From the Guidelines
Divalproex sodium is typically started at 250-500 mg twice daily for bipolar disorder, with gradual titration to reach therapeutic blood levels of 50-125 mcg/mL, as recommended in the most recent guidelines 1.
Dosing and Administration
The usual maintenance dose ranges from 1000-2500 mg per day, divided into two or three doses. Extended-release formulations allow for once-daily dosing, which may improve adherence.
- Dosing should be individualized based on clinical response and tolerability, with regular monitoring of serum valproate levels.
- Common side effects include gastrointestinal distress, sedation, tremor, and weight gain.
- Liver function tests, complete blood counts, and pregnancy tests (for women of childbearing potential) should be performed before starting treatment and periodically thereafter.
Mechanism of Action and Efficacy
Divalproex works by enhancing GABA neurotransmission and inhibiting sodium channels, which helps stabilize mood.
- It is particularly effective for manic episodes and may have some efficacy in preventing depressive episodes.
- Taking divalproex with food can reduce gastrointestinal side effects, and starting at a lower dose with gradual increases can improve tolerability.
Special Considerations
For patients with clearly defined bipolar disorder, stimulant medications may be helpful for addressing ADHD symptoms once the patient’s mood symptoms are adequately controlled on a mood stabilizer regimen, as shown in a randomized, controlled trial 1.
- Comorbid disruptive behavioral disorders and ADHD predict a poorer response to treatment, and thus, additional interventions may be necessary in conjunction with pharmacotherapy.
From the Research
Divalproex Dose for Bipolar Disorder
- The optimal dose of divalproex for bipolar disorder is not explicitly stated in the provided studies, but its efficacy in treating bipolar I disorder, manic or mixed episode, is well-established 2.
- Divalproex has a broad spectrum of activity in the treatment of bipolar depression and rapid cycling, psychotic symptoms, impulsive aggression, and post-traumatic stress disorder 2.
- The use of divalproex in the treatment of bipolar and other related psychiatric disorders has been reviewed, highlighting its potential as a mood stabilizer 2.
- A placebo-controlled study found that divalproex was effective in reducing symptoms of depression and anxiety in patients with bipolar I depression 3.
- The study used an 8-week, double-blind, placebo-controlled, randomized clinical trial design, with a primary outcome measure of the 17-item Hamilton Rating Scale for Depression 3.
Treatment Guidelines
- First-line therapy for bipolar disorder includes mood stabilizers, such as lithium, anticonvulsants, such as valproate, and atypical antipsychotic drugs, such as quetiapine, aripiprazole, asenapine, lurasidone, and cariprazine 4.
- Valproic acid (VPA) is considered effective for atypical forms of bipolar disorder, such as mixed-prevalence and rapid-cycling 5.
- The association of atypical antipsychotics with mood stabilizers is commonly used in the treatment of acute phases, but it is also being explored in maintenance pharmacotherapy 5.
- Quetiapine and, less consistently, Aripiprazole have been proposed as adjunctive strategies for maintenance treatment when mood stabilizers are not enough 5.