What are the common GABAergic (Gamma-Aminobutyric Acid) drug formulations, such as benzodiazepines (e.g. Xanax (alprazolam)) and non-benzodiazepines (e.g. Neurontin (gabapentin)), used for various medical conditions?

Common GABAergic Drug Formulations and Their Medical Uses

GABAergic medications are widely used for various conditions including anxiety, insomnia, seizures, neuropathic pain, and alcohol withdrawal, with benzodiazepines and gabapentinoids being the most common formulations.

Benzodiazepines

Benzodiazepines work by enhancing the effect of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system.

Common Benzodiazepine Formulations:

• Alprazolam (Xanax)

  • Formulations: 0.25mg, 0.5mg, 1mg, 2mg tablets; extended-release tablets
  • Indications: Anxiety disorders, panic disorder with or without agoraphobia 1, 2
  • Dosing: Starting dose 0.25-0.5mg three times daily; maximum 4mg/day (higher doses may be needed for panic disorder) 1
  • Cautions: Risk of dependence, withdrawal reactions including seizures, especially with doses >4mg/day and treatment >12 weeks 1

• Lorazepam (Ativan)

  • Formulations: 0.5mg, 1mg, 2mg tablets; injectable solution
  • Indications: Anxiety, insomnia, status epilepticus, alcohol withdrawal, agitation in delirium 3
  • Dosing: 1mg SC/IV for acute management; 0.5-2mg orally for scheduled dosing 3
  • Special considerations: Can be given PO, SL, SC, or IV; preferred in patients with hepatic impairment 3

• Diazepam (Valium)

  • Formulations: 2mg, 5mg, 10mg tablets; injectable solution
  • Indications: Anxiety, alcohol withdrawal, muscle spasms, seizures 3, 4
  • Dosing: 5-10mg PO/IV/IM every 6-8 hours for alcohol withdrawal 3

• Clonazepam (Klonopin)

  • Formulations: 0.5mg, 1mg, 2mg tablets
  • Indications: Seizure disorders, panic disorder, neuropathic pain 3

• Temazepam (Restoril)

  • Formulations: 7.5mg, 15mg, 30mg capsules
  • Indications: Short-term treatment of insomnia 3
  • Dosing: 15-30mg at bedtime; 7.5mg in elderly or debilitated patients 3

Non-Benzodiazepine Benzodiazepine Receptor Agonists:

• Zolpidem (Ambien)

  • Formulations: 5mg, 10mg tablets; controlled-release 6.25mg, 12.5mg tablets
  • Indications: Sleep-onset insomnia 3
  • Dosing: 10mg at bedtime; 5mg in elderly or hepatic impairment 3

• Eszopiclone (Lunesta)

  • Formulations: 1mg, 2mg, 3mg tablets
  • Indications: Sleep-onset and maintenance insomnia 3
  • Dosing: 2-3mg at bedtime; 1mg in elderly or debilitated patients 3

• Zaleplon (Sonata)

  • Formulations: 5mg, 10mg capsules
  • Indications: Sleep-onset insomnia 3
  • Dosing: 10mg at bedtime; 5mg in elderly or hepatic impairment 3

Gabapentinoids

These drugs bind to the α2-δ subunit of voltage-gated calcium channels, inhibiting the release of excitatory neurotransmitters.

• Gabapentin (Neurontin)

  • Formulations: 100mg, 300mg, 400mg, 600mg, 800mg tablets/capsules; oral solution
  • Indications: Postherpetic neuralgia, adjunctive therapy for partial seizures 5, 3
  • Dosing: Starting dose 100-300mg at bedtime, increasing to 900-3600mg/day in divided doses 3
  • Special considerations: Requires dose adjustment in renal impairment 3

• Pregabalin (Lyrica)

  • Formulations: 25mg, 50mg, 75mg, 100mg, 150mg, 200mg, 225mg, 300mg capsules
  • Indications: Neuropathic pain, fibromyalgia, adjunctive therapy for partial seizures 3
  • Dosing: Starting dose 50mg three times daily, increasing to 100mg three times daily 3
  • Advantages: More efficiently absorbed than gabapentin, allowing for more predictable dosing 3

Other GABAergic Medications

• Baclofen

  • Formulations: 10mg, 20mg tablets; intrathecal solution
  • Mechanism: GABAB receptor agonist
  • Indications: Spasticity, trigeminal neuralgia, alcohol use disorder 3
  • Dosing: 5mg three times daily initially, titrated up as needed 3

• Sodium Oxybate (GHB)

  • Formulations: Oral solution
  • Indications: Narcolepsy, alcohol withdrawal 3
  • Special considerations: Controlled substance with abuse potential 3

• Tiagabine (Gabitril)

  • Formulations: 2mg, 4mg, 12mg, 16mg tablets
  • Mechanism: GABA reuptake inhibitor
  • Indications: Adjunctive treatment for partial seizures 3

• Valproate/Divalproex Sodium (Depakote)

  • Formulations: 125mg, 250mg, 500mg tablets/capsules; extended-release tablets; oral solution
  • Indications: Seizures, bipolar disorder, migraine prophylaxis, agitation 3
  • Dosing: Initial 125mg twice daily, titrate to therapeutic blood level (40-90 mcg/mL) 3
  • Monitoring: Liver enzyme levels, platelets, coagulation studies 3

Clinical Considerations

• For anxiety disorders: Benzodiazepines provide rapid relief but carry risks of dependence and cognitive impairment. Short-term use is recommended 4, 6

• For insomnia: Non-benzodiazepine receptor agonists or intermediate-acting benzodiazepines are preferred for short-term use 3

• For neuropathic pain: Gabapentinoids are first-line options, often requiring gradual titration to effective doses 3

• For alcohol withdrawal: Benzodiazepines are the treatment of choice, with lorazepam preferred in patients with liver disease 3

• For elderly patients: Lower starting doses are recommended for all GABAergic medications due to increased sensitivity and risk of adverse effects 3

• Common adverse effects: Sedation, dizziness, cognitive impairment, and risk of falls with most GABAergic medications 3

• Withdrawal considerations: Abrupt discontinuation of benzodiazepines can lead to withdrawal symptoms including rebound anxiety, insomnia, and seizures; tapering is essential 1

GABAergic medications should be prescribed at the lowest effective dose for the shortest duration necessary to minimize adverse effects and dependence potential 4.