Dosing strategies for switching from oral risperidone to paliperidone palmitate: Effects on clinical outcomes.

INTRODUCTION: There are currently no guidelines for switching patients from oral risperidone to paliperidone palmitate (Invega Sustenna®). Furthermore, the paliperidone long-acting injectable (LAI) package insert does not recommend bridging with oral antipsychotics, which may result in inadequate serum concentrations in patients on ≥4 mg/d risperidone. METHODS: This study evaluated the effects of suboptimal dosing and bridging in patients switched from oral risperidone to paliperidone LAI on hospitalization days, emergency department (ED)/mental health urgent care visits, and no-shows/cancellations to mental health appointments. Patients were categorized into optimal or suboptimal dosing based on their loading and maintenance paliperidone doses. Patients on risperidone ≥4 mg/d were categorized as bridged if they received risperidone for ≥7 days after the first paliperidone injection. RESULTS: There were no significant differences in outcomes between optimally and suboptimally dosed patients. There were statistically significant reductions in hospitalization days in patients who were bridged compared with patients who were not bridged. There were statistically significant reductions in hospitalization days and ED/mental health urgent care visits after switching to paliperidone LAI. DISCUSSION: The results of this study indicate that bridging patients who are on ≥4 mg/d risperidone, when converting to paliperidone LAI, is associated with reductions in hospitalization days. However, more research is required to determine the optimal dose and duration of the bridge. The results also indicate that switching patients from oral risperidone to paliperidone LAI, even if the dose is suboptimal, is associated with reductions in hospitalization days and ED/mental health urgent care visits.

A prospective study of risk factors for nonadherence with antipsychotic medication in the treatment of schizophrenia.

OBJECTIVES: This study aimed to prospectively identify the best single predictor and the best set of predictors of risk for nonadherence with anti-psychotic medication in the treatment of patients with schizophrenia. METHOD: We used data from 1579 patients in a 3-year, prospective, naturalistic, nonrandomized, multisite study of schizophrenia patients conducted from July 1997 to September 2003 (U.S. Schizophrenia Care and Assessment Program). Adherence with any oral antipsychotic medication was assessed using patient-reported medication adherence and an indirect adherence measure based on medical record prescription information. Patients who reported poor medication adherence or had a medication possession ratio < or = 80% (percentage of days with prescriptions for any oral antipsychotic) during the first year after enrollment were defined as nonadherent (N = 296, 18.8%). Thirty-nine previously reported potential risk factors of nonadherence with antipsychotic medication were assessed at enrollment with valid and reliable measures. Risk factors represented patient-, environment-, and treatment-related domains, including sociodemographics, symptom severity, substance use, threat to safety of self and others, other illness-related factors, need for supervision, medication-related adverse events, and prior medication-utilization patterns. RESULTS: The best single predictor of future nonadherence was nonadherence during the 6 months prior to enrollment (odds ratio = 4.1, 95% confidence interval = 3.1 to 5.6, p < .001). The best set of predictors of nonadherence, ordered by strength of association, included prior non-adherence, recent illicit drug use, recent alcohol use, prior treatment with antidepressants, and greater patient-reported, medication-related cognitive impairment. CONCLUSION: Nonadherence with antipsychotic medication is associated with a well-defined set of risk factors that can be used to identify patients who are predisposed to poor adherence.

Antipsychotic medication adherence: is there a difference between typical and atypical agents?

OBJECTIVE: Pharmacy refill records were used to compare medication adherence in outpatient veterans receiving typical versus atypical antipsychotic medications. METHOD: Consecutive patients meeting selection criteria and receiving prescriptions for haloperidol (N=57), perphenazine (N=60), risperidone (N=80), olanzapine (N=63), and quetiapine (N=28) over a 3-month period were identified from a computerized database. The hospital policy at the time of this study required failure in trials of at least two typical antipsychotics before initiation of an atypical agent. Patients' adherence with the antipsychotic regimen was calculated by analyzing refill records for up to 12 months. The cumulative mean gap ratio (the number of days when medication was unavailable in relation to the total number of days) and the compliant fill rate (the number of prescription fills indicating adherence in relation to the total number of prescription fills) at 6 and 12 months were calculated. RESULTS: Adherence rates at 6 and 12 months were moderately higher in patients who received atypical antipsychotics than in those who received typical agents. Cumulative mean gap ratios were 23.2% for typical and 14.1% for atypical antipsychotics at 12 months; thus, patients who received typical agents were without medication for an average of 7 days per month, compared with 4 days per month for those who received atypical agents. At 12 months, compliant fill rates were 50.1% for typical and 54.9% for atypical antipsychotics. CONCLUSIONS: Interventions to improve adherence are warranted even for patients who receive atypical antipsychotic medications.

Adherence to treatment with antipsychotic medication and health care costs among Medicaid beneficiaries with schizophrenia.

OBJECTIVE: The authors' goal was to evaluate the relationship between adherence to treatment with antipsychotic medication and health expenditures. A secondary objective was to identify risk factors predictive of nonadherence. METHOD: Data included Medicaid eligibility and claims data from 1998 to 2000 for San Diego County, Calif. Pharmacy records were used to assess adherence to treatment with antipsychotic medication according to the cumulative possession ratio (the number of days medications were available for consumption divided by the number of days subjects were eligible for Medi-Cal). Regression models were used to examine risk factors, hospitalizations, and costs associated with nonadherence, partial adherence, adherence, and excess fills of antipsychotic medication. RESULTS: Forty-one percent of Medicaid beneficiaries with schizophrenia were found to be adherent to treatment with their antipsychotic medications: 24% were nonadherent, 16% were partially adherent, and 19% were excess fillers. Rates of psychiatric hospitalization were lower for those who were adherent (14%) than for those who were nonadherent (35%), partially adherent (24%), or had excess fills (25%). Rates of medical hospitalization were lower for those who were adherent (7%) than for those who were nonadherent (13%) or had excess fills (12%). Those who were adherent had significantly lower hospital costs than the other groups; pharmacy costs were higher among those who were adherent than among those who were nonadherent or partially adherent and were highest for excess fillers. Total costs for excess fillers (14,044 US dollars) were substantially higher than total costs for any other group. CONCLUSIONS: Despite the widespread use of atypical antipsychotic medications, alarmingly high rates of both underuse and excessive filling of antipsychotic prescriptions were found in Medicaid beneficiaries with schizophrenia. The high rates of antipsychotic nonadherence and associated negative consequences suggest interventions on multiple levels.

Adherence to antipsychotic and nonpsychiatric medications in middle-aged and older patients with psychotic disorders.

OBJECTIVE: The prevalence and consequences of nonadherence to antipsychotic medications in schizophrenia and related psychotic disorders have been well described; however, little is known about adherence to medications for nonpsychiatric conditions in patients with psychotic disorders. We wished to determine medication adherence in nondemented middle-aged and older Veterans Affairs outpatients with schizophrenia or other psychotic disorders who had been prescribed oral medications for hypertension, hyperlipidemia, or diabetes. METHODS: Medication adherence was assessed by review of medication fill records for 76 patients aged 40 years and older who had been prescribed an oral antipsychotic in addition to an oral agent for hypertension (N = 60), hyperlipidemia (N = 28), or diabetes (N = 24). Up to 12 months of therapy was reviewed, and a compliant fill rate (the number of adherent fills in proportion to the total number of prescription fills) and cumulative mean gap ratio (the number of days when medication was unavailable in relation to the total number of days) were calculated for each medication. RESULTS: The 12-month mean compliant fill rates for antipsychotics, antihypertensives, antihyperlipidemics, and antidiabetics ranged from 52% to 64%. Nonpsychiatric medication adherence rates were similar in patients on typical vs. atypical antipsychotics and did not correlate significantly with antipsychotic adherence rates. CONCLUSIONS: Nonadherence rates were found to be equally problematic for both antipsychotic and nonpsychiatric medications in middle-aged and older patients with psychotic disorders. Interventions to improve adherence to both antipsychotic and nonpsychiatric medications are needed.

Prevalence of and risk factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature.

OBJECTIVE: Nonadherence to prescribed antipsychotic medications places patients with schizophrenia at a greatly increased risk of illness exacerbation and rehospitalization. Identification of risk factors for nonadherence is an initial step toward designing effective interventions. This article reviews recent literature on the prevalence of and risk factors for medication nonadherence in patients with schizophrenia. DATA SOURCES: We searched the MEDLINE/HealthSTAR and PsycINFO databases using combinations of the keywords risk factor(s), adherence, compliance, antipsychotic, neuroleptic, schizophrenia, and psychosis for articles published since 1980 that identified risk factors for medication nonadherence in schizophrenia patients. We included reports that (1) were published in English and (2) specifically examined risk factors for medication nonadherence. Thirty-nine articles met our selection criteria. DATA SYNTHESIS: Among the 10 reports that met a strict set of study inclusion criteria, we found a mean rate of nonadherence of 41.2%; the 5 reports that met a stricter set of inclusion criteria had a mean nonadherence rate of 49.5%. In the 39 articles reviewed, factors most consistently associated with nonadherence included poor insight, negative attitude or subjective response toward medication, previous nonadherence, substance abuse, shorter illness duration, inadequate discharge planning or aftercare environment, and poorer therapeutic alliance. Findings regarding an association between adherence and medication type were inconclusive, although few studies explored this relationship. Other factors such as age, gender, ethnicity, marital status, education level, neurocognitive impairment, severity of psychotic symptoms, severity of medication side effects, higher antipsychotic dose, presence of mood symptoms, route of medication administration, and family involvement were not found to be consistent predictors of nonadherence. Limitations of the published literature are discussed. CONCLUSION: Efforts to improve medication adherence in patients with schizophrenia should target relevant risk factors.

Serum Haloperidol Levels in Older Psychotic Patients.

The authors measured serum levels of haloperidol (HL) in outpatients ages 45-83 years with psychosis treated with HL for at least 1 month. Blood was collected from 32 patients with either schizophrenia (n = 23) or Alzheimer's disease (AD) (n = 9). HL daily dose was greater in patients with schizophrenia (median age, 59) than in AD patients (median age, 80) (P < 0.0005), but no significant group differences in HL serum concentrations were observed. In the total sample, age correlated negatively with HL dose (P < 0.001) and positively with the ratio of serum HL level/dose (P < 0.05). The ratio of HL level/dose was higher in the elderly AD patients than in younger subjects with schizophrenia (P < 0.005). Serum HL levels were much lower than those reported in younger schizophrenia patients, but comparable to those reported in elderly patients with AD. Aging-related and disease-associated pharmacokinetic and pharmacodynamic changes may reduce the need for higher neuroleptic doses as well as higher blood levels in older patients.

Do people with schizophrenia have differential impairment in episodic memory and/or working memory relative to other cognitive abilities?

Efforts to identify differential or core cognitive deficits in schizophrenia have been made for several decades, with limited success. Part of the difficulty in establishing a cognitive profile in schizophrenia is the considerable inter-patient heterogeneity in the level of cognitive impairment. Thus, it may be useful to examine the presence of relative cognitive weaknesses on an intra-person level. In the present study we examined the rates of significant intra-person differences between crystallized verbal ability versus five other cognitive abilities among 127 persons with schizophrenia or schizoaffective disorder and 127 demographically matched normal comparison (NC) subjects. We found that the rates of significant discrepancies above the NC group base-rates was significantly greater in reference to those discrepancies involving visual memory relative to those associated with auditory memory, working memory, processing speed, and perceptual organization. The findings conflict with prior suggestions that working memory or auditory episodic memory are differential or core deficits in schizophrenia, and highlight the importance of considering visual memory in characterizing the cognitive effects of this condition.

Antipsychotic Adherence Intervention for Veterans over 40 with Schizophrenia: Results of a Pilot Study.

This pilot study tested the feasibility, acceptability, and effect-sizes of a multimodal, individual intervention designed to optimize antipsychotic medication use in patients >/=40 years of age with schizophrenia or schizoaffective disorder. METHODS: We randomized 40 patients into two groups: usual care (UC) or a nine-session, manualized, antipsychotic adherence intervention (AAI). The AAI attempted to improve adherence by combining three psychosocial techniques: a) education, b) skills training, and c) alliance building. Sessions employed a semi-structured format to facilitate open communication. The primary outcome was antipsychotic adherence at study end. We obtained qualitative data regarding patient preferences for the duration and modality for receiving the adherence intervention. RESULTS: Compared to the UC group, a greater proportion of the AAI group was adherent post-intervention (65% vs. 55.6%; OR=1.49), a difference that was statistically not significant. The entire AAI group reported that they intended to take medications, and 75% were satisfied with the intervention. CONCLUSIONS: The AAI was feasible and acceptable. Preliminary data on its effectiveness warrant a larger study. Qualitative data shows that patients prefer brief adherence interventions and accept telephone strategies.

Adherence and persistence to typical and atypical antipsychotics in the naturalistic treatment of patients with schizophrenia.

OBJECTIVE: To compare adherence and persistence to typical versus atypical antipsychotics and between specific atypical agents in the usual care of schizophrenia and to examine the association between adherence and persistence. METHOD: Data were drawn from a 3-year prospective, nonrandomized, noninterventional study of schizophrenia conducted during 1997-2003. Initiators on haloperidol, risperidone, olanzapine, quetiapine, and clozapine with at least 1 year of follow-up were included (n = 878). Adherence (Medication Possession Ratio, MPR) and persistence (time to all-cause medication discontinuation) were assessed using medical record prescription information. Analyses employed multivariate statistics adjusted for group differences. RESULTS: Overall, 58% of the patients were deemed adherent (MPR >80%). Adherence rates were higher: for atypical (59.4%) than typical antipsychotics (34.5%, p < 0.001), for clozapine (77%) than each comparator excluding olanzapine (p < 0.01), and for olanzapine (64%) than risperidone (57%, p = 0.027) and quetiapine (52%, p = 0.019). Differences between risperidone and quetiapine were not statistically significant. Adherence and persistence were highly correlated (r = 0.957, p < 0.001). CONCLUSION: In the usual care of schizophrenia, medication adherence and persistence appear to be highly correlated and to significantly differ between typical and atypical antipsychotics and among atypical agents. The choice of antipsychotic may play a meaningful role in patients' adherence to and persistence with antipsychotic medications.

Medication adherence skills training for middle-aged and elderly adults with bipolar disorder: development and pilot study.

OBJECTIVES: To present the rationale, development, and pilot study of a medication adherence skills training (MAST-BD) intervention for older adults with bipolar disorder (BPD). We developed a 12-week manualized group intervention that combined educational, motivational, medication management skills and symptom management training adapted for older adults. METHODS: Among 21 older outpatients with BPD (mean age = 60 years; SD = 6), the feasibility and acceptability of MAST-BD were assessed in a quasi-experimental clinical trial. We also obtained preliminary effect sizes associated with pre-post change on measures of self-reported adherence to psychiatric medications, performance-based medication management ability, attitudes toward medication, depressive and manic symptoms, and health-related quality of life. RESULTS: At baseline, 55% of participants reported recent non-adherence to psychiatric medications and were, on average, suffering from moderately severe depressive symptoms and minimal symptoms of mania. A total of 76% of participants completed the intervention, and 86% of sessions were attended by completers. Participants reported high levels of satisfaction with the intervention and manual. Pre-post improvement by small to medium effect sizes (Cohen's d = 0.30-0.57) was seen in medication adherence, medication management ability, depressive symptoms, and selected indices of health-related quality of life. CONCLUSIONS: Notwithstanding the limitations of this small preliminary study, the results are encouraging in that the MAST-BD intervention was feasible, acceptable to patients, and associated with improvement in key outcomes. Suggestions for further development of medication adherence interventions for this neglected group of patients are discussed.

Antihypertensive medication adherence and blood pressure control in patients with psychotic disorders compared to persons without psychiatric illness.

The authors compared antihypertensive medication adherence and blood pressure control among middle-aged and older outpatients with schizophrenia and related those with psychotic disorders versus persons without any psychiatric illness. A total of 178 subjects were included in the investigation (89 patients with a psychotic disorder and 89 randomly selected, age-matched comparison subjects). Although the two groups had similar antihypertensive medication adherence, the patients with a psychotic disorder were significantly less likely to have had controlled blood pressure during the 1-year study period. The results highlight the need for clinicians to monitor closely the management of medical comorbidity in patients with schizophrenia and related disorders.

Interventions to improve antipsychotic medication adherence: review of recent literature.

Antipsychotic nonadherence is an important barrier to the successful treatment of schizophrenia and can lead to clinical and economic burdens. Interventions capable of significantly improving medication adherence in patients with schizophrenia would be beneficial in maximizing treatment outcomes with antipsychotics. This article reviews recent literature reporting interventions designed to improve antipsychotic adherence in patients with schizophrenia. We searched the Medline, Healthstar, and PsycInfo electronic databases for articles published since 1980 on interventions to improve medication adherence in schizophrenia. Twenty-one studies met our selection criteria. In this review, educational, behavioral, affective, or a combination of these approaches to improve adherence were examined. A total of 23 interventions were tested, as 2 studies investigated more than 1 intervention. While study design and adherence measures varied across the trials reviewed, medication adherence was noted to moderately improve with 15 of the 23 interventions tested. Interventions of a purely educational nature were the least successful at improving antipsychotic adherence. The greatest improvement in adherence was seen with interventions employing combinations of educational, behavioral, and affective strategies with which improvements in adherence were noted in 8 out of 12 studies, with additional secondary gains such as: reduced relapse, decreased hospitalization, decreased psychopathology, improved social function, gains in medication knowledge, and improved insight into the need for treatment. Longer interventions and an alliance with therapists also appeared important for successful outcomes. The continuing development and study of successful interventions to improve medication adherence are necessary to maximize the usefulness of pharmacologic treatment of schizophrenia.

Brief evaluation of medication influences and beliefs: development and testing of a brief scale for medication adherence.

PURPOSE: The purpose of this study was to develop and test a brief scale (Brief Evaluation of Medication Influences and Beliefs [BEMIB]) designed to identify patients who are more likely to be nonadherent to their antipsychotic medication. METHODS: Sixty-three outpatients with schizophrenia and related psychotic disorders were enrolled and given an assessment battery including the BEMIB, a previously published adherence scale, extrapyramidal symptom rating scales, and an adherence assessment with patient self-report and prescription refill records. The BEMIB consisted of 8 statements derived from the health belief model with a 5-point Likert-type scale for each statement. Subjects chose a single answer for each item depending on their level of agreement or disagreement. RESULTS: According to refill records, subjects meeting BEMIB-based criteria for nonadherence had significantly larger gaps in antipsychotic therapy (greater nonadherence) compared with those of participants not meeting criteria for nonadherence. For the 1-week test-retest reliability, the BEMIB total score and 5 of 8 single items correlated significantly. BEMIB total scores correlated significantly with an established assessment of adherence (Drug Attitude Inventory), demonstrating adequate construct validity. CONCLUSION: The BEMIB represents a promising scale for identifying patients more likely to be nonadherent to their medications.