Table 5. Summary of findings from RCTs.
| Authors | n | Setting and palliative care diagnosis | Intervention (dose, route, duration) | Control | Main outcomes | Secondary outcomes | Depression measures | Results (depression) | Side effects |
|---|---|---|---|---|---|---|---|---|---|
| Salas26 | 20 (11 intervention, nine control) | Palliative care unit; locally advanced or metastatic cancer and pain refractory to opioids | A single continuous 48-h IV infusion of morphine + ketamine (0.5-1.0 mg/kg) | A single continuous 48-h IV infusion of morphine + placebo (not described) | Pain | Depression, tiredness, nausea, anxiety, drowsiness, lack of appetite, well-being, shortness of breath, sedation, satisfaction | ESAS score at baseline (T0), 2 h (T1), 24 h (T2), and 48 h (T3) | No differences were found (T2: ketamine = 0.27-2.41 placebo = -1.13-2.53 p = 0.13; T3: ketamine = 0.60-1.43 placebo = -2.38-3.50 p = 0.08) | One patient died in the placebo group No ketamine-related adverse effects |
| Wang27 | 417 (313 intervention, 104 control) | Hospital; women with cervical carcinoma undergoing laparoscopic total hysterectomy | A single IV injection 1 h after analgesia of 0.5 mg/kg R/S-ketamine (n=104), 0.5 mg/kg S-ketamine (n=104); or 0.25 mg/kg S-ketamine (n=104) | A single IV injection 1 h after analgesia of 50 mL normal saline (104 patients) | Depression, pain | None | HAMD-17 score at baseline and days 1, 2, 3, 5, and 7 | In all treatment groups, the HAMD-17 scores were lower at 1, 2, and 3 days than in the control group (p < 0.05)The high-dose S-ketamine (0.5 mg/kg) group had the lowest HAMD-17 scores (p < 0.05) No difference at 5 postoperative days |
No difference in operative time, bleeding, length of hospital stay, or 1-month complication rate (nausea, dizziness, vomiting) |
| Fan28 | 37 (20 intervention, 17 control) | Hospital; newly diagnosed cancer (various) | A single 40-min IV infusion of 0.5 mg/kg IV R/S-ketamine | A single 40-min IV infusion of 0.05 mg/kg midazolam | Suicidal ideation | Depression | MADRS score at baseline and days 1, 3, and 7 | The ketamine group was less depressed on days 1 (MADRS = 24.46±8.04 vs. 31.89±7.39, p = 0.0339) and 3 (25.09±7.07 vs. 32.03±7.21, p = 0.0546) No difference on day 7 |
No increase in emergent psychiatric symptoms |
| Xu29 | 50 (25 intervention, 25 control) | Hospital; female patients undergoing modified radical mastectomy of unilateral breast cancer | A single 10-min IV infusion of 0.5 mg/kg ketamine 1 h after the start of anesthesia | A single 10-min IV infusion of isotonic saline 1 h after the start of anesthesia | Depression | Pain | HAMD-17 score at baseline as well as days 1, 3 and 7 | The ketamine group had significantly lower HAMD-17 scores than the control group at 1 and 3 postoperative days (p < 0.05) At postoperative day 7, there was no significant between-group difference (p > 0.05) |
No between-group difference in the incidence of adverse reactions The ketamine group had one case of nausea, two cases of irritability, and one case of mild respiratory depression |
| Fallon30 | 214 (107 intervention, 107 control) | Unspecified setting; cancer-related neuropathic pain | Daily doses of 40-400 mg oral ketamine (2-week titration followed by fixed dose for 16 days) | Placebo (not described) | Pain | Depression, anxiety | HADS score (time points not specified) | No between-group difference Mean HADS (ketamine) = -3.481; mean HADS (placebo) = -3.654; median difference = 0.173 (-0.500 to 0.958) |
Eight and 10 adverse events in the ketamine and placebo groups, respectively (cognitive disturbance, dizziness, fatigue, nausea, somnolence) |
| Liu31 | 303 (203 intervention, 100 control) | Hospital; female breast cancer patients who received modified radical mastectomy | A single IV infusion of 0.125 mg/kg of R/S-ketamine (n=102); or 0.125 mg/kg of S-ketamine (n=101) | A single IV infusion of normal saline (n=100) | Depression | Pain | HAMD-17 at baseline and days 3, 7, 30 and 90 | HAMD-17 scores were lower at three days, 1 week, and 1 month after surgery in both ketamine groups when compared to the control group Scores in the S-ketamine group were lower than in the R/S-ketamine group (p < 0.05)No difference at 3 months |
No side effects are reported |
| Zhou32 | 84 (41 intervention, 43 control) | Hospital; patients undergoing elective surgical resection of supratentorial brain tumor | A single 40-min IV infusion of 0.5 mg/kg ketamine | A single 40-min IV infusion of normal saline | Depression | Anxiety, delirium, pain | PHQ-9 and MADRS scores at baseline; days 1, 2, and 3; and at discharge. | The ketamine group had a higher proportion of patients with treatment response on day 3 than the placebo group (41.5 vs 16.3%, respectively; RR: 2.25, 95%CI 1.18-5.50) The rate of remission on discharge was higher with ketamine than with placebo (29.3 vs. 7.0%; RR: 4.20, 95%CI 1.28-13.80) |
Three days after surgery, there was no significant between-group difference in the number of patients who experienced manic symptoms (4.9 vs. 2.3%), psychotic symptoms (7.3 vs. 9.3%), or dissociative symptoms (7.3 vs. 2.3%) |
ESAS = Edmonton Symptom Assessment Scale; HADS = Hospital Anxiety and Depression Rating Scale; HAMD-17 = Hamilton Depression Rating Scale; IV = intravenous; MADRS = Montgomery-Asberg Depression Rating Scale; PHQ-9 = Patient Health Questionnaire; RCT = randomized clinical trials; RR = relative risk.