Ketamine Dosing for Psychiatric Disorders
For treatment-resistant depression, the standard protocol for intravenous ketamine administration is 0.5 mg/kg infused over 40 minutes, which has demonstrated rapid antidepressant effects. 1, 2
Intravenous Ketamine Dosing
- The most common and well-studied dose for treatment-resistant depression is 0.5 mg/kg administered intravenously over 40 minutes 3, 1, 4
- Some patients may respond to doses as low as 0.1-0.2 mg/kg, while others may require up to 0.75 mg/kg 2
- For acute suicidal ideation, doses of 0.2-0.5 mg/kg have demonstrated rapid reduction in suicidal thoughts, with effects beginning as quickly as 40 minutes post-administration 1, 5
- Lower doses (0.2 mg/kg) administered in emergency department settings have shown significant reductions in suicidal ideation for up to 10 days 1
Esketamine (Intranasal) Dosing
- Intranasal esketamine is FDA-approved as an adjunctive treatment for treatment-resistant depression 6
- Esketamine is typically administered twice weekly at doses of 56 mg or 84 mg, with the possibility of titrating up to 84 mg starting with the second dose 6
- Esketamine must be administered under medical supervision according to FDA risk evaluation and mitigation strategy (REMS) 7
Alternative Routes of Administration
While intravenous administration is the most common route, ketamine has also been administered effectively via other routes 2:
- Intranasal
- Oral
- Sublingual
- Transmucosal
- Intramuscular
- Subcutaneous
Bolus administration is safe and effective when ketamine is administered intramuscularly or subcutaneously 2
Treatment Frequency and Duration
- For acute treatment of depression, a series of 6 infusions administered thrice weekly over 2 weeks has shown cumulative antidepressant effects 8
- Response rates approximately double with repeated infusions compared to single infusions, with 59% of patients meeting response criteria after repeated administration 8
- Maintenance treatment with weekly infusions has been shown to maintain antidepressant response in those who initially respond 8
- The ideal frequency for maintenance treatment is individualized, with ketamine typically dosed shortly before the effect of the previous session is expected to wear off 2
Prolonged Infusion Protocol
- A prolonged infusion protocol (96 hours) at 0.15 mg/kg/h titrated toward 0.6 mg/kg/h has shown sustained remission of treatment-resistant depression for up to 8 weeks 9
- This approach resulted in marked reduction of depressive symptoms from baseline that was sustained at both 2 weeks and 8 weeks post-infusion 9
Important Considerations and Side Effects
- Ketamine at therapeutic doses can cause transient dissociative and psychotomimetic effects, which are usually mild and well-tolerated 4
- Transient elevation of heart rate and blood pressure often occur but are rarely responsible for treatment discontinuation 4
- Psychotomimetic effects appear to be dose-dependent, with higher incidence at doses approaching or exceeding 0.5 mg/kg 1
- Monitoring for psychotomimetic experiences and hypertension is recommended during administration 10
- The VA/DoD Clinical Practice Guideline notes that ketamine lacks long-term efficacy and safety trials in major depressive disorder 3, 10
Clinical Applications
- Ketamine should be considered for patients with treatment-resistant depression who have failed at least two adequate trials of antidepressants 3, 1
- It is particularly valuable for patients with acute suicidal ideation given its rapid onset of action 1, 5
- The American Psychiatric Association indicates ketamine should be reserved for patients who have not responded to conventional depression treatments 10