Table 3.
Studies included regarding adherence and persistence
| Study | Source of data [period] | Population | Results |
|---|---|---|---|
| Adherence and persistence outcome: adherence and persistence | |||
| Baldessarini et al14 | Proprietary research database containing eligibility information and pharmacy and medical claims data from a large commercial USA health plan (concentration in the South and Midwest) [2000–2004] | n=7,406 BD patients aged ≥17 years (55.4% BD-I) | 2,197 patients with MS monotherapy prescription: only 28% considered adherent (MPR – percentage of the past 365 days with apparent access to an initial mood stabilizer – ≥80%) Factors independently associated with MS adherence: older age, lack of substance abuse, treatment by a psychiatrist (vs primary care physician), and lower illness complexity |
| Bates et al34 | Data collected via a self-report, web-based survey from USA patients aged 18–65 years who reported a diagnosis of BD and current use of psychotropic medication [2008] | 1,052 patients with high risk of BD according to the CIDI-BD score ≥7 | Nonadherent: 49.5% of patients Adherencea positively associated with college degree, higher satisfaction with antipsychotic medication scale score, and monotherapy treatment. Adherence negatively associated with alcohol use, higher burden of symptoms (24-item Behavior and Symptom Identification Scale), and higher side effect burden (Liverpool University Neuroleptic Side-effect Rating Scale) |
| Berger et al17 | Truven MarketScan® Commercial Claims and Encounters Database (a health insurance claims database) and the Truven MarketScan Hospital Drug Database (admission-level database) [2001–2008] | n=84 BD patients receiving SGAs (aripiprazole, quetiapine, or ziprasidone) at hospital discharge | During the 6-month period of follow-up, mean MPR=37.3%, suggesting a poor adherence in BD patients discharged on SGA |
| Burns et al18 | Analysis of Medicaid and Medicare administrative data, nationally representative cohort [2004–2007] | n=1,431 adults, dual beneficiaries, with diagnosed BD-I | Average percentage of beneficiaries with MPRb ≥80%=62% |
| Chen et al20 | Three MarketScan research databases: Commercial Claims and Encounters Database (“commercial”), Medicare supplemental and coordination of benefits database (“Medicare”), and multistate Medicaid database [2002–2008] | n=16,807 patients (34.7% from commercial/Medicare and 65.3% from Medicaid database) aged ≥18 years with BD-I who newly initiated an oral SGA | Adherence generally poor (8.3%; mean MPR=0.19) Mean MPR and adherence by SGA: quetiapine (0.23/10.4%), aripiprazole (0.18/5.9%), risperidone (0.17/6.8%), and olanzapine (0.16/6.8%) Average time to first noncompliance (gap between refills between 15 and 30 days): aripiprazole (102 days), quetiapine (90 days), olanzapine (87 days), and risperidone (84 days) |
| Hassan et al25 | Claims data from a Medicaid database [1999–2001] | n=620 BD patients receiving SGA; n=205 receiving FGA | Mean MPR: quetiapine (71%), risperidone (68%), olanzapine (68%), and FGA (46%) Mean persistence (days treatment until discontinuation or switching for another medication): quetiapine (219.8), olanzapine (200.9), risperidone (194.8), and FGA (179.2) |
| Lage and Hassan27 | Extracted data from the PharMetrics database* [2000–2006] | n=7,769 BD patients | Mean MPR for antipsychotics: 41.7% (MPR ≥80% was present in only 15.82% of the patients) Mean days prescribed for any SGA: 175.08 days (12-month study period) |
| Lang et al28 | Retrospective cohort analysis of Medicaid patients [2004–2006, 1-year follow-up] | n=9,410 patients with BD-I aged ≥18 years, and filled one or more prescription for antipsychotic medication | MPR ≥80% (mean MPRb): 38.9% (63%) oral SGA monotherapy; 46.3% (66%) oral FGA and SGA; 42.7% (57%) oral FGA monotherapy; 52.9% (74%) LAI SGA; 51.6% (70%) LAI FGA; overall rate of 40.6% (63%) Mean persistencec in patients: 0.84 oral SGA monotherapy; 0.90 oral FGA and SGA; 0.79 oral FGA monotherapy; 0.94 LAI SGA; 0.93 LAI FGA; overall mean persistence of 0.85 Factors significantly related to nonadherence (MPR <80%, adjusted analysis): new starts (vs continuing users), age <45 (vs ≥45 years), baseline substance abuse diagnosis, and baseline psychiatric hospitalization Factors significantly related to adherence (adjusted analysis): baseline MS use, baseline other psychosis diagnosis, baseline anticonvulsant use, baseline anticholinergic use, and LAI SGA (vs oral FGA) |
| Perlis et al40 Outcome: poor adherence |
Prospective data from two cohorts of individuals from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study [1999–2005] | n=3,640 BD patients | Poor adherence (≥25% of milligrams for each medication missed in the past week) reported on 12.8% of visits (average). Nonadherence on ≥20% visits: 23.9% patients; adherence at all visits: 46.4% patients Poor adherence – significantly associated clinical features: alcohol use disorder (OR=1.35), anxiety disorder (OR=1.33), rapid cycling in the lifetime (OR=1.23), and earlier onset of illness (OR=0.8 for each 10-year increase) |
| Rascati et al29 | Retrospective analysis of claims data for Medicaid patients from eight states (claims extracted from the Texas Medicaid Vendor Drug, Texas Medicaid Medical Services, and MarketScan databases) [2002–2008] | n=2,446 BD patients | Patients with clinically recommended doses: 58% considered adherent (MPRb). Adherence rates per drug: ziprasidone (62%), aripiprazole (60%), olanzapine (58%), quetiapine (55%), and risperidone (58%) Median time to non-persistenced: 96 days (117 days for ziprasidone; 93 days for aripiprazole; 72 days for olanzapine; 112 days for quetiapine; and 95 days for risperidone) 12-month persistence rates (whole cohort)=18% (no relevant differences among different antipsychotics). Gap between refills >30 days |
| Sajatovic et al41 | VA National Psychosis Registry;** VA pharmacy benefits management strategic health care group [2003] | 73,964 BD patients | Mean MPR for individuals receiving SGAs: 75% (84% clozapine, 75% risperidone, 75% olanzapine, 77% quetiapine, 77% ziprasidone, and 79% aripiprazole) Persistence – median SGA treatment duration=240 days Factors associated with nonadherence: younger age, minority ethnicity, comorbid substance abuse, and homelessness |
| Sajatovic et al30 | VA National Psychosis Registry;** VA pharmacy benefits management strategic health care group [2003] | 44,637 BD patients receiving lithium and anticonvulsants | Mean MPR for individuals receiving lithium or anticonvulsants: 77% (79% lithium, 80% carbamazepine, 76% valproate, and 81% lamotrigine) Persistence – median MS treatment duration=270 days |
| Adherence and persistence outcome: other outcomes | |||
| Baldessarini et al15 Outcome: time to discontinuation of index drug; time to augmentation |
USA national MarketScan research database was used to quantify utilization rates for psychotropic drug classes in patients with ICD-9 BD [2002–2003] | n=7,760 BD patients (69.2% with BD-I) | Median time to discontinuation of the initial drug (weeks): lithium (58.3), divalproex (36.1), and SGAs (29.1) Median time to augmentation (adding one or more drugs, weeks): lithium (39.1), divalproex (14.9), and SGAs (10.6) |
| Adherence and persistence outcome: factors related to medication adherence and nonadherence | |||
| Baldessarini et al33 | Survey including 131 randomly selected prescribing psychiatrists and their adult BD patients in five geographic regions in the USA [2005] | n=429 (32.5%) BD patients (79% BD-I) | Prominent AE associated with treatment nonadherence (n=145): weight gain (58.5%), excessive sedation (54.2%), and physical awkwardness or tremor (33.1%) Multivariate models identified nine factors independently, ranked by significance: alcohol dependence (OR=4.89); younger age (OR=1.03), greater number of affective symptoms (OR=1.1), not being in full remission (OR=4.12), side effect as a major source of patient frustration (OR=1.9); cognitive impairment (OR=2.59), “anticholinergic side effects” (OR=3.84), comorbid obsessive–compulsive disorder (OR=7.24), and recent mania or hypomania (OR=2.77) |
| Sajatovic et al41 | VA National Psychosis Registry**; VA pharmacy benefits management strategic health care group [2003] | 73,964 BD patients | Factors associated with nonadherence: younger age, minority ethnicity, comorbid substance abuse and homelessness. |
Notes:
a
Medication adherence – assessed via the Morisky Medication Adherence Scale, with scores ≥2 considered nonadherent.
b
MPR – defined as ratio between number of days’ supply for all index medication fills during the study period and the number of days between index and end date of the last index medication dispensed during the study period.
c
Persistence – defined as the number of days between the first and last day receiving an antipsychotic divided by the number of days remaining in the period after the first antipsychotic was dispensed.
d
Non-persistence – defined as duration of therapy from initiation of the index medication until discontinuation.
*
PharMetrics database – contains information on 55 million commercially insured individuals.
**
VA National Psychosis Registry – consists of records for all patients who received a diagnosis of psychosis during inpatient stays and outpatient visits and received VA Services.
Abbreviations: AE, adverse effect; BD, bipolar disorder; BD-I, BD type I; CIDI, Composite International Diagnostic Interview; FGA, first-generation antipsychotic; ICD-9, International Classification of Diseases, Ninth Revision; LAI, long-acting injectable; MPR, medication possession rate; MS, mood stabilizer; OR, odds ratio; SGA, second-generation antipsychotic; VA, Veterans Affairs.