From the Guidelines
Ketamine is a recommended treatment option for patients with major depressive disorder who have not responded to several adequate pharmacologic trials, as evidenced by the 2022 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline [ 1 ].
Key Points
- Ketamine infusion and intranasal esketamine have been shown to improve depressive symptoms in patients with treatment-resistant depression (TRD) [ 1 ].
- A meta-analysis of 20 RCTs found that single-dose ketamine resulted in significant improvement in depressive symptoms after 24 hours, with improvements persisting at 3- and 4-day follow-up visits [ 1 ].
- Esketamine, an FDA-approved nasal spray, has been found to improve depressive symptoms when used as augmentation therapy to ongoing oral antidepressant use [ 1 ].
Administration and Side Effects
- Ketamine is typically administered as intravenous infusions or as esketamine nasal spray under medical supervision [ 1 ].
- Side effects of ketamine can include dissociation, dizziness, nausea, and increased blood pressure during administration [ 1 ].
Considerations
- Ketamine is not first-line therapy due to concerns about long-term effects, potential for abuse, and cost considerations [ 1 ].
- Treatment protocols often involve repeated treatments, as the antidepressant effects of ketamine are typically temporary, lasting days to weeks [ 1 ].
From the Research
Efficacy of Ketamine as an Antidepressant
- Ketamine has been shown to have rapid yet often transient antidepressant effects in patients with treatment-resistant depression 2.
- Maintenance ketamine treatment appears promising in sustaining antidepressant effects, with various routes of administration (intravenous, intranasal, oral, intramuscular, and subcutaneous) being effective 2.
- Combination therapy with transcranial magnetic stimulation (TMS) and ketamine has also been found to be effective in treating treatment-resistant depression, with some studies showing sustained remission for up to two years 3, 4.
Safety and Tolerability of Ketamine
- Tachyphylaxis, cognitive impairment, addiction, and serious renal and urinary problems seem uncommon with maintenance ketamine treatment 2.
- However, possible effects of ketamine on cognitive function have not yet been investigated in randomized controlled trials (RCTs), and chronic recreational use of ketamine has been reported to substantially impair cognitive function 5.
- Oral ketamine has been found to have good overall tolerability, with no clinically significant adverse effects reported in some studies 6.
Routes of Administration and Dosage
- Intravenous ketamine has rapid and robust antidepressant effects, but poor accessibility often limits its use 6.
- Oral ketamine is being investigated as an alternative route of administration, with some studies showing significant antidepressant effects with good tolerability 6.
- Dosages and frequency of administration vary, with most studies providing dosages of 1-2 mg/kg every 1-3 days 6.
Future Directions
- Further studies are needed to determine the position of maintenance ketamine treatment within routine clinical practice, including controlled and naturalistic studies with long-term follow-up and sufficient power 2.
- The development of glutamatergic drugs without ketamine-like adverse events is expected to be a future direction for antidepressant research 5.
- Optimization of combination therapy with TMS and ketamine is also warranted 4.