Does gabapentin (Neurontin) increase or decrease appetite?

Gabapentin and Its Effects on Appetite and Weight

Gabapentin typically causes increased appetite and weight gain in patients, with weight increases commonly occurring within 2-3 months of treatment initiation and stabilizing after 6-9 months of therapy. 1

Evidence for Weight Gain with Gabapentin

Gabapentin has been documented to cause significant weight gain in patients taking it for seizure disorders. In a study of 44 patients on chronic, high-dose gabapentin therapy:

• 10 patients (23%) gained more than 10% of their baseline weight
• 15 patients (34%) gained 5-10% of their baseline weight
• 16 patients (36%) had no significant change in weight
• Only 3 patients (7%) lost weight (5-10% of baseline) 1

This pattern of weight gain typically begins between the second and third months of treatment and tends to stabilize after 6-9 months, even when the medication dose remains unchanged.

Mechanism of Action

The exact mechanism by which gabapentin causes weight gain is not fully understood, but several theories exist:

• Enhanced GABA-mediated neurotransmission may increase appetite, particularly for carbohydrates, and reduce energy expenditure 2
• Lowered blood glucose levels may stimulate eating through effects on the hypothalamus 2
• Competition between drug binding and long-chain fatty acids may affect insulin production and glucose metabolism 2

Comparison with Other Anticonvulsants

Gabapentin belongs to a group of anticonvulsants associated with increased appetite and weight gain. When comparing different anticonvulsant medications:

• Medications associated with weight gain: Valproic acid (most significant), pregabalin, perampanel, and gabapentin 3
• Medications with minimal impact on weight: Oxcarbazepine, eslicarbazepine, lamotrigine, levetiracetam, lacosamide, carbamazepine, vigabatrin, and clobazam 3
• Medications associated with weight loss: Fenfluramine, topiramate, zonisamide, felbamate, rufinamide, stiripentol, cannabidiol, brivaracetam, and ethosuximide 3

Clinical Implications

Monitoring Recommendations

• Monitor weight regularly during gabapentin therapy, especially during the first 6 months
• Be particularly vigilant in patients with pre-existing obesity, diabetes, or cardiovascular disease
• Weight gain of >2 kg in a month or ≥7% increase from baseline warrants attention 4

Management Strategies

For patients experiencing significant weight gain on gabapentin:

1. Dietary counseling: Provide nutritional advice and recommend regular physical exercise 5
2. Medication adjustment: Consider dose adjustment if clinically appropriate
3. Alternative medications: If weight gain is problematic, consider switching to an anticonvulsant with neutral weight effects (like lamotrigine or levetiracetam) if clinically appropriate for the patient's condition

Special Considerations

Weight gain with gabapentin occurs regardless of concurrent medications. The study by DeToledo et al. showed that weight gain occurred in patients taking gabapentin:

• As monotherapy
• In combination with other antiepileptic drugs 1

Conclusion

When prescribing gabapentin, clinicians should inform patients about the potential for increased appetite and weight gain. Regular monitoring of weight is recommended, particularly during the first 6-9 months of therapy when most weight changes occur.