What are the potential side effects of topiramate (antiepileptic medication)?

Topiramate Side Effects

Topiramate causes a wide range of side effects from common paresthesias and cognitive impairment to serious complications including acute angle-closure glaucoma, kidney stones, metabolic acidosis, and teratogenic effects—requiring careful patient selection, slow titration, and vigilant monitoring.

Most Common Side Effects

• Paresthesias (tingling in arms and legs) are the most frequent adverse effect, occurring in 4-23% of patients 1
• Cognitive impairment and difficulty with concentration occur frequently, particularly at higher doses 1
• Insomnia affects 5-10% of patients 1
• Weight loss and decreased appetite are common and can be significant 1
• Nausea occurs in 8-10% of patients 1
• Constipation affects 3-10% of patients 1
• Dry mouth (xerostomia) occurs in up to 19% of patients 1
• Hair loss (alopecia) affects 1-6% of patients 1
• Diarrhea has been reported 1
• Fatigue, dizziness, and ataxia are common CNS-related effects 2, 3

Serious and Vision-Threatening Side Effects

Acute Angle-Closure Glaucoma

• Acute angle-closure glaucoma with sudden vision loss is a medical emergency requiring immediate discontinuation 1, 2
• This can occur with or without eye pain and involves blockage of fluid causing increased intraocular pressure 2
• These problems can lead to permanent blindness if not treated immediately 2
• Rare cases of severe maculopathy (potentially irreversible) and visual field defects have been reported 4

Metabolic Complications

• Metabolic acidosis occurs due to carbonic anhydrase inhibition and requires serum bicarbonate monitoring 1, 2
• Symptoms include tiredness, loss of appetite, irregular heartbeat, and impaired consciousness 2
• Kidney stones (nephrolithiasis) are a significant risk due to carbonic anhydrase inhibition 1, 2
• Patients should drink plenty of fluids to decrease kidney stone risk 2

Neuropsychiatric Effects

• Depression and emergent suicidal ideation are serious concerns requiring specific counseling before initiation 1
• Cognitive slowing, memory problems, and impaired concentration are particularly problematic at higher doses 1, 2
• Confusion, problems with attention, and speech difficulties can occur 2
• Mood problems, nervousness, and aggression have been reported 2

Other Serious Effects

• Decreased sweating (oligohidrosis) and fever, especially in children and hot temperatures, may require hospitalization 2
• High blood ammonia levels affecting mental activities, particularly when combined with valproic acid 2
• Severe headaches requiring discontinuation 1
• Overstimulation and panic attacks 1

Critical Contraindications and Warnings

Pregnancy and Women of Childbearing Age

• Pregnancy is an absolute contraindication due to teratogenic effects including cleft lip/palate 1
• Topiramate reduces the efficacy of oral contraceptives and other hormonal contraceptives—women must be explicitly informed of this interaction before prescribing 1
• Women of childbearing age require mandatory counseling about both teratogenic risks and contraceptive interactions 1
• Reliable contraception is essential for women taking topiramate 1

Cardiovascular Contraindications

• Uncontrolled hypertension is an absolute contraindication 1
• History of cardiovascular disease, especially when combined with phentermine, is contraindicated 1
• Blood pressure and heart rate should be monitored, especially during initial titration 1

Drug Interactions

• Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days after MAOI use is absolutely contraindicated 1

Discontinuation Rates and Clinical Impact

• Approximately 26% of patients discontinue topiramate due to side effects 1
• Most adverse events that are dose-limiting or lead to discontinuation occur during the titration phase 5
• Common reasons for discontinuation include memory concerns, severe headaches, depression, and urticaria 1

Essential Monitoring Requirements

• Serum bicarbonate levels must be monitored periodically to detect metabolic acidosis 1, 2
• Renal function should be monitored in patients with kidney disease due to acute kidney injury risk 1
• Blood pressure and heart rate monitoring during initial titration 1
• Watch for signs of decreased sweating and fever, especially in children 2
• Monitor for emergence of depression or suicidal ideation 1, 2

Risk Mitigation Strategies

• Slow upward titration starting at 25-50 mg/day and increasing by 25-50 mg increments every 3-7 days minimizes adverse effects 6, 5
• Avoid alcohol, which worsens sleepiness and dizziness 2
• Avoid other CNS depressant medications unless prescribed 2
• Ensure adequate hydration to prevent kidney stones 2
• Do not drive or operate heavy machinery until effects are known 2