Switching from Lithium to Risperidone for Bipolar Depression Management
It is not appropriate to taper off lithium and start risperidone at 1.5 mg for bipolar depression management. 1
Rationale for Maintaining Lithium Therapy
- Lithium is the gold standard treatment for bipolar disorder and the only FDA-approved agent for bipolar disorder in adolescents age 12 and older 1, 2
- Lithium shows superior evidence for prevention of both manic and depressive episodes in long-term maintenance therapy 1
- Withdrawal of maintenance lithium therapy is associated with an increased risk of relapse, especially within the 6-month period following discontinuation 3, 1
- Studies show that >90% of adolescents who were non-compliant with lithium treatment relapsed 3, 1
Concerns with Switching to Risperidone
- Risperidone is FDA-approved for acute mania in bipolar disorder, not for bipolar depression 4
- Several atypical antipsychotics, including risperidone, have limited or no therapeutic activity in bipolar depression 5
- For bipolar depression, the American Academy of Child and Adolescent Psychiatry recommends olanzapine-fluoxetine combination as a first-line option, not risperidone 1
Managing Lithium's Gastrointestinal Side Effects
- Instead of discontinuing lithium due to gastric side effects, consider these approaches:
- Switch to a once-daily dosing schedule of lithium, which has been shown to maintain efficacy while reducing side effects 6
- Administer lithium with food or after meals to reduce gastric irritation 7
- Consider a slow-release formulation of lithium which may cause less gastric irritation 7
- Ensure adequate hydration to minimize gastrointestinal side effects 1
Alternative Approaches for Bipolar Depression
If lithium side effects remain intolerable despite optimization:
- Consider quetiapine monotherapy, which has demonstrated significant improvements with a large effect size in bipolar depression 8, 5
- Olanzapine-fluoxetine combination has shown efficacy for bipolar depression 1, 5
- Lurasidone has demonstrated efficacy for bipolar depression and is ranked second for response after olanzapine-fluoxetine combination 1, 5
- Lamotrigine may be considered for maintenance therapy, particularly for preventing depressive episodes 1
Medication Discontinuation Protocol
If lithium must be discontinued despite the recommendations above:
- Develop a monitoring plan for the discontinuation trial, as patients with mood disorders may experience a return of symptoms weeks to months after their last dose 3
- Taper lithium slowly to avoid withdrawal symptoms or rebound worsening of symptoms 3
- Ensure that an effective alternative medication regimen is established before completing the lithium taper 3, 1
- Educate the patient about early signs and symptoms of mood episodes so that resumption of therapy can be initiated if necessary 3
Conclusion
Maintaining lithium therapy while addressing side effects is preferable to switching to risperidone for bipolar depression. If lithium truly cannot be tolerated despite optimization efforts, consider evidence-based alternatives for bipolar depression such as quetiapine, olanzapine-fluoxetine combination, or lurasidone.