Study Background: Post-Traumatic Stress Disorder (PTSD) and its associated comorbidities develop after exposure to the traumatic events. In the recent years a global increase in the rate of PTSD and its comorbidities has been observed, especially in the developing countries like Pakistan that is continually suffering from war on terrorism, domestic violence, coupled by poverty and cultural constraints. Due to increasing rates of PTSD and lack of treatment facilities in Pakistan, it is imperative to find a mechanism for controlling mental illnesses in Pakistan. This situation also motivates research on testing the efficacy of modern psychotherapies like EMDR and CBT. Aim: The present study aims at determining the efficacy of EMDR by comparing it with CBT for the treatment of PTSD and comorbid Major Depressive Disorder(MDD) in Pakistan. Research Design: A two arms Crossover Randomized Controlled Trial (RCT) with Repeated Measures Design will be selected. Consolidated Standards of Reporting Trials (CONSORT) group flow diagram will be followed to carry out and report this study. Participants and Setting: This study will be conducted at two rehabilitation centres situated in the district Peshawar, Pakistan. A formal sample size cannot be calculated at this stage because the exact number of PTSD patients located in the selected area is not known. However, participants will be recruited through consecutive sampling technique with a rolling recruitment strategy. The outdoor and indoor patients, who pass exclusion criteria and are positively screen for PTSD symptoms will be recruited for this study. The sample size will be 100 patients depending on the availability and willingness of patients. The patients will be randomly allocated either to EMDR or CBT with an allocation ratio of 1:1. Interventions: Patients will be screened (Time: 01, baseline) then they will undertake 06 psychotherapy sessions. After completing 06 sessions, patients will be assessed (Time: 02, during treatment). Additional 08 psychotherapy sessions will be carried out and after completing 14 sessions, the patients will be once again assessed (Time: 03, post treatment) and then assessed after 06 months (Time: 04, follow-up). Statistical Analyses: All analyses will be performed according to the intention-to-treat (ITT) principle. Variations in symptoms with regard to demographic/baseline characteristics will be analysed by using descriptive statistics, χ2 tests for categorical variables, t-tests, and one way ANOVA for continuous variables. Non-inferiority testing will be used to know whether EMDR is not worse than CBT. To examine changes in PTSD and its associated comorbidities across Time :01, Time: 02, Time: 03 and Time :04 and to check the efficacy of each treatment, a series of Linear Mixed Models, with Maximum Like hood Estimation will be run, including main effects of treatment and time and the interaction effects of treatment\*time. Moreover, a series of multi-level lagged mediation analysis along with moderated mediation analysis will be performed to check the bi-directional mediation between changes PTSD (as mediator) and changes in outcome variables (comorbid symptoms) over time. Means and standard deviations will be used to compute effect sizes (Cohen's d) for pre and post treatment and 6 months follow up
