Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD)

Summary & key facts

Researchers tested one single ketamine infusion given into a vein over 40 minutes in 99 adults with depression that had not improved after at least two antidepressant treatments. People were randomly given one of four low doses of ketamine or an active placebo drug called midazolam. The usual clinical dose of ketamine and a higher dose reduced depression symptoms quickly by the next day, but most of that benefit was gone by day three. Higher ketamine doses caused more brief dissociation and short-lived rises in blood pressure. The study shows some ketamine doses can act fast, but the effects were short and the study looked only at one infusion, so it does not prove long-term benefit.

Key facts:

• Ninety-nine adults aged 18 to 70 who had not gotten better after at least two antidepressant courses took part in the trial.
• Each person received a single 40 minute infusion into a vein of either ketamine at one of four doses or the active placebo midazolam.
• The ketamine doses tested were about 0.1, 0.2, 0.5, and 1.0 milligrams per kilogram of body weight.
• The standard ketamine dose and the higher dose were clearly better than the placebo at reducing depressive symptoms one day after treatment.
• By day three after the infusion, the differences between ketamine and the placebo were no longer clearly significant.
• Higher ketamine doses caused more short-term dissociation and temporary increases in blood pressure compared with the placebo.
• This study tested only a single infusion given alongside people’s regular antidepressant medicines and followed them for 30 days, so it cannot say whether repeated treatments or long-term use would work or be safe.

Abstract

Numerous placebo-controlled studies have demonstrated the ability of ketamine, an NMDA receptor antagonist, to induce rapid (within hours), transient antidepressant effects when administered intravenously (IV) at subanesthetic doses (0.5 mg/kg over ...

Topics

Mental Health Research Topics Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Alternative medicine Amygdala Anesthesia Antidepressant Depression (economics) Dose-ranging study Double blind Economics Hippocampus Internal medicine Ketamine Macroeconomics Major depressive disorder Medicine Midazolam Pathology Pharmacology Placebo Sedation Treatment-resistant depression

Substances

Ketamine

Conditions & symptoms

Depression Lack of energy or motivation Sadness or low mood