Baclofen exerts its therapeutic effects through its action on the gamma-aminobutyric acid (GABA) system in the central nervous system. Its key mechanisms include:

1. GABA-B Receptor Agonism:
   • Baclofen is a selective agonist at GABA-B receptors, which are located presynaptically and postsynaptically in the spinal cord and brain.
   • Activation of GABA-B receptors inhibits the release of excitatory neurotransmitters such as glutamate and aspartate, reducing neuronal excitability.
2. Inhibition of Monosynaptic and Polysynaptic Reflexes:
   • Baclofen suppresses the transmission of nerve signals in the spinal cord, reducing muscle spasticity and rigidity.
3. Muscle Relaxation:
   • By modulating GABAergic activity, baclofen reduces muscle tone and spasticity, improving mobility and reducing pain.

Baclofen is approved for specific clinical conditions, including:

1. Muscle Spasticity:
   • Treatment of muscle spasticity associated with multiple sclerosis, spinal cord injuries, and cerebral palsy.
2. Off-Label Uses:
   • Chronic pain management (e.g., neuropathic pain, trigeminal neuralgia).
   • Intractable hiccups.
   • Alcohol withdrawal syndrome.
   • Management of spasticity in stroke patients.

The dosage of baclofen varies depending on the indication, patient age, and clinical response. The following dosing guidelines are based on the British National Formulary (BNF) and clinical pharmacology references:

1. Oral Baclofen:
   • Adults: Start with 5 mg three times daily, increasing by 5 mg every 3 days to a maintenance dose of 30–75 mg daily in divided doses. The maximum dose is 100 mg daily.
   • Children (3–12 years): Start with 0.3 mg/kg/day in divided doses, increasing gradually to a maintenance dose of 0.75–2 mg/kg/day.
2. Intrathecal Baclofen:
   • Adults and Children: Administered via an implanted pump, starting with a test dose of 50–100 mcg. The maintenance dose is adjusted based on response, typically ranging from 100–800 mcg/day.

Important Considerations:

• Baclofen is available in oral tablets and intrathecal formulations.
• Dose adjustments may be necessary for patients with renal impairment.
• Baclofen should be tapered gradually to avoid withdrawal symptoms.

Baclofen is associated with a range of side effects, some of which can be serious. Common side effects include:

1. Central Nervous System:
   • Drowsiness, dizziness, and fatigue.
   • Confusion and headache.
2. Gastrointestinal:
   • Nausea, vomiting, and constipation.
3. Other:
   • Muscle weakness and hypotension.

Serious Side Effects:

• Respiratory Depression: Particularly with intrathecal use or in patients with pre-existing respiratory conditions.
• Withdrawal Symptoms: Abrupt discontinuation can lead to symptoms such as hallucinations, seizures, and rebound spasticity.
• Psychiatric Symptoms: Depression, hallucinations, and psychosis (rare).

Baclofen requires careful monitoring and adherence to specific precautions to ensure patient safety:

1. Withdrawal Symptoms:
   • Baclofen should be tapered gradually to avoid withdrawal symptoms, particularly in patients on long-term therapy.
2. Pregnancy and Lactation:
   • Baclofen should be used during pregnancy only if the potential benefits outweigh the risks. It is excreted in breast milk, so breastfeeding is generally not recommended.
3. Elderly Patients:
   • Lower doses may be required due to increased sensitivity to side effects, particularly sedation and cognitive impairment.
4. Renal Impairment:
   • Dose adjustments are necessary for patients with impaired kidney function. The dose should be reduced in patients with a creatinine clearance (CrCl) of less than 60 mL/min.
5. Psychiatric Conditions:
   • Use with caution in patients with a history of psychiatric disorders, as baclofen may exacerbate symptoms.

Baclofen has a moderate potential for drug interactions due to its effects on the central nervous system. Key interactions include:

1. Central Nervous System Depressants:
   • Alcohol, opioids, and benzodiazepines can enhance sedation and respiratory depression.
2. Antihypertensives:
   • Baclofen may enhance the hypotensive effects of antihypertensive medications.
3. Other Interactions:
   • Levodopa: Baclofen may reduce its efficacy.
   • Tricyclic Antidepressants: Increased risk of sedation and anticholinergic effects.

Baclofen is the generic name for this medication. It is marketed under various brand names, depending on the country and manufacturer. Some examples include:

• Lioresal (a well-known brand in the United States and other regions).
• Baclofen Accord.
• Baclofen Mylan.
• Baclofen Intrathecal (for intrathecal use).