Side Effects of Lamotrigine (Lamictal), Aripiprazole (Abilify), and Hydroxyzine
When taking these three medications together, you should be aware of both individual and potentially overlapping side effects, with particular attention to serious risks like rash with lamotrigine and movement disorders with aripiprazole.
Lamotrigine (Lamictal) Side Effects
Most Serious Risk
- Serious skin rash (including Stevens-Johnson Syndrome): Occurs in 10-17% of patients, can be life-threatening 12
- Risk increases with rapid dose escalation or when combined with valproic acid
- Watch for bumps on lips, oral lesions, diffuse rash involving palms/soles, and fever 3
Common Side Effects
The most frequent adverse events include 1:
- Ataxia (lack of coordination)
- Dizziness
- Diplopia (double vision)
- Somnolence (sleepiness)
- Headache
Additional Notable Effects
- Blurred vision, runny nose 2
- Nausea and vomiting 2
- Trouble with balance and coordination 2
- Psychiatric symptoms: Can cause affective switches, psychotic episodes, and hallucinations 4
- May cause false-positive PCP on urine drug screens 5
Important Warnings
- Can cause aseptic meningitis 2
- May affect heart rhythm in susceptible individuals 2
- Interacts with birth control pills—may reduce lamotrigine effectiveness or cause side effects when starting/stopping contraceptives 2
Aripiprazole (Abilify) Side Effects
Common Side Effects in Overdose/High Doses
The most frequently reported include 6:
- Vomiting
- Somnolence (sleepiness)
- Tremor
Movement-Related Side Effects
- Akathisia (inner restlessness, inability to sit still)—particularly concerning when combined with lamotrigine 7
- Agitation/activation—most common in elderly patients (8% incidence) 8
- Parkinsonian side effects 9
Metabolic and Hormonal Effects
When used as part of antipsychotic polypharmacy 9:
- Hyperprolactinemia (elevated prolactin)
- Sexual dysfunction
- Weight gain (though aripiprazole may actually reduce this when added to other antipsychotics)
- Diabetes mellitus risk
- Dyslipidemia
Serious Adverse Events (from overdose data)
6 reports these can occur:
- QT prolongation (heart rhythm abnormality)
- Seizures/convulsions
- Blood pressure changes (both high and low)
- Cardiac arrhythmias
- Altered consciousness
Cognitive Effects
- Sedation/somnolence 9
- Cognitive impairment (though this may be dose-related rather than drug-specific) 9
Hydroxyzine Side Effects
While not extensively covered in the provided evidence, hydroxyzine is an antihistamine commonly used for:
- Sedation/drowsiness (primary effect)
- Dry mouth
- Dizziness
- Used therapeutically for pruritus (itching) 3
Critical Drug Interaction Concerns
Combined Lamotrigine + Aripiprazole Risk
Severe akathisia, increased anxiety, and suicidal ideation can develop when these drugs are combined, especially with antidepressants 7. This case report specifically warns:
- Start aripiprazole at low doses when combined with lamotrigine
- Monitor closely for akathisia, anxiety, or suicidal thoughts
- These limiting side effects require discontinuation of the drug 7
Overlapping Sedation Risk
All three medications can cause drowsiness/sedation:
Do not drive or operate machinery until you know how these medications affect you 2.
Monitoring Recommendations
For Lamotrigine
- Watch for any rash, especially in first 8 weeks
- Report immediately: lip bumps, mouth sores, rash on palms/soles, fever 3
- Monitor for mood changes or new psychiatric symptoms 4
For Aripiprazole
- Monitor for restlessness, inability to sit still (akathisia) 7
- Watch for increased agitation, especially in first days of treatment 8
- Be alert for suicidal thoughts when combined with lamotrigine 7
For the Combination
- Report any worsening anxiety or suicidal thoughts immediately 7
- Monitor for excessive sedation affecting daily function
- Regular metabolic monitoring (weight, glucose, lipids) given aripiprazole use 9
Common Pitfalls to Avoid
- Never stop lamotrigine suddenly—can cause seizures even if not taking it for epilepsy 2
- Don't ignore early rash symptoms—Stevens-Johnson Syndrome can develop despite appropriate dosing 3
- Don't dismiss restlessness as anxiety—may be akathisia requiring medication adjustment 7
- Be aware that the combination specifically increases risk of akathisia beyond either drug alone 7