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Multiple mediation analysis of the peer-delivered Thinking Healthy Programme for perinatal depression: findings from two parallel, randomised controlled trials

  • Daisy R. Singla (a1), David P. MacKinnon (a2), Daniela C. Fuhr (a3), Siham Sikander (a4), Atif Rahman (a5) and Vikram Patel (a6)...



Low-intensity psychosocial interventions have been effective in targeting perinatal depression, but relevant mechanisms of change remain unknown.


To examine three theoretically informed mediators of the Thinking Healthy Programme Peer-delivered (THPP), an evidence-based psychosocial intervention for perinatal depression, on symptom severity in two parallel, randomised controlled trials in Goa, India and Rawalpindi, Pakistan.


Participants included pregnant women aged ≥18 years with moderate to severe depression, as defined by a Patient Health Questionnaire 9 (PHQ-9) score ≥10, and were randomised to either THPP or enhanced usual care. We examine whether three prespecified variables (patient activation, social support and mother–child attachment) at 3 months post-childbirth mediated the effects of THPP interventions of perinatal depressive symptom severity (PHQ-9) at the primary end-point of 6 months post-childbirth. We first examined individual mediation within each trial (n = 280 in India and n = 570 in Pakistan), followed by a pooled analysis across both trials (N = 850).


In both site-specific and pooled analyses, patient activation and support at 3 months independently mediated the intervention effects on depressive symptom severity at 6 months, accounting for 23.6 and 18.2% of the total effect of THPP, respectively. The intervention had no effect on mother–child attachment scores, thus there was no evidence that this factor mediated the intervention effect.


The effects of the psychosocial intervention on depression outcomes in mothers were mediated by the same two factors in both contexts, suggesting that such interventions seeking to alleviate perinatal depression should target both social support and patient activation levels.

Declaration of interest



Corresponding author

Correspondence: Daisy R. Singla, Department of Psychiatry, Sinai Health System, University of Toronto, Rm914A, 600 University Ave, Toronto, Ontario M5G-1X5, Canada. Email:


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1Ferrari, AJ, Charlson, FJ, Norman, RE, Patten, SB, Freedman, G, Murray, CJ, et al. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoS Med 2013; 10(11): e1001547.
2Rahman, A, Fisher, J, Bower, P, Luchters, S, Tran, T, Yasamy, MT, et al. Interventions for common perinatal mental disorders in women in low-and middle-income countries: a systematic review and meta-analysis. Bull World Health Organ 2013; 91: 593601.
3Sockol, LE, Epperson, CN, Barber, JP. A meta-analysis of treatments for perinatal depression. Clin Psychol Rev 2011; 31(5): 839–49.
4Singla, DR, Kohrt, B, Murray, LK, Anand, A, Chorpita, BF, Patel, V. Psychological treatments for the world: lessons from low-and middle-income countries. Ann Rev Clin Psychol 2017; 13: 149–81.
5World Health Organization (WHO). Mental Health Global Action Programme Humanitarian Intervention Guide (mhGAP-HIG): Clinical Management of Mental, Neurological, and Substance Use Conditions in Humanitarian Emergencies. WHO, 2015 (
6Hafeman, DM, Schwartz, S. Opening the black box: a motivation for the assessment of mediation. Int J Epidemiol 2009; 38(3): 838–45.
7Kazdin, AE. Mediators and mechanisms of change in psychotherapy research. Annu Rev Clin Psychol 2007; 3: 127.
8Kraemer, HC. Messages for clinicians: moderators and mediators of treatment outcome in randomized clinical trials. Am J Psychiatry 2016; 173(7): 672–9.
9Fuhr, DC, Weobong, B, Lazarus, A, Vanobberghen, F, Weiss, HA, Singla, DR, et al. Delivering the Thinking Healthy Programme for perinatal depression through peers: an individually randomised controlled trial in India. Lancet Psychiatry 2019; 6: 115–27.
10Sikander, S, Ahmad, I, Atif, N, Zaidi, A, Vanobberghen, F, Weiss, HA, et al. Delivering the Thinking Healthy Programme for perinatal depression through volunteer peers: a cluster randomised controlled trial in Pakistan. Lancet Psychiatry 2019; 6: 128–39.
11Rahman, A, Malik, A, Sikander, S, Roberts, C, Creed, F. Cognitive behaviour therapy-based intervention by community health workers for mothers with depression and their infants in rural Pakistan: a cluster-randomised controlled trial. Lancet 2008; 372(9642): 902–9.
12Haq, Z, Iqbal, Z, Rahman, A. Job stress among community health workers: a multi-method study from Pakistan. Int J Ment Health Syst 2008; 2(1): 15.
13Sikander, S, Lazarus, A, Bangash, O, Fuhr, DC, Weobong, B, Krishna, RN, et al. The effectiveness and cost-effectiveness of the peer-delivered Thinking Healthy Programme for perinatal depression in Pakistan and India: the SHARE study protocol for randomised controlled trials. Trials 2015; 16(1): 534.
14Singla, D, Lazarus, A, Atif, N, Sikander, S, Bhatia, U, Ahmad, I, et al. ‘Someone like us’: delivering maternal mental health through peers in two South Asian contexts. J Affect Disord 2014; 168: 452–8.
15Rahman, A. Challenges and opportunities in developing a psychological intervention for perinatal depression in rural Pakistan–a multi-method study. Arch Womens Ment Health 2007; 10(5): 211–9.
16Atif, N, Krishna, RN, Sikander, S, Lazarus, A, Nisar, A, Ahmad, I, et al. Mother-to-mother therapy in India and Pakistan: adaptation and feasibility evaluation of the peer-delivered Thinking Healthy Programme. BMC Psychiatry 2017; 17(1): 79.
17Dimidjian, S, Barrera, M Jr, Martell, C, Muñoz, RF, Lewinsohn, PM. The origins and current status of behavioral activation treatments for depression. Ann Rev Clin Psychol 2011; 7: 138.
18Dimidjian, S, Goodman, SH, Sherwood, NE, Simon, GE, Ludman, E, Gallop, R, et al. A pragmatic randomized clinical trial of behavioral activation for depressed pregnant women. J Consult Clin Psychol 2017; 85(1): 26.
19Patel, V, Weobong, B, Weiss, HA, Anand, A, Bhat, B, Katti, B, et al. The Healthy Activity Program (HAP), a lay counsellor-delivered brief psychological treatment for severe depression, in primary care in India: a randomised controlled trial. Lancet 2017; 389(10065): 176–85.
20O'mahen, H, Richards, D, Woodford, J, Wilkinson, E, McGinley, J, Taylor, RS, et al. Netmums: a phase II randomized controlled trial of a guided Internet behavioural activation treatment for postpartum depression. Psychol Med 2014; 44(08): 1675–89.
21Richards, DA, Ekers, D, McMillan, D, Taylor, RS, Byford, S, Warren, FC, et al. Cost and Outcome of Behavioural Activation versus Cognitive Behavioural Therapy for Depression (COBRA): a randomised, controlled, non-inferiority trial. Lancet 2016; 388(10047): 871–80.
22Stein, A, Gath, DH, Bucher, J, Bond, A, Day, A, Cooper, PJ. The relationship between post-natal depression and mother–child interaction. Br J Psychiatry 1991; 158(1): 4652.
23Stewart, RC, Umar, E, Tomenson, B, Creed, F. Validation of the multi-dimensional scale of perceived social support (MSPSS) and the relationship between social support, intimate partner violence and antenatal depression in Malawi. BMC Psychiatry 2014; 14(1): 180.
24Field, T. Prenatal depression effects on early development: a review. Infant Behav Dev 2011; 34(1): 114.
25Gaynor, ST, Harris, A. Single-participant assessment of treatment mediators: strategy description and examples from a behavioral activation intervention for depressed adolescents. Beh Modif 2008; 32(3): 372402.
26Weobong, B, Weiss, HA, McDaid, D, Singla, DR, Hollon, SD, Nadkarni, A, et al. Sustained effectiveness and cost-effectiveness of the Healthy Activity Program, a brief psychological treatment for depression delivered by lay counsellors in primary care: twelve-month follow-up of a randomised controlled trial. PLoS Med 2017; 14(9): e1002385.
27Toth, SL, Rogosch, FA, Oshri, A, Gravener-Davis, J, Sturm, R, Morgan-López, AA. The efficacy of interpersonal psychotherapy for depression among economically disadvantaged mothers. Dev Psychopathol 2013; 25(4pt1): 1065–78.
28Singla, DR, Kumbakumba, E, Aboud, FE. Effects of a parenting intervention to address maternal psychological wellbeing and child development and growth in rural Uganda: a community-based, cluster-randomised trial. Lancet Global Health 2015; 3(8): e45869.
29O'Rourke, HP, MacKinnon, DP. Reasons for testing mediation in the absence of an intervention effect: a research imperative in prevention and intervention research. J Stud Alcohol Drugs 2018; 79(2): 171–81.
30Spitzer, RL, Kroenke, K, Williams, JB; Patient Health Questionnaire Primary Care Study Group. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. JAMA 1999; 282(18): 1737–44.
31Patel, V, Araya, R, Chowdhary, N, King, M, Kirkwood, B, Nayak, S, et al. Detecting common mental disorders in primary care in India: a comparison of five screening questionnaires. Psychol Med 2008; 38(2): 221–8.
32World Health Organization (WHO). mhGAP Intervention Guide for Mental, Neurological and Substance use Disorders in Non-Specialized Health Settings. WHO, 2010 (
33Lemmens, LH, Galindo-Garre, F, Arntz, A, Peeters, F, Hollon, SD, DeRubeis, RJ, et al. Exploring mechanisms of change in cognitive therapy and interpersonal psychotherapy for adult depression. Behav Res Ther 2017; 94: 8192.
34MacKinnon, DP, Pirlott, AG. Statistical approaches for enhancing causal interpretation of the M to Y relation in mediation analysis. Pers Soc Psychol Rev 2015; 19(1): 3043.
35Manos, RC, Kanter, JW, Luo, W. The behavioral activation for depression scale–short form: development and validation. Behav Ther 2011; 42(4): 726–39.
36Zimet, GD, Dahlem, NW, Zimet, SG, Farley, GK. The multidimensional scale of perceived social support. J Pers Assess 1988; 52(1): 3041.
37Akhtar, A, Rahman, A, Husain, M, Chaudhry, IB, Duddu, V, Husain, N. Multidimensional scale of perceived social support: psychometric properties in a South Asian population. J Obstet Gynaecol Res 2010; 36(4): 845–51.
38Condon, JT, Corkindale, CJ. The assessment of parent-to-infant attachment: development of a self-report questionnaire instrument. J Reprod Infant Psychol 1998; 16(1): 5776.
39Sikander, S, Ahmad, I, Bates, LM, Gallis J, Hagaman, A, O'Donnell, K, et al. Cohort profile: perinatal depression and child socioemotional development; the Bachpan cohort study from rural Pakistan. BMJ Open 2019; 9: e025644.
40MacKinnon, DP, Fairchild, AJ, Fritz, MS. Mediation analysis. Annu Rev Psychol 2007; 58: 593614.
41Muthén, LK, Muthén, BO. Mplus User's Guide. Eighth Edition. Muthén & Muthén, 1998–2017 (
42Selig, JP, Preacher, KJ. Monte Carlo method for assessing mediation: an interactive tool for creating confidence intervals for indirect effects [Computer Software]. 2008 (
43MacKinnon, DP, Lockwood, CM, Williams, J. Confidence limits for the indirect effect: distribution of the product and resampling methods. Multivariate Behav Res 2004; 39(1): 99128.
44MacKinnon, DP, Lockwood, CM, Hoffman, JM, West, SG, Sheets, V. A comparison of methods to test mediation and other intervening variable effects. Psychol Methods 2002; 7(1): 83.
45Selig, JP, Preacher, KJ. Mediation models for longitudinal data in developmental research. Res Hum Dev 2009; 6(2–3): 144–64.
46MacKinnon, DP, Warsi, G, Dwyer, JH. A simulation study of mediated effect measures. Multivariate Behav Res 1995; 30(1): 4162.
47Cox, MG, Kisbu-Sakarya, Y, Miočević, M, MacKinnon, DP. Sensitivity plots for confounder bias in the single mediator model. Eval Rev 2013; 37(5): 405–31.
48VanderWeele, TJ, Ding, P. Sensitivity analysis in observational research: introducing the E-value. Ann Intern Med 2017; 167(4): 268–74.
49Reyes-Portillo, JA, McGlinchey, EL, Yanes-Lukin, PK, Turner, JB, Mufson, L. Mediators of interpersonal psychotherapy for depressed adolescents on outcomes in Latinos: the role of peer and family interpersonal functioning. J Latina/o Psychol 2017; 5(4): 248.
50Murray, L, Fiori-Cowley, A, Hooper, R, Cooper, P. The impact of postnatal depression and associated adversity on early mother-infant interactions and later infant outcome. Child Dev 1996; 67(5): 2512–26.
51Bradley, RH, Caldwell, BM. The HOME Inventory and family demographics. Dev Psychol 1984; 20(2): 315.
52Maselko, J, Sikander, S, Bhalotra, S, Bangash, O, Ganga, N, Mukherjee, S, et al. Effect of an early perinatal depression intervention on long-term child development outcomes: follow-up of the Thinking Healthy Programme randomised controlled trial. Lancet Psychiatry 2015; 2(7): 609–17.
53Ackerman, SJ, Hilsenroth, MJ. A review of therapist characteristics and techniques positively impacting the therapeutic alliance. Clin Psychol Rev 2003; 23(1): 133.
54Murray, L, Cooper, PJ, Wilson, A, Romaniuk, H. Controlled trial of the short-and long-term effect of psychological treatment of post-partum depression: 2. Impact on the mother-child relationship and child outcome. Br J Psychiatry 2003; 182(5): 420–7.
55Holmes, EA, Ghaderi, A, Harmer, CJ, Ramchandani, PG, Cuijpers, P, Morrison, AP, et al. The Lancet Psychiatry Commission on psychological treatments research in tomorrow's science. Lancet Psychiatry 2018; 5(3): 237–86.
56Lemmens, LH, Muller, VN, Arntz, A, Huibers, MJ. Mechanisms of change in psychotherapy for depression: an empirical update and evaluation of research aimed at identifying psychological mediators. Clin Psychol Rev 2016; 50: 95107.
57VanderWeele, T, Vansteelandt, S. Conceptual issues concerning mediation, interventions and composition. Stat Interface 2009; 2(4): 457–68.



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Multiple mediation analysis of the peer-delivered Thinking Healthy Programme for perinatal depression: findings from two parallel, randomised controlled trials

  • Daisy R. Singla (a1), David P. MacKinnon (a2), Daniela C. Fuhr (a3), Siham Sikander (a4), Atif Rahman (a5) and Vikram Patel (a6)...
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