Does baclofen (GABA receptor agonist) lower blood pressure, specifically causing hypotension?

Does Baclofen Lower Blood Pressure?

Yes, baclofen can cause hypotension as an adverse effect, with reported incidence of 0-9% in patients taking this medication. 1

Mechanism and Effects

• Baclofen is a GABA-B receptor agonist that functions as a centrally acting muscle relaxant 2
• When injected into specific areas of the hypothalamus (particularly the ventromedial hypothalamus), baclofen produces dose-related decreases in sympathetic nerve activity, blood pressure, and heart rate 3
• The hypotensive effect appears to be mediated through peripheral sympathetic depression rather than parasympathetic activation 3
• At higher doses, however, baclofen can paradoxically increase blood pressure through central sympathetic stimulation 4

Clinical Significance

• The FDA drug label for baclofen lists hypotension as an adverse reaction occurring in 0-9% of patients 1
• Patients with kidney disease are at higher risk of baclofen toxicity, which can manifest as neurotoxicity and hemodynamic instability including hypotension 5
• Baclofen should be used with dose reduction in patients with moderate kidney impairment (eGFR 30-60 mL/min/1.73m²) and avoided in those with severe kidney impairment (eGFR <30 mL/min/1.73m²) 5

Comparison to Other Muscle Relaxants

• Tizanidine, another centrally acting muscle relaxant (α2-adrenergic receptor agonist), has more pronounced hypotensive effects than baclofen 2
• Tizanidine can cause significant hypotension and sedation, especially when combined with CYP1A2 inhibitors 2
• Unlike baclofen, tizanidine's hypotensive effects are well-documented and may even be beneficial in some perioperative settings 2

Clinical Management Considerations

• Patients taking baclofen should be monitored for hypotension, particularly when:

  • Starting therapy or increasing doses 1
  • They have pre-existing cardiovascular conditions 2
  • They have renal impairment 5
  • They are taking other medications that may lower blood pressure 2

• If hypotension occurs while on baclofen:

  • Consider dose reduction rather than immediate discontinuation 2
  • Monitor for other signs of hypoperfusion which would warrant more urgent intervention 2
  • Be aware that abrupt discontinuation of baclofen can lead to withdrawal symptoms including tachycardia, which may mask hypotension 2

Special Populations

• In patients with obstructive sleep apnea, baclofen may worsen upper airway collapse during sleep and affect central apneas or hypoventilation 2
• In patients with alcohol use disorder, baclofen has been used to maintain abstinence, but its cardiovascular effects should be monitored 2
• In hypertensive patients, the blood pressure-lowering effect of baclofen may be more pronounced in those with spontaneous hypertension compared to normotensive individuals 3

While baclofen is not classified as an antihypertensive medication, its GABA-ergic mechanism can influence blood pressure regulation, and clinicians should be aware of its potential to cause hypotension, especially in vulnerable populations.