Lamotrigine and Aripiprazole Combination Can Increase Suicidal Thoughts Due to Akathisia
The combination of Lamictal (lamotrigine) and Abilify (aripiprazole) can increase suicidal thoughts primarily through the development of severe akathisia, anxiety, and agitation, particularly when used with other medications like antidepressants. 1
Mechanism of Increased Suicidal Risk
Akathisia-Mediated Pathway
- Aripiprazole causes akathisia in approximately 18% of patients with bipolar disorder 1
- This risk significantly worsens when aripiprazole is combined with lamotrigine and antidepressants
- Akathisia presents as:
- Intense inner restlessness
- Inability to remain still
- Severe anxiety
- These symptoms can directly trigger or exacerbate suicidal thoughts
Medication Interaction Effects
- The combination appears to have synergistic effects that increase akathisia beyond what either medication would cause alone 1
- This interaction is particularly concerning in mood disorder patients who may already have baseline suicidal ideation
Monitoring and Management Recommendations
Initial Prescription Considerations
- Start aripiprazole at low doses when combining with lamotrigine 1
- Monitor closely during the first 1-2 weeks of therapy initiation, as this is the highest risk period for suicidal thoughts 2
- Be particularly vigilant with patients under 24 years of age, who have heightened vulnerability to medication-induced suicidality 3
Warning Signs to Monitor
- Emergence of akathisia symptoms (restlessness, inability to sit still)
- Increased anxiety or agitation
- New or worsening suicidal thoughts
- Changes in behavior, irritability, or mood worsening 2, 3
When to Discontinue Treatment
- If limiting side effects like akathisia, increased anxiety, or suicidal thoughts develop, discontinuation of aripiprazole is recommended 1
- Do not attempt to push through these symptoms, as they indicate a significant adverse reaction
Alternative Treatment Approaches
Medication Alternatives
- Consider lithium as an alternative mood stabilizer, which has demonstrated suicide prevention effects 4
- If an antipsychotic is needed, quetiapine may be considered as it has lower rates of akathisia 3
- For patients with bipolar disorder, mood stabilizing agents generally show protective effects against suicide attempts in long-term treatment 5
Risk Mitigation Strategies
- Avoid rapid dose escalation of either medication
- Consider using more sedating antidepressants for acutely suicidal patients 4
- Implement non-pharmacological interventions alongside medication adjustments 3
Important Caveats
- The combination of lamotrigine and aripiprazole has also been associated with increased risk of Stevens-Johnson syndrome in some case reports 6
- The absolute risk of suicidal ideation with these medications is relatively low, but the need for monitoring remains critical 3
- Inadequate treatment of underlying mood disorders poses a greater suicide risk than medication side effects in adults 7
Clinical Pearls
- The highest risk period for suicide attempts is during the first 1-2 months of treatment 2
- Regular assessment of therapeutic response and adverse effects should begin within 1-2 weeks of starting therapy 2
- Document baseline mental status and suicidal ideation before starting treatment to better identify medication-induced changes