Table 4.

Summary of selected clinical research with dissociatives.

Study	Drug (dose) / Design	Total N (no. females) / Diagnosis	Key Findings
Berman et al., 2000	Ketamine (0.5 mg/kg, i.v.) / randomized double-blind placebo-controlled	9 (5) / MDD a (n=8); BPD b (n=1)	Significant decrease in depression from 4 to 72 hours post-ketamine infusion, with mean Hamilton Depression Rating Scale (HDRS) scores decreased by 14 ± SD 10 points vs. 0 ± 12 points, respectively during active and sham treatment (p = 0.02).
Cummings et al., 2015	DXM (20–60 mg daily) + quinidine (10–20 mg daily) / randomized double-blind placebo-controlled	220 (126) / AD d with agitation	Significantly reduced Neuropsychiatric Inventory Agitation / Aggression scores for dextromethorphan-quinidine vs. placebo (p < 0.001).
Diazgranados et al., 2010b	Ketamine (0.5 mg/kg, i.v.) / randomized double-blind placebo-controlled	18 (12) / treatment-resistant BPD, current depressive episode	Significant decrease in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from 40 minutes to 3 days post-ketamine infusion (p < 0.001); 71% of volunteers responded to ketamine vs. 6% responded to placebo.
Feder et al., 2014	Ketamine (0.5 mg/kg, i.v.) / randomized double-blind active placebo (midazolam)	41 (19) / chronic PTSDd	Significant and rapid reduction in PTSD symptom severity on the Impact of Event Scale in ketamine vs. midazolam at 24 hours post-treatment (p = 0.02).
Krupitsky & Grinenko, 1997	Ketamine (2.5 mg/kg, i.m) with psychotherapy / open label vs. control (TAU) e	211 (0) / chronic alcohol dependence	Significantly greater abstinence in ketamine group (65.8%) vs. treatment as usual control group (24%) at 12-month follow-up (p < 0.01).
Krupitsky et al., 2002	Ketamine (2.0 mg/kg, i.m) with psychotherapy / randomized double-blind active placebo (0.2 mg/kg ketamine, i.m.)	70 (15) / opioid dependence	Significantly greater biochemically verified opioid abstinence in ketamine group vs. active-placebo control group at 12-month and 24-month follow-up (p < 0.05).
Murrough et al., 2014	Ketamine (0.5 mg/kg, i.v.) / randomized double-blind active placebo (midazolam)	73 (37) / treatment-resistant MDD	Significantly greater decrease in MADRS scores in the ketamine group than control group 24 hours post-treatment (p ≤ 0.002); 64% of volunteers responded to ketamine vs. 28% to placebo at 24 hours post-treatment.
Nagele et al., 2015	N2O f (50% + 50% oxygen inhalation for 60min) / randomized double-blind placebo-controlled cross-over	20 (12) / treatment-resistant MDD	Significantly greater decrease in HDRS scores at 2 hours and 24 hours after N2O vs. placebo (p < 0.001). 20% of volunteers responded to N2O vs. 5% responded to placebo at 24 hours post-treatment.
Rodriguez et al., 2013	Ketamine (0.5 mg/kg, i.v.) / randomized double-blind placebo-controlled cross-over	15 (7) / OCD g	Significantly greater decrease in Yale-Brown Obsessive Compulsive Scale scores in ketamine than placebo group (p < 0.01); 50% of volunteers responded to ketamine vs. 0% responded to placebo at 7 days post-treatment.
Zarate et al., 2006	Ketamine (0.5 mg/ kg, i.v.) / randomized double-blind placebo-controlled	18 (12) / treatment-resistant MDD	Significant decrease in HDRS scores from 110 minutes to 7 days post-ketamine infusion vs. placebo (p < 0.05); 71% of volunteers responded to ketamine vs. 0% placebo at 24 hours post-treatment.

Note.

^aMDD= Major depressive disorder.

^bBPD = Bipolar disorder.

^cAD = Alzheimer’s disease.

^dPTSD = Post-traumatic stress disorder.

^eTAU = Treatment as usual.

^fN2O = Nitrous oxide.

^gOCD = Obsessive-compulsive disorder.