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

Table 1 Rates of medication non-adherence in bipolar disorder: Reviews

Ref.	Review based on	Non-adherence rates
Van Putten[20], 1975	7 studies	20%-30% (only lithium)
Jamison and Akiskal[21], 1983	10 studies	33%-50% (only lithium)
Cochran[5], 1986	13 studies from 1966-1986	9%-57% (only lithium)
Goodwin and Jamison[22], 1990	50 studies	18%-53% (only lithium)
Lingam and Scott[6], 2002	3 studies and 1 review	20%-66%, median 41%
Perlick et al[7], 2004	25 papers from 1979-2004	23%-68%, median 42%
Colom et al[4], 2005	6 studies	20%-64%, mean 25%
Gaudiano et al[18], 2008	3 reviews	20%-60%, mean 40%
Basco and Smith[8], 2009	9 studies	8%-64%
Busby and Sajatovic[3], 2010	6 studies	20%-60%
Foster et al[23], 2011	7 studies	21%-50%
Leclerc et al[12], 2013	27 studies(rates derived from 6 studies)	12%-64%
García et al[16], 2016	9 studies	23%-60% (only antipsychotics)

Other reviews have also estimated non-adherence rates to be in the range of 20%-68% with a median rate of 41%-42% in BD including Schou[24] (1988), Guscott and Taylor[25] (1994), Scott[26] (1995), Schou[19] (1997), Berk et al[17] (2004), Sajatovic et al[27] (2004), Byrne et al[28] (2006), Depp and Lebowitz[29] (2007), Depp et al[14] (2008), Pompili et al[10] (2009), Crowe et al[15] (2011) and Rakofsky et al[11] (2011). BD: Bipolar disorder.

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.

Table 3 Rates of medication non-adherence in bipolar disorder: Studies of mood stabilizers

Ref.	Study	Non-adherence rates
Bech et al[30], 1976	n = 76 on lithium (49 with BD); duration - 2 yr; retrospective case record data and serum levels	24%
Jamison et al[9], 1979	n = 47 on lithium; cross-sectional study; self-report and psychiatrists’ estimations	Patients - 47% non-adherent; psychiatrists - 35% non-adherent
Connelly et al[109], 1982	n = 48 on lithium; duration - 9 mo; serum levels and > 75% clinic attendance	25%
Connelly et al[110], 1984	n = 75 on lithium; duration - 6 mo; serum levels and > 75% clinic attendance	33%
Cochran[31], 1984	n = 28 on lithium; duration - 6 mo; self-report; case notes; clinical interview and serum levels	93% had major or minor non-adherence
Danion et al[111], 1987	n = 73 on lithium (36 with BD); duration - 2 yr; retrospective psychiatric assessments and serum levels	56% - subjective 19%; objective 56%
Aagaard et al[112], 1988	n =133 on lithium (47 with BD); duration - 6 mo; clinical interview	23%
Maarbjerg et al[113], 1988
Cochran and Gitlin[114], 1988	n = 48 on lithium (43 with BD); cross-sectional study; patient questionnaires	46% fully or partially non-adherent
Vestergaard and Schou[115], 1988	n = 480 on lithium (187 with BD); duration - 7 yr; medical records based on serum levels and clinical interviews	50% in first 6 mo; 25% per year during the first 2 yr; 10% per year after 4-5 yr
Lenzi et al[116], 1989	n = 67 women on lithium or carbamazepine; duration - 8 mo; self-report and serum levels	45%
Nilsson and Axelsson[117], 1989	n = 64 with mood disorders on lithium; duration - 7 yr; serum levels and medical records	25%
Aagaard and Vestergaard[118], 1990	n = 133 on lithium (61 with BD); duration - 2 yr; clinical interview	42%
Courtney et al[38], 1995	n = 15 on lithium; cross-sectional study; serum levels	0%
Lee et al[119], 1992	n = 50 on lithium; duration 12 mo; self-report; clinical interview; serum levels	30%
Berghöfer et al[120], 1996	n = 86 (55 with BD) on lithium; retrospective follow-up over a mean of 8.9 yr based on clinical interview and serum levels	24%
Keck et al[121], 1997	n = 140 on mood stabilizers; duration - 12 mo; clinical interview	51% fully or partially non-adherent
Maj et al[122], 1998	n = 402 on lithium; duration - 5 yr; clinical interview and serum levels	28%
Schumann et al[123], 1999	n = 75 (31 with BD) on lithium; duration-6 yr; retrospective medical records based on interviews and serum levels	55%
Wong et al[124], 1999	n = 80 with mood disorders on lithium (60 with BD cross-sectional study; self-reports; clinical interviews; serum levels	27.50%
Licht et al[125], 2001	n = 148 on mood stabilizers (132 on lithium): duration 24 mo; retrospective analysis of treatment charts, serum levels and clinical interviews	20%
McCleod and Sharp[37], 2001	n = 30 on lithium; cross-sectional study; self-reports, clinical ratings and serum levels	0%
Svarstad et al[52], 2001	n = 53 on lithium; duration 12 mo; retrospective claims data	26% irregular use
Scott[126], 2002	n = 98 (85 with BD) on mood stabilizers; cross-sectional study; self-reports-ROMI and TRQ	30% partially adherent
Scott and Pope[127], 2002a	n = 98 on mood stabilizers (78 with BD); duration- 24 mo; TRQ and serum levels	partial non-adherence - 47% over 2 yr; 32%over past month; 27% over past week; full non-adherence - 20% over 2 yr
Scott and Pope[128], 2002b	n = 98 on mood stabilizers (78 with BD); duration - 18 mo; TRQ and serum levels	TRQ - 32% partial adherence; serum levels - 36%
Dharmendra and Eagles[43], 2003	n = 411; duration - 3 yr; retrospective study based on self-reports and serum levels	15%
Pope and Scott[129], 2003	n = 72 on lithium (61 with BD); duration - 2 yr; self-report-RSM	46%
Bowden et al[130], 2005	n = 372 on lithium or valproate; duration - 52 wk; clinical interview	54%-75% premature discontinuations
Calabrese et al[56], 2005	n = 254 with RCBD on lithium or valproate; duration 20 mo; clinical interviews and serum levels	10%-28%
Patel et al[131], 2005	n = 32 adolescents on mood stabilizers; duration - 12 mo; clinical interviews and medical records	Treatment time without full adherence in 47%
Salloum et al[41], 2005	n = 59 with BD and alcohol dependence on lithium or lithium and valproate; duration - 24 wk; self-report and serum levels	13%-14%
Gonzalez-Pinto et al[132], 2006	n = 72; duration - 10 yr; clinical interviews and serum levels	22%
Drotar et al[133], 2007	n = 107 adolescents; on lithium and valproate; duration - 20 wk; serum levels, pill counts, self/parent report and clinical interview	16%-34% (average 17%) non-adherent on various measures
Kessing et al[134], 2007	n = 14277 on lithium; duration 6 yr; nation-wide register and pharmacy data	25% stopped lithium within 45 d
Manwani et al[135], 2007	n = 115 on mood stabilizers; duration - 10 mo; clinical interview	34% lifetime adherence in those with SUD 17% in those without SUD
Rosa et al[136], 2007	n = 106; cross-sectional study; self-report-MARS and serum and RBC levels	14% (based on levels) 33% (based on MARS)
Sajatovic et al[137], 2007a	n = 44637 on mood stabilizers; duration - 3 mo or more; retrospective claims data-MPR based	46% partially or fully non-adherent; took medications less than 50%-80% of the time
Baldessarini et al[138], 2008b	n = 2197 on single mood stabilizers; duration - 12 mo; national health plan claims data; MPR based	72% took medications less than 80% of the time
Vega et al[139], 2009	n = 72 on lithium; duration - 5 yr; clinical interviews and serum levels	8% (women)-39% (men)
Bauer et al[44], 2010	n = 312 on mood stabilizers; duration - 6 mo; self-report	11% partially or fully non-adherent
Sajatovic et al[86], 2011b	n = 136; duration - 1 mo; self-report-TRQ	18% in the past week or month
Scott et al[140], 2012	n = 81 on mood stabilizers; cross-sectional study; self-report -TRQ	26% - past month
Bauer et al[45], 2013a	n = 206 on mood stabilizers; duration 100 d; self-report	14% mean percent of days of missing doses
Arvilommi et al[101], 2014	n = 168 on mood stabilizers; duration 18 mo; clinical interview	40% fully or partially non-adherent
Sylvia et al[42], 2014	n = 283 on lithium; duration - 6 mo; self-report-TRQ	4.5%-7% reported missing at least 30% of their medications in the past week
Col et al[141], 2014	n = 78 on mood stabilizers; cross-sectional study; self-report-MARS	42%

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.

Table 4 Rates of medication non-adherence in bipolar disorder: studies of antipsychotics and antidepressants

Ref.	Study	Non-adherence rates
Antipsychotics
Keck et al[142], 1996b	n = 77 on antipsychotics; duration - 6 mo; clinical interview	32%
Svarstad et al[52], 2001	n = 56 on antipsychotics; duration 12 mo; retrospective claims data	23% irregular use
Patel et al[131], 2005	n = 32 adolescents on antipsychotics; duration - 12 mo; clinical interviews and medical records	Treatment time without full adherence in 44%
Sajatovic et al[143], 2006b	n = 32993 on antipsychotics; duration - 3 mo or more; retrospective claims data-MPR based	48% partially or fully non-adherent; took antipsychotics less than 50%-80% of the time
Sajatovic et al[144], 2007b	n = 73964 on antipsychotics; duration - 3 mo or more; retrospective claims data-MPR based	39% among those > 60 yr and 50% in those < 60 yr took antipsychotics less than 50%-80% of the time
Hassan and Lage[145], 2009	n = 1973 on antipsychotics; duration - 12 mo; retrospective claims based data-MPR based	56% took antipsychotics less than 50% of the time and 73% less than 75% of the time
Lage and Hassan[146], 2009	n = 7,769 on antipsychotics; duration- 12 mo; retrospective claims data-MPR based	62% took antipsychotics less than 50% of the time and 79% less than 75% of the time
Lang et al[147], 2011	n = 9410 on antipsychotics; duration - 12 mo; retrospective claims data-MPR based	60% took antipsychotics less than 80% of the time
Rascati et al[148], 2011	n = 2446 on SGAs; duration - 18 mo; retrospective claims data-MPR based	42% took antipsychotics less than 80% of the time
Berger et al[34], 2012	n = 84 on SGAs: Duration-6 mo; retrospective claims data-MPR and CMG based	85% took antipsychotics less than 80% of times (50% according to CMGs)
Stephenson et al[149], 2012	n = 162 patients with BD on SGAs and 153 physicians; duration - 12 mo; retrospective claims data and physician survey	57% with low-moderate adherence; physicians overestimated adherence in 67% patients
Montes et al[150], 2013	n = 303; cross-sectional study; self-reports- DAI-10 and MMAS, CRS	69%
Kutzelnigg et al[151], 2014	Olanzapine alone or in combination with mood stabilizers; n = 891 at entry; 657 at 2 yr; clinical interview	33% at baseline; 20% at 2 yr
Arvilommi et al[101], 2014	n = 168 on SGAs; duration 18 mo; clinical interview	46% fully or partially non-adherent
Sajatovic et al[152], 2016	n = 1114 on lurasidone; duration- 27 mo; retrospective claims data-MPR based	67%took lurasidone less than 80% of the time
Antidepressants
Svarstad et al[52], 2001	n = 22 on antidepressants; duration 12 mo; retrospective claims data	27% irregular use
Bauer et al[153], 2013b	n = 144 on antidepressants; duration - daily for 100 d; self-report	19% (missing/changing doses) to 41% (drug holidays)

ANT: Attitudes towards neuroleptic treatment; BD: Bipolar disorder; CMG: Cumulative medication gaps; 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.

Table 5 Studies of demographic correlates of medication non-adherence in bipolar disorder

Demographic correlates	Studies with positive associations	Studies without positive associations	Others
Any demographic variable		Jamison et al[9], 1979; Aagaard and Vestergaard[118], 1990; Maj et al[122], 1998; Schumann et al[123], 1999; Colom et al[51], 2000; Licht et al[125], 2001; Scott [126], 2002; Scott and Pope[127], 2002a; Kliendienst and Griel[156], 2004; Revicki et al[155], 2005; Yen et al[157], 2005; Sajatovic et al[59], 2006a; Sajatovic et al[40], 2008; Taj et al[69], 2008; Sajatovic et al[72], 2009a; Clatworthy et al[71], 2009; Martinez-Aran et al[74], 2009; Sharifi et al[73], 2009; González-Pinto et al[78], 2010; Cely et al[83], 2011; Murru et al[90], 2012; Bauer et al[45], 2013a; Bauer et al[153], 2013b; Jónsdóttir et al[99], 2013; Col et al[141], 2014; Sylvia et al[42], 2014; Ghaffari-Nejad et al[103], 2015; Levin et al[106], 2015; Mert et al[107], 2015
Young age	Frank et al[158], 1985; Kleindienst and Greil[156], 2004; Sajatovic et al[143], 2006b; Sajatovic et al[137], 2007a; Sajatovic et al[144], 2007b; Johnson et al[61], 2007; Baldessarini et al[66], 2008a; Baldessarini et al[138], 2008b; Copeland et al[67], 2008; Mazza et al[75], 2009; Bates et al[76], 2010; Bauer et al[44], 2010; Hou et al[79], 2010; Perlis et al[82], 2010; Lang et al[147], 2011; Savaş et al[85], 2011; Barraco et al[88], 2012; Montes et al[150], 2013; Hajda et al[104], 2015; Levin et al[106], 2015; Mousavi et al[32], 2016	Danion et al[111], 1987; Maarbjerg et al[113], 1988; Lenzi et al[116], 1989; Colom et al[51], 2000; Licht et al[125], 2001; Coletti et al[57], 2005; Gonzalez-Pinto et al[132], 2006; Drotar et al[133], 2007; Rosa et al[136], 2007; Sajatovic et al[144], 2007b; Sajatovic et al[63], 2007 c; Zeber et al[68], 2008; Savaş et al[85], 2011; Belzeaux et al[95], 2013; Hibdye et al[98], 2013; Murru et al[100], 2013; Kutzelnigg et al[151], 2014; Azadforouz et al[108], 2016	Both young and old age- Kessing et al[134], 2007 Old age - Lehman and Rabins[159], 2006; Rascati et al[148], 2011; Sharma et al[94], 2012
Male gender	Frank et al[158], 1985; Aagaard et al[112], 1988; Vestergaard and Schou[115], 1988; McCleod and Sharp[37], 2001; Gonzalez-Pinto et al[132], 2006; Drotar et al[133], 2007; Vega et al[139], 2009; Savaş et al[85], 2011; Mousavi et al[32], 2016	Danion et al[111], 1987; Maarbjerg et al[113], 1988; Licht et al[125], 2001; Gonzalez-Pinto et al[132], 2006; Rosa et al[160], 2006; Rosa et al[136], 2007; Sajatovic et al[143], 2006b; Sajatovic et al[137], 2007a; Sajatovic et al[144], 2007b; Sajatovic et al[63], 2007c; Johnson et al[61], 2007; Baldessarini et al[66], 2008a; Baldessarini et al[138], 2008b; Mazza et al[75], 2009; Bauer et al[44], 2010; Hou et al[79], 2010; Perlis et al[82], 2010; Rascati et al[148], 2011; Sajatovic et al[86], 2011b; Barraco et al[88], 2012; Sharma et al[94], 2012; Hibdye et al[98], 2013; Montes et al[150], 2013; Kutzelnigg et al[151], 2014; Hajda et al[104], 2015; Azadforouz et al[108], 2016	Female gender - Keck et al[142], 1996b; Keck et al[121], 1997; Jose et al[161], 2003; Sajatovic et al[46], 2005; Kessing et al[134], 2007; Copeland et al[67], 2008; Zeber et al[68], 2008; Bates et al[76], 2010; Belzeaux et al[95], 2013; Murru et al[100], 2013
Not married	Frank et al[158], 1985; Aagaard et al[112], 1988; Connelly et al[109], 1982; Connelly et al[110], 1984; Gonzalez-Pinto et al[132], 2006; Sajatovic et al[137], 2007a; Vega et al[139], 2009; Perlis et al[82],2010; Sajatovic et al[162], 2011a; Hajda et al[104], 2015	Lenzi et al[116], 1989; Licht et al[125], 2001; Gonzalez-Pinto et al[132], 2006; Sajatovic et al[144], 2007b; Sajatovic et al[63], 2007c; Zeber et al[68], 2008; Mazza et al[75], 2009; Bauer et al[44], 2010; Hou et al[79], 2010; Savaş et al[85], 2011; Barraco et al[88], 2012; Sharma et al[94], 2012; Belzeaux et al[95], 2013; Hibdye et al[98], 2013; Murru et al[100], 2013; Azadforouz et al[108], 2016; Mousavi et al[32], 2016
Poorly educated	Frank et al[158], 1985; Connelly et al[110], 1984; Danion et al[111], 1987; Johnson et al[61], 2007; Sajatovic et al[63], 2007c; Bates et al[76], 2010; Savaş et al[85], 2011; Hajda et al[104], 2015; Mousavi et al[32], 2016	Aagaard et al[112], 1988; Maarbjerg et al[113], 1988; Gonzalez-Pinto et al[132], 2006; Zeber et al[68], 2008; Bauer et al[44], 2010; Hou et al[79], 2010; Perlis et al[82], 2010; Sharma et al[94], 2012; Belzeaux et al[95], 2013; Hibdye et al[98], 2013
Unemployment	Aagaard et al[112], 1988; Perlis et al[82], 2010; Hibdye et al[98], 2013; Montes et al[150], 2013	Sajatovic et al[63], 2007c; Bauer et al[44], 2010; Hou et al[79], 2010; Perlis et al[82], 2010; Savaş et al[85], 2011; Barraco et al[88], 2012; Sharma et al[94], 2012; Murru et al[100], 2013; Hajda et al[104], 2015
Low socioeconomic status or income	DelBello et al[60], 2007; Perlis et al[82], 2010	Aagaard et al[112], 1988; Maarbjerg et al[113], 1988; Lenzi et al[116], 1989; Aagaard and Vestergaard[118], 1990; Johnson et al[61], 2007; Zeber et al[68], 2008; Savaş et al[85], 2011; Sharma et al[94], 2012
Ethnic minority status	Keck et al[121], 1997; Strakowski et al[49], 1998; Kleindienst and Greil[156], 2004; Sajatovic et al[143], 2006b; Sajatovic et al[137], 2007a; Sajatovic et al[144], 2007b; Sajatovic et al[63], 2007c; Johnson et al[61], 2007; Copeland et al[67], 2008; Zeber et al[68], 2008; Perlis et al[82], 2010; Rascati et al[148], 2011; Sajatovic et al[162] 2011a; Sajatovic et al[92], 2012	Fleck et al[58], 2005; Patel et al[131], 2005; Drotar et al[133], 2007; Baldessarini et al[66], 2008a; Baldessarini et al[138], 2008b; Bates et al[76], 2010; Hibdye et al[98], 2013; Kutzelnigg et al[151], 2014
Living alone/homeless	Lenzi et al[116], 1989; Kleindienst and Greil [156], 2004; Sajatovic et al[143], 2006b; Sajatovic et al[137], 2007a; Sajatovic et al[144], 2007b	Zeber et al[68], 2008; Montes et al[150], 2013; Murru et al[100], 2013; Hajda et al[104], 2015
Family factors: Dysfunction, poor social support, negative attitudes	Aagaard et al[112], 1988; Drotar et al[133], 2007; Cely et al[83], 2011; Sajatovic et al[162], 2011a; Scott et al[140], 2012; Sharma et al[94], 2012; Col et al[141], 2014	Sajatovic et al[72], 2009a; Sajatovic et al[86], 2011b

BD: Bipolar disorder.

Table 6 Studies of clinical correlates of medication non-adherence in bipolar disorder

Clinical correlates	Studies with positive associations	Studies without positive associations	Others
Early age of onset	Aagaard et al[112], 1988; Maarbjerg et al[113], 1988; Drotar et al[133], 2007 Perlis et al[82], 2010; Barraco et al[88], 2012	Colom et al[51], 2000; Scott and Pope[127], 2002a; Sajatovic et al[59], 2006a; Gonzalez-Pinto et al[132], 2006; González-Pinto et al[78], 2010; Murru et al[90], 2012; Levin et al[106], 2015; Azadforouz et al[108], 2016	Later onset - Col et al[141], 2014 Hajda et al[104], 2015
Short durations of illness	Aagaard et al[112], 1988; Maarbjerg et al[113], 1988; González-Pinto et al[78], 2010; Belzeaux et al[95], 2013; Azadforouz et al[108], 2016	Danion et al[111], 1987; Aagaard and Vestergaard[118], 1990; Schumann et al[123], 1999; Colom et al[51], 2000; Licht et al[125], 2001; Scott and Pope[127], 2002a; Jose et al[161], 2003; Gonzalez-Pinto et al[132], 2006; Taj et al[69], 2008; Sajatovic et al[72], 2009a; Hou et al[79], 2010; Savaş et al[85], 2011; Murru et al[90], 2012; Sharma et al[94], 2012; Montes et al[150], 2013; Col et al[141], 2014	Longer durations - Coletti et al[57], 2005; Belzeaux et al[95], 2013
Greater number of hospitalizations	Aagaard et al[112], 1988; Maarbjerg et al[113], 1988; Aagaard and Vestergaard[118], 1990; Colom et al[51], 2000; Svarstad et al[52], 2001; Scott[126], 2002; Scott and Pope[128], 2002b; Gonzalez-Pinto et al[132], 2006; Baldessarini et al[138], 2008b; Gianfrancesco et al[168], 2008; Hassan and Lage[145], 2009; Lage and Hassan[146], 2009; Martinez-Aran et al[74],2009; Vega et al[139], 2009; Bates et al[76], 2010; González-Pinto et al[78], 2010; Hong et al[84], 2011; Lang et al[147], 2011; Savaş et al[85], 2011; Scott et al[140], 2012; Kutzelnigg et al[151], 2014	Johnson and McFarland[169], 1996; Keck et al[47], 1996a; Schumann et al[123], 1999; Jose et al[161], 2003; Sajatovic et al[59], 2006a; Sajatovic et al[143], 2006b; Sajatovic et al[144], 2007b; Sajatovic et al[40], 2008; Clatworthy et al[71], 2009; Sharifi et al[73], 2009; Bauer et al[44], 2010; González-Pinto et al[78], 2010; Hou et al[79], 2010; Murru et al[90], 2012; Sharma et al[94], 2012; Montes et al[150], 2013; Hajda et al[104], 2015; Azadforouz et al[108], 2016	Fewer hospitalizations - Sajatovic et al[137], 2007a; Col et al[141], 2014
Higher total number of episodes	Danion et al[111], 1987; Gonzalez-Pinto et al[132], 2006; Vega et al[139], 2009; Gutiérrez-Rojas et al[81], 2010; Murru et al[100], 2013	Lenzi et al[116], 1989; Keck et al[47], 1996a; Jose et al[161], 2003; Martinez-Aran et al[74], 2009; Murru et al[90], 2012; Belzeaux et al[95], 2013; Col et al[141], 2014	Fewer episodes - Colom et al[51], 2000
Higher number of manic episodes	Gonzalez-Pinto et al[132], 2006; Vega et al[139], 2009; Murru et al[100], 2013	Johnson et al[61], 2007; Zeber et al[68], 2008; Martinez-Aran et al[74], 2009; Bates et al[76], 2010; Gutiérrez-Rojas et al[81], 2010; Murru et al[90], 2012; Col et al[141], 2014	Fewer hypomanic episodes - Colom et al[51], 2000
Higher number of depressive episodes	Danion et al[111], 1987; Gutiérrez-Rojas et al[81], 2010; Col et al[141], 2014	Gonzalez-Pinto et al[132], 2006; Johnson et al[61], 2007; Martinez-Aran et al[74], 2009; Vega et al[139], 2009; Bates et al[76], 2010; Murru et al[90], 2012	Fewer depressive episodes - Colom et al[51], 2000
Higher number of mixed episodes/rapid cycling	Calabrese et al[56], 2005; Perlis et al[82], 2010	Maarbjerg et al[113], 1988; Colom et al[51], 2000; Sajatovic et al[59], 2006a; Gonzalez-Pinto et al[132], 2006; Sajatovic et al[40], 2008; Martinez-Aran et al[74], 2009; Murru et al[90], 2012; Murru et al[100], 2013
BD vs UP disorders	Arvilommi et al[101], 2014; Mert et al[107], 2015	Connelly et al[109], 1982; Maarbjerg et al[113], 1988; Lenzi et al[116], 1989; Aagaard and Vestergaard[118], 1990; Schumann et al[123], 1999; McCleod and Sharp[37], 2001; Scott and Pope[127], 2002a; Taj et al[69], 2008; Ghaffari-Nejad et al[103], 2015
BP I vs BP II	Martinez-Aran et al[74], 2009; Mazza et al[75], 2009	Jamison et al[9], 1979; Colom et al[51], 2000; Sajatovic et al[59], 2006a; Sajatovic et al[40], 2008; Baldessarini et al[66], 2008a; Baldessarini et al[138], 2008b; Bauer et al[44], 2010; Perlis et al[82], 2010; Montes et al[150], 2013; Sylvia et al[42], 2014	Higher in BP II - Murru et al[100], 2013
Polarity of episodes	Gutiérrez-Rojas et al[81], 2010; Montes et al[150], 2013	Danion et al[111], 1987; Maarbjerg et al[113], 1988; Sajatovic et al[59], 2006a; Col et al[141], 2014
Overall severity of illness	Baldessarini et al[66], 2008a; Sajatovic et al[72], 2009a; Sajatovic et al[40], 2008; Bates et al[76], 2010; González-Pinto et al[78], 2010; Cely et al[83], 2011; Barraco et al[88], 2012; Sharma et al[94], 2012; Kutzelnigg et al[151], 2014; Hajda et al[104], 2015	Danion et al[111], 1987; Nilsson and Axelsson[117], 1989; Sajatovic et al[63], 2007 c; Sajatovic et al[72], 2009a; Mazza et al[75], 2009; Hong et al[84], 2011; Sajatovic et al[86], 2011b; Montes et al[150], 2013; Sylvia et al[42], 2014; Azadforouz et al[108], 2016; Sajatovic et al[152], 2016
Manic symptoms	Van Putten[20], 1975; Connelly et al[109], 1982; Keck et al[47], 1996a; Keck et al[142], 1996b; Lenzi et al[116], 1989; Miklowitz et al[171], 2000; Miklowitz et al[172], 2003; Bowden et al[130], 2005; Gonzalez-Pinto et al[132], 2006; Gaudiano and Miller[173], 2006; Baldessarini et al[66], 2008a; Copeland et al[67], 2008; Bauer et al[44], 2010; González-Pinto et al[78], 2010; Perlis et al[82], 2010; Hong et al[84], 2011; Barraco et al[88], 2012; Montes et al[150], 2013; Sylvia et al[42], 2014; Levin et al[106], 2015	Colom et al[51], 2000; Rosa et al[136], 2007; Sajatovic et al[59], 2006a; Sajatovic et al[63], 2007 c; Sajatovic et al[40], 2008; Clatworthy et al[71], 2009; Mazza et al[75],2009; Martinez-Aran et al[74], 2009; Sajatovic et al[86], 2011b; Murru et al[90], 2012; Belzeaux et al[95], 2013; Hibdye et al[98], 2013; Jónsdóttir et al[99], 2013; Ghaffari-Nejad et al[103], 2015; Azadforouz et al[108], 2016; Sajatovic et al[152], 2016
Depressive symptoms	Bowden et al[130], 2005; Gaudiano and Miller[173], 2006; Johnson et al[61], 2007; Martinez-Aran et al[74], 2009; Bates et al[76], 2010; Bauer et al[44], 2010; Perlis et al[82], 2010; Hong et al[84], 2011; Barraco et al[88], 2012; Montes et al[150], 2013; Arvilommi et al[101], 2014; Bauer et al[45], 2013a; Bauer et al[153], 2013b; Murru et al[100], 2013; Gibson et al[97], 2013; Levin et al[106], 2015; Azadforouz et al[108], 2016; Sajatovic et al[152], 2016	Colom et al[51], 2000; Miklowitz et al[171], 2000; Miklowitz et al[172], 2003; Sajatovic et al[143], 2006b; Sajatovic et al[63], 2007c; Rosa et al[136], 2007; Sajatovic et al[40], 2008; Sajatovic et al[72], 2009a; Clatworthy et al[71], 2009; González-Pinto et al[78], 2010; Sajatovic et al[86], 2011b; Murru et al[90], 2012; Hibdye et al[98], 2013; Sylvia et al[42], 2014; Ghaffari-Nejad et al[103], 2015	Better adherence with depression - Lenzi et al[116], 1989
Mixed symptoms	Bowden et al[130], 2005; González-Pinto et al[78], 2010; Perlis et al[82], 2010	Licht et al[125], 2001; Azorin et al[70], 2009; Hibdye et al[98], 2013; Ghaffari-Nejad et al[103], 2015
Psychotic symptoms	Miklowitz et al[174], 1992; Maj et al[122], 1998; Yen et al[157], 2005; Martinez-Aran et al[74], 2009; González-Pinto et al[78], 2010; Murru et al[90], 2012; Murru et al[100], 2013; Levin et al[106], 2015; Sajatovic et al[152], 2016	Danion et al[111], 1987; Aagaard and Vestergaard[118], 1990; Colom et al[51], 2000; Sajatovic et al[59], 2006a; Sajatovic et al[40], 2008; Sajatovic et al[72], 2009a; Perlis et al[82], 2010; Belzeaux et al[95], 2013; Azadforouz et al[108], 2016
Cognitive impairment	Danion et al[111], 1987; Jose et al[161], 2003; Baldessarini et al[66], 2008a; Depp et al[175], 2008; Martinez-Aran et al[74], 2009; Eker and Harkin[89], 2012	Maarbjerg et al[113], 1988; Jónsdóttir et al[99], 2013
Familial psychiatric disorder	Drotar et al[133], 2007	Colom et al[51], 2000; Gonzalez-Pinto et al[132], 2006; Martinez-Aran et al[74], 2009; Savas et al[85], 2011; Murru et al[90], 2012; Col et al[141], 2014; Hajda et al[104], 2015
Poor insight	Schumann et al[123], 1999; Greenhouse et al[54], 2000; Jose et al[161], 2003; Fleck et al[58], 2005; Yen et al[157], 2005; Rosa et al[160], 2006; Rosa et al[136], 2007; Copeland et al[67], 2008; Sajatovic et al[72], 2009a; González-Pinto et al[78], 2010; Cely et al[83], 2011; Sajatovic et al[86], 2011b; Savaş et al[85], 2011; Vieta et al[93], 2012; Kutzelnigg et al[151], 2014; Mert et al[107], 2015; Novick et al[176], 2015	Wong et al[124], 1999; Jonsdottir et al[99], 2013
Comorbid SUD	Aagaard et al[112], 1988; Maarbjerg et al[113], 1988; Weiss et al[50], 1998; Aagaard and Vestergaard[118], 1990; Keck et al[121], 1997; Keck et al[48], 1998; Strakowski et al[49], 1998; Licht et al[125], 2001; Fleck et al[58], 2005; Gonzalez-Pinto et al[132], 2006; Sajatovic et al[59], 2006a; Sajatovic et al[143], 2006b; Sajatovic et al[137], 2007a; Sajatovic et al[144], 2007b; DelBello et al[60], 2007; Manwani et al[135], 2007; Baldessarini et al[138], 2008b; Copeland et al[67], 2008; Darling et al[177], 2008; Zeber et al[68], 2008; Sajatovic et al[72], 2009a; van Rossum et al[178], 2009; Vega et al[139], 2009; Bates et al[76], 2010; González-Pinto et al[78], 2010; Perlis et al[82], 2010; Cely et al[83], 2011; Hong et al[84], 2011; Lang et al[147], 2011; Sajatovic et al[162], 2011a; Teter et al[179], 2011; Barraco et al[88], 2012; Vieta et al[93], 2012; Hibdye et al[98], 2013; Jónsdóttir et al[99], 2013; Montes et al[150], 2013; Arvilommi et al[101], 2014	Nilsson and Axelsson[117],1989; Schumann et al[123], 1999; Colom et al[51], 2000; Sajatovic et al[63], 2007c; Sajatovic et al[40], 2008; Mazza et al[75], 2009; Sharifi et al[73],2009; Rascati et al[148], 2011; Sajatovic et al[86], 2011b; Murru et al[90], 2012; Sharma et al[94], 2012 Murru et al[100], 2013; Col et al[141], 2014; Kutzelnigg et al[151], 2014; Sylvia et al[42], 2014; Mert et al[107], 2015; Ghaffari-Nejad et al[103], 2015
Comorbid personality disorders	Danion et al[111], 1987; Aagaard et al[112], 1988; Maarbjerg et al[113], 1988; Colom et al[51], 2000; Murru et al[100], 2013; Arvilommi et al[101], 2014	Aagaard and Vestergaard[118], 1990; Schumann et al[123],1999; Kliendienst and Griel[156], 2004; Mazza et al[75], 2009; Murru et al[90], 2012; Kutzelnigg et al[151], 2014
Comorbid anxiety disorders or ADHD	DelBello et al[60], 2007; Baldessarini et al[66], 2008a; Taj et al[69], 2008; Perlis et al[82], 2010; Arvilommi et al[101], 2014	Sajatovic et al[59], 2006a; Sajatovic et al[144], 2007b; Drotar et al[133], 2007; Sajatovic et al[40], 2008; Cely et al[83], 2011; Rascati et al[148], 2011; Murru et al[90], 2012; Belzeaux et al[95], 2013; Kutzelnigg et al[151], 2014; Sylvia et al[42], 2014	Better adherence with comorbid anxiety disorder - Baldessarini et al[138], 2008b

ADHD: Attention deficit hyperactivity disorder; BD: Bipolar disorder; SUD: Substance use disorders; UP: Unipolar disorder.

Table 7 Studies of treatment correlates of medication non-adherence in bipolar disorder

Treatment correlates	Studies with positive associations	Studies without positive associations	Others
Differences between mood stabilizers	Weiss et al[50], 1998; Revicki et al[155], 2005; Baldessarini et al[138], 2008b; Sajatovic et al[137], 2007a	Baldessarini et al[66], 2008a; Darling et al[177], 2008; Bauer et al[45], 2013a; Col et al[141], 2014
Differences between antipsychotics	Gianfrancesco et al[184], 2005; Gianfrancesco et al[185], 2006; Hassan et al[186], 2007; Sajatovic et al[144], 2007b; Rascati et al[148], 2011; Ibrahim et al[105], 2015	Patel et al[131], 2005; Sajatovic et al[143], 2006b; Baldessarini et al[66], 2008a
Differences between mood stabilizers and antipsychotics or antidepressants	González-Pinto et al[78], 2010; Lang et al[147], 2011; Murru et al[100], 2013; Arvilommi et al[101], 2014; Ibrahim et al[105], 2015	Danion et al[111], 1987; Keck et al[48], 1998; Colom et al[51], 2000; Patel et al[131], 2005; Sajatovic et al[143], 2006b; Baldessarini et al[66], 2008a; Azorin et al[70], 2009; Clatworthy et al[71], 2009; Gianfrancesco et al[187], 2009; Martinez-Aran et al[74], 2009; Mazza et al[75], 2009; Bates et al[76], 2010; Cely et al[83], 2011; Savaş et al[85], 2011; Murru et al[90], 2012; Bauer et al[153], 2013b; Hibdye et al[98], 2013; Arvilommi et al[101], 2014; Hajda et al[104], 2015
Shorter duration of treatment	Johnson and McFarland[169], 1996; Colom et al[51], 2000; Lang et al[147], 2011; Azadforouz et al[108], 2016	Gonzalez-Pinto et al[132], 2006; Drotar et al[133], 2007; Darling et al[177], 2008; Sharma et al[94], 2012; Hibdye et al[98], 2013; Col et al[141], 2014	Longer durations - Jamison et al[9], 1979; Scott and Pope[127], 2002a Kessing et al[134], 2007 Sharifi et al[73], 2009; Short and long durations - Kutzelnigg et al[151], 2014
Greater number of medications	Keck et al[47], 1996a; Revicki et al[155], 2005; Baldessarini et al[138], 2008b; Gianfrancesco et al[187], 2009; Bates et al[76], 2010; Hou et al[79], 2010; Perlis et al[82], 2010; Cruz et al[35], 2011; Rascati et al[148], 2011; Bauer et al[45], 2013a; Bauer et al[153], 2013b; Ibrahim et al[105], 2015	Colom et al[51], 2000; Licht et al[125], 2001; Rosa et al[136], 2007; Baldessarini et al[66], 2008a; Darling et al[177], 2008; Depp et al[175], 2008; Taj et al[69], 2008; Martinez-Aran et al[74], 2009; Bauer et al[44], 2010; Sajatovic et al[86], 2011b; Savaş et al[85],2011; Miasso et al[91], 2012; Sharma et al[94], 2012; Col et al[141], 2014; Ghaffari-Nejad et al[103], 2015	Less intensive treatment - Johnson and McFarland[169], 1996; Keck et al[121], 1997; Sajatovic et al[59], 2006a; Sajatovic et al[143], 2006b; Sajatovic et al[137], 2007a; Sajatovic et al[144], 2007b; Sajatovic et al[40], 2008
Higher doses of medications	McCleod and Sharp[37], 2001; Gianfrancesco et al[185], 2006	Baldessarini et al[66], 2008a; Col et al[141], 2014; Hajda et al[104], 2015	Lower doses of medications - Mazza et al[75], 2009; Bauer et al[44], 2010
Complex medication regimens	Baldessarini et al[138], 2008b; Sajatovic et al[72], 2009a; Hibdye et al[98], 2013; Ibrahim et al[105], 2015	Keck et al[48], 1998; Baldessarini et al[66], 2008a; Miasso et al[91], 2012; Col et al[141], 2014	Fear of side effects - Cochran et al[31], 1984; Schumann et al[123], 1999; Scott[196], 2000; Scott[126], 2002; Scott and Pope[127], 2002a; Scott and Tacchi[197], 2002; Morselli et al[194], 2003; Morselli et al[195], 2004; Fleck et al[58], 2005; Rosa et al[160], 2006; Rosa et al[136], 2007; Clatworthy et al[36], 2007; Clatworthy et al[71], 2009; Sajatovic et al[198], 2009c; Kriegshauser et al[199], 2010; Cruz et al[35], 2011; Sajatovic et al[162], 2011a
Side effects	Bech et al[30], 1976; Vestergaard and Amdisen[188], 1983; Maarbjerg et al[113], 1988; Gitlin et al[189], 1989; Nilsson and Axelsson[117], 1989; Aagaard and Vestergaard[118], 1990; Maj et al[122], 1998; Weiss et al[50], 1998; Licht et al[125], 2001; Kliendienst and Griel[156], 2004; Lewis[190], 2005; Bowden et al[130], 2005; Calabrese et al[56], 2005; Fleck et al[58], 2005; Revicki et al[155], 2005; Johnson et al[61], 2007; Baldessarini et al[66], 2008a; Baldessarini et al[138], 2008b; Bates et al[76], 2010; Mączka et al[191], 2010; Wang and Henning[192], 2010; Cely et al[83], 2011; Cruz et al[35], 2011; Miasso et al[193], 2011; Sajatovic et al[162], 2011a; Teter et al[1179], 2011; Eker and Harkin[89], 2012; Sharma et al[94], 2012; Belzeaux et al[95], 2013; Gibson et al[97], 2013; Arvilommi et al[101], 2014; Sylvia et al[42], 2014; Ibrahim et al[105], 2015; Mert et al[107], 2015 Ghaffari-Nejad et al[103], 2015	Van Putten[20], 1975; Jamison et al[9], 1979; Connelly et al[109], 1982; Danion et al[111], 1987; Lenzi et al[116], 1989; Johnson and McFarland[169], 1996; Schuman et al[123], 1999; Scott[196], 2000; Scott[126], 2002; Scott and Pope[127], 2002a; Morselli et al[194], 2003; Morselli et al[195], 2004; Pope and Scott[129], 2003; Roy et al[33], 2005; Sajatovic et al[143], 2006b; Drotar et al[133],2007; Rosa et al[160], 2006; Rosa et al[136], 2007; Perlis et al[82], 2010; Savaş et al[85], 2011; Barraco et al[88], 2012; Vieta et al[93], 2012; Hibdye et al[98], 2013; Jónsdóttir et al[99], 2013; Kutzelnigg et al[151], 2014; Col et al[141], 2014
Efficacy	Bech et al[30], 1976; Jamison et al[9], 1979; Miklowitz et al[171], 2000; Miklowitz et al[172], 2003; Lewis[190], 2005; Fleck et al[58], 2005; Patel et al[131], 2005; Gaudiano and Miller[173], 2006; Drotar et al[133], 2007; Johnson et al[61], 2007; Sajatovic et al[198], 2009c; Cely et al[83], 2011

BD: Bipolar disorder. References in Tables 2-4 and text (No. 155-199).