This study aimed to evaluate the effectiveness of adding PM+ for CMDs to routine care in a specialized mental health care facility in Pakistan. We hypothesized that PM+ in combination with Treatment-as-Usual (TAU) will be superior compared to TAU alone, to reduce the symptoms of depression and anxiety measured with Hospital Anxiety and Depression Scale (HADS) total score at 20 weeks after baseline.
Design
We conducted a single-blind individual randomized controlled trial (RCT) to evaluate the effectiveness of PM+ plus Treatment-as-Usual (TAU) versus TAU alone in the treatment of CMDs in patients presenting in the out-patient department of Institute of Psychiatry, Rawalpindi, Pakistan. The study was conducted over the duration of 12 months. Ethical approval of the study was obtained from the Institutional Review and Ethics Board of the Rawalpindi Medical University and Allied Hospitals Rawalpindi (ethical approval certificate number ERC/RMU/01/06/2015). The full trial protocol is available online (16). Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12616000381482. Registered Retrospectively on March 23, 2016.
Study settings
The participants were recruited from the Institute of Psychiatry (IoP), WHO Collaborating Centre for Mental Health Research and Training, Benazir Bhutto Hospital-the public sector tertiary care hospital in Rawalpindi, Pakistan. IoP is the hub of mental health policy, services, training and research in Pakistan. It is the specialist referral facility for the patients with mental health problems presenting in the primary and secondary health care facilities in the north of Pakistan. Patient services include in-patients and out-patient services which are led by teams comprising of consultant psychiatrists and psychologists, trainee psychiatrists and psychologists, social workers and interns.
Participants
The target population for this study was adult (age 18-60 years) outpatient department attendees, referred for psychological support for depression, anxiety and stress related conditions by psychiatrists after clinical evaluation who (a) scored above 2 on a screening questionnaire for psychological distress (General Health Questionnaire-12; GHQ-12; (17, 18) and (b) scored above 16 on a screening questionnaire for functional impairments (WHO Disability Assessment Schedule – WHODAS 2.0) (19). As PM+ is not suitable for the treatment of severe mental health problems (including psychosis or risk of suicide) (13), participants with imminent risk of suicide, severe mental disorder (e.g. psychotic disorders, substance dependence), or severe cognitive impairment (e.g. severe intellectual disability, dementia) as assessed by psychiatrists, were excluded from the study.
Interventions
Problem Management plus (PM+)
The WHO PM+ intervention (individual version) (13) is based on established principles of problem solving and behavioral techniques and is delivered in five weekly face-to-face sessions administered on an individual basis. The average duration of each session is 90 minutes. The two key features of WHO PM+ program are (a) the program takes a task-shifting approach where non-specialists (workers without a professional license specific for mental health care such as, in Pakistan, psychology graduates, nurses and community volunteers) can deliver this program to adults experiencing common mental health problems (e.g. anxiety, stress, depression and grief) (b) it is trans-diagnostic - it addresses a range of symptoms for common mental disorders and does not require an expert diagnosis of condition to qualify treatment. PM+ providers in this study had a master’s degree (16 years of education) in psychology and received eight days training in PM+ by the master trainer followed by fortnightly supervision meetings with the master trainer.
Treatment‑as‑Usual (TAU)
Treatment-as-usual in the outpatient’s department consists of an initial assessment by trainee psychiatrists followed by an expert consultation on the case by consultant psychiatrist. The main stay of treatment is pharmacotherapy and psychological support where needed. A psychological support session comprises of brief semi-structured psycho-education sessions for patients with depression and anxiety symptoms and training in anger and stress management strategies such as breathing exercises. A complete record of services received by trial participants in both study arms was obtained using the Client Services Receipt Inventory (CSRI).
Primary outcomes
The primary outcomes were (a) symptoms of anxiety and depression measured using the Hospital Anxiety and Depression Scale (HADS) (20, 21) and (b) functional impairment as measured by WHODAS 2.0 (22) at 20 weeks after baseline
a) The HADS is a well-established 14-item scale consisting of two subscales: HADS-A (anxiety, seven items, and scores range from 0–21) and HADS-D (depression, seven items, scores range from 0–21), where higher scores indicate more anxiety and/or depression. In our study, we used a previously validated Urdu version of HADS (20).
b) Functional impairment was assessed using the 12-item WHO Disability Assessment Schedule (WHODAS 2.0) (22). WHODAS 2.0 assesses participants’ health-related difficulties in the level of functioning in six domains of life (understanding and communicating; moving and getting around; attending to one’s hygiene, dressing, eating and staying alone; interacting with other people; domestic responsibilities, leisure, work and school and joining in community activities, participating in society) over the past 30 days. WHODAS 2.0 has been extensively used in different populations and health conditions including mental health and established itself as gold standard to measure functioning (23).
All the study tools were administered in local (i.e. Urdu) language and have been previously used in the similar settings of Pakistan (9, 10, 24).
An independent assessment team, trained in the ethical conduct of research and assessments and blinded to the allocation status of the trial participants, conducted baseline and post-intervention assessments.
Secondary outcomes
The secondary clinical outcomes included;
The Patient Health Questionnaire-9 (PHQ-9), which is a 9-item instrument measuring presence and severity of depression during the past 2-weeks on a 4-point Likert scale ranging from ‘not at all’ to ‘nearly every day’. The PHQ-9 total severity score ranges from 0 to 27 (25). Higher scores indicate more severe depression. We used the previously validated Urdu version of PHQ-9 (26, 27).
The 17 item Post Traumatic Stress Symptoms-Checklist (PCL-C) was used to measure DSM-IV based posttraumatic stress disorder symptoms. The participants are asked to rate their responses on a 5-point scale during the past week. The PCL-C has been used previously in Pakistan (28) and found to have good psychometric properties (Mushtaq, unpublished data, 2013). In the current study, we changed the reporting time of PCL from last month to last week to enhance the sensitivity of tool to detect change at the 3 months’ post-intervention.
Psychological profile outcome (PSYCHLOPS)- (29) assesses personally identified problems. It consists of four questions that encompass three domains: problems (2 questions), functioning (1 question) and wellbeing (1 question). Participants are asked to give free text responses to the problem and function domains. Responses are scored on an ordinal 6-point scale producing a maximum score of 20 (6 points per domain). The PSYCHLOPs version administered at post-treatment and follow-up also includes an overall evaluation question (determining self-rated outcome ranging from ‘much better’ to ‘much worse’) in relation to the identified problem. PSYCHLOPS has been validated in primary care populations across several countries (30, 31).
The Multidimensional Scale of Perceived Social Support (MSPSS) (32) aims to measure perceived social support. It includes 12 items which cover three dimensions: support from family, friends and significant other. Each item is rated on a 7-point Likert-scale (1 = very strongly disagree; 7 = very strongly agree). A total score is calculated by summing the responses of all items (range 12–84) with higher scores indicating higher levels of perceived social support. The MSPSS has been validated in Urdu. (33)
Services accessed by participants were recorded using the Client Services Receipt Inventory (CSRI). The CSRI was developed for the collection of data on service utilization and related characteristics of people with mental disorders, as the basis for calculating the costs of care for mental health cost-effectiveness research (34). It has been previously used in Pakistan and India (34, 35).
Procedure
Patients who presented at the out-patients’ departments between July 2015 and November 2016 for treatment of CMDs were evaluated by a psychiatrist. After clinical evaluation, if the psychiatrist decided psychological support was indicated, s/he introduced the study and took verbal consent for participation in the study. Written informed consent was obtained from eligible participants by the study coordinator. Participants were randomized to intervention or control arm on a 1:1 basis using computerized software by an independent researcher. The allocation concealment was ensured by keeping random sequence in sequentially numbered, opaque, sealed envelopes, at the off-site center. The intervention arm participants received a total of five weekly individual sessions of PM+ program by PM+ providers and TAU from the psychiatrists/psychologists. The control arm participant received TAU from the psychiatrist/psychologists at the mental health facility. Post-treatment assessments were carried out at two-time points a) seven-week after baseline and b) 20 weeks after baseline. Participants who developed severe psychiatric problems (e.g., psychosis, imminent suicidality) at follow-up were referred to psychiatrists for specialist care (n=3).
Statistical analysis
Sample size calculation was based on a multicenter study of culturally-adapted cognitive behavioral therapy (CBT)-based intervention conducted in Pakistan that used the HADS as the primary outcome measure (36). A two-point reduction in HADS depression score between the intervention and control arm is considered to be clinically relevant (36). With p < .05 and 90% power, a total of 96 participants were needed. Accounting for an expected drop-out rate of 50%, the total sample size was 192 participants, who were equally randomized to PM+ (n = 96) and TAU (n = 96).
The data was analyzed using an Intent-To-Treat (ITT) analysis approach. The primary outcome was summarized using number of participants (n), means and standard deviations (SD). To estimate the treatment effect, a linear mixed model was employed for the primary endpoint analysis, which had treatment, visit, interaction between treatment and visit as fixed effects, baseline measurement of primary endpoint as covariate, and subject as random effects. The mean difference between two treatment arms at each visit/time together with its 95% confidence interval was derived from the mixed model. Covariate-adjusted mixed model of primary endpoint (20 weeks after baseline) was also performed by adding pre-specified covariates at baseline into the above model. Secondary continuous outcomes were analyzed in a similar way. Missing data was treated as missing at random in the mixed model analysis and no imputation of primary and secondary endpoints was made. All analyses were performed using SAS 9.3.