Is Meclizine (meclizine) contraindicated in Lambert-Eaton Myasthenic Syndrome (LEMS)?

Meclizine is Contraindicated in Lambert-Eaton Myasthenic Syndrome

Meclizine should be avoided in patients with Lambert-Eaton Myasthenic Syndrome (LEMS) due to its anticholinergic properties that can worsen neuromuscular transmission deficits and exacerbate muscle weakness.

Pathophysiology of LEMS and Medication Concerns

Lambert-Eaton Myasthenic Syndrome is an autoimmune paraneoplastic syndrome characterized by:

• Antibodies directed against voltage-gated calcium channels (VGCCs) at the presynaptic nerve terminal 1
• Decreased calcium influx into the presynaptic nerve terminal 1
• Reduced release of acetylcholine vesicles 1
• Resulting in decreased synaptic transmission at the neuromuscular junction 1

These pathophysiological changes manifest clinically as:

• Progressive proximal muscle weakness (predominantly at the hip girdle) 1
• Depressed or absent tendon reflexes
• Autonomic dysfunction

Why Meclizine is Contraindicated

Meclizine, as an anticholinergic agent, can:

1. Further reduce acetylcholine availability at the neuromuscular junction
2. Exacerbate the already compromised neuromuscular transmission in LEMS
3. Worsen muscle weakness and other symptoms

Recommended Management for LEMS

First-Line Symptomatic Treatment

• 3,4-Diaminopyridine (Amifampridine) is the first-line symptomatic treatment for LEMS 2, 3, 4
  • Mechanism: Blocks potassium channels in nerve terminals, increasing acetylcholine release
  • Dosage: Up to 80 mg daily, divided 3-4 times per day 2
  • Side effects: Generally mild, most commonly paresthesia 2

Additional Treatment Options

1. Immunomodulating therapy when symptomatic treatment is inadequate:

   • Intravenous immunoglobulin (IVIg) 1, 5
   • Plasma exchange

2. Immunosuppressive therapy for long-term management:

   • Combination of IVIg, methylprednisolone, and cyclophosphamide may provide transient stabilization 1

3. Anti-tumor treatment for paraneoplastic LEMS:

   • Treating the underlying malignancy (often small cell lung cancer) can improve LEMS symptoms 1
   • More than 90% of LEMS cases have antibodies against VGCC type P/Q 1

Medications to Avoid in LEMS

Several medication classes can worsen LEMS symptoms and should be avoided:

1. Anticholinergics (including meclizine)
2. Neuromuscular blocking agents
3. Calcium channel blockers
4. Magnesium sulfate
5. Aminoglycoside antibiotics
6. Botulinum toxin

Clinical Pearls

• LEMS is present in approximately 1-1.6% of patients with small cell lung cancer 1
• Diagnosis is based on clinical features, electromyography findings, and anti-VGCC antibodies 1
• Craniocaudal progression of proximal muscle weakness is characteristic 1
• Routine measurement of VGCC antibodies is not recommended in the absence of clinical features of LEMS 1
• Regular monitoring for disease progression and treatment response is essential

Conclusion

When managing patients with LEMS, it is critical to avoid medications that can worsen neuromuscular transmission, including anticholinergic agents like meclizine. Instead, focus treatment on agents that enhance acetylcholine release (such as 3,4-diaminopyridine) and address the underlying autoimmune process when necessary.