Gabapentin and Olfactory Changes: Clinical Management
Direct Recommendation
Gabapentin does not cause olfactory dysfunction and is not an effective treatment for smell disturbances. If a patient on gabapentin reports changes in smell, investigate alternative etiologies rather than attributing symptoms to the medication 1, 2.
Evidence Analysis
Gabapentin's Lack of Association with Olfactory Dysfunction
Gabapentin is not listed among medications that cause olfactory disturbances. The primary drug classes associated with smell changes include anticholinergics, corticosteroids, and dopaminergic agents—gabapentin does not appear in this category 3.
Common adverse effects of gabapentin are well-characterized and do not include olfactory changes. The established side effect profile consists of somnolence (reported by 80% at 2400 mg/day), dizziness, peripheral edema, weight gain, and neuropsychological reactions 4, 5, 6.
In a rigorous randomized controlled trial specifically examining gabapentin for post-COVID-19 olfactory dysfunction, gabapentin showed no efficacy. Among 68 participants, only 44% in the gabapentin group versus 46% in placebo group reported improvement, demonstrating no clinically meaningful benefit (percent difference 1.7%; 95% CI, -31.6% to 28.2%) 1.
Alternative Etiologies to Investigate
When a patient on gabapentin reports olfactory changes, systematically evaluate:
Neurological causes requiring urgent exclusion:
- Temporal lobe seizures or brain tumors (meningiomas, esthesioneuroblastomas affecting temporal/frontal lobes) must be ruled out first, as these represent life-threatening pathology 3.
- Neurodegenerative conditions including Parkinson's disease and Alzheimer's disease, both strongly associated with olfactory dysfunction 3.
- Head trauma history, particularly frontobasal trauma causing neural damage to olfactory pathways 3.
Post-infectious etiologies:
- COVID-19 and other viral upper respiratory infections can cause olfactory dysfunction in 59-86% of infected patients, presenting as an initial symptom in 11.9-22% of cases 3.
- Post-viral olfactory loss accounts for approximately 20-25% of cases presenting to specialist clinics 4.
Sinonasal pathology:
- Chronic rhinosinusitis with nasal polyposis causing conduction loss from obstruction 3.
- Inflammatory lesions including sarcoidosis and granulomatosis with polyangiitis affecting the cribriform plate 3.
Other medication causes:
- Review all concurrent medications for anticholinergics, corticosteroids, and dopaminergic agents that actually do cause olfactory disturbances 3.
Nutritional deficiencies:
- Vitamin B12, iron, and zinc deficiency can cause sensory disturbances including phantosmia, particularly relevant in patients with restrictive diets 3.
Clinical Workup Algorithm
Step 1: Neurological assessment
- Perform thorough neurological examination focusing on focal deficits, cranial nerve function, and mental status 3.
- Obtain neuroimaging (MRI brain with attention to temporal lobes) to exclude structural lesions before considering psychiatric causes 3.
Step 2: Sinonasal evaluation
- Conduct nasal endoscopy to rule out sinonasal pathology 3.
- Consider CT sinuses if chronic rhinosinusitis suspected 4.
Step 3: History refinement
- Document recent infections, particularly COVID-19 or upper respiratory infections 3.
- Complete medication review for all potentially causative agents beyond gabapentin 3.
- Assess for occupational exposures to volatile toxic chemicals 3.
Step 4: Laboratory evaluation
- Check vitamin B12, iron studies, and zinc levels 3.
Step 5: Quantitative olfactory testing
- Perform validated psychophysical testing (e.g., University of Pennsylvania Smell Identification Test) to objectively characterize the deficit 4, 2.
Critical Pitfalls to Avoid
Never discontinue gabapentin abruptly if the patient requires it for neuropathic pain or seizures, as this can precipitate withdrawal symptoms or seizure recurrence; taper gradually over at least 1 week 5.
Do not assume psychiatric origin without excluding organic causes first, particularly temporal lobe pathology 3.
Do not overlook that the underlying condition being treated with gabapentin (e.g., HIV-associated neuropathy, diabetic neuropathy) may have its own neurological complications that could affect olfaction 4.
Special Population Considerations
Elderly patients:
- Have increased vulnerability to gabapentin's sedative effects and may experience dizziness contributing to fall risk, but olfactory dysfunction is not an expected adverse effect 5.
- Require dose adjustment based on creatinine clearance, as gabapentin is renally eliminated 5.
Patients with renal impairment:
- Mandatory dose reduction required based on creatinine clearance to prevent drug accumulation and toxicity, though accumulated symptoms manifest as somnolence and confusion rather than olfactory changes 5.
Anecdotal Exception
One case report described resolution of idiopathic phantosmia with pregabalin (a GABA-analogue closely related to gabapentin), where a 47-year-old man with 3 years of daily smoke-like phantosmia experienced complete resolution during 4 weeks of pregabalin 50 mg three times daily, with no recurrence at 7 months follow-up 2. However, this represents a single uncontrolled case without proof of causality, and the large RCT with gabapentin for COVID-19 olfactory dysfunction showed no benefit 1. This does not support using gabapentin to treat olfactory dysfunction in routine practice, but suggests GABA-analogues warrant further study for idiopathic phantosmia specifically 2.