Authors: Sanne Y Smith-Apeldoorn; Jolien KE Veraart; Jan Spijker; Jeanine Kamphuis; Robert A Schoevers · Research
Is Maintenance Ketamine Treatment Effective and Safe for Depression?
This review examines the efficacy, safety and tolerability of maintenance ketamine treatment for depression across different administration routes.
Source: Smith-Apeldoorn, S. Y., Veraart, J. K. E., Spijker, J., Kamphuis, J., & Schoevers, R. A. (2022). Maintenance ketamine treatment for depression: a systematic review of efficacy, safety, and tolerability. The Lancet Psychiatry, 9(11), 907-921. https://doi.org/10.1016/S2215-0366(22)00317-0
What you need to know
- Maintenance ketamine treatment shows promise for sustaining antidepressant effects in treatment-resistant depression across multiple administration routes.
- Intravenous, intranasal, and oral ketamine appear effective for maintaining response for up to 6 months in most studies.
- Serious adverse effects seem uncommon, but long-term risks are still uncertain.
- More rigorous long-term studies are needed to determine the optimal use of maintenance ketamine in clinical practice.
Background on Ketamine for Depression
Ketamine has emerged as a rapid-acting antidepressant treatment option for people with treatment-resistant depression. However, the antidepressant effects of a single ketamine dose typically only last 1-2 weeks. This has led researchers to explore maintenance ketamine treatment as a way to sustain the initial benefits.
This systematic review examined the current evidence on the efficacy, safety, and tolerability of maintenance ketamine treatment for depression. The authors looked at studies using various routes of ketamine administration, including intravenous, intranasal, oral, intramuscular, and subcutaneous.
Efficacy of Maintenance Ketamine Treatment
The review found evidence supporting the efficacy of maintenance ketamine treatment across multiple administration routes:
Intravenous Ketamine
- Short-term (up to 6 months): 72-100% of initial responders maintained response
- Mid-term (6-12 months): 40% maintained response
- Long-term (over 1 year): 21-60% maintained response
Intranasal Ketamine/Esketamine
- Short-term: 73-77% maintained response
- Mid-term and long-term: Some evidence of sustained response, but exact rates unclear
Oral Ketamine
- Short-term: 50-100% maintained response
- Mid-term: 93% maintained response
- Long-term: 82% maintained response
Intramuscular Ketamine
Limited data, but some evidence of sustained response in small samples.
Subcutaneous Esketamine
Very limited data, but one study showed maintained improvement in anhedonia over 6 weeks.
Overall, the evidence suggests maintenance ketamine can sustain antidepressant effects for many patients across different administration routes, at least in the short-term. However, relapse rates increase over longer periods.
Safety and Tolerability
The review found that adverse effects during maintenance treatment were generally mild and transient for most patients. Some key findings on safety:
- Serious adverse events were uncommon
- Cognitive impairment was rarely reported
- Addiction/dependence was reported in only one case
- Urinary/bladder problems were infrequent
- No evidence of significant cognitive decline over time
The most common side effects included dissociation, dizziness, nausea, and headache. These tended to attenuate with repeated dosing.
There were some reports of suicidal ideation/behavior and manic symptoms, highlighting the need for careful monitoring. A few deaths were reported but were not clearly linked to ketamine treatment.
Overall, the safety profile appears similar to that seen with short-term ketamine use. However, the authors note that longer follow-up is needed to detect potential rare or delayed adverse effects.
Limitations and Future Directions
The authors highlight several important limitations of the current evidence:
- Most studies were uncontrolled and had small sample sizes
- Many studies had inadequate assessment of outcomes
- There was high heterogeneity between studies in terms of ketamine dosing, frequency, and duration
- Long-term data beyond 1 year is limited
They emphasize the need for both controlled trials and naturalistic studies with longer follow-up periods and larger sample sizes. This would help clarify the optimal protocols for maintenance ketamine treatment and its long-term risks and benefits.
Conclusions
Despite the limitations in the current evidence, the authors conclude that maintenance ketamine treatment shows therapeutic potential for sustaining antidepressant effects in treatment-resistant depression. The available data suggests it can be effective for many patients while having an acceptable short-term safety profile.
However, they stress the need for caution given the uncertainties about long-term effects. They recommend that maintenance ketamine only be offered to select patients after careful consideration of risks and benefits. Close monitoring and follow-up is essential.
Overall, this review suggests maintenance ketamine could become a valuable option for some patients with treatment-resistant depression, but more research is needed to optimize its use in clinical practice. Both clinicians and patients should be aware of the current evidence base and uncertainties when considering this treatment approach.