Suicidal Risks during Treatment of Bipolar Disorder Patients with Lithium versus Anticonvulsants

The aim of this study was to compare suicidal risks during long-term treatment of bipolar disorder (BPD) patients with lithium versus anticonvulsants (ACs).

Medline^® searching identified 6 reports of direct comparisons of patients diagnosed with BPD by modern criteria, treated ≥6 months with lithium versus ACs (carbamazepine, divalproex, lamotrigine), with non-zero risk of suicide or attempts in at least one study-arm. We extracted rates (events/persons/exposure time) for each treatment arm, and applied random-effects meta-analysis to determine pooled risk ratio, risk difference, and their 95% confidence intervals (CI).

Overall, rates of suicidal acts were 2.86-times (95% CI: 2.29–3.57; p<0.0001) higher during treatment with ACs versus lithium, and no AC emerged as clearly superior to the others.

Comparisons of suicidal risks during treatment with lithium versus ACs remain rare and methodologically limited, but favor lithium and encourage further study in this era of growing regulatory concern about possible adverse effects of ACs.

References

• 1 Ahrens B, Muller-Oerlinghausen B. Does lithium exert and independent antisucidal effect?.  Pharmacopsychiatry. 2001;  34 132-136
• 2 Baldessarini RJ, Tarazi FI. Pharmacotherapy of psychiatric disorders. Chapters 17 and 18 in: Brunton LL, Lazo JS, Parker KL, eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 11th edition. McGraw-Hill Press, New York 2005: 429-500
• 3 Baldessarini RJ, Tondo L. Lithium and suicidal risk.  Bipolar Disord. 2008;  10 114-115
• 4 Baldessarini RJ, Tondo L, Davis P. et al . Decreased risk of suicides and attempts during long-term lithium treatment: meta-analytic review.  Bipolar Disord. 2006;  8 625-639
• 5 Baldessarini RJ, Tondo L, Hennen J. Antisuicidal effects of lithium in manic-depressive disorders.  J Clin Psychiatry. 1999;  60 ((Suppl. 2)) 77-84
• 6 Bowden CL, Calabrese JR, Sachs G. et al . Placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder.  Arch Gen Psychiatry. 2003;  60 392-400
• 7 Calabrese JR, Bowden CL, Sachs G. et al . Placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder.  J Clin Psychiatry. 2003;  64 1013-1024
• 8 Collins JC, MacFarland BH. Divalproex, lithium and suicide among Medicaid patients with bipolar disorder.  J Affect Disord. 2008;  107 23-28
• 9 Goodwin FK, Fireman B, Simon GE. et al . Suicide risk in bipolar disorder during treatment with lithium and divalproex.  JAMA. 2003;  290 1467-1473
• 10 Greil W, Ludwig-Mayerhofer W, Erazo N. et al . Lithium vs. carbamazepine in the maintenance treatment of bipolar disorders: randomized study.  J Affect Disord. 1997;  43 151-161
• 11 Kallner G Lindelius E, Petterson U, Stockman O. et al . Mortality in 497 patients with affective disorders attending a lithium clinic or after having left.  Pharmacopsychiatry. 2000;  33 8-13
• 12 Kessing LV, Søndergård L, Kvist K. et al . Suicide risk in patients treated with lithium.  Arch Gen Psychiatry. 2005;  62 860-866
• 13 Meltzer HY, Alphs L, Green AI. et al . Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT).  Arch Gen Psychiatry. 2003;  60 82-91
• 14 Müller-Oerlinghausen B. Pharmacological suicide prevention under special consideration of lithium salts.  Psychiatr Prax. 2007;  34 ((Suppl. 3)) S292-S295
• 15 Simhandl C, Mersch J. Lithium and bipolar disorder – a renaissance?.  Neuropsychiatrie. 2007;  21 121-130
• 16 Tondo L, Baldessarini RJ. Risks of suicidal ideation, attempts and suicides among 2 826 men and women with types I and II bipolar, and recurrent major depressive disorders.  Acta Psychiatr Scand. 2007;  116 419-428
• 17 Tondo L, Baldessarini RJ, Hennen J. et al . Lithium treatment and risk of suicidal behavior in bipolar disorder patients.  J Clin Psychiatry. 1998;  59 405-414
• 18 Tondo L, Isacsson G, Baldessarini RJ. Suicide in bipolar disorder: Risk and prevention.  CNS Drugs. 2003;  17 491-511
• 19 US Food and Drug Administration (FDA) . Antiepileptic drugs statistical review and evaluation: Antiepileptic Drugs AEDs) and Suicidality. , Accessed at: http://http.www.fda.gov/ohrms/dockets/ac/08/ briefing/2008-4372b1-01-fda.pdf , on 20 August, 2008; 
• 20 Yerevanian BI, Koeka RJ, Mintz J. Lithium, ACs and suicidal behavior in bipolar disorder.  J Affect Disord. 2003;  73 223-228
• 21 Yerevanian BI, Koek RJ, Mintz J. Bipolar pharmacotherapy and suicidal behavior: lithium, divalproex, and carbamazepine.  J Affect Disord. 2007;  103 5-11

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