Cochrane Database of Systematic Reviews
June 28, 2017
Rae Frances Bell, Christopher Eccleston, Eija Kalso
246 citations
Evidence is insufficient to assess the benefits and harms of adding ketamine to opioids for refractory cancer pain. Three small trials (20, 10, and 185 participants) were included. Two older, very small studies reported reduced pain and opioid needs with ketamine, but a newer, larger placebo-controlled trial found no difference in pain intensity between groups. Rapid dose escalation of subcutaneous ketamine to 500 mg did not show clinical benefit and nearly doubled adverse events, including serious ones like cardiac arrest. The overall quality of evidence is very low, meaning the true effect is highly uncertain.
Cochrane Database of Systematic Reviews
September 12, 2021
R. Dean, Claudia C. Hurducas, K. Hawton et al.
97 citations
A systematic review of 64 randomized controlled trials (5299 participants) examined glutamate receptor modulators for unipolar major depression. Ketamine and esketamine may reduce depressive symptoms more than placebo within 24 hours, but the evidence for ketamine is very uncertain, while esketamine shows moderate-certainty evidence for increased remission. No difference in dropout rates was found between these drugs and placebo. Evidence for other glutamate modulators (memantine, lanicemine, etc.) is very limited. The authors call for long-term trials and real-world monitoring to establish safety and efficacy.
Cochrane Database of Systematic Reviews
October 8, 2021
Rebecca L. Dean, Tahnee Marquardt, Claudia C. Hurducas et al.
41 citations
A Cochrane review of ten randomized controlled trials (647 participants) examined glutamate receptor modulators for bipolar depression. Only ketamine appeared more effective than placebo for response rate 24 hours after a single intravenous dose, but evidence was low-certainty and limited to two small trials. Ketamine did not show better remission rates than placebo. Evidence for other modulators—memantine, cytidine, N-acetylcysteine, and riluzole—was insufficient or showed no benefit. The review concludes that while ketamine may have a rapid, transient antidepressant effect, the evidence is too uncertain to draw reliable conclusions, and more rigorous studies are needed.
Cochrane Database of Systematic Reviews
September 11, 2024
Sivan Schipper, Kabir Nigam, Yasmin Schmid et al.
34 citations
Psychedelic-assisted therapy using psilocybin or LSD may help treat anxiety, depression, and existential distress in people with life-threatening diseases, and appears well tolerated with no serious adverse events reported in reviewed studies. However, the evidence is low to very low certainty, meaning results are uncertain and could change with future research. As of 2024, these drugs remain illegal in many countries. Blinding issues and small sample sizes limit confidence; more rigorous studies with active placebos and larger samples are needed. Research is restricted in the US due to Schedule I classification but is increasing.