Can ketamine cause insomnia or suicidal ideation at low doses?

Ketamine's Effects on Suicidal Ideation and Insomnia at Low Doses

Ketamine appears to reduce suicidal ideation rapidly at low doses (0.5 mg/kg IV) rather than cause it, though evidence supporting its clinical use for this purpose remains preliminary and limited. 1, 2

Effects on Suicidal Ideation

• Ketamine has demonstrated a rapid albeit transient effect in reducing suicidal ideation in patients with mood disorders, with effects beginning within hours rather than weeks 2, 3
• The antisuicidal effect typically lasts up to 72 hours post-infusion but does not persist thereafter 4
• Most studies used intravenous ketamine at 0.5 mg/kg infused over 40 minutes, showing significant reductions in suicidal ideation compared to placebo 1
• The effect size for ketamine's reduction of suicidal ideation is moderate to large (Cohen's d=0.48-0.85) within the first week after administration 3

Relationship to Sleep and Insomnia

• There is no substantial evidence in the provided literature indicating that ketamine at low therapeutic doses causes insomnia 1
• The FDA drug label mentions that insomnia has been reported as a potential symptom when ketamine is used as a drug of abuse, but does not specifically list it as an adverse effect at therapeutic doses 5
• The focus of most studies has been on ketamine's antisuicidal and antidepressant properties rather than its effects on sleep 6, 7

Important Clinical Considerations

• Ketamine's effect on suicidal ideation appears to be partially independent of its effects on overall depression symptoms 3
• The American Psychiatric Association suggests considering ketamine infusion (0.5 mg/kg) for rapid reduction of suicidal ideation in acute suicidal crisis 2
• The evidence supporting ketamine's use specifically for suicidal ideation is still preliminary, with limitations including:
  • Small sample sizes in most studies 1, 4
  • Exclusion of patients with significant suicidal ideation at baseline from many studies 1
  • Potential functional unblinding when saline is used as placebo 1
  • Limited data on maintaining the antisuicidal effects long-term 1

Safety Concerns

• The FDA warns that ketamine has potential for abuse and dependence, with reports of anxiety, dysphoria, disorientation, insomnia, flashbacks, hallucinations, and psychotic episodes when used as a drug of abuse 5
• All studies reviewed examined ketamine's effects on suicidal ideation, not on actual suicidal behavior; whether effects on ideation translate to reduced behavior has not been established 1, 4
• Any consideration of ketamine for clinical use should weigh the known risks against the limited evidence of efficacy 1

Mechanism and Neurological Effects

• Low-dose ketamine improves brain network integrity, including increased degree centrality and clustering coefficient in the angular gyrus and right thalamus 8
• These neurofunctional changes in the thalamus and default-mode network may be associated with ketamine's antidepressant and antisuicidal effects 8

In conclusion, the current evidence suggests that low-dose ketamine reduces rather than causes suicidal ideation, with no clear evidence that it causes insomnia at therapeutic doses. However, clinicians should be aware of ketamine's potential for abuse and associated adverse effects, including possible insomnia when misused. Further controlled trials are needed to establish long-term efficacy and safety profiles.