This study is a parallel randomized controlled trial with two groups: MBCT-A vs. CBT-A (with a 1:1 allocation ratio). We did not include a no-treatment control group because we were comparing a relatively new treatment with a well-established treatment, and we considered our study to be more ethical if all participants received some form of intervention (26).
The study was approved by the Ethics Committee of the Sixth Hospital of Peking University before initiation of the trial. Each participant was fully informed and agreed to the randomization process. Informed consent forms were obtained from all participants.
The trial was registered at chic.org.cn (registration number: ChiCTR1800019150, registration date: 27/10/2018).
Population and Recruitment
Participants were recruited from the Outpatient Department of the Sixth Hospital of Peking University from November 2018 to November 2019 via a) posters distributed in outpatient clinics and b) recommendations from psychiatrists who worked in the Sixth Hospital of Peking University but were not involved in the study.
A trained research assistant first screened all interested participants by telephone or in-person appointments. Diagnostic screenings were then independently made by an attending psychiatrist in accordance with the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). The principal investigator (B.X.H) conducted a final screening using the study inclusion and exclusion criteria to determine eligibility.
All patients concurrently continued their regular outpatient psychiatry visits for medication management during the study period (treatment-as-usual, TAU) at the Sixth Hospital of Peking University. The regular outpatient psychiatry visits did not include psychotherapy, and the average consulting time was about 10 min per patient, with an average of one visit every two weeks.
We used the following inclusion criteria:(a) Aged 18-65 years; (b) diagnosis of GAD; (c) score of ≥14 on the Hamilton Anxiety Rating Scale (HAMA)(27); (d) medication for on a stable dose for ≥1 month; (e) ability to understand and communication in Chinese. Exclusion criteria were: (a) Diagnosis of any organic mental disorder, schizophrenia, schizoaffective disorder, major depression disorder, or bipolar disorder; (b) abuse of alcohol or other substances in the past 12 months; (c) any conditions that were potentially life-threatening or could severely limit participation (e.g. serious suicidal ideation, antisocial personality disorder, severe or unstable medical illness, pregnancy, breastfeeding); (d) current engagement in psychological treatment for GAD; (e) a history of attending 4 or more mindfulness sessions in the past 2 years. Participants were withdrawn from the study if they (a) had any suicidal behavior or suicide attempts; (b) withdrew their informed consent; or (c) were absent for more than three therapy sessions during the study period.
Randomization Allocation, Concealment, and Blinding
Randomization was performed using computer-generated random numbers that were generated by an independent statistician. Sealed envelopes were used to conceal the randomization sequence. The intervention types were written on sheets of paper that were placed inside opaque envelopes. After the informed consent forms were signed, research assistants opened the envelopes in order and noted the group assignment for the corresponding participants. The participants were notified that the treatments received in both study groups could be helpful in improving anxiety symptoms.
The study was approved by the Ethics Committee of the Sixth Hospital of Peking University before initiation of the trial.
Intervention and Control
The adapted MBCT-A protocol followed the manual described by Segal, Williams, and Teasdale(13, 28). We made several adaptations to render the MBCT appropriate for treating GAD. These changes were developed on the basis of (1) the dissimilar characteristics between GAD and depression, (2) the different needs when attempting to improve current anxiety symptoms vs. preventing a relapse of depression, and 3) clinical experience. The first author (S.S.J) and co-first author (X.H.L) wrote the adapted manualized protocol, which largely reflected the classic protocol for MBCT.
Qualified instructors with more than two years of experience delivered the MBCT-A program. The MBCT-A instructors were supervised by 2 certified MBCT supervisors during the intervention period. The MBCT-A group attended weekly 2-hour sessions over an 8-week period with 20–25 participants in each session. In the MBCT-A manual, the pre-course orientation information was integrated into Session one; psychoeducation about anxiety was integrated into Session four; one-day retreat part of the program was integrated into Session six. Practices in the MBCT-A included mindful eating, body scans, sitting meditation, 3-min breathing space exercises, mindful stretching, and mindful walking.
During the intervention period, participants in the MBCT-A group were given daily audio homework exercises. All participants were instructed to practice mindfulness meditation for 30 min a day and to report their daily mindfulness practice via a messaging and social media application (WeChat).
The CBT-A program followed a manualized protocol originally authored by the corresponding author (X.B.H), that had been used successfully in previous clinical trials(29). The main aim of CBT is to change or challenge the “dysfunctional” thoughts related to generalized anxiety, and to introduce the participant to various relaxation techniques.
Two qualified therapists with either a psychiatry or psychotherapy background led each CBT-A group. The corresponding author X. B. H supervised the CBT-A therapists during the study period. Participants in the CBT-A group attended weekly 1.5 h sessions over 8 weeks with 10–15 participants in each group. Each CBT-A session had a particular theme. Weekly homework was assigned at the end of each session, and was handed in to the therapists and discussed in the following session.
The outcome measures were collected at baseline (T1), week 8 (post-intervention, T2), and at a 3-month follow-up assessment (T3). Four trained psychiatric residents who kept blind to patient’s treatment allocation conducted patient assessments. Demographic and baseline clinical information including age, sex, education history, marital status, ethnicity, residential location, religious beliefs, age of onset, course of GAD, and use of medication was collected using a questionnaire.
The primary outcomes were anxiety response and remission, as measured by the HAMA (27) at 8 weeks and at a 3-month follow-up assessment. The HAMA is a 14-item scale used to evaluate symptom severity in patients with anxiety disorders. For this study, remission was defined as a HAMA total score of less than 7, and response was defined as a ≥ 50% decrease relative to the baseline.
The secondary outcome measures included the total, psychological, and somatic anxiety symptoms measured by the HAMA, state and trait anxiety symptoms measured by the state-trait anxiety inventory (STAI-S, STAI-T), depressive symptoms measured by the Hamilton Depression Rating Scale (HAMD), overall illness severity measured by the Clinical Global Impression-Severity (CGI-S) scale, and quality of life measured by the 12-item Short-Form Health Survey (SF-12). Mindfulness was measured using the Five Facet Mindfulness Questionnaire (FFMQ), on which a higher total score (range 39–195) suggests a higher level of mindfulness(30). This scale has been translated into Chinese and validated(30).
Because no previous studies had compared MBCT with CBT for the treatment of GAD, we used the findings from two studies, one which compared the effects of CBT and medication(29) and the other which compared the effects of MBCT-A and medication(31), for our sample size calculation. Assuming the response rate for MBCT was 0.767 and the response rate for CBT was 0.636 with a type I error-set of 5% and a type II error-set of 20%, we calculated the sample size per group to be 57 participants. With a presumed drop-out rate of 20%, we aimed to recruit 69 participants per group.
All analyses were based on the intention-to-treat principle and statistics were conducted using IBM SPSS Statistics ver. 22.
The baseline characteristics of the two groups were compared using an independent samples t-test or Mann-Whitney’s U test for continuous variables and the χ2 test for categorical variables.
For our primary analyses, we used the χ2 test to analyze the response and remission rates in the two groups at each assessment time (8 weeks after the start of the treatment, 3-month follow-up). The effect size estimates were presented using Cohen's d, and were interpreted as small effects (0.2–0.5), moderate effects (0.5 to 0.8), and large effects (≥ 0.8)(32). For the secondary analyses, we performed separate two-way mixed ANOVAs to compare the mean differences in all secondary outcomes. Group (MBCT-A vs. CBT-A) was used as a between-subjects factor and time (baseline, 8 weeks after treatment onset, 3-months follow-up) was used as a within-subjects factor. The Bonferroni post hoc test was used for post hoc comparisons at each assessment. Partial eta squared (η2p) values were calculated for all significant findings. Significance level was set at p < 0.05.