Can Depakote (valproate) cause suicidal ideation?

Depakote Can Cause Suicidal Ideation

Yes, Depakote (valproate) can cause suicidal ideation, as it carries an FDA black box warning for increased risk of suicidal thoughts and behavior like all antiepileptic drugs. 1 The risk is approximately twice that of placebo in clinical trials, with an estimated incidence rate of 0.43% in antiepileptic drug-treated patients compared to 0.24% in placebo-treated patients.

FDA Warning and Risk Assessment

Valproate, like all antiepileptic drugs (AEDs), carries the following risks:

• Pooled analyses of 199 placebo-controlled clinical trials showed patients taking AEDs had approximately twice the risk of suicidal thinking or behavior compared to placebo (adjusted Relative Risk 1.8,95% CI: 1.2.7) 1
• This represents approximately one additional case of suicidal thinking or behavior for every 530 patients treated 1
• The increased risk was observed as early as one week after starting treatment and persisted throughout the treatment duration assessed 1
• The risk applies across all AEDs regardless of their mechanism of action and across all indications 1

Risk Factors and Monitoring

Certain patient populations may be at higher risk for developing suicidal ideation when taking Depakote:

• Patients with pre-existing psychiatric disorders
• Patients with epilepsy (higher relative risk than psychiatric or other conditions, though absolute risk differences were similar) 1
• Children and adolescents (FDA warning specifically addresses this population) 2

Healthcare providers should:

• Monitor all patients taking Depakote for the emergence or worsening of depression, suicidal thoughts or behavior, and unusual changes in mood or behavior 1
• Be particularly vigilant during the first few months of treatment and after dose changes 1
• Educate patients, caregivers, and families about the risk and advise them to be alert for concerning symptoms 1

Comparative Risk Among Antiepileptic Drugs

While the FDA warning applies to all antiepileptic drugs as a class, there are some differences in the literature regarding specific medications:

• A 2007 review suggested that valproate might have some protective effects against suicidality due to its serotonergic properties, unlike phenobarbital and phenytoin which were associated with higher suicide risk 3
• However, a 2019 systematic review and meta-analysis found no significant difference in the incidence rates of suicide attempts (RR 0.921; 95% CI 0.383-2.215) or completed suicides (RR 0.607; 95% CI 0.180-2.043) between bipolar patients receiving divalproex versus no medication 4

Clinical Implications

When prescribing Depakote:

1. Perform a thorough suicide risk assessment before initiating treatment
2. Discuss the risk of suicidal ideation with patients and caregivers
3. Schedule more frequent follow-up visits during the initial treatment period and after dose adjustments
4. Instruct patients and caregivers to report any emergence of suicidal thoughts, depression, or unusual changes in behavior immediately
5. Consider the risk-benefit ratio, especially in patients with a history of suicidal ideation or attempts

Conclusion

While Depakote is an effective medication for several conditions including epilepsy and bipolar disorder, clinicians must balance its therapeutic benefits against the risk of suicidal ideation. The FDA black box warning applies to all antiepileptic drugs including Depakote, requiring careful monitoring throughout treatment.