A Prospective Observational Study Of Suıcıdal Ideatıon, Dıssocıactive Symptoms And Treatment Response In Psychıatrıc Patients Receıvıng Electroconvulsıve Therapy
Conditions: Major Depression, Bipolar Affective Disorder, Bipolar Depression Depressed Phase
Sponsor: Nurdan Sağbaş

STUDY PROTOCOL AND STATISTICAL ANALYSIS PLAN
A Prospective Observational Study of Suicidal Ideation, Dissociative Symptoms, and
Treatment Response in Psychiatric Patients Receiving Electroconvulsive Therapy
NCT Number: Not yet assigned
Study Site: Pamukkale University Hospital, Department of Mental Health and Diseases
Principal Investigator: Res. Asst. Dr. Nurdan Sağbaş
Study Type: Non-Interventional, Prospective Observational Study
Version Date: May 20, 2025

1. Rationale and Aim of the Study
Major Depressive Disorder (MDD) is one of the most prevalent psychiatric disorders worldwide,
affecting 16–20% of the population. According to DSM-5, MDD is diagnosed when at least five
characteristic symptoms — including depressed mood, loss of interest or pleasure, sleep and appetite
disturbances, psychomotor changes, fatigue, feelings of worthlessness, difficulty concentrating, and
recurrent thoughts of death or suicide — persist for at least two weeks and cause significant functional
impairment.
Conventional antidepressant treatments targeting serotonin, dopamine, and noradrenaline systems
typically  require  several  weeks  to  produce  a  clinical  response.  Despite  multimodal  treatment
approaches, approximately one-third of patients fail to achieve functional recovery, meeting criteria
for Treatment-Resistant Depression (TRD), defined as inadequate response to at least two adequate
antidepressant trials from different classes.
Bipolar disorder is a chronic mood disorder characterized by manic, hypomanic, and depressive
episodes,  associated  with  significant  disability,  comorbidity,  and  elevated  suicide  risk.  Bipolar
depression accounts for the majority of illness burden and is the leading cause of long-term functional
impairment across the bipolar spectrum.
Electroconvulsive Therapy (ECT) is an established and highly effective biological treatment for
treatment-resistant depression and bipolar depression, in use since 1938. The choice of anesthetic
agent during ECT has gained increasing attention, as it may influence both treatment efficacy and side
effect profile. Ketamine, an NMDA receptor antagonist with rapid-onset antidepressant properties, and
propofol, a short-acting sedative-hypnotic agent, are both used in ECT anesthesia. While some studies
report superior antidepressant effects with ketamine compared to propofol, others have found no
significant difference. The combination of ketamine and propofol (ketofol) has been proposed as a
strategy to balance efficacy and tolerability.
This  study  aims  to  observationally  evaluate  the  effects  of  ketamine+propofol  versus  propofol
anesthesia on depression severity, suicidal ideation, and dissociative symptoms in patients receiving
ECT for MDD or bipolar depression. Anesthetic agent selection will be made solely by the treating
clinician; researchers will perform observational assessments only.
2. Study Design
Parameter
Details
Study Type
Non-interventional, prospective observational study
Study Model
Prospective cohort with two naturally assigned groups
Time Perspective
Prospective
Study Site
Pamukkale University Hospital, Department of Mental Health and Diseases
Study Duration
Approximately 2 years (following Ethics Committee approval)

Sample Size
65 patients (Group 1: 30; Group 2: 35)
3. Study Population
3.1 Inclusion Criteria
Age 18–65 years
Inpatient at Pamukkale University Hospital, Department of Mental Health and Diseases
Diagnosis of Major Depressive Disorder or Bipolar Disorder, Depressive Episode, according to
DSM-5 criteria
Clinical indication for ECT treatment
No contraindication to anesthesia
Voluntary written informed consent
3.2 Exclusion Criteria
Intellectual disability or cognitive disorder
Active psychotic state
History of neurological disease
Active substance use disorder
Illiteracy (inability to complete self-report scales)
4. Study Groups
Patients will be allocated to one of two groups based on the anesthetic agent selected by the treating
clinician as part of routine clinical care. Researchers will not influence this decision.
Group
Anesthetic Protocol
n
Group 1
Ketamine + Propofol (Ketofol)
30
Group 2
Propofol alone
35
5. Assessment Schedule
All participants will be assessed at four time points using three validated clinical scales:
Time Point
Assessment
T0 – Baseline (before first ECT session)
MADRS, Beck Suicidal Ideation Scale, CADSS
T1 – After 1st ECT session
MADRS, Beck Suicidal Ideation Scale, CADSS
T2 – After 3rd ECT session
MADRS, Beck Suicidal Ideation Scale, CADSS
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T3 – After final ECT session
MADRS, Beck Suicidal Ideation Scale, CADSS
6. Outcome Measures
6.1 Primary Outcome Measure
Change  in  Depression  Severity  (MADRS): Change  from  baseline  in  Montgomery–Åsberg
Depression Rating Scale (MADRS) total score, measured at baseline, after the 1st, 3rd, and final ECT
sessions.
6.2 Secondary Outcome Measures
Change in Suicidal Ideation (Beck Suicidal Ideation Scale): Change from baseline in Beck Suicidal
Ideation Scale total score across all assessment time points.
Change in Dissociative Symptoms (CADSS): Change from baseline in Clinician-Administered
Dissociative States Scale (CADSS) total score across all assessment time points.

7. Assessment Instruments
7.1 Montgomery–Åsberg Depression Rating Scale (MADRS)
A 10-item clinician-rated scale developed in 1979 to assess depression severity. Each item is scored
0–6; total score ranges from 0 to 60. Higher scores indicate greater severity. Widely used to measure
treatment response in ECT and pharmacological studies. Turkish validity and reliability established by
Yapıcı et al. (2003); Cronbach's alpha: 0.79–0.86.
7.2 Beck Suicidal Ideation Scale (BSI)
A 19-item self-report scale assessing the intensity of suicidal ideation, planning, and intent. Each item
is rated 0–2; higher scores indicate greater suicidal ideation. Used to monitor changes in suicide risk
during treatment. Turkish adaptation by Hisli-Şahin (1991); Cronbach's alpha: 0.87.
7.3 Clinician-Administered Dissociative States Scale (CADSS)
A  19-item  clinician-administered  scale  evaluating  dissociative  symptoms  across  three  domains:
amnesia, depersonalization, and derealization. Each item is rated 0–4. Particularly used to assess
ketamine-induced dissociative states. Turkish validity and reliability established by Sar and Ozturk
(2016); Cronbach's alpha: 0.89.
8. Statistical Analysis Plan
8.1 General Approach
All statistical analyses will be performed using SPSS (version 25.0 or later) or an equivalent statistical
software package. A two-tailed p-value of <0.05 will be considered statistically significant.
8.2 Descriptive Statistics
Continuous variables will be summarized as mean ± standard deviation (SD) or median (interquartile
range),  as  appropriate.  Categorical  variables  will  be  presented  as  frequencies  and  percentages.
Normality of distribution will be assessed using the Shapiro-Wilk test.
8.3 Group Comparisons
Independent samples t-test (or Mann-Whitney U test for non-normal distributions): For between-
group comparisons of continuous variables at each time point.
Chi-square test (or Fisher's exact test): For between-group comparisons of categorical variables.
Repeated measures ANOVA (or Friedman test): To evaluate within-group changes in MADRS,
BSI, and CADSS scores across the four assessment time points (T0–T3).
Mixed-model ANOVA: To assess the interaction between group (ketamine+propofol vs. propofol)
and time on outcome measures.
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8.4 Regression Analysis
Logistic regression analysis will be used to identify predictors of treatment response (defined as ≥50%
reduction in MADRS score from baseline). Covariates will include age, sex, diagnosis (MDD vs.
bipolar depression), number of ECT sessions, and anesthetic agent group.
8.5 Missing Data
Missing data will be handled using last observation carried forward (LOCF) or multiple imputation
methods, as appropriate. The extent of missing data will be reported.
8.6 Definitions
Treatment Response: ≥50% reduction in baseline MADRS score
Partial Response: 25–49% reduction in baseline MADRS score
Non-Response: <25% reduction in baseline MADRS score
Remission: MADRS total score ≤10
9. Ethical Considerations
This study will be conducted in accordance with the Declaration of Helsinki and applicable national
regulations.  Ethics  Committee  approval  from  Pamukkale  University  Non-Interventional  Clinical
Research Ethics Committee will be obtained prior to study initiation. Written informed consent will be
obtained from all participants. Patient confidentiality will be maintained throughout the study; data
will be anonymized for analysis and publication. Participation is entirely voluntary, and withdrawal at
any time will not affect the participant's clinical care.
10. Expected Outcomes
This study is expected to provide prospective observational evidence on the differential effects of
ketamine+propofol  versus  propofol  anesthesia  on  depression  severity,  suicidal  ideation,  and
dissociative symptoms in ECT-treated patients. Findings will contribute to the existing literature on
anesthetic agent selection in ECT and may inform clinical decision-making in this patient population.
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