Treatment patterns in patients with type 2 diabetes mellitus treated with glucagon-like peptide-1 receptor agonists: Higher adherence and persistence with dulaglutide compared with once-weekly exenatide and liraglutide.

AIMS: To compare adherence (proportion of days covered [PDC]), persistence, and treatment patterns among patients with type 2 diabetes mellitus (T2DM) newly initiating glucagon-like peptide-1 receptor agonists (GLP-1RAs). More specifically, the main objectives were to compare dulaglutide vs exenatide once weekly and dulaglutide vs liraglutide. METHODS: Patients with T2DM newly initiating dulaglutide, albiglutide, exenatide once weekly, exenatide twice daily and liraglutide between November 2014 and April 2015 were hierarchically selected from Truven Health's MarketScan Research Databases. Propensity score matching was used to account for selection bias. Adherence to and persistence with the index GLP-1RA, and switching and augmentation patterns were assessed during the 6-month post-index period. RESULTS: Mean adherence for the matched cohorts was significantly higher for dulaglutide than for exenatide once weekly (0.72 vs 0.61; P < .0001) and liraglutide (0.71 vs 0.67; P < .0001). The percentage of patients achieving PDC ≥ 0.80 was significantly higher for dulaglutide compared with exenatide once weekly (54.2% vs 37.9%; P < .0001) and liraglutide (53.5% vs 44.3%; P < .0001). The mean (standard deviation) days on treatment for all matched patients was significantly higher for patients in the dulaglutide cohort compared with those in the exenatide once-weekly (148.4 [55.4] vs 123.6 [61.6]; P < .0001) and liraglutide cohorts (146.0 [56.9] vs 137.4 [60.1]; P < .0001). A significantly lower proportion of patients on dulaglutide discontinued treatment compared with those on exenatide once weekly (26.2% vs 48.4%; P < .0001) and those on liraglutide (28.0% vs 35.6%; P < .0001). CONCLUSIONS: Dulaglutide initiators had significantly higher adherence, were more persistent, and had lower discontinuation rates compared with initiators of exenatide once weekly or liraglutide during the 6-month follow-up period.

The importance of unresolved fatigue in depression: costs and comorbidities.

OBJECTIVE: To assess the cost outcomes of patients with a history of depression and clinically significant fatigue. METHODS: Adults with ≥ 2 claims with depression diagnosis codes identified from the HealthCore Integrated Research Database were invited to participate in this study linking survey data with retrospective claims data (12-mo presurvey and postsurvey periods). Patient surveys included measures for depression (Quick Inventory of Depressive Symptomatology), fatigue (Fatigue Associated with Depression Questionnaire), anxiety (7-item Generalized Anxiety Disorder scale), sleep difficulty (Athens Insomnia Scale), and pain (Brief Pain Inventory). After adjusting for demographic and clinical characteristics using propensity scores, postsurvey costs were compared between patients with and without fatigue using nonparametric bootstrapping methods. RESULTS: Of the 1982 patients who had completed the survey and had complete claims data, 653 patients had significant levels of fatigue. Patients with fatigue reported significantly higher scores, indicating greater severity, on measures of depression, pain, sleep difficulty, and anxiety (all p < 0.05). These patients also had higher levels of overall medication use and were more likely to have lower measures of socioeconomic status than patients without significant levels of fatigue (all p < 0.05). Mean annual total costs were greater for patients with fatigue than those without fatigue ($14,462 vs $9971, respectively, p < 0.001). These cost differences remained statistically significant after adjusting for clinical and demographic differences. CONCLUSIONS: Clinically significant fatigue appears to add to the economic burden of depression. This reinforces the need for aggressive treatment of all symptoms and further examination of the variability of this relationship as patients approach remission.

Duloxetine use in employees with low back pain: treatment patterns and direct and indirect costs.

OBJECTIVE: The study aims to examine real-world effects of duloxetine treatment for low back pain (LBP). METHODS: The study identified employees with ≥1 LBP diagnosis and ≥1 duloxetine prescription within a year after LBP diagnosis from a privately insured claims database (2004-2007). Duloxetine-treated employees were propensity score matched to employees initiating another pharmacological/noninvasive treatment in the same month from LBP diagnosis. Treatment patterns and costs were compared over the 6 months following treatment initiation. RESULTS: Relative to controls, duloxetine-treated employees (N = 753) had significantly lower rates of other pharmacological/noninvasive therapies and a similar LBP surgery rate (1.7% vs 2.8%, P = 0.1573). Duloxetine-treated employees, despite higher pharmacy costs, had similar direct (health care) costs ($4,935 vs $5,649, P = 0.2662), and significantly lower indirect (workloss) costs ($1,723 vs $2,198, P = 0.0036). CONCLUSIONS: Duloxetine treatment in LBP employees was associated with reduced rates of many nonsurgical therapies and lower indirect costs. The findings are limited by the observational study design and unmeasured potential confounders.

What do network members know? Network members as reporters of depression among Caucasian-American and African-American older women.

OBJECTIVE: To determine whether family members and friends can be accurate reporters of depression in older women and whether their reports predict diagnostic depression concurrently and across a one-year time interval. METHOD: African-American and Caucasian older women (N = 153; mean age = 75) previously screened for depression nominated network members (NMs) who could be contacted as informants. NMs completed an informant version of the CES-D, described their closeness to the participant, the extent of the participant's support from family and friends, and their assessment of the participant's typical coping strategies. These reports were then used to predict participant CES-D, Hamilton depression scores, and Structured Clinical Interview (SCID) depression diagnoses concurrently and at six-month and one-year intervals. RESULTS: NMs' estimates of participants CES-D status were highly correlated with participants own CES-D scores, and also predicted Hamilton depression scores and SCID diagnoses concurrently and at six months and one year later. NMs' ratings of participants' use of positive coping also predicted depression at six months and one year. CONCLUSION: NMs knew when elderly women were depressed and their reports were accurate predictors of depression even one year later, which implies that elderly depression does not abate spontaneously. Future research should test the possibility that family and friends might be recruited as allies in encouraging earlier treatment and in providing support to older adults through difficult life transitions.

The direct and indirect costs among U.S. privately insured employees with hypogonadism.

INTRODUCTION: While previous studies have noted that hypogonadism (HG) may pose a significant economic and quality-of-life burden, no studies have evaluated the impact of HG on healthcare utilization and costs in the United States. AIM: Compare direct (health care) and indirect (disability leave or medical absence) costs between privately insured U.S. employees with HG and controls without HG. METHODS: The study sample included 4,269 male employees, ages 35-64, with ≥ 2 HG diagnoses (International Classification of Diseases, Ninth Revision, Clinical Modification: 257.2x) or ≥ 1 HG diagnosis and ≥ 1 claim for testosterone therapy, 1/1/2005-3/31/2009, identified from a large, private insurance administrative database that includes medical, prescription drug, and disability claims data. The index date was the most recent HG diagnosis that had continuous eligibility for at least 1 year before (baseline period) and 1 year after (study period). Employees with HG were matched 1:1 on age, region, salaried vs. nonsalaried employment status, and index year to controls without HG. MAIN OUTCOME MEASURES: Descriptive analyses compared demographic characteristics, comorbidities, resource utilization, direct and indirect costs inflated to USD 2009. Multivariate analyses adjusting for baseline characteristics were used to estimate risk-adjusted costs. RESULTS: HG employees and controls had a mean age of 51 years. HG employees compared with controls had higher baseline comorbidity rates, including hyperlipidemia (50.2% vs. 25.3%), hypertension (37.7% vs. 21.1%), back/neck pain (32.0% vs. 15.7%), and human immunodeficiency virus/acquired immunodeficiency syndrome (7.1% vs. 0.3%) (all P < 0.0001). HG employees had higher mean study period direct ($10,914 vs. $3,823) and indirect costs ($3,204 vs. $1,450); HG-related direct costs were $832 (all P < 0.0001). Risk-adjusted direct ($9,291 vs. $5,248) and indirect ($2,729 vs. $1,840) costs were also higher for HG employees (all P < 0.0001). CONCLUSIONS: Employees with HG had higher comorbidity rates and costs compared with controls. Given the low HG-related costs, a primary driver of costs among HG patients appears to be their comorbidity burden.

A cross-validation of the provisional diagnostic instrument (PDI-4).

BACKGROUND: The Provisional Diagnostic Instrument (PDI-4) is a brief, adult self-report instrument for 4 common psychiatric diagnoses in primary care patients: major depressive episode (MDE), generalized anxiety disorder (GAD), attention deficit hyperactivity disorder (ADHD), and bipolar I disorder based on past or present mania. Our objective was to assess validity of the PDI-4 in a population independent of the study population originally used to develop the scale. METHODS: An online version of the 17-item PDI-4 was administered to 1,047 adults in the US; respondents also completed the PHQ-9, HADS-A, CAARS-S, and MDQ within the online survey. Respondents self-reported diagnosis by a healthcare professional with the terms depression (n=221), anxiety (n=218), attention deficit disorder (n=206), bipolar or manic depressive disorder (n=195), or none of these (n=207). Statistical analyses examined convergent and discriminant validity, and operating characteristics of the PDI-4 relative to the individual, validated, self-rated scales PHQ-9, HADS-A, CAARS-S, and MDQ, for each PDI-4 diagnosis. RESULTS: Convergent validity of the PDI-4 was supported by strong correlations with the corresponding individual scales (range of 0.63 [PDI-4 and MDQ] to 0.87 [PDI-4 and PHQ-9]). Operating characteristics of the PDI-4 were similar to results in the previous site-based study. The scale exhibited moderate sensitivities (0.52 [mania] to 0.70 [ADHD]) and strong specificities (0.86 [mania] to 0.92 [GAD]) using the individual scales as the gold standards. ANOVAs demonstrated that PDI-4 discriminated between subsets of patients defined by pre-specified severity level cutoff scores of the individual scales. However, overlapping symptoms and co-morbidities made differentiation between mental diagnoses much weaker than differentiation from the control group with none of the diagnoses. CONCLUSIONS: The PDI-4 appears to be a suitable, brief, self-rated tool for provisional diagnoses of common mental disorders. However, the high level of symptom overlap between these diagnoses emphasizes that such brief scales are not a replacement for thorough diagnostic evaluation by trained medical providers.

Real-world role of tricyclic antidepressants in the treatment of fibromyalgia.

OBJECTIVE: To examine the real-world role of tricyclic antidepressants (TCAs) in fibromyalgia (FM) treatment. METHODS: Using privately insured U.S. administrative claims data, this study examined TCA use for newly diagnosed FM patients. Patients ages 18 to 64 years with ≥ 2 FM diagnoses (ICD-9-CM: 729.1) during Q1:2007 to Q1:2009, no previous FM diagnosis, and continuous eligibility for insurance during the year before and after the first FM diagnosis ("study period") were identified as newly diagnosed (N = 10,129). Treatment with TCAs was examined over the first treatment episode (allowing up to a 45-day gap between refills). A sensitivity analysis was performed excluding patients with depression/anxiety diagnoses during the study period. RESULTS: During the study period, 8.9% of patients with FM used TCAs at anytime, 5.0% used TCAs during the year before FM diagnosis, and 7.2% used TCAs during the year after. The mean (median) duration of the first treatment episode was 150 (58) days. During this episode, 84.0% used other medications concomitantly, with 60.3% using analgesics and 39.6% using other antidepressants. Additionally, 60.8% augmented TCA use with other drugs, 61.8% switched to another drug at the end of their TCA episode, and 22.8% discontinued TCAs without switching. Similar patterns were observed for the subset of patients with no depression or anxiety (N = 7,655). DISCUSSION: Research covering 1999 to 2005 using the same methods found that 15.9% of patients with FM used TCAs during the year before FM diagnosis and 20.7% used TCAs during the year after. These findings suggest that TCA use among the patients with FM is uncommon and may be declining in real-world practice.

A provisional screening instrument for four common mental disorders in adult primary care patients.

OBJECTIVE: To develop an adult self-report instrument for provisional diagnosis of four common mental disorders in primary care patients. METHODS: Primary care patients were evaluated during routine clinic visits with a self-report screening tool comprised of 85 DSM-IV symptom-based candidate questions. Patients with a physician-assessed provisional diagnosis for generalized anxiety disorder (GAD), major depressive episode (MDE), past/present mania, and adult attention-deficit/hyperactivity disorder (ADHD), or none of these, completed additional self-report clinical questionnaires, and then were interviewed on the telephone by a trained rater for a SCID/ACDS diagnosis. Responses to the symptom-based candidate questions were used to calculate sensitivity and specificity for a SCID/ACDS diagnosis (GAD, N = 24; MDE, N = 89; Mania, N = 24; ADHD, N = 65) and to select the optimal four questions for each diagnosis to be included in the instrument. RESULTS: Analyses resulted in a 17-item instrument for provisional differential diagnosis of GAD, MDE, past/present mania, and ADHD. Comparison of limited symptom-based versus full DSM-IV criteria-based diagnosis showed minimal differences for relative diagnostic accuracy. Sensitivities and specificities, respectively, were 83% and 75% for GAD, 80% and 80% for MDE, 83% and 82% for mania, and 82%and 73% for ADHD. CONCLUSIONS: Based on this preliminary work, the Provisional Diagnostic Instrument-4 is a brief, easily scored, self-report instrument that may assist primary care physicians to identify potential cases of GAD, MDE, past/present mania, and ADHD.

Treatment patterns associated with Duloxetine and Venlafaxine use for Major Depressive Disorder.

BACKGROUND: Duloxetine and venlafaxine extended release (venlafaxine XR) are SNRIs indicated for the treatment of MDD. This study addresses whether duloxetine and venlafaxine XR are interchangeable in their patterns of use with patients who are depressed or are used more selectively based on treatment history, background characteristics, and presenting symptoms. METHODS: This was a retrospective analysis of an administrative insurance claims database. We studied patients in managed care with major depressive disorder (MDD) treated with duloxetine or venlafaxine XR. Predictors of treatment and cost were assessed using Chi-square and logistic regression analyses of demographics and past-year medication use and comorbidities. RESULTS: Patients with MDD treated with duloxetine (n = 9,641) versus venlafaxine XR (n = 8,514) tended to be older, slightly more likely to be female, and treated by a psychiatrist (P < 0.0001). In the prior year, more duloxetine patients (vs. venlafaxine XR) received ≥ 3 unique antidepressants (20.8% vs. 16.6%), ≥ 3 unique pain medications (25.5% vs. 15.6%), and had ≥ 8 unique diagnosed comorbid medical and psychiatric conditions (38.6% vs. 29.1%). The prior 6-month total health care costs were $1,731 higher for duloxetine than for venlafaxine XR and declined for both medications in the 6 months after treatment began. Logistic regression analysis revealed that 61% of duloxetine patients and 61% of venlafaxine XR patients were predictable from prior patient and treatment factors. CONCLUSIONS: Patients with MDD treated with duloxetine tended to have a more complex and costly antecedent clinical presentation compared with venlafaxine XR patients, suggesting that physicians do not use the medications interchangeably.

Comparison of medication adherence and healthcare costs between duloxetine and pregabalin initiators among patients with fibromyalgia.

OBJECTIVE: To examine and compare medication adherence and direct healthcare costs between duloxetine and pregabalin initiators among patients with fibromyalgia. METHODS: A retrospective analysis of commercially insured fibromyalgia patients aged 18 to 64 was conducted among those who initiated duloxetine or pregabalin between January 1, 2006 and December 31, 2006. The first initiation date was defined as the index date. All patients included had continuous enrollment in the 12-month pre- and post-index periods. Each individual was classified in the duloxetine or pregabalin cohort based on the initiating agent. The pregabalin cohort was constructed via propensity scoring controlling for differences in demographics, pre-index clinical and economic characteristics, and pre-index treatment patterns. Medication adherence (ie, medication possession ratio [MPR] and proportion of patients with MPR≥80%) and healthcare costs over the 12 months post-index period were examined between cohorts. RESULTS: The study cohorts included 3,711 duloxetine and 4,111 pregabalin patients with the mean age of 51 years. The common comorbidities included neuropathic pain other than diabetic peripheral neuropathic pain, low back pain, cardiovascular disease, headache, and osteoarthritis. Over 80% of the duloxetine or pregabalin initiators used opioids. Controlling for demographics, pre-index clinical and economic characteristics, and prior medication history, duloxetine patients had significantly higher MPR (0.7 vs. 0.5, P<0.05), higher proportion of patients with MPR≥80% (46.5% vs. 26.4%, P<0.05), but significantly lower total healthcare costs ($19,378 vs. $27,045, P<0.05) over the 12 months post-index period than pregabalin patients. CONCLUSION: Fibromyalgia patients on duloxetine had significantly higher medication adherence, but significantly lower direct healthcare costs than those on pregabalin.

Screening for depression in African American and Caucasian older women.

OBJECTIVE: To assess the performance of a two-choice (yes/no), 10-item shortened form of the CES-D in both African American (AA) and Caucasian (CA) older women. The CES-D is a widely used screening instrument, but its use has been questioned for routine screening because of its length and the complexity of its four-choice format. There is also little data available about its suitability low-income AA respondents. METHOD: Telephone screening for depression followed by in-home diagnostic interviews were conducted in a community sample of 256 CA and 186AA low-income older women who ranged in age from 64 to 94 years. Standard receiver operator curves were plotted to determine the sensitivities and specificities of the screening instrument at different cut-scores against a criterion of SCID-based diagnoses of current major depressive episode (CMDE). RESULTS: Sensitivity and specificity of the 10-item scale and an even shorter 5-item version was slightly higher for AA than for CA women. While both short forms produced significant numbers of false positives against a criterion of CMDE, many of the women identified by the screen did have significant depressive symptomatology. Significantly, fewer AA women received a diagnosis of CMDE primarily because they did not show diminution of functioning associated with their depressive symptoms. CONCLUSION: Short, easy to administer forms of the CES-D can provide useful information in working with older patients. Clinicians should be aware of ethnic differences in symptom expression and levels of functional impairment that are likely to occur in follow-up medical and psychiatric exams.

Characteristics of depressed and nondepressed adult offspring of depressed and matched nondepressed parents.

BACKGROUND: Our aim was to compare adults who were depressed or nondepressed offspring of depressed or matched nondepressed parents on functioning. METHODS: Participants were adult children of depressed (n=143) or nondepressed (n=197) parents who participated in a larger study. They completed self-report measures of depression symptoms, medical conditions and pain, family and social functioning, life stressors and coping, and help used for mental health problems. RESULTS: In the depressed-parent group, depressed offspring had poorer personal functioning than did nondepressed offspring. Factors associated with offspring depressed status were being unmarried and having a diagnosed medical condition, more severe pain, a more severe recent stressor, and more reliance on emotional discharge coping. In the nondepressed-parent offspring, factors associated with depressed status were more disability, family disagreements and disorganization, negative events, and reliance on emotional discharge coping. Depressed offspring of depressed parents had more severe depression than depressed offspring of nondepressed parents; they also had more medical conditions, pain, disability, and severe stressors and, accordingly, relied more on approach coping. In contrast, nondepressed offspring of depressed or nondepressed parents were quite similar on functioning. LIMITATIONS: Measures were self-report and participants were not followed continuously. CONCLUSIONS: Because parental depression increased the risk of impairment among depressed offspring, family history should be considered in the treatment of depression. Offspring of depressed parents who are not experiencing depression are often able to maintain normal functioning in adulthood.

ADHD and anger contexts: electronic diary mood reports from mothers and children.

OBJECTIVE: Using electronic diaries (eDiaries), this study examined temporal links between child and maternal anger, as well as positive mood and perceived stress, in children with attention-deficit/hyperactivity disorder (ADHD) versus comparison peers. METHODS: Across 7 days, half-hourly eDiaries were completed independently by mothers and their 8-12-year-old children (51 receiving medication for ADHD and 58 comparison peers). RESULTS: Cross-informant analyses revealed systematic patterns of negative maternal moods in relation to child anger in both groups along with evidence of slower recovery in the ADHD group. Analogously, for both groups, children's anger reports increased and good-mood reports decreased in relation to maternal anger, whereas elevated stress in relation to maternal anger was restricted to children with ADHD. CONCLUSIONS: The findings indicate that a negative affective climate is more likely to persist in ADHD than in comparison families. They also affirm the utility of child as well as parent eDiary reports and suggest that children may be willing to report low positive mood when reluctant to report negative mood. The promise of incorporating real-time data on mood patterning into tailored treatments for children with ADHD and their families is discussed.

The cost of comorbid depression and pain for individuals diagnosed with generalized anxiety disorder.

Patients with generalized anxiety disorder (GAD) often have comorbid medical and psychiatric disorders and may incur higher costs. In this study, a total of 36,435 GAD patients aged 18 to 64 were identified from a claims database. Patient's total health care and component costs were compared between GAD patients with and without comorbid depression and pain using general linear models. The average total annual cost for all the GAD patients in the study was $7451. Compared with patients with GAD-only, the estimated total cost was $762 higher for GAD with depression (p < 0.001), $2989 higher for GAD with pain (p < 0.001), and $6073 higher for GAD with both depression and pain (p < 0.001). Comorbid depression and pain had significant impact on costs, especially those with pain or with both depression and pain. This suggests that an optimal strategy for GAD should take into account comorbid pain and depression.

Parental depression as a moderator of secondary deficits of depression in adult offspring.

This study examined whether having a depressed parent intensifies the secondary deficits that often co-occur with offspring's depression symptoms. The sample was adult offspring of parents who had been diagnosed with depression 23 years earlier (N = 143) and demographically matched nondepressed parents (N = 197). Respondents completed mailed questionnaires. After controlling for demographic factors, offspring who were more depressed experienced more impairment: physical dysfunction, pain, and disability; anxiety, smoking, and drinking-related problems; poorer social resources; negative events and severe stressors; and reliance on emotional discharge coping. Parental status (depressed or not depressed) was not directly related to offspring impairment once offspring depression symptoms were controlled. However, parental status moderated associations between offspring's depression severity and their impairment: relationships between depression and impairments were generally stronger for offspring of depressed parents than for offspring of nondepressed parents. Depressed individuals who are offspring of depressed parents may be at particular risk for the secondary deficits of depression.

Examining quality of life in patients with generalized anxiety disorder: clinical relevance and response to duloxetine treatment.

BACKGROUND: Duloxetine, a serotonergic noradrenergic reuptake inhibitor, improved functional outcomes in each of three clinical studies for the treatment of adults with generalized anxiety disorder (GAD). Using comparison norms, the current work describes the clinical relevance of these functional improvements in terms of return to normative functioning and symptom remission. METHODS: Data were pooled at the individual patient level from three double-blind, placebo-controlled trials of duloxetine treatment (9-10 weeks acute therapy, dose ranges 60-120mg). Inclusion/exclusion criteria were consistent across studies, and outcome measures included the Sheehan Disability Scale (SDS), Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF), and European Quality of Life 5 Dimensions (EQ-5D). RESULTS: Adult patients (mean age=42.4 years; 65% women) were randomly assigned to duloxetine (N=668) or placebo (N=495). At baseline, the majority of patients were impaired on the SDS global functioning (89%), Q-LES-Q-SF maximum percent (95%), and EQ-5D (76%) scores. On each measure, a greater percentage of duloxetine-treated patients converted from an impaired baseline to a normative endpoint score than did placebo-treated patients (p0.001, all comparisons). Remission defined as a HAMA total score at endpoint of 10, compared with 7, captured a greater proportion of patients who were functionally in remission. CONCLUSIONS: GAD is associated with substantial impairment in functioning and subjective well-being, and patients treated with duloxetine 60-120mg/day, compared with placebo, experienced a greater return to normative functioning. Attention to role functioning and quality of life may refine our definition of remission when using standard symptom measures of anxiety.

Emotional expression in children treated with ADHD medication: development of a new measure.

OBJECTIVE: Although existing instruments contain items addressing the effect of ADHD medications on emotional expression, a review of measures did not yield any instruments that thoroughly evaluated positive and negative aspects of emotional expression. METHOD: The Expression and Emotion Scale for Children (EESC), a parent-report measure, was developed from an analysis of qualitative data from parent focus groups and expert opinion. Data from 179 parents and children treated with stimulants or atomoxetine are used to examine the psychometric properties of the EESC. RESULTS: The EESC demonstrates good internal consistency and test-retest reliability. A factor analysis yields three factors (positive, flat, and emotional lability) that were consistent with the predicted structure of the measure. Small to moderate correlations between the EESC and psychological symptom measures are found, with the strength of the relationships varying by symptom measure. CONCLUSION: The EESC shows appropriate psychometric properties and is appropriate for use in clinical and research settings.

Differential antidepressant symptom efficacy: placebo-controlled comparisons of duloxetine and SSRIs (fluoxetine, paroxetine, escitalopram).

OBJECTIVE: To test the hypothesis that in patients with major depressive disorder (MDD), the response for specific Hamilton Depression Rating Scale items will differ for duloxetine compared with selective serotonin reuptake inhibitors (SSRIs) and that patterns of response will differ based on symptom severity at baseline. METHOD: Data were pooled from all Lilly-sponsored clinical trials where duloxetine was compared with placebo and an SSRI in patients with MDD: 7 randomized, double-blind, fixed-dose, 8-week studies of duloxetine (n = 1,133) versus SSRI (n = 689) versus placebo (n = 641). Duloxetine doses were 40, 60, 80 and 120 mg/day. SSRI doses were 10 mg/day (escitalopram) and 20 mg/day (fluoxetine and paroxetine). RESULTS: Compared to SSRI-treated patients, duloxetine-treated patients had a significantly greater (p < or = 0.05) reduction in the 17-item Hamilton Depression Rating Scale (HAMD17) total score and HAMD17 items of work and activities, psychomotor retardation, genital symptoms and hypochondriasis. Differences favoring the SSRIs approached significance for middle insomnia (p = 0.057) and late insomnia (p = 0.06), with effect sizes at least twice the magnitude of the corresponding effect sizes for duloxetine. Similarly, the advantage for duloxetine versus the SSRIs approached significance for general somatic symptoms (p = 0.056), with an effect size twice that observed for the SSRIs. The HAMD17 total score difference was driven mostly by patients with lower baseline MDD severity (HAMD17 total score < or = 19), where the HAMD17 effect size advantage for duloxetine over combined SSRIs was statistically significant (p = 0.031). CONCLUSION: Potentially important differences in symptom response patterns were found between duloxetine and the combined SSRIs depending on symptom severity, and different HAMD17 items responded differently to duloxetine compared with SSRIs. Understanding these differences may be useful in tailoring antidepressant therapy for individual patients.

An electronic diary study of contextual triggers and ADHD: get ready, get set, get mad.

OBJECTIVE: This study was designed to examine context effects or provocation ecologies in the daily lives of children with ADHD. METHOD: Across 7 days, mothers and children (27 children with attention-deficit/hyperactivity disorder [ADHD] taking stimulant medication; 25 children without ADHD; ages 7-12 years) provided electronic diary reports every 30 +/- 5 minutes during non-school hours. Child and maternal perceptions of behaviors, moods, and interaction quality during preparatory and transitional ("getting ready") activities were compared with those during other activities. RESULTS: Maternal reports revealed that child symptomatic behaviors and negative moods, maternal negative moods, and parent-child disagreement were elevated in the ADHD but not in the comparison group while getting ready versus other activities. Children's self-ratings also revealed situational effects, indicating that school-age children with ADHD can give meaningful self-reports using carefully structured electronic diaries. CONCLUSIONS: Even when children with ADHD are receiving stimulant pharmacotherapy, the preparatory tasks of daily living are especially challenging and linked disproportionately to child behavior problems, parent negative affect, and contentious interactions. Treatment targeted on these transitional hurdles may improve child behavior patterns and enhance parent-child relationships and family harmony.

Higher costs and therapeutic factors associated with adherence to NCQA HEDIS antidepressant medication management measures: analysis of administrative claims.

OBJECTIVE: To determine if the type of antidepressant drug is related to adherence to National Committee for Quality Assurance (NCQA) Antidepressant Medication Management (AMM) quality measures and to assess the 6-month health care costs among newly diagnosed depressed patients. METHODS: The MarketScan Commercial Claims and Encounter database for medical and pharmacy claims from January 2001 to September 2004 was used to assess adherence to the 3 AMM quality-of-care measures. AMM measures include (a) acute phase, the percentage of eligible members who remained on antidepressant medication continuously for 3 months after the initial diagnosis as determined by at least 84 days supply of antidepressant drugs during the first 114 days following receipt of the index antidepressant; (b) continuation phase, the percentage of eligible members who remained on antidepressant medication continuously for the 6 months after the initial diagnosis as determined by at least 180 days supply of antidepressants during the first 214 days following receipt of the index antidepressant; and (c) practitioner contacts, the percentage of members who received at least 3 follow-up office visits or telephone contacts with health care providers, including at least 1 contact with a practitioner licensed to prescribe (may not necessarily be the prescriber of the antidepressant). A fourth measure, overall adherence, was added, if all 3 AMM measures were met. Multivariate regression models determined demographic, clinical (such as receipt of mental health specialty care, the Charlson Comorbidity Index score, and co-occurring bipolar or schizophrenia), and therapy-related factors associated with outcomes of adherence and costs (paid amounts for insurance-reimbursable health care services for inpatient admissions, emergency department services, outpatient services, and outpatient prescription drugs). Health care expenditures (both total and mental-health-specific costs) were measured for each patient for 6 months following the date of service for the index antidepressant. RESULTS: A total of 60,386 adult patients (10.7%) of 562,898 patients with a depression diagnosis met NCQA inclusion criteria in the AMM Technical Specifications (e.g., aged 18 years or older, newly diagnosed with depression and initiating antidepressant therapy, 365 days of continuous enrollment; patients were excluded if there were missing data on dose or quantity of index drug in pharmacy claims or initiated therapy on 2 or more antidepressants as the index medication, exclusion criteria not in the AMM Technical Specifications). Only 19% of patients achieved overall adherence. Rates for the 3 AMM measures were 39% for practitioner contacts, 65% for acute phase, and 44% for continuation phase. Receipt of mental health specialty care was the only factor that was positively associated with greater adherence on all 4 measures (overall measure: odds ratio [OR]=3.895, 95% confidence interval [CI], 3.72-4.07; acute OR=1.38, 95% CI, 1.33-1.43; continuation OR=1.46, 95% CI, 1.41-1.51; contacts OR=5.83, 95% CI, 5.62-6.06). Most patients were initiated on selective serotonin reuptake inhibitors (SSRIs, 69.5%), followed by venlafaxine (21.4%), tricyclic antidepressants (TCAs, 21.4%), bupropion (11.0%), and other antidepressants (e.g., mirtazapine, nefazadone, trazadone; 7.2%). Before adjustment for confounding factors, patients initiated on venlafaxine, TCAs, or other antidepressants had higher rates of adherence on the overall performance measure versus initiators on SSRIs, but the absolute differences were relatively small: 21.4% for venlafaxine and TCAs and 23.1% for other antidepressants versus 18.5% for SSRIs (P <0.001). Patients initiated on venlafaxine, TCAs, or other antidepressants were also more likely to receive care from a mental health specialist, 16.8%, 15.0%, and 54.8%, respectively, compared with SSRIs (13.0%, all P <0.001). Regression analysis showed that only venlafaxine had a higher OR (1.13; 95% CI, 1.05-1.22) compared with SSRIs for adherence on the overall measure. Initiating dose level was in the target range for 70.0% of all patients (24.9% were below target dose and 5.2% above target dose), and adherent patients on all 3 AMM measures were less likely than nonadherent patients (70.4% vs. 68.4%, P <0.001) to be initiated in the target dose range. After multivariate adjustment, the initiating dose (target vs. high) was a significant factor in explaining adherence to the overall measure (OR=1.26; 95% CI, 1.16- 1.37). Adherent patients had 6-month median unadjusted total health care expenses that were nearly 2 times higher compared with nonadherent patients ($5,169 vs. $2,734) and mental health expenditures that were nearly 3 times higher ($1,922 vs. $677). After adjustment, adherent patients compared with nonadherent patients incurred an additional $644 in mental health expenditures and $806 in overall health care expenditures in the 6 months following initiation of antidepressant therapy. CONCLUSIONS: Only 19% of depressed patients initiated on antidepressants met all 3 criteria set forth in the NCQA Health Plan Employer Data and Information Set (HEDIS) AMM quality-of-care performance measures. Receipt of mental health specialty care was the single factor most strongly associated with quality treatment by these measures. Type and dosage level of initial antidepressant was associated with adherence to the NCQA HEDIS AMM measures, but the absolute difference in rates of adherence were relatively small among types of antidepressants. Costs were higher for guideline-adherent individuals in the 6 months following treatment initiation. These analyses were limited to administrative claims that lack indicators of depression disease severity.