Depressive disorder requiring treatment with electroconvulsive treatment (ECT) MedDRA version: 14.1 Level: PT Classification code 10012378 Term: Depression System Organ Class: 10037175 - Psychiatric disorders
Conditions
Interventions
Trade Name: Ketalar
Product Name: Ketalar
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: ketamine hydrochloride
Sponsors
Manchester Mental Health and Social Care Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patient Inclusion criteria: 1.Male or female aged 18 years and above; 2.Current DSM-IV diagnosis of a major depressive episode, moderate or severe as part of unipolar or bipolar disorder mood disorder diagnosed by the Mini International Neuropsychiatric Interview (MINI) 3.American Society of Anaesthesiologists (ASA) score (excluding mental health considerations in the scoring) of 1, 2 or stable 3, and judged as suitable to receive ketamine by an anaesthetist; 4.Verbal IQ = 85, sufficiently fluent in English to validly complete neuropsychological testing; 5.Capacity to give informed consent; 6.Willing to undertake neuropsychological testing as part of the study. Healthy control inclusion criteria: 1.Aged 18 years or more; 2.Currently psychiatrically well, confirmed through MINI interview and no current psychotropic medication; 3.In good physical health. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: Patient exclusion criteria: 1.DSM-IV diagnosis of a primary psychotic or schizoaffective disorder, current primary obsessive compulsive disorder or anorexia nervosa; 2.History of drug or alcohol dependence (DSM-IV criteria) within the last year; 3.ECT in last 6 months (to avoid confounding the assessment of cognitive outcomes) or has previously received ECT in the current trial; 4.Known hypersensitivity or contraindication to ketamine or excipients in the injection; including significant cardiovascular disease, uncontrolled hypertension, glaucoma, cirrhosis or significant liver impairment; 5.Known hypersensitivity or contraindication to concomitant medications used for ECT: thiopentone (thiopental), propofol and suxamethonium or excipients in the injections; 6.Evidence of organic brain disease including dementia, neurological illness or injury, or medical illness which may significantly affect neuropsychological function; 7.Detained under the Mental Health Act (1983 as amended 2007) or unable to give informed consent; 8.Pregnancy, or at risk of pregnancy and not taking adequate contraception, breastfeeding; 9.Score = 24 on the Mini Mental State Examination (MMSE); 10.In the subgroup receiving MRI based investigation (fMRI, MRS and ASL) contraindication to MRI (eg metal implants or foreign bodies such as from a surgical implant, accident or injury). Control exclusion Criteria: 1.Personal history of psychiatric disorder, as revealed by MINI interview; 2.First degree family history of major psychiatric illness requiring treatment; 3.Significant physical illness including organic brain disease, neurological illness or injury that could interfere with interpretation of results; 4.Psychotropic medication or other medication that could interfere with interpretation of results; 5.Score = 24 on the Mini Mental State Examination (MMSE); 6.In the subgroup receiving MRI based investigation (fMRI, MRS and ASL) contraindication to MRI (eg metal implants or foreign bodies such as from a surgical implant, accident or injury).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Ketamine vs saline treatment will reduce ECT-induced cognitive impairments as measured by being able to learn new verbal information (anterograde verbal memory), remember personal events from their past (autobiographical memory) and saying the names of objects fluently (verbal fluency);Secondary Objective: CLINICAL HYPOTHESES 1) Four months after ECT a significant difference between ketamine and saline groups in cognitive function will remain only for autobiographical memory 2). Ketamine vs saline treatment will result in a greater decrease in depression scores after 4 treatments 3) Compared with saline, patients receiving ketamine will need fewer ECT treatments to achieve remission MECHANISTIC HYPOTHESES 4) Ketamine vs saline, treatment will increase frontal cortex activation as measured by brain imaging (fNIRS and fMRI) in response to a verbal fluency, but not a working memory task, and this will relate to group differences in task performance. 5) Ketamine vs saline treatment will result in stronger frontal cortex-hippocampal connections (measured by functional connectivity analysis with fMRI with the verbal fluency task). 6) Ketamine treatment vs saline treatment will be associated with a relative increase in frontal brain blood oxygenation which will be related to differences;Primary end point(s): Change in memory between baseline and end of ECT course measured by: Hopkins Verbal Learning Test – Revised (HVLT-R) Autobiographical Memory Interview - short form (AMI-SF) Controlled Oral Word Association Test (COWAT);Timepoint(s) of evaluation of this end point: Changes between baseline and end of ECT course | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: A: Changes between baseline and one and 4 month follow up. B: Changes between baseline and end of ECT, and one and 4 month follow up. C and D: Baseline, after 4 ECT treatments, at end of ECT and at one and 4 month follow up. E: Baseline and end of ECT;Secondary end point(s): A Changes in memory between baseline and one and 4 month follow up measured by: Hopkins Verbal Learning Test – Revised (HVLT-R) Autobiographical Memory Interview - short form (AMI-SF) Controlled Oral Word Association Test (COWAT) B Cognitive changes between baseline and end of ECT, and one and 4 month follow up measured by: Medical College of Georgia Complex Figure Test (MCG complex figure test) Digit span Self-reported Global Self Evaluation of Memory (GSE-My) C Symptoms ratings measured from baseline to after 4 ECT treatments, at end of ECT and at one and 4 month follow up measured by: Mongomery Asberg Depression Rating Scale Clinical Anxiety Scale Brief Psychiatric Rating Scale Remission at end of ECT (MADRS =10) Number of ECT treatments to achieve remission Response at end of ECT (= 50% decrease in MADRS from baseline) Clinical Global Impression – Severity and Improvement (CGI-S, CGI-I) Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) Proportion significantly worsening after end of ECT (MADRS increase of =4 points + CGI-S increase of =1 point to CGI-S =3 compared with assessment at end of ECT. D Mechanistic outcomes in subgroups between baseline and end of ECT, and at one and 4 month follow up: Haemodynamic response to verbal fluency and working memory tasks using fNIRS Tissue oxygenation index measured by NIRS E Mechanistic outcomes in subgroups between baseline and end of ECT: Haemodynamic response to verbal fluency and working memory tasks using fMRI Brain glutamate concentration measured by magnetic resonance spectroscopy Frontal blood flow measure by arterial spin labelling fMRI | — |
Countries
United Kingdom
Contacts
Public ContactProf Ian Anderson
University of Manchester
Outcome results
None listed