Assessing Medication Adherence and Healthcare Utilization and Cost Patterns Among Hospital-Discharged Patients with Schizoaffective Disorder

BACKGROUND: Hospital-discharged patients with schizoaffective disorder have a high risk of re-hospitalization. However, limited data exist evaluating critical post-discharge periods during which the risk of re-hospitalization is significant. OBJECTIVE: Among hospital-discharged patients with schizoaffective disorder, we assessed pharmacotherapy adherence and healthcare utilization and costs during sequential 60-day clinical periods before schizoaffective disorder-related hospitalization and post-hospital discharge. METHODS: From the MarketScan(®) Medicaid database (2004–2008), we identified patients (≥18 years) with a schizoaffective disorder-related inpatient admission. Study measures including medication adherence and healthcare utilization and costs were assessed during sequential preadmission and post-discharge periods. We conducted univariate and multivariable regression analyses to compare schizoaffective disorder-related and all-cause healthcare utilization and costs (in 2010 US dollars) between each adjacent 60-day post-discharge periods. No adjustment was made for multiplicity. RESULTS: We identified 1,193 hospital-discharged patients with a mean age of 41 years. The mean medication adherence rate was 46 % during the 60-day period prior to index inpatient admission, which improved to 80 % during the 60-day post-discharge period. Following hospital discharge, schizoaffective disorder-related healthcare costs were significantly greater during the initial 60-day period compared with the 61- to 120-day post-discharge period (mean US$2,370 vs US$1,765; p < 0.001), with rehospitalization (36 %) and pharmacy (40 %) accounting for over three-fourths of the initial 60-day period costs. Compared with the initial 60-day post-discharge period, both all-cause and schizoaffective disorder-related costs declined during the 61- to 120-day post-discharge period and remained stable for the remaining post-discharge periods (days 121–365). CONCLUSIONS: We observed considerably lower (46 %) adherence during 60 days prior to the inpatient admission; in comparison, adherence for the overall 6-month period was 8 % (54 %) higher. Our study findings suggest that both short-term (e.g., 60 days) and long-term (e.g., 6–12 months) medication adherence likely are important characteristics to examine among patients with schizoaffective disorder and help provide a more holistic view of patients’ adherence patterns. Furthermore, we observed a high rate of rehospitalization and greater healthcare costs during the initial 60-day period post-discharge among patients with schizoaffective disorder. Further research is required to better understand and manage transitional care after discharge (e.g., monitor adherence), which may help reduce the likelihood of rehospitalization and the associated downstream costs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40258-014-0095-8) contains supplementary material, which is available to authorized users

Item response analysis of the Positive and Negative Syndrome Scale

<p>Abstract</p> <p>Background</p> <p>Statistical models based on item response theory were used to examine (a) the performance of individual Positive and Negative Syndrome Scale (PANSS) items and their options, (b) the effectiveness of various subscales to discriminate among individual differences in symptom severity, and (c) the appropriateness of cutoff scores recently recommended by Andreasen and her colleagues (2005) to establish symptom remission.</p> <p>Methods</p> <p>Option characteristic curves were estimated using a nonparametric item response model to examine the probability of endorsing each of 7 options within each of 30 PANSS items as a function of standardized, overall symptom severity. Our data were baseline PANSS scores from 9205 patients with schizophrenia or schizoaffective disorder who were enrolled between 1995 and 2003 in either a large, naturalistic, observational study or else in 1 of 12 randomized, double-blind, clinical trials comparing olanzapine to other antipsychotic drugs.</p> <p>Results</p> <p>Our analyses show that the majority of items forming the Positive and Negative subscales of the PANSS perform very well. We also identified key areas for improvement or revision in items and options within the General Psychopathology subscale. The Positive and Negative subscale scores are not only more discriminating of individual differences in symptom severity than the General Psychopathology subscale score, but are also more efficient on average than the 30-item total score. Of the 8 items recently recommended to establish symptom remission, 1 performed markedly different from the 7 others and should either be deleted or rescored requiring that patients achieve a lower score of 2 (rather than 3) to signal remission.</p> <p>Conclusion</p> <p>This first item response analysis of the PANSS supports its sound psychometric properties; most PANSS items were either very good or good at assessing overall severity of illness. These analyses did identify some items which might be further improved for measuring individual severity differences or for defining remission thresholds. Findings also suggest that the Positive and Negative subscales are more sensitive to change than the PANSS total score and, thus, may constitute a "mini PANSS" that may be more reliable, require shorter administration and training time, and possibly reduce sample sizes needed for future research.</p

Use of NON-PARAMETRIC Item Response Theory to develop a shortened version of the Positive and Negative Syndrome Scale (PANSS)

<p>Abstract</p> <p>Background</p> <p>Nonparametric item response theory (IRT) was used to examine (a) the performance of the 30 Positive and Negative Syndrome Scale (PANSS) items and their options ((levels of severity), (b) the effectiveness of various subscales to discriminate among differences in symptom severity, and (c) the development of an abbreviated PANSS (Mini-PANSS) based on IRT and a method to link scores to the original PANSS.</p> <p>Methods</p> <p>Baseline PANSS scores from 7,187 patients with Schizophrenia or Schizoaffective disorder who were enrolled between 1995 and 2005 in psychopharmacology trials were obtained. Option characteristic curves (OCCs) and Item Characteristic Curves (ICCs) were constructed to examine the probability of rating each of seven options within each of 30 PANSS items as a function of subscale severity, and summed-score linking was applied to items selected for the Mini-PANSS.</p> <p>Results</p> <p>The majority of items forming the Positive and Negative subscales (i.e. 19 items) performed very well and discriminate better along symptom severity compared to the General Psychopathology subscale. Six of the seven Positive Symptom items, six of the seven Negative Symptom items, and seven out of the 16 General Psychopathology items were retained for inclusion in the Mini-PANSS. Summed score linking and linear interpolation was able to produce a translation table for comparing total subscale scores of the Mini-PANSS to total subscale scores on the original PANSS. Results show scores on the subscales of the Mini-PANSS can be linked to scores on the original PANSS subscales, with very little bias.</p> <p>Conclusions</p> <p>The study demonstrated the utility of non-parametric IRT in examining the item properties of the PANSS and to allow selection of items for an abbreviated PANSS scale. The comparisons between the 30-item PANSS and the Mini-PANSS revealed that the shorter version is comparable to the 30-item PANSS, but when applying IRT, the Mini-PANSS is also a good indicator of illness severity.</p

Aggression and Quantitative MRI Measures of Caudate in Patients With Chronic Schizophrenia or Schizoaffective Disorder

Caudate dysfunction is implicated in schizophrenia. However, little is known about the relationship between aggression and caudate volumes. Forty-nine patients received magnetic resonance imaging scanning in a double-blind treatment study in which aggression was measured. Caudate volumes were computed using a semiautomated method. The authors measured aggression with the Overt Aggression Scale and the Positive and Negative Syndrome Scale. Larger caudate volumes were associated with greater levels of aggression. The relationship between aggression and caudate volumes may be related to the iatrogenic effects of long-term treatment with typical anti-psychotic agents or to a direct effect of schizophrenic processes on the caudate

Paliperidone ER and oral risperidone in patients with schizophrenia: a comparative database analysis

<p>Abstract</p> <p>Background</p> <p>To compare the efficacy and tolerability of paliperidone extended-release (ER) with risperidone immediate-release using propensity score methodology.</p> <p>Methods</p> <p>Six double-blind, randomized, placebo-controlled, short-term clinical trials for acute schizophrenia with availability of individual patient-level data were identified (3 per compound). Propensity score pairwise matching was used to balance observed covariates between the paliperidone ER and risperidone patient populations. Scores were generated using logistic regression models, with age, body mass index, race, sex, baseline Positive and Negative Syndrome Scale (PANSS) total score and baseline Clinical Global Impressions–Severity (CGI-S) score as factors. The dosage range of paliperidone ER (6-12 mg/day) was compared with 2 risperidone dosage ranges: 2-4 and 4-6 mg/day. The primary efficacy measure was change in PANSS total score at week 6 end point. Tolerability end points included adverse event (AE) reports and weight. AEs with rates ≥5% and with a ≥2% difference between paliperidone ER and risperidone were identified.</p> <p>Results</p> <p>Completion rates for placebo-treated subjects in paliperidone ER trials (n = 95) and risperidone trials (n = 122) groups were 36.8% and 51.6%, respectively; end point changes on PANSS total scores were similar (p = 0.768). Completion rates for subjects receiving paliperidone ER 6-12 mg/day (n = 179), risperidone 2-4 mg/day (n = 113) or risperidone 4-6 mg/day (n = 129) were 64.8%, 54.0% and 66.7%, respectively (placebo-adjusted rates: paliperidone ER vs risperidone 2-4 mg/day, p = 0.005; paliperidone ER vs risperidone 4-6 mg/day, p = 0.159). PANSS total score improvement with paliperidone ER was greater than with risperidone 2-4 mg/day (difference in mean change score, -6.7; p < 0.05) and similar to risperidone 4-6 mg/day (0.2; p = 0.927). Placebo-adjusted AEs more common with paliperidone ER were insomnia, sinus tachycardia and tachycardia; more common with risperidone were somnolence, restlessness, nausea, anxiety, salivary hypersecretion, akathisia, dizziness and nasal congestion. Weight changes with paliperidone ER and risperidone were similar (paliperidone ER vs risperidone 2-4 mg/day, p = 0.489; paliperidone ER vs risperidone 4-6 mg/day, p = 0.236).</p> <p>Conclusions</p> <p>This indirect database analysis suggested that paliperidone ER 6-12 mg/day may be more efficacious than risperidone 2-4 mg/day and as efficacious as risperidone 4-6 mg/day. The AE-adjusted incidence rates suggest differences between treatments that may be relevant for individual patients. Additional randomized, direct, head-to-head clinical trials are needed to confirm these findings.</p

Quantitative MRI measures of orbitofrontal cortex in patients with chronic schizophrenia or schizoaffective disorder

The relationship between orbitofrontal cortex (OFC) volumes and functional domains in treatment-resistant patients with schizophrenia or schizoaffective disorder is poorly undestood. OFC dysfunction is implicated in several of the behaviors that are abnormal in schizophrenia. However, little is known about the relationship between these behaviors and OFC volumes. Forty-nine (49) patients received magnetic resonance imaging scanning as part of a double-blind treatment study in which psychiatric symptomatology, neuropsychological function, and aggression were measured. OFC volumes were manually traced on anatomical images. Psychiatric symptomatology was measured with the Positive and Negative Syndrome Scale (PANSS). Aggression was measured with the Overt Aggression Scale (OAS) and with the PANSS. Neuropsychological function was assessed using a comprehensive test battery. Larger right OFC volumes were associated with poorer neuropsychological function. Larger left OFC gray matter volumes and larger OFC white matter volumes bilaterally were associated with greater levels of aggression. These findings are discussed in the context of potential iatrogenic effects

Advances in Cognitive Remediation Training in Schizophrenia: A Review

Cognitive Remediation Training (CRT) in schizophrenia has made great strides since its introduction in the 1990s. CRT was developed with the aim of improving the everyday functioning of individuals living with cognitive impairment. MEDLINE, PsychINFO, and Google Scholar were searched to extract peer-reviewed randomized controlled trials to produce the current review article. The aim of the present review is to summarize CRT effects on addressing cognitive changes in patients undergoing CRT as defined by the Cognitive Remediation Experts Workshop and to describe the areas of greatest impact in specific cognitive domains. Another area of this review aims to summarize the modalities of intervention (paper and pencil; computerized; home bound), the persistence of improvements, and their generalization to other domains of functioning. Finally, this review delineates barriers for wider dissemination of CRT, such as the transfer of research findings into clinical everyday practice and future developments of CRT

Onset and Resolution of Key Adverse Events in Valbenazine-Treated Patients with Tardive Dyskinesia: Pooled Analyses from Two Long-Term Clinical Trials.

ObjectiveTardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Long-term safety of the approved TD medication, valbenazine, was demonstrated in 2 clinical trials (KINECT 3 [NCT02274558], KINECT 4 [NCT02405091]). Data from these trials were analyzed post hoc to evaluate the onset and resolution of adverse events (AEs).MethodsParticipants in KINECT 3 and KINECT 4 received up to 48 weeks of once-daily valbenazine (40 or 80 mg). Data from these studies were pooled and analyzed to assess the incidence, time to first occurrence, and resolution for the following AEs of potential clinical interest: akathisia, balance disorder, dizziness, parkinsonism, somnolence/sedation, suicidal behavior/ideation, and tremor.ResultsIn the pooled population (N=314), all AEs of potential clinical interest occurred in &lt;10% of participants, with somnolence (9.6%), suicidal behavior/ideation (6.4%), and dizziness (5.7%) being the most common AEs. Mean time to first occurrence ranged from 36 days (akathisia [n=9]) to 224 days (parkinsonism [n=2]). By end of study (or last study visit), resolution of AEs was as follows: 100% (suicidal ideation/behavior, parkinsonism); &gt;85% (somnolence/sedation, dizziness); &gt;70% (akathisia, balance disorder, tremor).ConclusionsIn long-term clinical trials, the incidence of AEs of potential clinical interest was low (&lt;10%) and most were resolved by end of treatment (&gt;70-100%). All patients taking valbenazine should be routinely monitored for AEs, particularly those that may exacerbate the motor symptoms associated with TD.FundingNeurocrine Biosciences, Inc