Zarate 2012.
| Study characteristics | ||
| Methods | Double‐blind randomised placebo‐controlled cross‐over study | |
| Participants |
Diagnosis: DSM‐IV bipolar I or II diagnosis without psychotic features, currently experiencing a major depressive episode of at least 4 weeks. MADRS > 19 at screening and at the start of each infusion N: 15 randomised. Age: 46.7 years (SD = 10.4) Sex: 8 females, 7 males. Baseline depression severity: ketamine group = 34.143 (SD = 5.429); placebo group = 35.625 (SD = 5.854) |
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| Interventions | Ketamine (7 in phase 1) vs placebo (8 in phase 1) as add‐on treatment to either lithium or valproate within the specified range during the entirety of the study (levels obtained weekly) 0.5 mg/kg single dose intravenous ketamine infusions Placebo saline solution (0.9%) No concomitant treatment with psychotropic medications in 2 weeks before randomisation (5 weeks for fluoxetine) other than lithium or valproate (2‐week washout period) |
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| Outcomes | MADRs scores HRSD scores BDI scores Visual Analogue Scale Hamilton Anxiety Rating Scale BPRS Clinician Administered Dissociative Scale YMRS Adverse events Response rates (50% improvement from baseline on MADRS) Remission rates (MADRS < 10) Effects on suicidal ideation |
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| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomly assigned using a random number chart |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | All staff, including the anaesthesiologist, were blind to whether placebo or drug was being administered. Study solutions were supplied in identical 50 mL syringes |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Not reported |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Dropout rates recorded and 'n' provided for each time point |
| Selective reporting (reporting bias) | Unclear risk | No results tables available in original publication. All requested data received through correspondence |
| Other bias | Unclear risk | No other bias was identified in this study, but this possibility cannot be ruled out |
AEs: adverse effects; BDI: Beck Depression Inventory; BDNF: Brain Derived Neurotrophic Factor; BDRS: Bipolar Depression Rating Scale; BL: Baseline;BL: Baseline; BPRS: Brief Psychiatric Rating Scale; CGI‐I: Clinical Global Impression;CRP: C‐reactive protein; DSM‐IV: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition;HRSD: Hamilton Rating Scale for Depression; IL‐6; interleukin 6;LIFE‐RIFT: Range of Impaired Functioning Tool; LOCF: Last Observation Carried Forward; MADRS: Montgomery‐Asberg Depression Rating Scale; MINI: Mini International Neuropsychiatric Interview; NAC: N‐acetyl cysteine; PGI‐I: Patient Global Imression of Improvement; POMS: Profile of Mood States;Q‐LES‐Q: Quality of Life Enjoyment and Satisfaction Questionnaire; SD: standard deviation; SOFAS: Social and Occupational Functioning Assessment Scale; WAIS: Wechsler Adult Intelligence Scale; YMRS: Young Mania Rating Scale.