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Promoting medication adherence among patients with bipolar disorder: a multicenter randomized controlled trial of a multifaceted intervention

  • A. H. Pakpour (a1) (a2), A. Modabbernia (a3), C.-Y. Lin (a4), M. Saffari (a5), M. Ahmadzad Asl (a6) and T. L. Webb (a7)...



The present research aimed to investigate the efficacy of a multifaceted intervention that included motivational interviewing (MI) and psychoeducation in improving medication adherence (MA) among patients with bipolar disorder (BD).


A multicenter, cluster randomized, observer-blind, controlled, parallel-group trial was conducted in ten academic centers in Iran. Patients with BD were randomly assigned to the experimental group (EXP; n = 136) or the usual care group (UC; n = 134). The EXP group received five sessions of MI and psychoeducation together with their family members. The primary outcome measure was changes in scores on the Medication Adherence Rating Scale from baseline to 6 months post-intervention. Other outcome measures included serum levels of mood stabilizers, clinical symptoms, quality of life, as well as measures of intention, beliefs about medicine, perceived behavioral control, automaticity, action and coping planning, and adverse reactions.


Medication adherence improved over time in both groups, but patients in the EXP group improved more (baseline score: 6.03; score at the sixth month: 9.55) than patients in the UC group (baseline score: 6.17; score at the sixth month: 6.67). In addition, patients in the EXP group showed greater improvement than patients in the UC group in almost all secondary outcomes 6 months following the intervention.


Multifaceted interventions that include motivational-interviewing and psychoeducation can significantly improve MA and clinical and functional outcomes in patients with BD.

Trial Registration Number: The trial was registered with database (NCT02241863)


Corresponding author

*Address for correspondence: Dr A. H. Pakpour, Ph.D., Associate Professor, Social Determinants of Health Research Center, Qazvin University of Medical Sciences, Shahid Bahounar BLV, Qazvin, 3419759811, Iran. (Email:


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Aflakseir, A (2012). Role of illness and medication perceptions on adherence to medication in a group of Iranian patients with type 2 diabetes. Journal of Diabetes 4, 243247.
Bauer, MS, McBride, L, Williford, WO, Glick, H, Kinosian, B, Altshuler, L, Beresford, T, Kilbourne, AM, Sajatovic, M, Cooperative Studies Program 430 Study T (2006 a). Collaborative care for bipolar disorder. I. Intervention and implementation in a randomized effectiveness trial. Psychiatric Services 57, 927936.
Bauer, MS, McBride, L, Williford, WO, Glick, H, Kinosian, B, Altshuler, L, Beresford, T, Kilbourne, AM, Sajatovic, M, Cooperative Studies Program 430 Study T (2006 b). Collaborative care for bipolar disorder. II. Impact on clinical outcome, function, and costs. Psychiatric Services 57, 937945.
Berk, M, Berk, L, Castle, D (2004). A collaborative approach to the treatment alliance in bipolar disorder. Bipolar Disorders 6, 504518.
Bermúdez-Ampudia, C, García-Alocén, A, Martínez-Cengotitabengoa, M, Alberich, S, González-Ortega, I, Resa, SB, González-Pinto, A (2016). Mixed-effects models: family burden and functionality in patients with bipolar disorder. European Psychiatry 33, S331.
Bilderbeck, AC, Atkinson, LZ, McMahon, HC, Voysey, M, Simon, J, Price, J, Rendell, J, Hinds, C, Geddes, JR, Holmes, E, Miklowitz, DJ (2016). Psychoeducation and online mood tracking for patients with bipolar disorder: a randomised controlled trial. Journal of Affective Disorders 205, 245251.
Cakir, S, Bensusan, R, Akca, ZK, Yazici, O (2009). Does a psychoeducational approach reach targeted patients with bipolar disorder? Journal of Affective Disorders 119, 190193.
Culpepper, L (2014). The diagnosis and treatment of bipolar disorder: decision-making in primary care. Primary Care Companion for CNS Disorders 16, 3.
Daneshpour, M (1998). Muslim families and family therapy. Journal of Marital and Family Therapy 24, 355368.
Dean, BB, Gerner, D, Gerner, RH (2004). A systematic review evaluating health-related quality of life, work impairment, and healthcare costs and utilization in bipolar disorder. Current medical Research and Opinion 20, 139154.
Depp, CA, Lebowitz, BD, Patterson, TL, Lacro, JP, Jeste, DV (2007). Medication adherence skills training for middle-aged and elderly adults with bipolar disorder: development and pilot study. Bipolar Disorders 9, 636645.
Folco, EG, Lee, C-S, Dufu, K, Yamazaki, T, Reed, R (2012). The Proteins PDIP3 and ZC11A Associate with the Human TREX Complex in an ATP-Dependent Manner and Function in mRNA Export. PLoS ONE 7, e43804.
Forte, A, Baldessarini, RJ, Tondo, L, Vazquez, GH, Pompili, M, Girardi, P (2015). Long-term morbidity in bipolar-I, bipolar-II, and unipolar major depressive disorders. Journal of Affective Disorders 178, 7178.
Gardner, B, Abraham, C, Lally, P, de Bruijn, GJ (2012). Towards parsimony in habit measurement: testing the convergent and predictive validity of an automaticity subscale of the Self-Report Habit Index. International Journal of Behavioral Nutrition and Physical Activity 9, 102.
Geddes, JR, Miklowitz, DJ (2013). Treatment of bipolar disorder. Lancet 381, 16721682.
Hidalgo-Mazzei, D, Mateu, A, Reinares, M, Murru, A, del Mar Bonnín, C, Varo, C, Valentí, M, Undurraga, J, Strejilevich, S, Sánchez-Moreno, J, Vieta, E (2016). Psychoeducation in bipolar disorder with a SIMPLe smartphone application: feasibility, acceptability and satisfaction. Journal of Affective Disorders 200, 5866.
Horne, R, Weinman, J, Hankins, M (1999). The beliefs about medicines questionnaire: the development and evaluation of a new method for assessing the cognitive representation of medication. Psychology and Health 14, 124.
Hubbard, AA, McEvoy, PM, Smith, L, Kane, RT (2016). Brief group psychoeducation for caregivers of individuals with bipolar disorder: a randomized controlled trial. Journal of Affective Disorders 200, 3136.
IsHak, WW, Brown, K, Aye, SS, Kahloon, M, Mobaraki, S, Hanna, R (2012). Health-related quality of life in bipolar disorder. Bipolar Disorders 14, 618.
Javadpour, A, Hedayati, A, Dehbozorgi, GR, Azizi, A (2013). The impact of a simple individual psycho-education program on quality of life, rate of relapse and medication adherence in bipolar disorder patients. Asian Journal of Psychiatry 6, 208213.
Kallestad, H, Wullum, E, Scott, J, Stiles, TC, Morken, G (2016). The long-term outcomes of an effectiveness trial of group versus individual psychoeducation for bipolar disorders. Journal of Affective Disorders 15, 3238.
Krull, JL, MacKinnon, DP (1999). Multilevel mediation modeling in group-based intervention studies. Evaluation Review 23, 418444.
Lacro, JP, Dunn, LB, Dolder, CR, Leckband, SG, Jeste, DV (2002). Prevalence of and risk factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature. Journal of Clinical Psychiatry 63, 892909.
Lingam, R, Scott, J (2002). Treatment non-adherence in affective disorders. Acta Psychiatrica Scandinavica 105, 164172.
Lundahl, B, Moleni, T, Burke, BL, Butters, R, Tollefson, D, Butler, C, Rollnick, S (2013). Motivational interviewing in medical care settings: a systematic review and meta-analysis of randomized controlled trials. Patient Education and Counseling 93, 157168.
MacDonald, L, Chapman, S, Syrett, M, Bowskill, R, Horne, R (2016). Improving medication adherence in bipolar disorder: a systematic review and meta-analysis of 30 years of intervention trials. Journal of Affective Disorders 194, 202221.
McIntyre, RS, Mancini, DA, Srinivasan, J, McCann, S, Konarski, JZ, Kennedy, SH (2004). The antidepressant effects of risperidone and olanzapine in bipolar disorder. Canadian Journal of Clinical Pharmacology 11, e218e226.
Merikangas, KR, Akiskal, HS, Angst, J, Greenberg, PE, Hirschfeld, RM, Petukhova, M, Kessler, RC (2007). Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Archives of General Psychiatry 64, 543552.
Michalak, EE, Murray, G, Collaborative RTtSPIiBD (2010). Development of the QoL.BD: a disorder-specific scale to assess quality of life in bipolar disorder. Bipolar Disorders 12, 727740.
Miller, WR, Rollnick, S (2012). Motivational Interviewing: Helping People Change. Guilford Press.
Montgomery, SA, Asberg, M (1979). A new depression scale designed to be sensitive to change. British Journal of Psychiatry 134, 382389.
O'Carroll, R, Whittaker, J, Hamilton, B, Johnston, M, Sudlow, C, Dennis, M (2011). Predictors of adherence to secondary preventive medication in stroke patients. Annals of Behavioral Medicine 41, 383390.
Orbell, S, Verplanken, B (2010). The automatic component of habit in health behavior: habit as cue-contingent automaticity. Health Psychology 29, 374383.
Pakpour, AH, Gellert, P, Asefzadeh, S, Updegraff, JA, Molloy, GJ, Sniehotta, FF (2014). Intention and planning predicting medication adherence following coronary artery bypass graft surgery. Journal of Psychosomatic Research 77, 287295.
Pakpour, AH, Gholami, M, Esmaeili, R, Naghibi, SA, Updegraff, JA, Molloy, GJ, Dombrowski, SU (2015). A randomized controlled multimodal behavioral intervention trial for improving antiepileptic drug adherence. Epilepsy & Behavior 52, 133142.
Rollnick, S, Miller, WR, Butler, CC, Aloia, MS (2008). Motivational Interviewing in Health Care: Helping Patients Change Behavior. The Guilford Press: New York.
Rouget, BW, Aubry, JM (2007). Efficacy of psychoeducational approaches on bipolar disorders: a review of the literature. Journal of Affective Disorders 98, 1127.
Sachs, GS, Guille, C, McMurrich, SL (2002). A clinical monitoring form for mood disorders. Bipolar Disorders 4, 323327.
Scott, J, Pope, M (2002 a). Nonadherence with mood stabilizers: prevalence and predictors. Journal of Clinical Psychiatry 63, 384390.
Scott, J, Pope, M (2002 b). Self-reported adherence to treatment with mood stabilizers, plasma levels, and psychiatric hospitalization. Journal of Clinical Psychiatry 159, 19271929.
Spearing, MK, Post, RM, Leverich, GS, Brandt, D, Nolen, W (1997). Modification of the Clinical Global Impressions (CGI) Scale for use in bipolar illness (BP): the CGI-BP. Psychiatry Research 73, 159171.
Tsai, MC, Strong, C, Lin, CY (2015). Effects of pubertal timing on deviant behaviors in Taiwan: a longitudinal analysis of 7th- to 12th-grade adolescents. Journal of Adolescence 42, 8797.
Williams, AA, Wright, KS (2014). Engaging families through motivational interviewing. Pediatric Clinics of North America 61, 907921.
Young, RC, Biggs, JT, Ziegler, VE, Meyer, DA (1978). A rating scale for mania: reliability, validity and sensitivity. British Journal of Psychiatry 133, 429435.


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