Mariam Hassan

Quetiapine monotherapy in the treatment of depressive episodes of bipolar I and II disorder: Improvements in quality of life and quality of sleep

INTRODUCTION The depressive symptoms of bipolar disorder impact health-related quality of life, quality of sleep and functioning. The BOLDER I and II trials demonstrated that quetiapine significantly improves depressive symptoms in patients with acute bipolar depression. Post-hoc analysis of the BOLDER I and II data permits a detailed investigation of the effects of quetiapine on these other measures in this patient population. METHODS Secondary analysis was performed on data from BOLDER I and II, which were two 8-week, double-blind, randomized, placebo-controlled studies of quetiapine at fixed doses (300 or 600 mg/day) in a total of 1051 patients with acute depressive episodes of bipolar I or II disorder. Measures included the Short-Form Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q SF) in BOLDER I and II, the Pittsburgh Sleep Quality Index (PSQI) in BOLDER I, and the Sheehan Disability Scale (SDS) in BOLDER II. Analyses of Q-LES-Q SF score changes were based on data from the combined BOLDER I and II populations, and analyses of PSQI and SDS score changes were based on BOLDER I and BOLDER II populations, respectively. RESULTS Assessments at day 57 by mixed-model repeated measures analysis demonstrated that quetiapine relative to placebo provided significant or numerical improvements in rating scale score on the Q-LES-Q SF (10.89 with 300 mg/day and 12.14 with 600 mg/day vs. 7.79 with placebo; p<0.001 for each quetiapine dose), PSQI (-5.34 and -6.00 vs. -3.35; p<0.001, each dose), and SDS (-7.78 and -8.25 vs. -6.49; p=0.156 and 0.054, respectively). Effect sizes at day 57 with quetiapine 300 and 600 mg/day, respectively, were 0.34 and 0.46 for Q-LES-Q SF, 0.59 and 0.79 for PSQI, and 0.17 and 0.23 for SDS. Improvements were evident at first post-baseline assessment on day 29 and were consistent over the majority of rating scale domains. Quetiapine was generally well tolerated and most adverse events were of mild to moderate intensity. CONCLUSIONS Quetiapine monotherapy is effective in improving impairment in important aspects of life that accompany improvements in depressive symptoms in patients with acute bipolar depression.

The relationship between antipsychotic medication adherence and patient outcomes among individuals diagnosed with bipolar disorder: a retrospective study

BackgroundReducing hospitalizations and emergency room visits is important to improve patient outcomes. This observational study examined the association between adherence to antipsychotics and risk of hospitalizations and emergency room (ER) visits among patients with bipolar disorder.MethodsClaims data from commercial healthcare plans (Pharmetrics; January 2000 to December 2006) for patients with bipolar disorder receiving an antipsychotic prescription were examined. Adherence was analyzed over a 12-month follow-up period after the receipt of first prescription of an antipsychotic. Adherence to antipsychotics was measured by the medication possession ratio (MPR). The MPR was calculated as the number of days that an antipsychotic medication was filled as compared with the total number of days during the follow-up period. Logistic stepwise regressions examined the association between achievement of various adherence goals and patient outcomes (hospitalization or ER visit for mental health or any reason).ResultsIn total, 7,769 patients with bipolar disorder were included. The mean MPR was 0.417, with 61.7% of individuals having an MPR < 0.50, and 78.7% an MPR < 0.75. As adherence improved, the risk of hospitalization or ER visit declined. A significant reduction in the risk of hospitalization (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.75 to 0.98) or an ER visit (OR 0.84, 95% CI 0.74 to 0.96) for any cause was associated with an MPR ≥ 0.75. An MPR ≥ 0.80 was associated with a significant reduction in the risk of a mental health-related hospitalization (OR 0.82, 95% CI 0.70 to 0.95), while an MPR ≥ 0.90 was associated with a significant reduction in risk of a mental health-related ER visit (OR 0.71, 95% CI 0.54 to 0.91).ConclusionPatients with lower antipsychotic adherence were at greater risk of hospitalizations and ER visits. Thus, any efforts to increase adherence, even in small increments, can be helpful in decreasing these risks.

Risk of rehospitalization among bipolar disorder patients who are nonadherent to antipsychotic therapy after hospital discharge

PURPOSE The relationship between nonadherence to antipsychotic medication after hospital discharge and risk of rehospitalization in patients who were previously hospitalized for treatment of bipolar disorder was studied. METHODS Administrative claims data from 2000 through 2006 were obtained from commercial insurance plans. Patients age 18-64 years who were discharged from a hospital with a diagnosis of bipolar disorder and given a prescription for an antipsychotic 0-14 days after discharge comprised the study sample. Adherence to antipsychotic medication was determined by measuring the number of unique days during which medication was supplied during the treatment period, a calculation known as the medication possession ratio (MPR). Rehospitalization was considered to be an indicator of relapse. A multivariate, stepwise logistic regression, which controlled for patient characteristics, type of bipolar disorder, general health status, and comorbid conditions, was used to assess the relationship between medication non-adherence and rehospitalization. RESULTS A total of 1973 individuals were included in the analyses. The mean +/- S.D. MPR for this patient population was 0.46 +/- 0.32. Patients whose MPR was 0.75 or greater had a lower risk of all-cause rehospitalization (odds ratio [OR], 0.730; 95% confidence interval [CI], 0.580-0.919) and a lower risk of a mental-health-related rehospitalization (OR, 0.759; 95% CI, 0.603-0.955). As medication adherence increased above the MPR of 0.75, the risk of rehospitalization significantly decreased. CONCLUSION Among patients who were previously hospitalized for treatment of bipolar disorder, those who were adherent to their antipsychotic medication at least 75% of the time had lower risks of all-cause rehospitalization and mental-health-related rehospitalization.

Comparing Adherence to and Persistence with Antipsychotic Therapy Among Patients with Bipolar Disorder

Background: Medication nonadherence is a significant problem among patients with bipolar disorder. Objective: To compare adherence and persistence among patients with bipolar disorder initiated on antipsychotics in a state Medicaid system over a 12 month follow-up period. Methods: Claims data for patients with bipolar disorder from a de-identified Medicaid database were examined. Patients were classified into 4 monotherapy treatment groups (risperidone, olanzapine, quetiapine, or typical antipsychotic) based on the first prescription filled between January 1, 1999, and December 31, 2001. Adherence and persistence were analyzed over a 12 month follow-up period. Adherence was measured using the Medication Possession Ratio (MPR). Persistence was defined as the total number of days from the initiation of treatment to therapy modification (ie, discontinuation, switching, or combination with another antipsychotic). Adjustment for confounding variables was undertaken using ordinary least-squares and Cox proportional hazard regression modeling. Results: The mean MPRs were 0.68 for risperidone (n = 231), 0.68 for olanzapine (n = 283), 0.71 for quetiapine (n = 106), and 0.46 for typical antipsychotics (n = 205). Patients initiated on typical antipsychotics were 23.6% less adherent than patients initiated on risperidone (p < 0.001). Mean persistence (days) was 194.8 for risperidone, 200.9 for olanzapine, 219.8 for quetiapine, and 179.2 for typical antipsychotics. Extended Cox regression modeling indicated no significant differences between antipsychotics in hazards of therapy modification within 250 days of initiation. However, patients initiated on typical antipsychotics were 5.2 times more likely to modify therapy compared with those initiated on risperidone after 250 days of antipsychotic therapy (p < 0.001). Conclusions: Adherence and persistence were similar between atypical antipsychotic groups. The typical antipsychotic group, however, demonstrated lower adherence and a greater likelihood of patients modifying therapy compared with the risperidone cohort

Assessing the Reliability and Validity of the Sheehan Irritability Scale in Patients With Major Depressive Disorder.

OBJECTIVE Irritability is a significant component in the clinical manifestation of major depressive disorder (MDD). The Sheehan Irritability Scale (SIS) was developed to assess irritability-related symptoms in patients with psychiatric disorders. Data from a phase 2 clinical trial (June 2008-July 2009) was utilized to evaluate the psychometric properties of the SIS. The trial population included patients diagnosed with MDD, according to DSM-IV and confirmed via the MINI diagnostic scale, who had inadequate response to citalopram. METHOD The secondary analyses included 586 patients from the United States and India. Data from the SIS, depression severity measures (17-item Hamilton Depression Rating Scale [HDRS-17], Montgomery-Asberg Depression Rating Scale [MADRS], Quick Inventory of Depressive Symptomatology-Self-Report [QIDS-SR]), and other measures (Sheehan Disability Scale [SDS], Clinical Global Impressions-Severity of Illness scale [CGI-S]) were used in the psychometric evaluation. All statistical tests used a significance level of .05 unless otherwise noted. RESULTS Internal consistency (0.92-0.99) and test-retest reliability (0.83 to 0.98) were excellent. Concurrent validity was demonstrated through strong correlations between the SIS total score and HDRS-17, QIDS-SR, SDS, CGI-S, and MADRS scores. SIS total scores were significantly different by clinical severity level (P < .001). Minimally important difference estimates suggest that a 7- to 8-point change in the SIS total score may be clinically meaningful. CONCLUSIONS The SIS has excellent reliability, acceptable validity, and good responsiveness, making the SIS appropriate for use in clinical research and practice. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00692445.

Content validity of the Sheehan Irritability Scale in patients with major depressive disorder.

The Sheehan Irritability Scale (SIS) measures the frequency, severity, and impairment associated with irritability in psychiatric patients. The content validity of the SIS in patients with major depressive disorder (MDD) has not been evaluated. A cross-sectional, qualitative research study was conducted to assess the content validity of the SIS among patients with MDD. One-on-one interviews were conducted, starting with open-ended questions to evaluate the consistency of the SIS content with patient experiences of irritability. Participants then completed the SIS and cognitive interviews around the comprehension of the SIS content (instructions, items, response options). Participants included 24 patients diagnosed with MDD who had an inadequate response to an antidepressant treatment. The sample was: 50.4 mean years, 66.7% female, and 91.7% white racial background. All concepts on the SIS were spontaneously mentioned by at least one participant, and when probed about the symptoms, the majority of participants (66.7–100%) reported the concepts being part of their experience. The majority of participants (70.8–100%) understood the SIS instructions, items, and response scales. This study provides evidence of content validity of the SIS in patients diagnosed with MDD, supporting the use as a measure of irritability in patients with depression.

PMH37 COMPARING ADHERENCE AND PERSISTENCE WITH ANTIPSYCHOTIC THERAPY AMONG PATIENTS WITH BIPOLAR DISORDER

RESULTS: Of the 230,738 eligible patients, 29.7% had depression diagnoses (n = 68,526), 71.4% were female, mean age was 44.6 years, and 77.9% initiated on SSRIs. Using logistic regression models for the depression cohort, patients initiating on duloxetine (n = 2061) versus all other initiators were associated with being older (OR 1.02), having more prior pain diagnoses (OR 1.11), depression-related diagnoses (OR 1.52), major depressive disorder recurrent episode diagnoses (OR 1.28), pain medications (OR 1.27), antidepressants (OR 1.46), and any psychotherapy (OR 1.14) (all p < 0.01). Duloxetine patients also were more likely to initiate therapy later in the study (OR 1.04; p < 0.0001) and were prescribed therapy by mental health (OR 2.32) and other specialists (OR 1.40) versus primary care. When depressive diagnoses were absent, duloxetine patients (n = 2346) were more likely to be female (OR 1.21; p < 0.001) versus other antidepressant initiators (n = 162,212). All other factors remained consistent. Trends over time are necessary to determine the robustness of results. CONCLUSIONS: In the first four months after the drug’s availability, duloxetine initiators were associated with worse prior diagnostic and treatment histories. Case mix differences should be made when comparing drug cohorts.