Ketamine for Depression, 4: In What Dose, at What Rate, by What Route, for How Long, and at What Frequency?

Summary & key facts

This paper reviews what is known about giving ketamine at low doses to treat serious depression. Researchers looked across many studies to summarize how much ketamine is usually given, how fast it is given, the different ways it can be given, and how long and how often treatment might go on. They found that ketamine can work for people who have not improved with other treatments, but there is not enough strong evidence yet to make firm rules about the best dose, speed, route, or schedule.

Key facts:

• Ketamine at doses lower than those used for anesthesia is used off-label to treat severe and treatment-resistant depression.
• The most common dose reported is 0.5 milligrams per kilogram of body weight, but some people respond to doses as low as 0.1 mg per kg and others may need up to about 0.75 mg per kg.
• A typical session lasts about 40 minutes, but studies have used sessions as short as 2 minutes and as long as 100 minutes and still reported safety and benefit.
• Intravenous (into a vein) delivery is the most common method, but benefits and safety have also been described with oral pills, under-the-tongue, nasal spray, injected into muscle, and injected under the skin.
• Giving a single quick dose is safe and effective when ketamine is injected into muscle or under the skin.
• People may get just one session, a short course of sessions during the urgent phase, or ongoing maintenance treatment for weeks to years in hard-to-treat cases.
• When treatment is continued over time, the best approach seems to be individualizing the schedule so each dose happens just before the previous effect is expected to wear off.
• The authors say there are complex interactions between dose, how fast it is given, how it is given, and how often it is given, and that we need direct comparison studies before making firm clinical recommendations.
• If ketamine is given at home, the risk that it could be misused or abused needs to be considered.

Abstract

BACKGROUND: Ketamine, administered in subanesthetic doses, is an effective off-label treatment for severe and even treatment-refractory depression; however, despite dozens of studies across nearly 2 decades of research, there is no definitive guidance on matters related to core practice issues. METHODS: This article presents a qualitative review and summary about what is known about ketamine dosing, rate of administration, route of administration, duration of treatment, and frequency of sessions. RESULTS: Ketamine is most commonly administered in the dose of 0.5 mg/kg, but some patients may respond to doses as low as 0.1 mg/kg, and others may require up to 0.75 mg/kg. The ketamine dose is conventionally administered across 40 minutes; however, safety and efficacy have been demonstrated in sessions ranging between 2 and 100 minutes in duration. Bolus administration is safe and effective when the drug is administered intramuscularly or subcutaneously. Whereas the intravenous route is the most commonly employed, safety and efficacy have been described with other routes of administration, as well; these include oral, sublingual, transmucosal, intranasal, intramuscular, and subcutaneous routes. Patients may receive a single session of treatment or a course of treatment during the acute phase, and treatment may rarely be continued for weeks to years to extend and maintain treatment gains in refractory cases. When so extended, the ideal frequency is perhaps best individualized wherein ketamine is dosed a little before the effect of the previous session is expected to wear off. CONCLUSIONS: There is likely to be a complex interaction between ketamine dose, session duration, route of administration, frequency of administration, and related practice. Until definitive studies comparing different doses, rates of administration, routes of administration, and other considerations are conducted, firm recommendations are not possible. From the point of view of clinical practicability, subcutaneous, intranasal, and oral ketamine warrant further study. If domiciliary treatment is considered, the risk of abuse must be kept in mind.

Topics

Forensic Toxicology and Drug Analysis Treatment of Major Depression Veterinary Pharmacology and Anesthesia

Categories

Health Sciences Medicine Pharmacology

Tags

Amygdala Anesthesia Astrobiology Dosing Internal medicine Ketamine Major depressive disorder Medicine Nasal administration Pharmacology Physics Refractory (planetary science) Route of administration Treatment-resistant depression

Substances

Ketamine

Conditions & symptoms

Depression Lack of energy or motivation Sadness or low mood