Alcohol Withdrawal

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Pharmacologic Treatment of Alcohol Use Disorder – Teaching Points

Overall Principles

  • Medications for alcohol use disorder provide modest benefit, especially during the first 6–12 months of recovery.

  • They are most effective when combined with psychosocial support (eg, counseling, behavioral therapy).

Naltrexone

  • Mechanism: Opioid receptor antagonist that blocks μ-opioid receptors, reducing activation of the dopamine-mediated mesolimbic reward pathway.

  • Clinical effect:

    • Decreases craving

    • Reduces pleasure from alcohol

    • May shorten relapse duration if drinking occurs

  • Forms:

    • Oral: 50–150 mg/day

    • Long-acting injectable: 380 mg IM once monthly

  • Key use: Helpful in patients who can maintain opioid abstinence.

  • Contraindication: Current opioid use (can precipitate withdrawal).

Acamprosate (Campral)

  • Dose: 2 g/day divided into 3 oral doses

  • Mechanism:

    • Inhibits NMDA (glutamate) receptors

    • Helps stabilize excitatory–inhibitory balance during abstinence

  • Clinical effect:

    • Reduces protracted withdrawal symptoms (eg, anxiety, insomnia, dysphoria)

    • Supports maintenance of abstinence

  • Key advantage:

    • No hepatic metabolism → safer in liver disease

  • Limitation:

    • Requires three-times-daily dosing, which may affect adherence

Combination Therapy

  • Naltrexone + acamprosate:

    • Generally well tolerated

    • Some studies suggest greater efficacy than either alone

    • Evidence is mixed; benefit not universal

Disulfiram

  • Dose: 250 mg/day

  • Mechanism:

    • Inhibits aldehyde dehydrogenase

    • Causes acetaldehyde accumulation when alcohol is consumed

  • Alcohol–disulfiram reaction:

    • Vomiting

    • Flushing

    • Autonomic instability

    • Can be life-threatening

  • High-risk populations:

    • Heart disease

    • Stroke

    • Diabetes mellitus

    • Hypertension

  • Adverse effects of disulfiram itself:

    • Depressive or psychotic symptoms

    • Peripheral neuropathy

    • Hepatotoxicity

  • Best use:

    • In highly motivated patients

    • Under supervision (eg, family member, clinic)

    • Particularly during high-risk drinking situations

High-Yield Clinical Pearl

  • Naltrexone and acamprosate reduce craving and relapse risk; disulfiram works by deterrence but carries higher risk and requires supervision.




DV - not good for liver faster, long acting has metabolites conversion is 5:1
AL - moderate, preferred
MV

When Diazepam is Often Preferred

  • Severe withdrawal (very high CIWA scores)

  • History of withdrawal seizures or delirium tremens

  • Need for long-acting effect to smooth symptoms overnight

  • Younger patients with normal liver function

Why: Diazepam has long active metabolites that provide a “built-in taper.”

Chlordiazepoxide (Librium) — also long acting, often used inpatient, but not ideal if significant liver disease.



 Practical Guidance in CIWA-Driven Protocol

  1. Assess CIWA score every 1–2 hours initially.

  2. If CIWA ≥ 8–10 → give scheduled benzodiazepine per protocol.

  3. Common dosing (example — follow institution policy):

    • Lorazepam: 1–2 mg PO/IV/IM every 1–2 hrs as needed

    • Diazepam: 5–10 mg PO/IV/IM every 1–2 hrs as needed

  4. Reassess after each dose — do not oversedate.

  5. When scores stabilize, extend intervals and taper dose

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