Can ketamine cause insomnia or suicidal ideation at doses less than 0.5 milligrams per kilogram (mg/kg)?

Ketamine's Effects on Insomnia and Suicidal Ideation at Doses Below 0.5mg/kg

At doses below 0.5mg/kg, ketamine has not been shown to cause insomnia, but it can reduce suicidal ideation with minimal dose-dependent psychotomimetic effects. 1

Effects on Suicidal Ideation

• Ketamine at doses of 0.2-0.5 mg/kg has demonstrated rapid reduction in suicidal ideation across multiple studies, with effects beginning as quickly as 40 minutes post-administration 1, 2
• Lower doses (0.2 mg/kg) administered in emergency department settings have shown significant reductions in suicidal ideation for up to 10 days following infusion 1, 2
• In patients with high baseline suicidal ideation, effect sizes for reduction are substantial (d=2.36 at 40 minutes and d=1.27 at 230 minutes) 2
• The antisuicidal effects of ketamine may be partially independent of its general antidepressant effects, though this requires further investigation 1, 3

Effects on Sleep and Insomnia

• At doses below 0.5 mg/kg, ketamine has not been specifically associated with insomnia in the available evidence 1
• The most recent and highest quality evidence indicates that ketamine at minimal doses (0.015 mg/kg/h infusion without bolus) does not significantly increase delirium or sleep disturbances compared to placebo 1
• Higher doses of ketamine (0.25-0.5 mg/kg) are more likely to cause psychotomimetic effects that could potentially disrupt sleep, including hallucinations and nightmares 1

Dose-Dependent Side Effects

• Psychotomimetic effects of ketamine appear to be dose-dependent, with higher incidence at doses approaching or exceeding 0.5 mg/kg 1
• In a three-arm randomized controlled trial, patients receiving low-dose ketamine (0.25 mg/kg bolus and 0.125 mg/kg/h infusion) had significantly higher delirium scores than both minimal-dose ketamine and placebo groups 1
• The PODCAST trial found that ketamine at doses of 0.5 mg/kg and 1.0 mg/kg increased the incidence of hallucinations (20% and 28% respectively vs. 18% for placebo) and nightmares (12% and 15% respectively vs. 8% for placebo) 1

Clinical Implications

• For patients requiring treatment for suicidal ideation, lower ketamine doses (0.2-0.25 mg/kg) may provide antisuicidal benefits while minimizing psychotomimetic effects 1, 2
• When using ketamine at any dose, monitoring for psychotomimetic experiences is recommended during administration 4
• Oral ketamine at 3 mg/kg (approximately 0.3 mg/kg bioavailable equivalent) has shown efficacy for reducing suicidal ideation with manageable side effects 5

Important Considerations

• The FDA drug label for ketamine notes that misuse or abuse may be associated with anxiety, dysphoria, disorientation, insomnia, flashbacks, and hallucinations 6
• The durability of ketamine's antisuicidal effects across all formulations and doses is limited, typically lasting up to 72 hours 7, 8
• Ketamine should be reserved for patients who have not responded to conventional depression treatments, particularly when rapid reduction of suicidal ideation is needed 4, 2

Conclusion

When considering ketamine administration at doses below 0.5 mg/kg, clinicians should be aware that while these doses can effectively reduce suicidal ideation, the risk of insomnia appears minimal compared to higher doses. However, even at lower doses, monitoring for psychotomimetic effects that could potentially impact sleep quality is warranted.