Frequent Gabapentin Use Tied to Higher Risk of Dementia and Cognitive Decline

• Gabapentin acts through calcium channel modulation — Unlike GABA, gabapentin does not bind to GABA receptors or enhance GABA signaling. Instead, it attaches to the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system. This reduces the release of excitatory neurotransmitters like glutamate and norepinephrine, helping to calm overactive nerve signaling.⁸

• A major marketing push helped drive off-label prescribing for unapproved uses — As interest in gabapentin grew, the drug’s manufacturer, Pfizer, launched an aggressive campaign to promote it beyond its approved use. The strategy focused on encouraging physicians to prescribe gabapentin for a wide range of unapproved indications, including migraines, anxiety, bipolar disorder, and general chronic pain.

• Despite legal penalties, gabapentin became a staple of chronic pain management — This marketing push eventually led to a federal investigation, uncovering evidence that the company had illegally promoted the drug for off-label uses. The case resulted in a nearly billion-dollar fine (one of the largest at the time), but the practice had already succeeded in embedding gabapentin into mainstream pain management.

Despite limited evidence for many of these uses, long-term prescribing has become routine. Patients are often kept on gabapentin for years without formal reassessment, and dose adjustments are rarely made even when the benefits are unclear.

• Gabapentin misuse is on the rise — Although often described as non-addictive, gabapentin is frequently misused, particularly in individuals with a history of substance use. It’s often taken in high doses to induce euphoria or sedation, mimicking opioids or benzodiazepines. Up to 22% of people with opioid use disorder report misusing gabapentin.⁹

• Over 26,000 adults were tracked across matched groups — Researchers analyzed medical records from adults with chronic low back pain who had no prior history of gabapentin use, dementia, epilepsy, stroke, or cancer. They created two well-matched groups — those prescribed gabapentin and those who weren’t.

They were then matched by age, gender, other health conditions, and use of pain medications and grouped by how many prescriptions they received, from just three to a dozen or more. This design helped isolate gabapentin as the key variable, strengthening the reliability of the results.

• Gabapentin use was linked to higher rates of cognitive decline — Patients who received six or more prescriptions had a 29% higher risk of developing dementia and an 85% higher risk of mild cognitive impairment compared to those who never took gabapentin. These results suggest that frequent gabapentin use contributes to cognitive decline, even in low-risk individuals.

• Younger adults faced the greatest increase in risk — In patients aged 18 to 64, gabapentin users had more than double the risk of being diagnosed with dementia and mild cognitive impairment compared to matched controls. These findings raise concern about neurological effects in people far younger than the typical age for cognitive disorders.

• More prescriptions meant greater risk — Patients who received gabapentin three to five times did not show a statistically significant increase in cognitive diagnoses, but those with 12 or more prescriptions had a 40% higher risk of dementia and a 65% higher risk of mild cognitive impairment. This suggests that chronic use, rather than occasional prescribing, drives the changes observed.

• Study limitations temper interpretation, but the trend is strong — As a retrospective study, the findings show association rather than direct causation. Data on dose, treatment duration, and adherence were not included, and some cognitive symptoms may have emerged before formal diagnosis.

Still, the clear dose-response pattern and the strength of the associations, especially in younger adults, support the need for clinical vigilance. The researchers concluded:

“Gabapentin prescription in adults with chronic low back pain is associated with increased risk of dementia and cognitive impairment, particularly in non-elderly adults. Physicians should monitor cognitive outcomes in patients prescribed gabapentin.”¹¹

• Large-scale data showed a 45% increased dementia risk — Researchers analyzed 206,802 patients, including 34,467 who had taken gabapentin or pregabalin for at least 90 days. After adjusting for age, gender, and other health conditions, users were 45% more likely to develop dementia than non-users. The elevated risk held steady across both sexes and a wide range of comorbidities.

• Younger adults faced a disproportionately high risk — Among patients under 50, those taking gabapentin or pregabalin were more than three times as likely to develop dementia compared to similar individuals who didn’t use the drugs. This finding raises concern that younger brains, with higher plasticity and different drug processing, are especially vulnerable to long-term cognitive effects.

• Risk increased with cumulative dose — Similar to the Regional Anesthesia and Pain Medicine research, this study found a clear dose-response relationship between dementia risk and the use of gabapentin or pregabalin. Those with low cumulative exposure showed no significant increase, but high-dose users had markedly elevated risk.

• Biological mechanisms explain the cognitive effects — As mentioned earlier, gabapentin and pregabalin bind to the alpha-2-delta subunit of voltage-gated calcium channels, which disrupts the balance between excitatory and inhibitory signaling in the brain.

The study provided further insights, highlighting that alpha-2-delta subunits are overexpressed in the hippocampus, the brain’s memory center, making this region especially sensitive to long-term interference.

• Cognitive and psychiatric effects — Many patients describe sleepiness, dizziness, lethargy, a creeping sense of mental fog, slowed thinking, and emotional numbness. These effects interfere with memory, attention, and emotional stability over time.¹³ Pregabalin has also been linked to episodes of confusion, agitation, hallucinations, and even psychosis.¹⁴

• Respiratory problems — In 2019, the U.S. Food and Drug Administration (FDA) issued a warning about gabapentin’s role in respiratory depression, especially when used with opioids or other central nervous system depressants. Even standard doses may dangerously slow breathing in older adults, people with lung issues, or patients on sedating medications.¹⁵

• Body and coordination issues — Long-term use is linked to weight gain, swelling (peripheral edema), digestive issues, and fatigue. Many users also report ataxia, which is a loss of coordination that makes them feel unsteady or “off balance.” These side effects are especially risky for older adults vulnerable to falls or frailty.¹⁶

1. Walk several times a day, even in small amounts — Many people assume walking should wait until pain improves, but it’s one of the most important tools for recovery. Short walks of around two to five minutes at a time help your spine gently compress and decompress, rehydrate discs, and activate stabilizing muscles. Walking multiple times daily also helps loosen the hips and lower back, especially when done consistently rather than in a single long session.

2. Break up sedentary time — Sitting for long stretches, whether at a desk, in a car, or on the couch, puts sustained pressure on spinal discs and weakens postural muscles. Even minor interruptions to sitting make a difference.

Stand up every 20 to 30 minutes, shift positions, or do a few slow movements to reset your body. A standing desk with a walking pad is also useful. Over time, this protects spinal tissues and reduces the risk of flare-ups.

3. Build core strength and glute stability — Back pain is rarely just about the back. Weak abdominal and gluteal muscles force the spine to absorb more strain. Targeted strength exercises, like bird-dogs, hip bridges, and wall sits, help restore balance across your body and prevent movement compensations that prolong or worsen pain. These exercises are simple, do not require equipment, and can be scaled to any ability level.

4. Take micro-breaks for movement and stress relief — Back pain often worsens when tension and anxiety build up, so weaving simple relaxation techniques into your day makes a real difference. Slow, steady breathing and gentle movements like neck rolls help release the muscle tightness and mental strain that fuel pain. Every couple of hours, take a moment to pause, close your eyes, and inhale deeply through your nose.

Exhale just as slowly, allowing your body to shift out of that tight, anxious state. This calms your nervous system and lowers stress hormones that tend to amplify pain. Follow it with a light, fluid movement. Lift your arms overhead, do a few easy lunges, or stretch your spine. Nothing strenuous, just enough to keep blood flowing and tension from settling in.

5. Prioritize nutrition and weight management — Excess body weight puts continuous strain on your spine, like hauling a heavy backpack everywhere you go. To ease that burden, steer clear of ultraprocessed foods loaded with seed oils high in linoleic acid, a known mitochondrial disruptor. Instead, fuel your body with whole foods and enough healthy carbohydrates to support steady cellular energy.

Even modest shifts in diet lighten the load your back carries with every step. As your weight decreases, movement becomes easier and less painful. You’ll also gain more stamina, making it easier to stay active and build momentum with daily habits that support long-term recovery.

6. Consider dimethyl sulfoxide (DMSO) — If you’re seeking additional relief from chronic back pain without turning to long-term pharmaceuticals, one lesser-known option that deserves attention is DMSO, a naturally derived compound that has been used for decades to reduce inflammation, relieve pain, and improve tissue healing.

Its ability to penetrate deeply into tissues and carry other substances with it has led to numerous successful therapies, especially for musculoskeletal injuries and chronic pain conditions. To learn more about how DMSO works, how it’s used, and how it may complement or even replace conventional treatments, read “Unlocking DMSO’s Potential — Revolutionary Combination Therapies for Pain, Infections, and More.”