Diazepam is the Preferred Benzodiazepine for Muscle Spasms
Diazepam is the only benzodiazepine with FDA approval specifically for skeletal muscle spasm and has demonstrated superiority over other benzodiazepines in head-to-head trials, though non-benzodiazepine muscle relaxants should be considered first-line due to lower abuse potential. 1
FDA-Approved Indication
Diazepam carries explicit FDA approval as "a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma), spasticity caused by upper motor neuron disorders (such as cerebral palsy and paraplegia), athetosis, and stiff-man syndrome." 1
No other benzodiazepine has this specific FDA indication for muscle spasm, making diazepam the only evidence-based choice within this drug class. 1
Comparative Efficacy Evidence
In direct comparison trials for acute musculoskeletal conditions, carisoprodol demonstrated superiority over diazepam (70% vs. 45% rated "excellent" or "very good"), though carisoprodol itself is inferior to non-benzodiazepine alternatives like cyclobenzaprine. 2
For chronic pain with muscle spasm, tetrazepam (not available in the US) showed benefit in pooled trial results, though this agent metabolizes to diazepam and nordazepam, suggesting diazepam's active role in muscle relaxation. 3, 4
One higher-quality trial found no difference between diazepam and placebo for acute low back pain, while another found diazepam superior for short-term pain relief, indicating inconsistent but present efficacy. 3
Practical Dosing Recommendations
Start with diazepam 2-5 mg two to three times daily, titrating based on response while monitoring closely for sedation, cognitive impairment, and paradoxical agitation (occurs in approximately 10% of patients). 5
Guidelines recommend infrequent, low doses of agents with short half-life are least problematic when benzodiazepines are used for muscle spasm specifically. 5
Limit treatment duration to short-term use only (days to 2-3 weeks maximum), as the effectiveness of diazepam in long-term use beyond 4 months has not been assessed by systematic clinical studies. 1
Critical Safety Considerations
Benzodiazepines carry substantial risks including tolerance, addiction, depression, cognitive impairment, and 50% higher total adverse events compared to placebo, with double the CNS adverse events. 5, 6
The high-risk profile in older adults usually obviates any potential benefit, though benzodiazepines may be justified when anxiety, muscle spasm, and pain coexist. 3, 6
For elderly patients, avoid diazepam entirely and use baclofen instead (starting at 5 mg three times daily, maximum 30-40 mg per day) due to fall risk and anticholinergic effects. 6, 5
Do not combine diazepam with other CNS depressants including alcohol without explicit patient counseling about additive sedation and respiratory depression risks. 5
When Benzodiazepines Are Appropriate
Benzodiazepines may help reduce catecholamine release during opioid withdrawal and help alleviate muscle cramps as well as anxiety in this specific context. 3
Consider benzodiazepines for acute muscle spasm when anxiety, muscle spasm, and pain coexist, particularly in younger patients without substance abuse history. 3, 6
Benzodiazepines are similarly effective to skeletal muscle relaxants for short-term pain relief but carry higher risks for abuse, addiction, and tolerance. 3
Preferred Alternative Strategy
Non-benzodiazepine muscle relaxants (cyclobenzaprine, methocarbamol, metaxalone) should be considered first-line over diazepam for acute musculoskeletal conditions, as they have similar efficacy without controlled substance classification. 2
Cyclobenzaprine 5 mg three times daily for 7-14 days is the preferred first-line agent for acute muscle spasm with moderate superiority over placebo. 6
For patients requiring long-term management, switch to baclofen (GABA-B agonist) starting at 5 mg three times daily with gradual weekly titration, as it provides sustained muscle relaxation without dependence risk. 5
Abrupt discontinuation of baclofen must be avoided due to risk of withdrawal symptoms including CNS irritability; slow tapering is required after prolonged use. 6
Common Pitfalls to Avoid
Never prescribe benzodiazepines for chronic muscle spasm, as there is no evidence of benefit beyond 2-3 weeks and risks accumulate with prolonged use. 6
Avoid prescribing anticholinergics like benztropine concurrently, as these add unnecessary side effect burden. 5
Do not use benzodiazepines in elderly patients with renal or hepatic impairment; choose baclofen or tizanidine with caution at lowest effective doses instead. 6
Concurrent use with opioids increases adjusted odds of high-dose benzodiazepine prescribing by 67% and substantially increases overdose death risk. 7