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Background: Depression is common among women during perinatal period and is associated with long-term adverse consequences for the mother and infant. In Nigeria, as in many other low- and-middle-income countries (LMIC), perinatal depression usually goes unrecognized and untreated. The aim of EXPONATE is to test the effectiveness and cost-effectiveness of an intervention package for perinatal depression delivered by community midwives in primary maternal care in which physician support and enhanced patient compliance are implemented using mobile phones. Methods/Study design: A pragmatic two-arm parallel cluster randomized controlled trial was designed. The units of allocation are the primary maternal care clinics. Thirty eligible and consenting clinics were randomized but, due to problems with logistics, 29 eventually participated. Consenting pregnant women with a gestational age between 16 and 28weeks who screened positive on the Edinburgh Postnatal Depression Scale (EPDS score ≥12), absent psychosis or bipolar disorder, and not actively suicidal were recruited into the trial (N-=-686). Midwives in the intervention arm were trained to deliver psychoeducation, problem solving treatment, and parenting skills. Eight weekly sessions were delivered following entry into the study. Further sessions during pregnancy and 6weeks following childbirth were determined by level of depressive symptoms. Clinical support and supervision, delivered mainly by mobile phone, were provided by general physicians and psychiatrists. Automated text and voice messages, also delivered by mobile phones, were used to facilitate patient compliance with clinic appointments and ‘homework’ tasks. Patients in the control arm received care as usual enhanced by further training of the providers in that arm in the recognition and standard treatment of depression. Assessments are undertaken at baseline, 2months following recruitment into the study and 3, 6, 9 and 12months after childbirth. The primary outcome is recovery from depression (EPDS-<-6) at 6months. Secondary outcomes include measures of disability, parenting skills, maternal attitudes, health care utilization as well as infant physical and cognitive development comprehensively assessed using the Bayley's Scales. Discussion: To the best of our knowledge, this is the largest randomized controlled trial of an intervention package delivered by community midwives in sub-Saharan Africa. Trial registration: Trial is registered with the ISRTCN registry at isrtcn.com; Trial number ISRCTN60041127. Date of registration is 15/05/2013.
The primary aim of this study is to test the effectiveness and cost-effectiveness of a stepped care intervention package for perinatal depression delivered by community midwives in primary maternal care, supported by physicians and mental health specialists through the use of mobile phones, compared to usual care in a randomized controlled trial. The primary hypothesis is that the intervention package will be more effective at alleviating depression at 6 months after childbirth compared to care as usual. The secondary hypotheses are that: 1) the intervention package will be more cost-effective; 2) will lead to better infant outcomes (in regard to cognition and growth) at 12 months; 3) will be associated with better parental skills of mothers; and 4) will lead to less experience of perceived stigma. This study was a two-arm parallel cluster randomized controlled trial comparing an intervention package for maternal depression consisting mainly of psychological interventions (psychoeducation, problem solving treatment and parenting skills) with care as usual. The unit of randomization was the primary maternal care clinic; interventions and outcome measures were however administered on individual participants. As the intervention was designed to be delivered by clinic staff, the cluster randomized design was chosen in order to reduce the potential risk of contamination within clinics. The study was conducted in Oyo State, Nigeria. The state has 33 local government areas (LGA). All 137 maternal and child care clinics (MCCs) in nine LGAs selected for the study (five rural and four urban) were assessed for eligibility to participate. MCCs are the main source of care for most low-income perinatal women and are therefore the appropriate place to test an intervention package that is designed to make a major impact on the delivery of care to this population. Maternal and child health services in these clinics are largely delivered by non-physician primary care providers and midwives, who have been trained as nurses, community health officers and community health extension workers. Each of these categories of providers has a minimum of 2–3 years post-secondary education and are certified by their respective boards. Supervision for all the clinics in each LGA is provided by one general practitioner employed by the government and designated as the Primary Health Care Coordinator for the Local Government. We used both urban and rural areas in order to capture the diversity of socioeconomic profile of the country and because access to medical treatment differs substantially between these two types of setting, thus making the demonstration of the utility of our program potentially more generalizable. Eligible clinics were those that offer full maternal and child health services (n = 49). The study procedures were described to the supervising physicians in each of the LGAs and to the facility managers in each of the eligible clinics. Only clinics providing explicit consent to participate were randomized into the trial. Of the 30 that did so, one was excluded because the staffing profile was too thin to permit for effective participation, thus leaving 29 included in the trial. Eligible and consenting maternal care clinics were stratified by local government area and allocated to intervention or control arm using a computer-generated random number sequence. Allocation was conducted by one of the authors (AAM) using anonymous codes for clinics and LGAs provided by other members of the research team, in order to avoid any risk of selection bias. The study was approved by the University of Ibadan/ University College Hospital Ibadan Ethical Review Committee and was conducted in strict compliance with the guidelines specified by the Committee. The conduct and progress of the study were monitored by three committees: 1) Trial Management Group: This was responsible for providing study oversight including giving operational direction to the study and monitoring progress. This Group, which had monthly teleconference and annual face-to-face meetings, included the investigators and senior researchers; 2) Trial Steering Committee: Its role was to monitor and supervise the implementation of the trial, ensure that there were no major deviations from protocol specifications, and offer advice to the investigators on the scientific conduct of the trial. The Committee was made up of three independent members and scheduled two annual meetings, one face-to-face and the other by teleconference. Additional teleconference meetings were called when information from the Principal Investigator required immediate advice; and 3) An independent Data Monitoring and Ethics Committee whose responsibility was to advise the TSC on ethical and safety issues, including whether such issues could affect the continuation of the study. Considering that allocation concealment and selection bias could be a problem in cluster randomized trials where all participants are not consented and recruited prior to allocation of clusters, consecutive attendees at the selected MCCs were invited to participate by trained research staff while waiting to see the midwife. They were briefly educated about perinatal depression and invited to take the screening interview. Those who agreed were screened with the Edinburgh Postnatal Depression Scale (EPDS). Women who screened positive (EPDS score of 12 or greater) and were eligible for the study (see eligibility criteria below) were invited to participate in the study. Those who provided signed consent following a full description of the study were entered into the trial. Consenting patients were handed their EPDS score and told to see one of the trained CMWs in the clinic. Women most commonly present for the first time for antenatal care early in the second trimester in these clinics. We aim for the findings of our study to be as widely generalizable as possible. We therefore have very limited exclusion criteria. Inclusion Criteria (patients must satisfy all of the following to be considered for study entry) Exclusion Criteria (patients were excluded from study entry if any of the following was met) The intervention package for EXPONATE was an adaptation of an intervention for adults with depression which we had developed and piloted in our earlier study of a stepped care intervention for depression in primary care [33]. The intervention was pragmatic, fully manualised, and took account of specific issues relating to pregnancy, childbirth, marital relationships and parental roles. It incorporated the treatment specifications of the WHO Mental Health Gap Action Programme Intervention Guide (mhGAP-IG) as adapted for the health system of Nigeria [34]. The manual consists of a step-by-step description of psychoeducation, problem solving treatment, social network activation and parenting skills. The intervention was developed following formative research assessing help seeking and experience of care for perinatal depression and contextualization workshops with care providers. These activities enabled us to incorporate culturally relevant experiences, norms, and contexts into the psychological component of the intervention. The intervention package is designed to be delivered in three steps determined by the patient’s score on the EPDS, time since enrollment and gestational status. (See Fig. 1). All consenting and eligible participants with a score of 12 or greater on the EPDS in the intervention arm of the trial were enrolled into Step 1. Step 1 comprised 8 sessions of psychological interventions delivered weekly in the antenatal period. At the end of these first 8 sessions, patients whose gestational age was less than 36 weeks and who still had depression (indicated by an EPDS score of 12 or greater) continued with fortnightly psychological intervention sessions. Step 2 commenced 6 weeks after delivery during the mother’s routine first post-natal clinic visit. Patients were assessed by the CMW using the EPDS. Patients who scored below 12 received 4 fortnightly top-up sessions of the problem solving treatment. Those whose EPDS score was 12 and above received 8 weekly intervention sessions. At the completion of step 2, patients who still had EPDS scores of 12 or more proceeded to step 3. In step 3, patients had to be reviewed by the community physician with a view to initiating pharmacotherapy in addition to continuing with the psychological intervention or referral to specialist service. Treatment flow chart Any patient in the intervention arm with a score of 18 or more or who had suicidal ideation at any time after entry into the trial was reviewed by the community physician who took a decision about the need for a psychiatric review/referral or prescription of medication in addition to the psychological intervention being delivered by the CMW. For patients who required medication, as assessed by the primary care physician, the first line was amitriptyline, which non-physician primary care providers in Nigeria are authorized to prescribe. Each session of the psychological intervention lasted approximately 30–45 min. The CMWs were encouraged to schedule sessions outside of busy clinic hours and at times that were agreeable to both the patient and the CMW. This ensured that sessions could be conducted in strict privacy and with less likelihood of intrusion. The first session was dedicated mostly to familiarizing patients with the health care provider, and providing psychoeducation. In psychoeducation, the nature of the patients’ illness and the modality of treatment were explained in simple language using local expressions while avoiding the labeling of ‘mental illness/disorder’. Patients were encouraged to ask questions and were free to express their feelings. In addition, patients were provided with information booklets written in Yoruba and supported with pictorial representations of depression and the intervention modalities provided in the program. Psychoeducation was continued at each subsequent session. Parenting skills and activity scheduling (behavioral activation) were introduced from the second session. In activity scheduling, patients worked with the CMW to schedule activities that were important or pleasurable to them. Patients were assisted to make a list of pleasurable activities and household chores that they had stopped doing on account of their depression; the CMW then worked with the patient to select at least one to be carried out over the next week. These activities were noted in the patients’ record book kept in the clinic as well as patients take-home card with ‘home work’ tasks. ‘Home work’ tasks from the preceding session were reviewed at the beginning of the next session. The parenting skills component was used to emphasize routine information provided to antenatal women (such as importance of routine antenatal visits, adequate nutrition and rest, preparation for delivery and signs that could indicate an emergency) as well as educate the woman on newborn care, infant nutrition and responsive parenting. Problem solving treatment (PST) was introduced at the third session. We delivered a local adaptation of Problem Solving Treatment for Primary Care (PST-PC), which had earlier been used by us in studies in primary care. PST is an effective seven-step common sense talk therapy that aims at helping patients resolve troublesome problems that contribute to causing or prolonging the depressive episode [35, 36]. It involves working with the patient to identify and explore the problems that they are currently faced with and aiding the patient to develop and implement practicable solutions. The CMW always reviewed with patients their attempts at problem solving at the beginning of each session, praising their efforts and relating improvement in depression symptoms to their improved ability to deal with problems. In the seventh session, using a problem solving approach, the CMW helped the patient to explore their social network with a view to selecting the most appropriate person to provide support for the patient in terms of caring for the new born, older children and household chores following delivery. Part of the patient’s take-home tasks for this session included contacting this caregiver. The last antenatal session was used to review the patients’ progress, emphasize on parenting skills learnt and encourage the patient to continue using the problem solving skills acquired in the course of the treatment sessions on their own. Psychological sessions conducted postnatally provided opportunities to revisit the issues discussed in the prenatal sessions, especially in light of arrival of the new baby, explore further the issues of social (and marital) support, and parenting skills. Subjects who were recruited in the control clinics were also provided with their EPDS scores and advised to show these to their health care providers. Subjects in this arm were provided with enhanced usual care which included all services normally available in the clinics; including antidepressant medications, brief psychotherapeutic interventions, medical consultations, or external referral for specialty treatment. Although all these options were potentially part of usual care, in reality, unstructured counselling was often all a patient with recognized perinatal depression will receive. Structured psychotherapy, consultation with a doctor or referrals to a specialist were very rarely offered. Our usual care is “enhanced” because providers in the control arm received training on the recognition and management of depression based on the specifications of the mhGAP-IG prior to commencement of recruitment into the trial. Prior to recruitment of patients, providers in the intervention arm received training on the recognition of depression, the delivery of the manualized intervention package, the procurement and documentation of support and supervision using mobile phones, and the use of the automated electronic support and documentation system. The training consisted of didactic lectures enhanced with clinical demonstrations and role playing over a 3-day period. They had a further 3-day top-up training about a month into the study to reinforce the skills previously acquired and to identify any difficulties they had encountered in administering the intervention. Training of the providers in the control arm was conducted separately. They received a 2-day training on identification and standard treatment of depression. This training was based on the mhGAP-IG but without detailed PST training or guidelines and procedure for obtaining structured support and supervision from physicians. The CMWs from the control clinics were also provided with manuals providing general information about perinatal depression. Lay research assistants were recruited and trained. The research assistants, all have at least a college degree, were trained to administer the outcome assessment instruments using the computer tablets provided. The research assistants had a 4-day training in the administration of the screening and outcome tools and conducted several trial live interviews before commencing field work. For the Bayley’s Scales of infant development, a Clinical Psychologist with vast experience in the use of the scale conducted an initial one-week training. During this training, the trainer gave didactic lectures on the use of the Scale and demonstration assessments of 2 infants. This was followed with supervised assessment of 2 infants by each of the 5 research assessors. Next, an inter-rater exercise with 20 infants was conducted with each of the assessors conducting 4 assessments that were independently rated by the others. Finally, a further paired assessment of 2 infants was interchangeably conducted by two assessors with one assessor conducting the assessment and the other observing and providing feedback afterwards. The components of and tasks for each treatment session as well as clinical decisions and steps were detailed in manuals and charts provided to the CMW and primary care physicians. To facilitate support and supervision to the CMW, we developed a technological support platform that incorporated a network of mobile telephones linked to an online record system hosted on a secure server. Mobile telephone lines were provided to each of the trained CMW from the intervention clinics and their supervisory community physicians and supervising psychiatrist. These mobile phone lines are linked in a closed user group network where calls within the network are free to facilitate consultation for difficult cases. The CMW were encouraged to call patients to remind them of their clinic appointments. Patients similarly received automated voice messages to reinforce key messages provided during sessions as well as remind them of clinic appointments. The Trial Manager monitored adherence to protocol specification throughout the period of the intervention. This was done by way of regular qualitative as well as quantitative assessments. An assessment of fidelity in the delivery of the intervention was conducted by an independent rater who observed three pre-selected live sessions by each of the providers in the intervention arm using a scale developed for the purpose. The outcome assessments, still on-going at the time of this report, are conducted mostly in the patients’ homes (except when patient prefers to have the assessment elsewhere) by the trained research staff. Outcome assessors have no involvement in delivering the intervention and are rotated between MCCs to collect outcome data. All consenting patients receive baseline assessment within 72 h of being screened and consenting to enter the trial. Follow-up assessments are conducted at 2 months following recruitment into the study and 3, 6, 9 and 12 months after childbirth. All scales are administered in their Yoruba versions, derived through standard iterative procedures which we have employed in previous studies. The primary outcome is recovery from depression at 6 months postpartum (i.e. no longer having significant depressive symptoms as indicated by EPDS score less than 6). The times and components of all scheduled outcome assessments are shown in Fig. 2. Outcome data is collected from every participant not known to have died at the time of follow-up and who has not withdrawn consent, regardless of compliance with allocated treatment. Timelines for outcome assessments Experience from our previous studies in primary health care (PHC) as well as from the control arm of a Pakistani trial among women with perinatal depression suggests a recovery rate of about 45 % for major depression with no active treatment and about 75 % with treatment [29]. In a Chilean study of postnatal women with depression, using a 3-point reduction in baseline score of the depression assessment tool, remission rate was 57 % with no active treatment and 73 % with active treatment [28]. For our sample size estimation, we sought to detect an absolute difference of 15 percentage points (40 % recovery in control and 55 % in intervention groups respectively) at 6 months, a difference that we think is both plausible for this type of intervention and would promote changes in practice. In our pilot study among antenatal women, we observed an intra-cluster correlation coefficient (ICC) of 0.026 for EPDS scores. In our pilot study among general adults with depression, we were able to collect primary outcome at 6 months from 87.8 % of the participants. We expect a higher follow-up rate among perinatal women who generally are less likely to move. However, we will use a conservative 6-month follow-up rate of 85 % for our estimate. We also assume a 7 % infant death rate within the period. The uninflated sample size requires 186 per arm for analysis to detect a difference of 55 % vs 40 % (equivalent odds ratio = 1.8) with 80 % power at the two-sided 5 % alpha level. We originally aimed to recruit 50 individuals per MCC. With 43 individuals per cluster available for the primary analysis and an ICC of 0.026, the design effect is 2.09 giving a total number required for analysis of 778. We therefore aimed to recruit a total of 916 individuals from a total of 18 MCCs. As participant recruitment was slower than anticipated, in January 2014 we recruited and randomised a further 11 MCCs, giving a total of 29 in the study. Participant recruitment took place between July 2013 and October 2014. Outcome assessments are still ongoing and will continue till one year post-delivery assessment is concluded for the last recruited participant. A full statistical analysis plan will be developed before any data are analyzed. The analysis and presentation of the trial will be in accordance with CONSORT guidelines for cluster randomized trials [46, 47]. The primary approach for comparative analyses will be to analyze participants as randomized without imputation of missing data, and with due emphasis placed on confidence intervals for the between-arm comparisons. We will use descriptive statistics to assess balance between the trial arms at baseline for both clinic and individual participant characteristics. In order to take appropriate account of the hierarchical nature of the data, we will use multivariable mixed effects regression models to estimate recovery from depression at 6 months for intervention group versus control, adjusting for baseline depression and LGA as a stratification variable. In a secondary analysis, we will further adjust for any variables that were imbalanced between trial arms at baseline. These analyses will be repeated for secondary outcomes. We will conduct sensitivity analyses to assess the potential effect of missing data, and will investigate the effect of adherence with the intervention. We will investigate whether between-group differences vary over time using data from all follow-up visits in repeated measures analyses. We will investigate whether there is any differential effect of the intervention according to baseline symptom severity (EPDS score <16, ≥16) by including appropriate interaction terms in the primary regression model. Since the trial is powered to detect overall differences between groups rather than interactions of this kind, the results will be interpreted with due caution. Data analysis will be conducted once all follow-up is complete. There are no planned interim analyses.
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