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

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.