Meta-analysis of short- and mid-term efficacy of ketamine in unipolar and bipolar depression

Abstract

Among treatments currently assessed in major depression, ketamine, has been proposed of great interest, especially because of its very rapid action. However, the time-course of the antidepressive action of ketamine remained unclear. In the present meta-analysis, we provided a clear and objective view regarding the putative antidepressive effect of ketamine and its time-course. We searched the MEDLINE and PsycINFO databases through December 2013, without limits on year of publication, using the key words ketamine and synonyms for mood disorder or episode. Six randomized, double-blind and placebo-controlled trials of ketamine in major depression (n=103 patients) were thus identified. Authors were contacted and they all provided original data necessary for this meta-analysis. Standardized mean differences (SMD) were calculated between the depression scores in ketamine and placebo groups at days 1, 2, 3-4, 7 and 14. Ketamine showed an overall antidepressive efficacy from day 1 to day 7. However, the maintenance of its efficacy over time failed to reach significance in bipolar depression after day 3-4. Significant SMDs were not explained by demographic or clinical characteristics of included samples. The present meta-analysis provides a high level of evidence that ketamine has a rapid antidepressive action during one week, especially in unipolar disorder.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

“…There may be additional benefits to using light therapy in combination with total sleep deprivation (level 2), although there is little clinical experience with this technique. While there is evidence from several small studies that intravenous ketamine (level 3)284 is a highly effective and fast‐acting antidepressant, due to its invasive nature, short duration of effect, and lack of long‐term safety data, it has been relegated to a third‐line treatment, with recommendations that it be reserved for patients with severe symptoms or significant suicidal ideation for whom other treatments have been unsuccessful. In clinical situations that prioritize rapidity of response to treatment, ketamine may be considered earlier in the treatment order, although clinicians need to be aware that the data for efficacy are limited and the effects do not appear to last longer.…”

“…In clinical situations that prioritize rapidity of response to treatment, ketamine may be considered earlier in the treatment order, although clinicians need to be aware that the data for efficacy are limited and the effects do not appear to last longer. Further, there are case reports of manic switch, but the clinical trial data have not provided any confirmatory evidence 284. Also, clinicians need to be aware of potential abuse of ketamine, especially in domiciliary use situations 285…”

Effects of single-dose ketamine infusion on behavioral parameters and neuronal activation in the medial prefrontal cortex of juvenile rats exposed to prenatal stress

“…[9] Effects of ketamine were tested in both patients with MDD and animal models of depression. [10,11] In these basic and clinical studies, morphological and functional alterations have been shown in the brain regions that are critical for the regulation of mood and cognition, including the prefrontal cortex (PFC). [12] Post mortem studies of patients with MDD revealed reduced number of synapses in the PFC.…”

Severe bilateral cerebellar edema from ingestion of ketamine: case report

“…Ketamine is also used to treat a number of psychiatric problems, including depression, bipolar disorder, anxiety, and chronic pain. 13,16,19 Ketamine has reinforcing and rewarding properties, leading to a potential for dependence. It is an increasingly popular "rave" drug.…”