What is Diaphoresis?
Diaphoresis is excessive sweating that results from sympathetic nervous system activation, commonly occurring as a withdrawal symptom when medications that suppress sympathetic tone—such as opioids, benzodiazepines, or pregabalin—are abruptly discontinued or rapidly tapered.
Physiological Mechanism
Diaphoresis represents a cardinal sign of sympathetic stimulation that emerges when the body's compensatory mechanisms are suddenly unmasked 1. When medications that antagonize sympathetic activity are removed, the unopposed sympathetic nervous system produces characteristic signs including:
- Profuse sweating (diaphoresis) as a direct manifestation of increased sympathetic outflow 1
- Associated autonomic symptoms including hypertension, tachycardia, tremor, and mydriasis (pupil dilation) 1
- Piloerection (goosebumps) occurring alongside the sweating 1
Diaphoresis in Pregabalin Withdrawal
When pregabalin is discontinued abruptly after prolonged or high-dose use, diaphoresis emerges as part of the withdrawal syndrome 2. The FDA label specifically identifies hyperhidrosis (the medical term for excessive sweating/diaphoresis) as a documented withdrawal symptom following rapid discontinuation 2.
Timing and Presentation
- Onset occurs within 2-3 half-lives after the last pregabalin dose 1, 3
- Given pregabalin's 6.3-hour half-life, withdrawal symptoms including diaphoresis typically begin 12-18 hours after discontinuation 4, 5
- Symptoms peak at 48-72 hours and generally resolve within 7-14 days 1
Complete Withdrawal Symptom Cluster
Diaphoresis rarely occurs in isolation during pregabalin withdrawal. The FDA mandates recognition of the full constellation 2:
- Insomnia (most common)
- Nausea
- Headache
- Anxiety
- Hyperhidrosis/diaphoresis
- Diarrhea
Clinical Recognition in Emergency Settings
Diaphoresis combined with altered mental status and agitation should trigger immediate blood glucose testing, as these signs can be confused with hypoglycemia, intoxication, or other withdrawal states 1. The Mayo Clinic guidelines emphasize that individuals exhibiting diaphoresis with confusion or combativeness require urgent evaluation to differentiate between:
- Hypoglycemia (in diabetic patients on insulin or sulfonylureas) 1
- Opioid withdrawal 1
- Benzodiazepine withdrawal 6, 7, 3
- Pregabalin/gabapentinoid withdrawal 2
- Alcohol withdrawal 7
Prevention Strategy
The FDA explicitly requires gradual tapering of pregabalin over a minimum of 1 week rather than abrupt discontinuation to minimize withdrawal symptoms including diaphoresis 2. This recommendation applies regardless of:
- Duration of therapy
- Total daily dose
- Indication for use (neuropathic pain, seizures, anxiety)
Critical Pitfall to Avoid
Never discontinue pregabalin abruptly in patients who have been on therapy for more than 5 days, as physiologic dependence develops rapidly 3. The risk of withdrawal-induced symptoms, including diaphoresis, increases with:
- Higher doses (particularly ≥300 mg daily) 2, 8
- Longer treatment duration 3
- Concurrent CNS depressants (opioids, benzodiazepines, alcohol) 2
Management When Diaphoresis Occurs
If a patient presents with diaphoresis and other withdrawal symptoms after pregabalin discontinuation:
- Reinitiate pregabalin at the previous effective dose to stabilize symptoms 2
- Implement a structured taper reducing by 10-25% every 1-2 weeks 6
- Monitor for seizure risk, particularly in patients with epilepsy, as abrupt discontinuation increases seizure frequency 2
- Provide supportive care for autonomic symptoms (hydration, temperature control, anxiolytics if severe) 1