What medication is indicated for a patient with severe Major Depressive Disorder (MDD) and suicidal ideation?

From the Guidelines

For a patient with severe Major Depressive Disorder (MDD) and suicidal ideation, ketamine is indicated as an adjunctive treatment for short-term reduction in suicidal ideation, as supported by the VA/DoD CPG 1.

Key Points:

• Ketamine has been shown to result in rapid improvement of suicidal ideation symptoms, with benefits beginning within 24 hours of infusion and continuing for at least 1 week 1.
• Esketamine is also approved for the treatment of depressive symptoms in adults with MDD and acute suicidal ideation or behavior, but its effectiveness in preventing suicide or reducing suicidal ideation or behavior has not been established 1.
• Close monitoring of the patient's mental status and suicidal ideation is essential, with regular follow-up appointments and adjustments to the treatment regimen as needed.
• Other medications such as lithium and clozapine may also be considered for their potential to reduce suicidal behaviors, but their use is limited by their side effect profiles and the need for close monitoring 1.
• Non-pharmacologic interventions, such as cognitive behavioral therapy (CBT), may also be effective in reducing suicidal ideation and behavior 1.

From the FDA Drug Label

The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD.

The FDA drug label does not answer the question.

From the Research

Medication Options for Severe Major Depressive Disorder (MDD) and Suicidal Ideation

• Venlafaxine has been found to be effective in the treatment of severe depression, with studies suggesting it may be particularly effective for severely ill patients 2.
• Ketamine has been reported to have rapid antidepressant effects and reduce suicidal ideation in patients with treatment-resistant depression, although one study found that repeated doses of ketamine did not outperform placebo in reducing depression severity or suicidal ideation 3, 4.
• Medications, in general, have been found to be effective in reducing suicidal ideation, with one study showing that medication yielded a significant reduction in suicide symptoms compared to placebo 5.

Considerations for Treatment-Resistant Depression

• Psychotherapy, such as cognitive-behavioral therapy (CBT), interpersonal therapy (IPT), and group dialectical behavioral therapy (DBT), has been found to be beneficial as an adjunct to usual care (with antidepressants) for patients with treatment-resistant depression, with moderate-quality evidence showing improvement in depressive symptoms and response and remission rates over the short term 6.
• The addition of CBT to usual care has been found to be cost-effective over the long term, with moderate-quality evidence showing no difference in acceptability (dropout) over the medium term and lower dropout over the long term 6.

Key Findings

• Venlafaxine and ketamine are potential medication options for severe MDD and suicidal ideation, although more research is needed to fully understand their effectiveness.
• Psychotherapy, particularly CBT, may be a beneficial adjunct to usual care for patients with treatment-resistant depression.
• Medications, in general, have been found to be effective in reducing suicidal ideation, although more research is needed to fully understand their effectiveness in this area.