tenderness, and range of motion compared to naproxen alone (P < 0.05) 7
• Combination therapy is associated with more side effects, primarily drowsiness, but faster resolution of functional deficits 7
• No well-controlled studies demonstrate that cyclobenzaprine enhances the clinical effect of aspirin or other analgesics in acute musculoskeletal conditions 4

Critical Safety Considerations and Agent Selection

Agents to Avoid

Carisoprodol should be avoided as it is a controlled substance with substantial abuse potential and the greatest toxicity among muscle relaxants 2, 6

• Carisoprodol is metabolized to meprobamate, a medication associated with risks for abuse and overdose 1
• The FDA classifies carisoprodol as a controlled substance due to escalating abuse and addiction potential 2
• Withdrawal symptoms can be severe, including insomnia, vomiting, tremors, muscle twitching, anxiety, ataxia, hallucinations, and delusions 2

Benzodiazepines

• Benzodiazepines (diazepam) are similarly effective to skeletal muscle relaxants for short-term pain relief but carry risks for abuse, addiction, and tolerance 1
• If a benzodiazepine is used, a time-limited course of therapy is recommended 1
• Pooled data from 20 trials found no difference between diazepam and cyclobenzaprine for short-term global improvement 1

Common Adverse Effects

• Central nervous system adverse effects, primarily sedation, are reported more frequently with skeletal muscle relaxants than placebo (RR 1.50) 1
• Cyclobenzaprine causes lethargy and anticholinergic side effects (dry mouth most common) and may have toxicity in overdose 6
• Approximately 50% of patients treated with muscle relaxants report adverse events 1
• Drowsiness decreases over time in all treatment groups 5

Special Populations

• For elderly patients requiring muscle relaxant therapy, baclofen is the preferred agent, starting at 5 mg three times daily with gradual titration 2
• Cyclobenzaprine should be used with caution in patients with mild hepatic impairment, starting with 5 mg and titrating slowly upward 4
• Use in moderate to severe hepatic impairment is not recommended due to lack of data 4

Chronic Muscle Spasm Considerations

For chronic low back pain, there is insufficient evidence to recommend skeletal muscle relaxants, as only one lower-quality trial of cyclobenzaprine has been conducted in this population 1

• Only sparse evidence exists for antispasticity drugs (dantrolene, baclofen) in low back pain 1
• Evidence for muscle relaxant efficacy in chronic pain is limited, with most trials involving acute rather than chronic pain 1
• Tricyclic antidepressants are an option for pain relief in patients with chronic low back pain 1

Clinical Algorithm

1. Start with acetaminophen or NSAIDs as first-line pharmacologic therapy 1
2. If inadequate response and muscle spasm is prominent, add cyclobenzaprine 5 mg three times daily 4, 3
3. Limit muscle relaxant duration to 2 weeks maximum 1, 2
4. If cyclobenzaprine is not tolerated, switch to methocarbamol or metaxalone (avoid carisoprodol) 2
5. Reassess after time-limited trial; if no response, consider alternative diagnoses or referral 1