Bleeding patterns with monophasic and triphasic low-dose ethinyl estradiol combined oral contraceptives.

BACKGROUND: This retrospective analysis evaluated the association of age and weight with cycle control in women using either of two formulations of low-estrogen-dose oral contraceptives. STUDY DESIGN: Data for this secondary analysis were derived from a randomized multicenter trial assessing the efficacy and safety of norgestimate (NGM) 180/215/250 mcg/ethinyl estradiol (EE) 25 mcg (n=1506) and norethindrone acetate 1 mg/EE 20 mcg (n=1057). In this retrospective analysis, the incidence of breakthrough bleeding/spotting (BTB/S) was evaluated in women stratified by age (18-24, 25-34 and >34 years) and weight (155 lb). RESULTS: A lower percentage of women experienced BTB/S with NGM/EE during most cycles, regardless of age or weight, compared with norethindrone acetate/EE. At Cycle 6, the incidences of BTB/S for NGM/EE versus norethindrone acetate/EE were as follows: 18-24 years, 10.9% versus 29.7% (p<.0001); 25-34 years, 10.9% versus 18.6% (p<.001); >34 years, 8.1% versus 19.1% (p<.005); 155 lb, 10.0% versus 18.3% (p<.01). CONCLUSION: NGM/EE provided better cycle control as defined by BTB/S compared with norethindrone acetate/EE, regardless of subject age or weight for six cycles.

Injury among stimulant-treated youth with ADHD.

OBJECTIVE: To assess risk factors for injury among children and adolescents treated with stimulants for ADHD. METHOD: An analysis was performed of pharmacy and service claims data from 2000-2003 California Medicaid (Medi-Cal) focusing on children and adolescents ages 6 to 17 years who initiated stimulant therapy for ADHD. Bivariate and multivariate analyses were performed to examine associations of demographic and clinical characteristics with injury. RESULTS: In a Cox proportional hazard model that controlled for background patient characteristics, patients ages 13 to 17 years, male gender, prescription of anxiolytic/hypnotic medications, and diagnosis of a mood disorder were each independently associated with increased risk of injury, whereas African American ancestry and other minority racial/ethnic ancestry were associated with lower risk. Youth with high stimulant medication possession ratios (MPR) had a nonsignificantly lower risk of injury as compared to those with a low stimulant MPR. CONCLUSION: These findings reveal several patient characteristics that may be associated with increased risk of injury among children and adolescents treated for ADHD.

Assessing the validity of the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form in adults with ADHD.

OBJECTIVE: The authors assessed the psychometric properties of the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-QSF) in adults with ADHD. METHOD: One hundred fifty ADHD and 134 non-ADHD adults from a case-control study and 173 adults randomized to placebo or methylphenidate were assessed with the Q-LES-QSF and the Social Adjustment Scale (SAS). Response to change was estimated by comparing change in Q-LES-QSF scores in responders and nonresponders in our randomized clinical trial. RESULTS: Internal consistency of the Q-LES-QSF items was .88, and the correlation between the Q-LES-QSF total score and the SAS total T score was .72 in adults with ADHD. ADHD cases had statistically significantly poorer scores on the Q-LES-QSF than controls (76.5 +/- 10.9 vs. 59.2 +/- 17.3, p < .001), whereas ADHD responders showed Q-LES-QSF improvement compared to nonresponders (76.1 +/- 12.0 versus 67.9 +/- 14.5, p < .001). CONCLUSION: These results support the validity of the Q-LES-QSF as a measure of quality of life in adults with ADHD.

Continuity in methylphenidate treatment of adults with attention-deficit/hyperactivity disorder.

BACKGROUND: Although stimulant therapy is commonly discontinued early in adults with attention-deficit/hyperactivity disorder (ADHD), the factors that contribute to continuity of stimulant therapy remain largely unknown. OBJECTIVE: To (1) compare the continuity of methylphenidate (MPH) therapy among adults who use immediate-release methylphenidate (IR-MPH) for ADHD with adults who use extended-release methylphenidate (ER-MPH) formulations, and (2) examine some of the methodological issues involved in research with administrative claims for ADHD. METHODS: An analysis of pharmacy and medical claims for 75 US managed care plans representing approximately 55 million beneficiaries for dates of service from January 1, 2000 through December 31, 2004. Patients had to be adults (aged 18 to 64 years) who had 1 or more outpatient medical claims for ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification code 314.xx) during the study period and who had initiated ER-MPH or IR-MPH treatment for ADHD. The study cohorts did not have a pharmacy claim for MPHs, amphetamines, pemoline, or atomoxetine for 6 months preceding the first (index) MPH pharmacy claim. Stimulant treatment episodes were defined to start on the index date and terminate on the last date supplied of the index medication. Episodes of treatment were also defined as terminated if there was a gap of > or =30 days between the end of the days supplied on the pharmacy claim and the date of the next pharmacy claim for the index medication. RESULTS: Less than one third (30.0%) of the adult patients who were prescribed MPH had 1 or more medical claims with a diagnosis code for ADHD. For the adult MPH patients with at least 1 medical claim with a diagnosis code for ADHD, the patients who initiated therapy with ER-MPH (N = 2,833) were significantly younger, were more likely to be male, and were less likely to be treated by a psychiatrist than were the patients who initiated therapy with IR-MPH (N = 2,289). Only 50.5% (n = 1,156) of IR-MPH patients and 61.4% (n = 1,739) of ER-MPH patients had more than 1 pharmacy claim for the index MPH medication. Adults treated with ER-MPH also had a significantly longer median duration of treatment with the index medication (ER-MPH: 68 days, 95% confidence interval [CI], 65-71 days vs. IR-MPH 39 days, 95% CI, 33-52 days). Controlling for group differences in age, gender, treatment by a psychiatrist, recently prescribed psychotropic medications, treated mental disorders, emergency mental health treatment, and inpatient mental health care, ER-MPH initiation was associated with an average 27% longer duration of treatment than with IR-MPH (survival time ratio: 1.27, 95% CI, 1.20-1.35). CONCLUSION: In management of adult ADHD, use of ER-MPH formulations was associated with a longer median duration of the initially prescribed medication than was use of IR-MPH. It is unknown whether the observed absolute unadjusted difference of 29 days in median length of therapy is clinically important.

Health care costs of adults treated for attention-deficit/hyperactivity disorder who received alternative drug therapies.

BACKGROUND: Many therapies exist for treating adult attention-deficit/hyperactivity disorder (ADHD), also referred to as attention-deficit disorder (ADD), but there is no research regarding cost differences associated with initiating alternative ADD/ADHD drug therapies in adults. OBJECTIVE: To compare from the perspective of a large self-insured employer the risk-adjusted direct health care costs associated with 3 alternative drug therapies for ADD in newly treated patients: extended-release methylphenidate (osmotic release oral system-MPH), mixed amphetamine salts extended release (MAS-XR), or atomoxetine. METHODS: We analyzed data from a US claims database of 5 million beneficiaries from 31 large self-insured employers (1999-2004). Analysis was restricted to adults aged 18 to 64 years with at least 1 diagnosis of ADD/ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 314.0x--attention deficit disorder; 314.00--attention deficit disorder without hyperactivity; or 314.01--attention-deficit disorder with hyperactivity) and at least 1 pharmacy claim for OROS-MPH, MAS-XR, or atomoxetine identified using National Drug Codes. In preliminary analysis, we calculated the duration of index ADHD drug therapy as time from index therapy initiation to a minimum 60-day gap. Because the median duration of index ADHD drug therapy was found to be approximately 90 days, the primary measures were total direct medical plus drug costs and medical-only costs computed over 6 months following therapy initiation. Adults were required to have continuous eligibility 6 months before and 6 months after their latest drug therapy initiation and no ADHD therapy during the previous 6 months. Cost was measured as the payment amount made by the health plan to the provider rather than billed charges, and it excluded patient copayments and deductibles. Medical costs included costs incurred for all-cause inpatient and outpatient/other services. Costs were adjusted for inflation to 2004 U.S. dollars using the consumer price index for medical care. T tests were used for descriptive cost comparisons. Generalized linear models (GLMs) were used to compare costs of adults receiving alternative therapies, adjusting for demographic characteristics, substance abuse, depression, and the Charlson Comorbidity Index. RESULTS: Of the 4,569 patients who received 1 of these 3 drug therapies for ADHD, 31.8% received OROS-MPH for a median duration of 99 days of therapy, 34.0% received MAS-XR for a median 128 days, and 34.2% received atomoxetine for a median 86 days. In the 6-month follow-up period, the mean (standard deviation) total medical and drug costs were $2,008 ($3,231) for OROS-MPH, $2,169 ($4,828) for MAS-XR, and $2,540 ($4,269) for atomoxetine-treated adults. The GLM for patient characteristics suggested that 6-month, risk-adjusted mean medical costs, excluding drug costs, for adults treated with OROS-MPH were $142 less (10.4%, $1,220 vs. $1,362) compared with MAS-XR (P =0.022) and $132 less (9.8%, $1,220 vs. $1,352) compared with atomoxetine (P =0.033); risk-adjusted mean medical costs were not significantly different between MAS-XR and atomoxetine. The GLM comparison of risk-adjusted total direct costs, including drug cost, was on average $156 less (8.0%, $1,782 vs. $1,938) for OROS-MPH compared with MAS-XR (P = 0.017) and $226 less (11.3%, $1,782 vs. $2,008) compared with atomoxetine (P <0.001); the risk-adjusted total direct costs were not significantly different between MAS-XR and atomoxetine. Two high-cost outliers (greater than 99.96th percentile, 1 each for OROS-MPH and atomoxetine) accounted for $47 (30%) of the $156 cost difference between OROS-MPH and MAS-XR and $11 (5%) of the $226 cost difference between OROS-MPH and atomoxetine, and the medical diagnoses for the highest-cost claims for these 2 outlier patients were unrelated to ADHD. CONCLUSIONS: After adjusting for patient characteristics including substance abuse, depression, and the Charlson Comorbidity Index, adults treated with OROS-MPH had, on average, slightly lower medical and total medical and drug costs than those treated with MAS-XR or atomoxetine over the 6-month period after drug therapy initiation. Approximately 30% of the cost difference compared with MAS-XR was attributable to 1 high-cost outlier with medical diagnoses for the highest-cost claim that were unrelated to ADHD.

Estimation of symptom-free days in generalized anxiety disorder.

OBJECTIVE: The efficacy of treatments for generalized anxiety disorder has usually been measured in terms of response or remission of symptoms. These endpoints, however, may not adequately capture the transient periods of symptom abatement and relapse characteristic of chronic psychiatric disorders. Here, we evaluate the measurement of treatment effectiveness in terms of the number of symptom-free days (SFDs). RESEARCH DESIGN AND METHODS: A pooled analysis was performed of data from five manufacturer-initiated trials of venlafaxine extended-release (XR) in patients with generalized anxiety disorder without co-morbid major depressive disorder. The trials were randomized, double-blind, placebo-controlled and of 8 weeks duration (total intent-to-treat population 1295 venlafaxine XR, 544 placebo). Two of the studies had extensions up to 6 months (intent-to-treat population 514 venlafaxine XR, 253 placebo). The patients were >or= 18 years of age with a Hamilton Rating Scale for Anxiety (HAM-A) score of >or= 18. MAIN OUTCOME MEASURES: SFDs were estimated using weekly scores on the HAM-A. Values of 7 and 0 SFDs, respectively, were assigned to each week the patient had a HAM-A score of or= 18 (the minimum threshold for anxiety). Fractional SFD values were assigned proportionately to weekly HAM-A scores between 7 and 18. RESULTS: The median (inter-quartile range) SFDs were 19 (2-36) for venlafaxine XR and 10 (0-27) for placebo in the 8-week studies (p < 0.0001). In the 6-month extension studies the SFDs were 102 (27-139) for venlafaxine XR and 36 (0-94) for placebo (p < 0.0001). CONCLUSIONS: SFDs differentiate between active treatment and placebo in clinical trials and may be an appropriate measure of treatment effectiveness.

Treatment patterns in psoriatic arthritis patients newly initiated on oral nonbiologic or biologic disease-modifying antirheumatic drugs.

INTRODUCTION: This study aimed to describe treatment changes (discontinuation, switching, and therapy add-on) following the initiation of biologic or nonbiologic oral disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA) patients. METHODS: Adult patients with ≥2 PsA diagnoses from physician office visits, initiated on a biologic or nonbiologic oral DMARD, were selected from the Truven Health Analytics MarketScan® Research Database (2005 to 2009). Patients were required to have continuous insurance coverage ≥6 months prior to and ≥12 months post index date (first prescription fill date). Treatment discontinuation, treatment switch, and therapy add-on were captured over the 1 year period following the index date. Treatment changes were described separately for patients initiated on nonbiologic and biologic DMARDs. RESULTS: A total of 1,698 and 3,263 patients were initiated on an oral nonbiologic DMARD and biologic DMARD respectively. For patients initiated on nonbiologic DMARDs, 69% had ≥1 therapy change over the 12 month study period (median time 85 days). Among patients who had a therapy change, 83% discontinued, 29% switched therapy (64% switched to a biologic DMARD), and 25% had a therapy add-on (76% added-on with a biologic DMARD). For patients initiated on a biologic DMARD, 46% had ≥1 therapy change (median time 110 days). Among patients who had a therapy change, 100% discontinued, 25% switched therapy (92% switched to another biologic DMARD), and 7% had a therapy add-on with a nonbiologic DMARD. CONCLUSION: This study suggests that PsA patients newly initiated on a nonbiologic/biologic DMARD do not remain on the index treatment for a long period of time. A better understanding of factors related to these early treatment changes in PsA patients is needed.

Time to initiation of pentosan polysulfate sodium treatment after interstitial cystitis diagnosis: effect on symptom improvement.

OBJECTIVES: Interstitial cystitis (IC) is a chronic, debilitating condition that is often associated with late diagnosis and a delay in initiation of appropriate IC-specific therapy. The purpose of this study was to determine whether the length of time from initial diagnosis to start of treatment impacts subsequent symptom improvement. METHODS: A retrospective analysis was conducted in 128 patients with IC who had been treated with pentosan polysulfate sodium (PPS) 300 mg/day for 32 weeks in a multicenter, randomized, double-blind, parallel-group clinical trial. Outcome measures included the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and the O'Leary-Sant Interstitial Cystitis Problem Index (ICPI). Early treatment was defined as treatment initiation 6 months or less after IC diagnosis, whereas late treatment was defined as treatment initiation 24 months or more after IC diagnosis. Efficacy data were analyzed by using the intent-to-treat, last-observation-carried-forward population. RESULTS: At the end of the study, mean changes from baseline in total ICSI and ICPI scores (+/- SEM) for early treatment (6 months or less) versus late treatment (24 months or more) were 3.97 +/- 0.59 versus 2.15 +/- 0.70 (P = 0.0472) and 3.94 +/- 0.56 versus 1.77 +/- 0.63 (P = 0.0117), respectively. Similar trends for both measures were observed when examining other times from IC diagnosis (3 months or less versus 24 months or more, 3 months or less versus 36 months or more, and 6 months or less versus 36 months or more). CONCLUSIONS: Initiation of PPS treatment within 6 months of establishing the diagnosis of IC may be associated with greater improvement in patient symptoms and symptom bother.

Association between response to pentosan polysulfate sodium therapy for interstitial cystitis and patient questionnaire-based treatment satisfaction.

OBJECTIVE: To evaluate the relationship between symptom reduction and satisfaction with pentosan polysulfate sodium (PPS) therapy in subjects with interstitial cystitis (IC). METHODS: A secondary analysis was conducted in 128 subjects treated with PPS 300 mg/day (US Food and Drug Administration-approved dose) from a 32-week multicenter, randomized, double-blind study of 380 subjects with IC who were treated with PPS 300 mg/day, 600 mg/day, or 900 mg/day. Self-rated outcome measures included the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and a treatment satisfaction questionnaire. Treatment responders were defined as subjects having > or =30% reduction in ICSI from baseline to study end point. RESULTS: A reduction in IC symptoms was associated with significantly higher satisfaction with PPS (p < 0.05). Compared with nonresponders, subjects achieving a > or = 30% reduction in ICSI were more likely to be pleased with PPS for IC symptoms, to have benefited from PPS for their IC symptoms, to recommend PPS for IC symptoms to others with the same condition, and to say that PPS provides better relief, based on prior experience with other IC treatments. Among all subjects at week 32, 75% said they would recommend PPS therapy for IC symptoms to others with the condition. CONCLUSION: Despite limitations (lack of placebo control, use of a nonvalidated instrument), this analysis demonstrated significantly increased treatment satisfaction with PPS therapy among treatment responders versus nonresponders. There was a significant positive correlation between ICSI scores and response on the treatment satisfaction questionnaire. Treatment response and patient satisfaction with treatment are important clinical considerations in the management of patients with IC.