Are Gabapentin and Amitriptyline the Same Thing?
No, gabapentin and amitriptyline are completely different medications with distinct chemical structures, mechanisms of action, and drug classes—they are not the same thing.
Different Drug Classes and Mechanisms
Gabapentin is an anticonvulsant (also called an antiepileptic) that binds to the α2δ-1 subunit of voltage-gated calcium channels, reducing calcium influx and decreasing neurotransmitter release into hyperexcited neurons 1.
Amitriptyline is a tricyclic antidepressant (TCA) that works on both opioid and monoaminergic pathways, affecting serotonin and norepinephrine reuptake 2.
Overlapping Clinical Uses Despite Being Different Drugs
While these are entirely different medications, they are both used to treat similar conditions, particularly neuropathic pain:
Both are considered first-line options for neuropathic pain, though guidelines vary on which to use first 2.
For painful diabetic neuropathy, a 2011 consensus recommended either tricyclic antidepressants (like amitriptyline) OR α2δ agonists (gabapentin/pregabalin) as initial therapy, with the choice based on contraindications and comorbidities 2.
For HIV-associated neuropathic pain, gabapentin is specifically recommended as first-line oral pharmacological treatment 2, 1.
The 2022 CDC guideline lists both tricyclic antidepressants and anticonvulsants (gabapentin, pregabalin) as recommended treatments for neuropathic pain, particularly diabetic neuropathy and postherpetic neuralgia 2.
Comparative Effectiveness
A 2011 randomized trial comparing amitriptyline with pregabalin (gabapentin's close relative) in painful diabetic neuropathy found little difference in efficacy, but pregabalin was preferred due to a superior adverse event profile 2.
A 2024 study concluded that gabapentin was superior to both pregabalin and amitriptyline with fewer adverse effects, leading to improved patient adherence for long-term use 3.
A 2006 comparison study found both drugs provided effective pain control in peripheral neuropathic pain, but gabapentin was more effective specifically for paroxysmal shooting pain and was better tolerated 4.
Different Side Effect Profiles
Gabapentin's adverse effects:
- Somnolence, dizziness, mental clouding (particularly problematic in older adults) 1
- Peripheral edema and weight gain 5
- Confusion, dry mouth, fatigue, nausea 2
Amitriptyline's adverse effects:
- Anticholinergic effects (dry mouth, constipation, urinary retention) 2
- Orthostatic hypotension 2
- Cardiovascular effects (contraindicated in cardiovascular disease) 2
- Potentially inappropriate for older adults (≥65 years) due to anticholinergic effects 2
Important Contraindications Differ
Amitriptyline is contraindicated in:
Gabapentin requires caution in:
- Renal impairment (requires dose adjustment based on creatinine clearance) 1
- Patients prone to edema 2
Clinical Bottom Line
These are two entirely separate medications from different drug classes that happen to treat similar pain conditions. The choice between them should be based on the patient's specific comorbidities, contraindications, and side effect tolerance rather than any equivalence between the drugs 2. They can even be used together in combination therapy when monotherapy fails 2.