Aripiprazole Monotherapy for Depression/Anxiety with Suicide History
Continue lithium and avoid aripiprazole monotherapy—lithium has unique anti-suicide properties that should not be discontinued, while aripiprazole monotherapy is not indicated for your patient's presentation and carries its own activation risks. 1
Why Lithium Should Be Maintained
Lithium has uniquely powerful anti-suicide effects that are unmatched by other mood stabilizers:
Lithium reduces suicide attempts by 8.6-fold and when discontinued, there is a 7-fold increase in suicide attempt rates and 9-fold increase in completed suicide rates in patients with major affective disorders 1
This anti-suicide effect appears unique to lithium and may be due to its serotonin-enhancing properties 1
Long-term lithium treatment reduces suicide attempts by approximately 10% and deaths by suicide by approximately 20% compared to other mood stabilizers 2
In Medicaid patients with bipolar disorder, divalproex users had 2.7 times higher risk of suicide attempts compared to lithium users 3
Critical caveat: Lithium requires careful third-person supervision due to lethal overdose potential, which is particularly relevant given your patient's history of suicide attempt by overdose 1
Why Aripiprazole Monotherapy Is Not Appropriate
Aripiprazole is not approved as monotherapy for depression or anxiety disorders:
The FDA label explicitly states that aripiprazole "is not approved as a single agent for treatment of depression and has not been evaluated in pediatric major depressive disorder" 4
Aripiprazole has only been studied in open-label trials for anxiety disorders, with no randomized controlled trials supporting its use 5
Aripiprazole carries significant activation and akathisia risks that mirror your patient's Prozac experience:
Approximately 18% of patients with mood disorders develop akathisia on aripiprazole 6
Case reports document severe akathisia, increased anxiety, and suicidal ideation when aripiprazole is combined with antidepressants and mood stabilizers 6
The FDA label warns about "anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania" particularly early in treatment 4
Akathisia has been specifically linked to fluoxetine-induced suicidality, and aripiprazole can cause similar akathisia 1, 7
Recommended Next Steps
Optimize current lithium therapy while addressing the activation issue:
Ensure lithium blood concentrations are maintained in the therapeutic range, as this is crucial for anti-suicide efficacy 2
Verify adequate dosing and duration of lithium treatment, as long-term appropriately modulated treatment is necessary for suicide prevention 2
Implement third-party supervision for lithium dispensing given overdose history 1
Consider alternative antidepressant strategies that avoid activation:
Try a different SSRI with lower activation potential than fluoxetine, as SSRIs have low lethal potential in overdose compared to tricyclics 1
Start with subtherapeutic "test" doses to assess for activation/agitation before titrating up 7, 8
Monitor specifically for akathisia, as this has been associated with SSRI-induced suicidality 1, 7
If augmentation is eventually needed after optimizing lithium:
Consider aripiprazole as an adjunct to lithium (not monotherapy), starting at very low doses with close monitoring for akathisia and increased anxiety 6
The combination of lithium and an antidepressant may reduce suicidal behaviors by addressing suicidal ideation prior to depressive symptoms 2
Implement comprehensive safety measures:
Restrict access to lethal medications and means through family involvement 1
Schedule frequent follow-up appointments to monitor for clinical worsening 7
Conduct systematic assessment for suicidal ideation at each visit 7, 8
Avoid benzodiazepines which may reduce self-control and potentially disinhibit suicidal behavior 7
Important Clinical Pitfalls
Do not discontinue lithium based on insufficient evidence for other agents: The 2025 VA/DoD guidelines note "insufficient evidence to recommend for or against lithium to reduce the risk of suicide," but this reflects limited recent trial data, not a reversal of lithium's established benefits 1. The older but robust meta-analyses showing lithium's unique anti-suicide properties remain valid 1, 2.
Do not switch to aripiprazole monotherapy thinking it's "safer": While aripiprazole has a better metabolic profile than some antipsychotics, it carries significant activation risks and lacks evidence for your patient's specific presentation 6, 5.
Address the overdose risk pragmatically: Dispense lithium in small quantities with third-party supervision rather than abandoning the most effective anti-suicide medication available 1.