Bipolar disorder: New strategy for checking serum valproate
Routine monitoring may not be necessary or cost-effective.
In the loading dose study by Hirschfeld et al,11 patients receiving divalproex, 20 to 30 mg/kg/d, did not experience a higher frequency or severity of side effects compared with patients receiving standard titration. Keck et al10 also reported minimal valproate-related side effects in their open-label study. Neither study suggested an upper-limit valproate level associated with increased side effects.
Discussion. Serum valproate >125 mcg/mL has been associated with increased side effects (Table 2), but more studies are needed.
Table 2
For bipolar disorder, suggested serum valproate therapeutic ranges*
| Serum valproate (mcg/mL) | |||
|---|---|---|---|
| Lower level | Upper level | Comments | |
| Acute mania | 45 to 50 | 125 | Upper level based on tolerability, not efficacy |
| Maintenance | 75 | 100 | Levels based primarily on retrospective analysis |
| Acute bipolar | Not established | Not established | |
| * Based on available data | |||
Clinical recommendations
Carefully consider when to monitor serum valproate levels in your patients with bipolar disorder:
- Obtaining routine serum levels can be expensive, and no data support the cost-effectiveness of this approach in bipolar disorder.
- Individualize valproate dosing; a specific patient’s therapeutic range may differ from another’s or from those published in the literature or used by a clinical laboratory.
- Monitoring serum valproate levels does not replace the need to adjust dosages based on patients’ therapeutic response and tolerance.
- American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry2002; 159(suppl 4):1–50.
- Depression and Bipolar Support Alliance. www.dbsalliance.org.
- Carbamazepine • Tegretol, Equetro
- Divalproex sodium • Depakote
- Felbamate • Felbatol
- Phenytoin • Dilantin
Dr. Kaneria reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Patel is a consultant to and speaker for Eli Lilly and Co. and a speaker for Pfizer.
Dr. Keck receives research support from or is a consultant to or advisor for Abbott Laboratories, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb Co., GlaxoSmithKline, Janssen Pharmaceutica, Eli Lilly and Co., Organon, Ortho-McNeil Pharmaceutical, Merck & Co., Pfizer, Shire, and UCB Pharma.
