What are the side effects of Pregabalin (Lyrica)?

Side Effects of Pregabalin

The most common side effects of pregabalin are dizziness (23-46% of patients), somnolence (15-25%), peripheral edema (10%), weight gain, blurred vision, dry mouth, and confusion, with these effects being dose-dependent and generally manageable through dose reduction. 1

Most Frequent Adverse Effects

Neurological Side Effects

• Dizziness occurs in 23-46% of patients and is the most common reason for treatment discontinuation (4-6% of patients stop therapy due to this) 2, 3
• Somnolence affects 15-25% of patients and leads to discontinuation in approximately 3% of cases 2, 3
• Ataxia, confusion, thinking abnormalities (difficulty with concentration/attention), tremor, abnormal gait, and amnesia occur less frequently but are still clinically significant 2, 1
• Cognitive effects including problems with concentration, language difficulties, and slowed thinking are reported, particularly at higher doses 1

Visual Disturbances

• Blurred vision occurs in 3-12% of patients depending on dose, with higher rates at 600 mg/day 1
• Diplopia (double vision) affects 2-12% of patients in epilepsy trials 1
• Visual field restriction has been reported in clinical trials, though rare 4
• Visual hallucinations represent a very rare but serious adverse effect, particularly at higher doses, requiring medication discontinuation 5

Metabolic and Physical Effects

• Weight gain is dose-dependent, occurring in 4-16% of patients, with higher rates at 600 mg/day 1
• Peripheral edema affects approximately 10% of patients and can be particularly problematic in elderly patients 2, 3
• Increased appetite occurs in 5-6% of patients 1

Gastrointestinal Effects

• Dry mouth affects 1-6% of patients 1
• Constipation occurs in 1-7% of patients, with higher rates at increased doses 1
• Nausea is reported as a common side effect, particularly with duloxetine comparison studies 2

Other Common Effects

• Headache is frequently reported 2
• Accidental injury rates increase (7-10% vs 5% placebo), likely related to dizziness and ataxia 1

Serious and Life-Threatening Adverse Effects

Respiratory Depression

• Serious breathing problems can occur when pregabalin is combined with opioid pain medications, benzodiazepines, or other CNS depressants 1
• Watch for increased sleepiness or decreased breathing when starting pregabalin or increasing the dose 1

Allergic Reactions

• Serious, even life-threatening allergic reactions including angioedema (swelling of face, mouth, lips, gums, tongue, throat, or neck) require immediate discontinuation 1
• Rash, hives, and blisters may occur 1

Cardiovascular Effects

• Heart failure has been reported in case reports, particularly in elderly patients or those with cardiac history 6
• The New York Heart Association issued warnings about using caution when prescribing pregabalin to type III-IV heart failure patients 6
• Peripheral and central edema can develop, which may be serious for patients with heart problems 1, 6

Psychiatric Effects

• Suicidal thoughts or actions occur in approximately 1 in 500 patients (similar to other antiepileptic drugs) 1
• Euphoria and "feeling high" are reported, leading to Schedule V controlled substance designation 1, 7
• Agitation, new or worse depression, anxiety, panic attacks, and unusual behavioral changes require immediate medical attention 1

Musculoskeletal Effects

• Muscle problems including muscle pain, soreness, or weakness, especially with fever, require immediate reporting to healthcare provider 1

Dose-Dependent Relationships

• Higher doses (600 mg/day) are associated with significantly greater adverse effects without consistently greater efficacy compared to 300 mg/day 2, 3
• The 300 mg/day dose provides the optimal benefit-to-risk ratio for most patients 3
• Withdrawal due to adverse events is moderate at standard doses but increases substantially at 600 mg/day 2

Special Population Considerations

Elderly Patients

• Elderly patients are more susceptible to falls, confusion, sedation, balance disorders, tremor, and coordination abnormalities 3
• Lower starting doses and slower titration are mandatory in this population 3
• Peripheral edema and weight gain are particularly problematic in elderly patients 4

Pediatric Patients (4-17 years)

• The most common side effects in children are weight gain, increased appetite, and sleepiness 1
• Somnolence led to discontinuation in 3 patients in pediatric epilepsy trials 1

Renal Impairment

• Dose adjustment is mandatory as pregabalin is eliminated unchanged by the kidneys 3, 4
• Even moderate renal failure (creatinine clearance below 60 mL/min) requires dose reduction 4

Critical Drug Interactions and Warnings

• Combination with ACE inhibitors increases risk of swelling and hives 1
• Combination with thiazolidinediones (Avandia, Actos) increases risk of weight gain and hand/foot swelling 1
• Combination with any CNS depressants (opioids, benzodiazepines, alcohol) increases risk of dizziness, sleepiness, and respiratory depression 1
• Alcohol consumption with pregabalin increases side effects such as sleepiness and dizziness 1

Withdrawal Effects

• Abrupt discontinuation can cause headaches, nausea, diarrhea, trouble sleeping, increased sweating, anxiety, and increased seizure frequency in epilepsy patients 1
• Taper gradually over a minimum of 1 week when discontinuing 3, 1

Rare but Documented Effects

• Skin sores occurred in animal studies but not in human trials; diabetic patients should monitor skin while taking pregabalin 1
• Haemangiosarcoma risk suggested in animal studies, though no human cases described 4
• Myoclonus (muscle twitching) occurs in approximately 2-4% of patients 1