Leo Sher, M.D.

A research paper, “Divalproex and its effect on suicide risk in bipolar disorder: A systematic review and meta-analysis of multinational observational studies” has recently been published in the Journal of Affective Disorders (1).

In general, studies on the effect of divalproex on suicide risk in patients with bipolar disorder have produced conflicting results. The authors used random-effects meta-analysis to calculate the relative risk and 95% confidence intervals for suicidality among patients receiving divalproex and those without. Six studies were included in the final meta-analysis (2-7). Four studies compared the suicidal risks between treatment with divalproex and no medication treatment (2-5) and four studies compared the suicidal risks between divalproex and carbamazepine (4-7). The clinical variables of interest were extracted from each study according to a predetermined list.

The authors did not find significant difference in the incidence rates of suicide attempts or suicide death between study participants receiving divalproex vs. no medication. The authors also did not observe significant difference in the incidence rates of suicide attempts or suicide death between participants receiving divalproex and carbamazepine. The authors noted that their results are consistent with previous findings indicating that divalproex does not increase the risk of suicide events in bipolar patients.

References

1. Chen TY, Kamali M, Chu CS, Yeh CB, Huang SY, Mao WC, Lin PY, Chen YW, Tseng PT, Hsu CY. Divalproex and its effect on suicide risk in bipolar disorder: A systematic review and meta-analysis of multinational observational studies. J Affect Disord 2019;245:812-818.
2. Ahearn EP, Chen P, Hertzberg M, Cornette M, Suvalsky L, Cooley-Olson D, Swanlund J, Eickhoff J, Becker T, Krahn D. Suicide attempts in veterans with bipolar disorder during treatment with lithium, divalproex, and atypical antipsychotics. J Affect Disord 2013;145:77-82.
3. Toffol E, Hatonen T, Tanskanen A, Lonnqvist J, Wahlbeck K, Joffe G, Tiihonen J, Haukka J, Partonen T. Lithium is associated with decrease in all-cause and suicide mortality in high-risk bipolar patients: a nationwide registry-based prospective cohort study. J Affect Disord 2015;183:159-165.
4. Goodwin GM, Haddad PM, Ferrier I.N., Aronson J.K., Barnes T., Cipriani A., Coghill DR, Fazel S, Geddes JR, Grunze H, Holmes EA, Howes O, Hudson S, Hunt N, Jones I, Macmillan IC, McAllister-Williams H, Miklowitz DR, Morriss R, Munafo M, Paton C, Saharkian BJ, Saunders K, Sinclair J, Taylor D, Vieta E, Young AH. Evidence-based guidelines for treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2016;30:495-553.
5. Tsai CJ, Cheng C, Chou PH, Lin CH, McInnis MG, Chang CL, Lan TH. The rapid suicide protection of mood stabilizers on patients with bipolar disorder: a nationwide observational cohort study in Taiwan. J Affect Disord 2016;196:71-77.
6. Collins JC. McFarland BH. Divalproex, lithium and suicide among Medicaid patients with bipolar disorder. J Affect Disord 2008;107:23-28.
7. Gibbons RD, Hur K, Brown CH, Mann JJ. Relationship between antiepileptic drugs and suicide attempts in patients with bipolar disorder. Arch Gen Psychiatry 2009;66:1354-1360.