| Systematic reviews (SR) and meta-analyses (MA) |
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| Major Depressive Disorder (MDD) |
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| Ford, 2014, France13 | Main findings:
Subgroup of Ketamine IV in MDD only
View in own window | Primary Outcome | Findings |
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| SMD of depression scores at 24 hours | −0.91; 95%CI −1.19, −0.64; P<0.01; I2=4.4% | | Secondary Outcome | Findings |
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| Efficacy on suicidal ideation | See chart under Suicidal Ideation | | Dose effect | No comment for specific subgroup | | Adverse events | Dissociative symptoms (i.e., feeling outside of one’s body or perceiving that time is moving more slowly or more quickly than normal), emotional blunting, euphoria, dizziness, headache, blurred vision, dry mouth, poor concentration, increased blood pressure, nausea, vomiting, increased libido, poor coordination, restlessness | | Duration of efficacy | No comment on specific subgroup |
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Author’s Conclusions:
There are no comments or conclusions from the authors regarding the ketamine IV in MDD subgroup population.
The authors have several notes about the use of ketamine in mental health:
“patients with alcohol dependence and substance abuse were excluded … as well as those with a history of psychotic episode” (page 12) “results cannot be extrapolated to date to … mood disorders in the elderly for whom the cardiovascular risk of ketamine administration may overweigh the benefit.” (page 12) “the calculation of a dose effect was not possible” (page 9)
And several recommendations:
“All patients should have a physical examination, routine hematologic and biochemical tests, urine toxicology measurements, and an electrocardiogram to detect unstable medical illness or substance use before ketamine administration.” (page 12) “it does not seem possible to determine if the presence of an anesthesiologist is necessary during ketamine administration in a psychiatric ward.” (page 12)
Overall Conclusions
“The present meta-analysis confirmed ketamine’s efficacy in depressive disorders.” (page 13) “The use of ketamine should remain cautious for patients with cardiovascular history.” (page 13) “Middle- and long-term efficacy and side effects are still not known to date.” (page 13)
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| Suicidal Ideation |
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| Fond, 2014, USA13 | Results:
“The effect of ketamine administration on suicidal thoughts was mostly measured by the suicide item of the depression scales in the non-ECT studies” (page 9)
“… patients who received ketamine had lower suicidal ideation scores from the 40th minute to day 2 and at day 10” (page 9) |
Author’s Conclusion
“Promising results … should be confirmed in future studies because of the high degree of heterogeneity of current protocols and assessments of suicidal ideations.” (page 12) “…not possible to conclude to a specific effect of ketamine on suicidal ideations” (page 12)
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| Naughton, 2014, Ireland6 | Results:
“[Studies] demonstrated that ketamine was associated with robust and rapid antisuicidal effects” (page 3)
“…early antisuicidal effects (within one day) were found with ketamine and these effects remained significant for several weeks” (page 3)
“Repeated ketamine infusions can also reduce suicidality ratings (MADRS-SI) but only as long as the duration of the12-day repeated infusion trial” (page 3) |
Author’s Conclusions:
“… provided us with clinical proof-of-concept that ketamine … have rapid antidepressant effects in affective disorders and appear to reduce suicidal ideation” (page 3) “… ketamine′s effect peaks at 24 hours post infusion and, in general, last 1–2 weeks” (page 3) “If these rapid-acting antidepressants could be safely integrated into treatment, one might shorten or mitigate hospitalization, prevent lost work or school days, reduce suicide and reduce healthcare costs” (page 9)
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| Katalinic, 2013, Australia15 | Results:
Three open-label studies have suggested that ketamine may be an appropriate treatment to rapidly reduce acute suicide risk in depressed patients
View in own window | Study | Time | Ham-D-SI |
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| Thakurta et al.,
(2012) | Baseline | 1.37 (1.3) | | 40 minutes | 0.41 | | 230 minutes | 1.37 | | | Suicidal Ideation item on MADRS |
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| Larkin and Beautrais (2011) | Baseline | 3.9 (SEM 0.4) | | 40 minutes | 0.6 (SEM 0.2) | | 80 minutes | 0.6 (SEM 0.2) | | 120 minutes | 0.7 (SEM 0.2) | | 240 minutes | 0.6 (SEM 0.1) | | Price et al., (2009) | Baseline | 2.85 (1.64) | | 24 hours | 0.77
Response defined as > 50% decrease |
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Author’s Conclusion:
No conclusions from authors about suicidal ideation “While almost all studies have found significant antidepressant effects with ketamine administration, it is clear that not all patients respond … research should begin to focus on identifying predictors of response” (page 16) “Of the studies that followed participants until relapse, about one-third reported relapse within 3 days, one-third reported relapse in about a week, and one-third reported relapse between 20 and 40 days” (page 16)
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| Randomized Controlled Trials |
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| Post-Traumatic Stress Disorder (PTSD) |
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| Feder, 2014, USA14 | Main Findings:
View in own window | Primary Outcome | Change in scores (95%CI) |
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| IES-R @ 24 hours, compared to crossover | 12.7 (2.5, 22.8; p=0.02) | | Secondary Outcome | Findings |
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| MADRS change @ 24 hrs, compared to crossover | 3.7 (−7.5, 14.9; p=0.51) | | QIDS-SR change @ 24 hrs, compared to crossover | 0.2 (−3.9, 4.3; p=0.93) | | CGI-S change @ 24 hrs, compared to crossover | 1.0 (0.1, 1.9; p=0.03) | | CGI-I change @ 24 hrs, compared to crossover | 1.2 (0.5, 1.9; p=0.003) | | Safety Outcomes | Findings |
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| Adverse Effects | Common: Blurred vision, dry mouth, restlessness, fatigue, nausea/vomit, poor coordination
Serious: 3 patients required acute beta-blocker use due to hypertensive urgency |
Author Identified Limitations
“… several patients did not receive a second infusion” (page 7)
“…ketamine was associated with transient but higher rates of dissociative symptoms than midazolam, likely affecting the blind” (page 7) |
Author’s Conclusions:
“A single dose of ketamine was associated with rapid reduction of core PTSD symptoms … in patients with chronic PTSD” (page 7) “We also demonstrated that a single dose of IV ketamine is a safe and generally well-tolerated intervention for patients with chronic PTSD” (page 7)
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| Suicidal Ideation |
| Price, 2014, USA16 | Results:
View in own window Primary
Outcome | Time | Ketamine | Midazolam |
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| SIcomposite | Baseline | 0.15 (2.66) | −0.21 (2.12) | | 24 hours | −2.23 (1.63) | −0.91 (2.52) | | | Cohen d = 0.82 (p=0.01) | | BSS | Baseline | 6.11 (6.76) | 6.19 (6.68) | | 24 hours | 1.13 (2.65) | 3.95 (6.46) | | MADRS-SI | Baseline | 1.61 (1.37) | 1.48 (1.03) | | 24 hours | 0.72 (1.05) | 1.24 (1.26) | | QIDS-SI | Baseline | 0.97 (0.84) | 0.76 (0.76) | | 24 hours | 0.22 (0.54) | 0.62 (0.74) |
“53% of ketamine-treated patients scored 0 on all three explicit suicide measures at 24 hours, compared with 24% of the midazolam group at 24 hours (P = 0.03) and 7% of all patients at baseline” (page 4) 86.1% of ketamine-treated patients scored below a BSS score of 4 (sometimes considered a clinically meaningful cut-off) at 24 hours compared to 61.9% of the midazolam group at 24 hours (p = 0.04) and 47.4% of all patients at baseline” (page 4)
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Author’s Conclusion:
“… ketamine-treated patients exhibited large, rapid reductions in explicit suicidal cognition, which were significantly greater than reductions observed in midazolam-treated patients” (page 6) “…results are consistent with the contention that ketamine’s rapid antidepressant actions could have life-saving potential” (page 7) “… ketamine may work most efficaciously in individuals at the highest risk of suicide” (page 7)
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