Why Gabapentin Causes Sweating
Gabapentin causes sweating through withdrawal mechanisms when discontinued abruptly, rather than as a direct pharmacologic effect during regular use. 1
Mechanism: Withdrawal-Related Sweating
The FDA drug label explicitly identifies sweating as a withdrawal symptom following abrupt discontinuation of gabapentin, not as a side effect during active treatment 1. The mechanism involves:
- Neuroadaptation reversal: Gabapentin binds to α2δ subunits of voltage-gated calcium channels, inhibiting excitatory neurotransmitter release 2. When stopped suddenly, the nervous system experiences rebound hyperexcitability
- Autonomic dysregulation: Abrupt cessation triggers autonomic nervous system instability, manifesting as sweating, anxiety, insomnia, nausea, and pain 1
Clinical Context: Sweating as Adverse Effect vs. Withdrawal
During active gabapentin treatment, sweating is NOT listed among common adverse effects in controlled trials 1. The FDA label documents the following adverse events occurring in ≥1% of patients during treatment:
- Somnolence (19%), dizziness (17%), ataxia (13%), nystagmus (8%), tremor (7%) 1
- Peripheral edema (2%), weight increase (3%) 1
- Sweating is conspicuously absent from this list 1
In contrast, sweating appears specifically in the postmarketing section as a withdrawal symptom: "Adverse reactions following the abrupt discontinuation of gabapentin have also been reported. The most frequently reported reactions were anxiety, insomnia, nausea, pain, and sweating." 1
Comparison with Other Medications
This distinguishes gabapentin from medications where sweating is a direct pharmacologic effect:
- SSRIs/SNRIs: Sweating occurs as a common side effect during active treatment (not just withdrawal), affecting patients through serotonergic mechanisms 2
- Opioids: Sweating occurs during withdrawal due to sympathetic nervous system activation 2
- Gabapentin: Follows the opioid pattern—sweating emerges during discontinuation, not during therapeutic use 1
Clinical Implications
To prevent withdrawal-related sweating, taper gabapentin gradually rather than stopping abruptly 1. The withdrawal syndrome can be avoided through:
- Slow dose reduction over days to weeks
- Recognition that doses ≥600 mg/day carry higher risk of adverse effects generally 3
- Monitoring for the constellation of withdrawal symptoms (anxiety, insomnia, nausea, pain, sweating) 1
Rare Exception: Therapeutic Use for Sweating
Paradoxically, gabapentin has been used successfully to treat idiopathic sweating in advanced cancer patients at doses of 600-1,800 mg/day 4. This suggests gabapentin's calcium channel effects may actually reduce pathologic sweating when used therapeutically, further supporting that sweating is not a direct adverse effect of the drug itself 4.