Why are patients prescribed diazepam?

Why Patients Are Prescribed Diazepam

Diazepam is prescribed primarily for anxiety disorders, acute alcohol withdrawal, skeletal muscle spasm, and as an adjunct in seizure disorders, with FDA approval for these specific indications. 1

FDA-Approved Indications

Diazepam has four main FDA-approved uses 1:

• Anxiety disorders – Management of anxiety disorders or short-term relief of anxiety symptoms (not for everyday stress) 1
• Acute alcohol withdrawal – Symptomatic relief of acute agitation, tremor, impending or acute delirium tremens, and hallucinosis 1
• Skeletal muscle spasm – Relief of reflex spasm from local pathology (inflammation, trauma), spasticity from upper motor neuron disorders (cerebral palsy, paraplegia), athetosis, and stiff-man syndrome 1
• Seizure disorders – Adjunctive treatment in convulsive disorders, though not as sole therapy 1

Clinical Context and Mechanism

Diazepam works by enhancing GABA-A receptor activity, acting as a full agonist with non-selective affinity for α1, α2, α3, and α5 subunits 2. This produces anxiolysis, sedation, muscle relaxation, and anticonvulsant effects 2.

Alcohol Withdrawal Management

For alcohol withdrawal syndrome, long-acting benzodiazepines like diazepam are specifically recommended to prevent seizures and manage autonomic hyperactivity. 3

• Diazepam has the shortest time to peak effect among benzodiazepines used for alcohol withdrawal, facilitating rapid symptom control and accurate titration 4
• Its long elimination half-life (20-120 hours) with active metabolites creates a self-tapering effect, resulting in smoother withdrawal with fewer breakthrough symptoms 2, 4
• The Korean Association for the Study of the Liver recommends benzodiazepines as first-line treatment for alcohol withdrawal syndrome 3
• Typical dosing: 5-10 mg PO/IV/IM every 6-8 hours 3

Anxiety Disorders

• Diazepam is recommended for acute stress reactions, episodic anxiety, fluctuations in generalized anxiety, and initial treatment of severe panic 5
• Should be given in single doses, very short (1-7 days) or short (2-4 weeks) courses, rarely for longer-term treatment 5
• The FDA notes that effectiveness beyond 4 months has not been systematically assessed 1

Seizure Management

• Diazepam is used as adjunctive therapy in convulsive disorders and is a drug of first choice for status epilepticus 1, 6
• Benzodiazepines provide rapid onset of action, high efficacy, and minimal toxicity in acute seizure management 6
• Clinical response to benzodiazepines is lost with prolonged status epilepticus, making early administration crucial 7

Muscle Spasm

• Indicated for skeletal muscle spasm due to reflex spasm from local pathology (inflammation, trauma) or spasticity from upper motor neuron disorders 1

Pharmacokinetic Profile

Diazepam's unique pharmacokinetics explain many of its clinical applications 2:

• Long half-life: 20-120 hours with active metabolites 2
• High lipid solubility: Results in quicker onset of sedation and larger volume of distribution 2
• Active metabolite: Desmethyldiazepam has a half-life of 50-95 hours, extending clinical effects 2
• Variable IM absorption: Should not be used intramuscularly when rapid control is needed 4

Critical Safety Warnings

Respiratory Depression

• Diazepam causes dose-dependent respiratory depression, with markedly increased risk when combined with opioids or alcohol 2
• Common respiratory effects include coughing, respiratory depression, and dyspnea 2

Special Populations

• Elderly patients: Reduce doses by 20% or more in patients over 60 due to decreased clearance and accumulation of active metabolites 2
• Hepatic/renal dysfunction: Prolonged sedation is more likely, especially with active metabolite accumulation 2
• Obstructive sleep apnea: Should be avoided due to respiratory depression risk 2

Contraindications

• Severe pulmonary insufficiency, severe liver disease, and myasthenia gravis (except in imminently dying patients) 2

Long-Term Use Risks

• Physical and psychological dependence develops with chronic use 2
• Withdrawal symptoms upon cessation include seizures, hallucinations, and suicidal thoughts 2
• Tolerance develops as GABA-A receptors undergo adaptive changes 2
• Cognitive impairment, falls, and confusion are common, particularly in elderly patients 2

Clinical Pitfalls to Avoid

• Do not use IM route when rapid symptom control is required—absorption is variable and unreliable 4
• Avoid in sleep apnea as it can worsen or precipitate obstructive episodes 2
• Monitor for propylene glycol toxicity with parenteral formulations (though this applies more to lorazepam) 8, 9
• Reassess periodically as the FDA notes effectiveness beyond 4 months is not established 1