From the Guidelines
Divalproex has limited effectiveness for bipolar 2 depression specifically, and its use should be considered as an adjunctive treatment when first-line options are ineffective. For bipolar 2 depression, first-line treatments typically include quetiapine (300-600mg daily), lamotrigine (titrated to 200mg daily), or lithium (aiming for blood levels of 0.6-0.8 mmol/L) 1.
Key Considerations
- Divalproex may be considered as an adjunctive treatment when first-line options are ineffective, typically starting at 250mg twice daily and titrating to a therapeutic blood level of 50-125 μg/mL.
- Treatment should continue for at least 6-8 weeks to assess effectiveness.
- Side effects include gastrointestinal distress, weight gain, hair loss, tremor, and potential liver toxicity, requiring regular blood monitoring.
- Divalproex works by enhancing GABA neurotransmission and stabilizing neuronal membranes, but its antidepressant mechanism in bipolar disorder is not fully understood.
- For bipolar 2 disorder, which features prominent depressive episodes with less severe hypomanic episodes, medications with stronger antidepressant properties are generally preferred over divalproex alone.
Treatment Approach
- The treatment approach should prioritize medications with established efficacy for bipolar 2 depression, such as quetiapine, lamotrigine, or lithium.
- Divalproex may be added as an adjunctive treatment if the patient does not respond to first-line options.
- Regular monitoring of blood levels, liver function, and side effects is crucial when using divalproex.
- A comprehensive treatment plan should also consider the patient's overall health, comorbidities, and potential interactions with other medications.
From the Research
Efficacy of Divalproex for Bipolar 2 Depression
- The efficacy of divalproex for bipolar 2 depression has been studied in several clinical trials 2, 3, 4, 5.
- A 12-week open trial of divalproex monotherapy in 19 bipolar II depressed outpatients found that 63% of patients responded to treatment, with a significant decrease in Hamilton Depression ratings 4.
- A double-blind, randomized, placebo-controlled trial of extended-release divalproex sodium in patients with bipolar I or II depression found that divalproex treatment produced statistically significant improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) scores compared with placebo from week 3 onward 5.
- However, subgroup analysis revealed no separation between divalproex and placebo for those with bipolar II diagnoses, suggesting that divalproex may be more effective for bipolar I depression or rapid-cycling type I presentations 5.
Comparison with Other Treatments
- Divalproex is considered a mood stabilizer and is often used in combination with other medications, such as antipsychotics or antidepressants, to treat bipolar disorder 3, 6.
- A review of the diagnosis and treatment of bipolar disorder found that mood stabilizers, such as lithium, valproate, and lamotrigine, are recommended as first-line therapy for bipolar disorder, while antidepressants are not recommended as monotherapy 6.