Medication non-adherence in bipolar disorder: Review of rates, demographic and clinical predictors

Table 2 Rates of medication non-adherence in bipolar disorder: Studies of all classes of medications

Ref.	Study	Non-adherence rates
Keck et al[47], 1996a	n = 101; duration-past month; clinical interview and serum levels	64% fully or partially non-adherent
Keck et al[48], 1998	n = 134; duration - 12 mo; clinical interview	53% fully or partially non-adherent
Strakowski et al[49], 1998	n = 109 (83 with BD); duration - 12 mo; clinical interviews	59% fully or partially non-adherent
Weiss et al[50], 1998	n = 44 with BD and SUD; cross-sectional study; clinical interviews	79% fully or partially non-adherent (35% took medications less than 67% of the time)
Colom et al[51], 2000	n = 200; duration 2 yr; clinical interviews with patients and relatives and serum levels for mood stabilizers	40% fully or partially non-adherent
Svarstad et al[52], 2001	n = 67; duration 12 mo; retrospective claims data	33% irregular use
Calabrese et al[53], 2000	n = 324 with RCBD; duration - 6 mo; clinical interview	34%
Greenhouse et al[54], 2000	n = 32: duration - 1 wk; self-report	25%
Lam et al[55], 2003	n = 52; duration - 6 mo; serum levels and self-reports	Serum levels - 7%-22%; self-report - 12%-33%
Calabrese et al[56], 2005	n = 254 with RCBD; duration - 30 mo; clinical interview	20%-28%
Coletti et al[57], 2005	n = 38 adolescents; duration - 1 mo; parent reports	66% fully or partially non-adherent
Fleck et al[58], 2005	n = 50; cross-sectional study; visual analogue scale	52% fully or partially non-adherent
Roy et al[33], 2005	n = 100 (42 with BD); cross-sectional study; clinical interview	91%
Sajatovic et al[46], 2005	n = 52; duration - 3 mo; self-reports and DAI-10	12%
Sajatovic et al[59], 2006a	n = 323; cross-sectional study; clinical interview	36% partially or fully non-adherent
Clatworthy et al[36], 2007	n = 16; cross-sectional study; self-report-qualitative data	81%
DelBello et al[60], 2007	n = 71 adolescents; duration 12 mo; clinical interviews	65% fully or partially non-adherent
Johnson et al[61], 2007	n = 469; cross-sectional study; web-based survey; self-report	30%
Montoya et al[62], 2007	n = 312; cross-sectional study; clinical interviews	40% fully or partially non-adherent
Sajatovic et al[63], 2007c	n = 205 with RCBD; duration - 6 mo; clinical interview	20%
Shabani and Eftekhar[64], 2007	n = 22; duration - 17 mo; clinical interview	38%
Strakowski et al[65], 2007	n = 96 (United States) and 46 (Taiwan); duration – 1 yr (Taiwan) to 8 yr (United States); clinical interviews	21% (Taiwan) - 41% (United States) followed up without full treatment adherence
Baldessarini et al[66], 2008a	n = 429; duration -last 10 d; self-report	34% (psychiatrists rated 6%-18% as non-adherent)
Copeland et al[67], 2008	n = 435; duration - past 4 d; self-report of missed dose and self-report-MMAS	27% on missed dose and 46% on MMAS
Sajatovic et al[40], 2008	n = 302; duration - 3 yr; clinical interview	12%
Zeber et al[68], 2008	n = 435; cross-sectional study; self-report and MMAS	Overall 30%; 23% (self-report) to 46% (MMAS)
Taj et al[69], 2008	n = 23; cross-sectional study; clinical interviews	26%
Azorin et al[70], 2009	n = 766; duration 2 yr; clinical interview	At baseline - 44% (pure mania) - 50% (mixed mania); at 2 yr - 8% (pure mania) - 16% (mixed mania)
Clatworthy et al[71], 2009	n = 223; cross-sectional study; self-report - MARS	30%
Martinez-Aran et al[74], 2009	n = 103; cross-sectional study; clinical interviews with patients and relatives and serum levels for mood stabilizers	41%
Mazza et al[75], 2009	n = 131 (94 with BD); duration - 12 mo; serum levels and relatives’ reports	22%
Sajatovic et al[72], 2009a	n = 140; cross-sectional study; self-report-TRQ	19%
Sajatovic et al[39], 2009b	n = 164; duration - 12 mo; self-report	19%
Sharifi et al[73], 2009	n = 76; duration - 8 wk; clinical interview	29%
Bates et al[76], 2010	n = 1052; cross-sectional study; web-based survey; self-report -MMAS	49.50%
Devulapalli et al[77], 2010	n = 140; duration - past month; self-report	19%
González-Pinto et al[78], 2010	n = 1831; duration - 24 mo; clinical interview	23%
Hou et al[79], 2010	n = 35; cross-sectional study; self-report -MMAS	54%
Jónsdóttir et al[80], 2010	n = 280 (114 with BD); duration- past week; self-report, MARS-5, serum levels	Serum levels - 34%; self-report - 16%
Gutiérrez-Rojas et al[81], 2010	n = 108; cross-sectional study; clinical interviews with patients and relatives and serum levels for mood stabilizers	17%
Perlis et al[82], 2010	n = 3640; duration - 12 mo; self-reports and clinical interviews	54% fully or partially non-adherent (24% non-adherent on 20% or more study visits)
Cely et al[83], 2011	n = 124; cross-sectional study; self-report-MMAS	30%
Cruz et al[35], 2011	n = 17 elderly subjects; cross-sectional study; self-report-MMAS	88%
Hong et al[84], 2011	n =1341; duration - 21 mo; clinical interview	24%
Savaş et al[85], 2011	n = 147; duration - 12 mo; self-report	27%
Sajatovic et al[86], 2011b	n= 140; duration - 1 mo; TRQ	18%
Mahmood et al[87], 2011	n = 40; duration - 1 mo; clinical interview	62%
Barraco et al[88], 2012	n = 650; duration - 12 mo; self-report-SMAQ and DAI-10	60% at baseline; 31% at 9 mo; 33% at 12 mo
Eker and Harkin[89], 2012	n = 71; duration - 6 wk; ANT, self-report-MARS, TOS	60%-61% at baseline; 13%-76% at 6wk
Murru et al[90], 2012	n = 76 schizoaffective disorder-bipolar type; duration - 10 yr; partly retrospective based on clinical interviews with patients and families and serum levels	41%
Miasso et al[91], 2012	n = 101; cross-sectional study; self-report-MMAS	63%
Sajatovic et al[92], 2012	n = 43; duration - 6 mo; self-report-TRQ, MMAS; Pill counts	TRQ - 48%-51% at baseline; 21%-25% at 6 mo - Pill counts - 58% at baseline
Vieta et al[93], 2012	n = 2448 psychiatrists; duration-3 mo; questionnaire survey	57% patients rated fully or partially non-adherent
Sharma et al[94], 2012	n = 127; cross-sectional study; self-report	40%
Belzeaux et al[95], 2013	n = 382; cross-sectional study; self-report - MARS and clinical interviews	25%
de Souza et al[96], 2013	n = 36 cross-sectional study; self-report - MMAS	78%
Gibson et al[97], 2013	n = 24; cross-sectional study; self-report	50%-77% fully or partially non adherent
Hibdye et al[98], 2013	n = 410; cross-sectional study; self-report - MMAS	51%
Jónsdóttir et al[99], 2013	n = 255 (109 with BD); duration - past week; self-report, serum levels	42% fully or partially non-adherent
Murru et al[100], 2013	schizoaffective disorder-bipolar type (n = 75) and BD (n = 151); duration - 10 yr; partly retrospective based on clinical interviews with patients and families and serum levels	BD - 33%; schizoaffective disorder-bipolar type - 44%
Arvilommi et al[101], 2014	n = 168; duration 18 mo; clinical interview	> 50% non-adherent
Kassis et al[102], 2014	n = 76; cross-sectional study; questionnaire based	55%
Ghaffari-Nejad et al[103], 2015	n = 123; duration-6 mo; DAI = 10	61% fully or partially non-adherent
Hajda et al[104], 2015	n = 33; cross-sectional study; self-report - DAI-10	58%
Ibrahim et al[105], 2015	n = 358 (177 with BD); cross-sectional study; self-report-MMAS-8	46%
Levin et al[106], 2015	n = 65; duration-3 mo; self-report-TRQ	32%-59% at baseline; 10%-40% at 3 mo
Mert et al[107], 2015	n = 68; duration - 6 mo; self-reports; relatives’ reports, medical records	45%
Azadforouz et al[108], 2016	n = 47; duration-6 mo; clinical interview	36%
Mousavi et al[32], 2016	n = 73 with BD and psychotic symptoms; cross-sectional study; clinical interviews	96%

ANT: Attitudes towards neuroleptic treatment; BD: Bipolar disorder; CRS: Compliance rating scale; DAI-10: Drug Attitude Inventory-10 item version; MARS: Medication Adherence Report Scale (MARS-5-five item version); MMAS: Morisky Medication Adherence Scale (MMAS-8-8 item version); MPR: Medication possession ration; RBC: Red blood cells; RCBD: Rapid cycling bipolar disorder; RSM: Reasons for Stopping Medication’ questionnaire; ROMI: Rating of Medication Influences Scale; SGA: Second generation antipsychotics; SMAQ: Simplified Medication Adherence Questionnaire; SUD: Substance use disorders; SRTAB: Self-reported Treatment Adherence Behaviours; TOS: Treatment Observation Form; TRQ: Tablet Routines Questionnaire.