I am taking lamotrigine (Lamictal) and have developed ataxia and clumsiness; is this a side effect and how should I manage it?

Lamotrigine-Induced Ataxia and Muscle Incoordination

Yes, ataxia and clumsiness are well-recognized signs of lamotrigine toxicity, and you should immediately reduce your dose or temporarily discontinue the medication while checking a lamotrigine serum level. 1

Recognizing Lamotrigine Toxicity

Ataxia (muscle incoordination) is a cardinal neurological manifestation of supratherapeutic lamotrigine levels, typically accompanied by:

• Dizziness and vertigo 2, 3, 4
• Diplopia (double vision) 1, 4
• Nystagmus (involuntary eye movements) 1
• Drowsiness and somnolence 5, 2
• Tremor 1
• Hyperreflexia 1

The appearance of nystagmus or ataxia signals supratherapeutic drug levels and requires immediate dose reduction or discontinuation rather than continuation of the current dose. 1

Immediate Management Steps

1. Stop or Reduce Lamotrigine Immediately

• Do not continue your current dose if you are experiencing ataxia or clumsiness 1
• Contact your prescribing physician urgently to discuss dose adjustment 1

2. Obtain a Lamotrigine Serum Level

• Request a trough (pre-dose) blood sample drawn 12-16 hours after your last dose or immediately before your morning dose 1
• The level should be drawn at steady state (at least 1 week after starting therapy or any dose change if not on valproate; 2-3 weeks if on valproate) 1
• A rapid lamotrigine assay should be ordered to avoid unnecessary stroke workup, particularly in older patients 4

3. Rule Out Stroke (Especially in Older Adults)

Lamotrigine toxicity is frequently misdiagnosed as posterior circulation stroke or transient ischemic attack, particularly in patients over 60 years old presenting with vertigo, ataxia, and diplopia 4. However:

• Request a lamotrigine level first before proceeding to expensive stroke imaging 4
• The mean age of patients misdiagnosed with stroke when actually experiencing lamotrigine toxicity was 62 years (range 43-79) 4
• Unnecessary CT scans add radiation exposure, contrast exposure, and significant cost 4

Common Causes of Lamotrigine Toxicity

Drug Interactions That Increase Lamotrigine Levels

Valproic acid is the most important interaction:

• Valproic acid increases lamotrigine half-life to 48-59 hours (from ~24-35 hours) 1
• Requires 50% dose reduction of lamotrigine when co-administered 1
• If you recently started valproic acid, this is likely the cause 1

Discontinuation of enzyme-inducing drugs:

• If you recently stopped carbamazepine, phenytoin, phenobarbital, or topiramate, your lamotrigine levels will rise 1
• These drugs shorten lamotrigine half-life to 13.5-15 hours; stopping them causes accumulation 1

Hormonal contraceptive changes:

• Starting or stopping combined hormonal contraceptives can alter lamotrigine levels by ~50% 1

Excessive Dosing

• The mean daily dose in patients presenting with toxicity symptoms was 621 mg (range 300-900 mg) 4
• Rapid titration beyond recommended 2-week intervals increases toxicity risk 6

Restarting Lamotrigine After Toxicity

If lamotrigine has been interrupted for more than 5 days, you must restart the full titration schedule (starting at 25 mg daily for standard regimen, or 12.5 mg daily if on valproic acid) rather than resuming your previous maintenance dose 1. This prevents rapid accumulation and serious adverse effects.

When to Seek Emergency Care

Seek immediate emergency evaluation if you develop:

• Severe unsteady gait with risk of falls
• Inability to perform coordinated movements
• Confusion or altered mental status
• Severe dizziness preventing ambulation

These symptoms warrant urgent assessment and may require temporary hospitalization for observation while lamotrigine levels decline 4.

Important Caveats

• Do not confuse lamotrigine toxicity with cerebellar stroke, especially if you are over 60 years old 4
• Ataxia from lamotrigine is dose-dependent and reversible with dose reduction 2, 3
• The neurological symptoms typically resolve within days as drug levels decline, given lamotrigine's half-life of 24-35 hours (longer if on valproic acid) 1