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Abstract: Background: Atomoxetine is a non-amphetamine medication approved to treat ADHD in children, adolescents, and adults. Previous studies demonstrated low abuse potential for atomoxetine in recreational drug users. This study assessed the abuse potential of atomoxetine in stimulant-preferring drug abusers compared to methylphenidate and phentermine as positive controls and desipramine and placebo as negative controls. Methods: Forty male and female, 32–53 years old stimulant-preferring drug abusers completed this balanced Latin-square designed study. Subjects received acute, double-blind doses of placebo, desipramine (100 and 200mg), methylphenidate (90mg), phentermine (60mg), and atomoxetine (45, 90, and 180mg). Subjective and physiological effects were collected for 24h following each drug treatment. Results: Methylphenidate and phentermine were liked significantly more than placebo, atomoxetine, or desipramine. No atomoxetine dose was liked significantly more than placebo and liking scores for atomoxetine were similar to, or significantly lower than, desipramine, as assessed by the Drug Rating Questionnaire-Subject. While atomoxetine 45 and 180mg did not significantly change any Addiction Research Center Inventory (ARCI) scores, atomoxetine 90mg significantly increased A and BG stimulant scores of the ARCI and both methylphenidate and phentermine produced greater A and BG increases than any atomoxetine dose and also increased MBG (euphoria) scores relative to placebo. Conclusions: Atomoxetine has significantly less abuse liability than methylphenidate or phentermine and no greater abuse liability than desipramine. [Copyright &y& Elsevier]

Objectives: This randomized, open-label trial was designed to help inform antipsychotic treatment policies. It compared the 1-year cost-effectiveness of initial treatment with olanzapine (OLZ) (n = 229) versus a “fail-first” algorithm on conventional antipsychotics (then olanzapine if indicated) (CON) (n = 214); and versus initial treatment with risperidone (RIS) (n = 221). Methods: Individuals with schizophrenia or schizoaffective disorder were recruited from May 1998 to September 2001. Clinical, functioning, and resource utilization data were collected at baseline and five postbaseline visits. Brief Psychiatric Rating Scale scores defined “clinical effectiveness;” Lehman Quality of Life Scale social relations scores defined “social effectiveness.” Results: Requiring failure on less expensive antipsychotics before use of olanzapine did not result in total cost savings, despite significantly higher antipsychotic costs with OLZ. Total 1-year mean costs were $21,283 for CON; $20,891 for OLZ; and $21,347 for RIS (pair-wise comparisons nonsignificant). Intent-to-treat effectiveness comparisons (nonsignificant) were augmented by analyses that adjusted for duration on initial antipsychotic treatment, and by comparisons of patients remaining on initial antipsychotic treatment versus those who required switching. When accounting for differential switching rates (OLZ 0.14 vs. CON 0.53, P < 0.0001; vs. RIS 0.31, P < 0.0001), OLZ was significantly more effective than CON on clinical ( P = 0.025) and social ( P = 0.043) measures, and significantly more effective than RIS on the social ( P = 0.002) measure. Further, patients initiated on an antipsychotic from which they needed to switch required additional resources for hospitalization ( P = 0.036) and crisis services ( P = 0.029). Conclusions: Approaches that integrate costs, effectiveness, and treatment patterns are important for providing optimal information regarding the value of first-line antipsychotic options for schizophrenia. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Early discontinuation of antidepressant therapy is associated with relapse and increased costs. This exploratory study examined demographical and pretreatment clinical predictors of duloxetine (Eli Lilly and Company, Indianapolis, IN) treatment persistence in patients treated in real-world clinical settings. Study Design: Using a large US managed-care claims database (PharMetrics Integrated Outcomes Database; PharMetrics Inc., Watertown, MA), study subjects were individuals aged 18 to 64 years who initiated duloxetine treatment between April 2005 and March 2006, had ≥1 claim associated with major depressive disorder diagnosis, and had continuous insurance coverage 6 months before and 12 months after initiation of duloxetine therapy. Treatment persistence was defined as continuous duloxetine treatment without a 30-day gap for ≥3 months. Chi-squared tests and logistic regression analysis were used to examine predictors of persistence. Results: Among 9148 patients (74.1% female; mean age 45.6 years) who initiated duloxetine treatment, 63.5% stayed on the medication for ≥3 months. Logistic regression analysis showed that an initial dose ≥60mg (odds ratio [OR] 1.43), older age groups (OR ≥1.49), and venlafaxine XR (OR 1.85) or selective serotonin reuptake inhibitor (OR 1.59) use in the prior 6 months were significantly associated with increased odds of treatment persistence, whereas prior benzodiazepine use (OR 0.86), comorbid alcohol dependence (OR 0.75), drug dependence (OR 0.76), and Parkinson disease (OR 0.36) were associated with decreased odds of treatment persistence. Findings were essentially unchanged with classification and regression tree analysis. Conclusion: The results suggest that multiple demographic and clinical variables are associated with treatment persistence of duloxetine therapy. The findings may have important implications for clinicians to take actions to prevent early therapy discontinuation. [Copyright &y& Elsevier]

Abstract: The Reasons for Antipsychotic Discontinuation Questionnaire (RAD-Q) was designed to assess clinicians'' perceptions of reasons for antipsychotic discontinuation or continuation. The current study examined psychometric properties of this instrument and patterns of antipsychotic discontinuation. The sample of 121 patients (81 discontinuation, 40 continuation) with schizophrenia or schizoaffective disorder was 66.9% male, with a mean age of 41.6 years. Treating clinicians reported a mean of 4.1 reasons for discontinuation and 7.5 reasons for continuation. RAD-Q domain scores were derived to quantify the impact of three factors on the decision to discontinue or continue: treatment benefits, adverse events, and distal reasons other than direct effects of the medication. Analysis of inter-rater reliability indicated an acceptable degree of agreement between clinicians (weighted Kappa for discontinuation scores=0.70–0.78). Correlations with symptom measures (Clinical Global Impression-Schizophrenia Scale (CGI-SCH), Positive and Negative Syndrome Scale (PANSS)) supported convergent validity of the benefits domain score (r=0.28–0.47; all p<0.05). Domain scores discriminated among groups of patients differing in clinician and patient-reported clinical variables. Results suggest that the RAD-Q is a useful detailed measure of reasons for antipsychotic discontinuation and continuation. Findings indicate that clinicians usually report multiple reasons for discontinuation, rather than a single reason for each patient. [Copyright &y& Elsevier]

Abstract: Background: Major depressive disorder (MDD) is a common illness that affects ∼7% of adults in the United States each year. Duloxetine is a dual reuptake inhibitor of serotonin and norepinephrine that has demonstrated efficacy and tolerability in the treatment of MDD. Objective: The purpose of our study was to examine dosing patterns and pretreatment predictors of high-dose duloxetine therapy for patients with MDD in the usual clinical setting. Methods: Data were from 6132 commercially insured patients with MDD initiated on duloxetine during 2005 and 2006. Patients had no duloxetine use in the previous 6 months and had continuous enrollment in a health plan for the 12 months immediately preceding and following initiation. Dosing patterns and predictors of high-dose therapy with duloxetine were examined. Results: Initial doses of duloxetine were <60 mg/d, 60 mg/d, 90 mg/d, and ≥120 mg/d for 32.4%, 60.9%, 3.1%, and 3.5% of patients, respectively. Maximum daily doses were <60 mg, 60 mg, 90 mg, and ≥120 mg for 16.3%, 59.3%, 11.0%, and 13.3% of patients, respectively. Patients treated with >60 mg/d for at least 2 months were older, were more likely to have been treated by a psychiatrist, had greater comorbidity, and had used more health care resources and psychotropic and pain medications in the previous year. The following factors were independently associated with doses of >60 mg/d: older age (odds ratio [OR] = 1.33–1.46); comorbid neuropathic pain (OR = 1.88); fibromyalgia (OR = 1.36); dysthymic disorder (OR = 1.24); prior injury/poisoning (OR = 1.19); physician specialty (psychiatrist, OR = 1.55); and prior use of psychostimulants (OR = 1.26), benzodiazepines (OR = 1.19), venlafaxine (OR = 1.35), or atypical antipsychotics (OR = 1.35). Conclusions: Most of the commercially insured patients in this dataset were initiated and maintained on a duloxetine dose of 60 mg/d. Although the data are limited in their generalizability, the characteristics associated with higher dose therapy describe a complex group of patients who may require more intensive drug treatment and monitoring. [Copyright &y& Elsevier]

Background: The efficacy of atomoxetine in maintaining symptom response following 1 year of treatment was assessed in children and adolescents (n = 163) with DSM-IV defined attention-deficit/hyperactivity disorder (ADHD). Methods: Subjects had previously responded to atomoxetine acutely and had completed 1 year of double-blind atomoxetine treatment. They were then randomly assigned in double-blind fashion to continued atomoxetine or placebo substitution for 6 months. Results: Atomoxetine was superior to placebo in preventing relapse (Wilcoxon test, p = .008) and in maintaining symptom response (ADHD Rating Scale IV score, p < .001). Among subjects assigned to discontinuation, the magnitude of symptom return was generally to a level of severity less than that observed at study entry. Conclusions: Following 1 year of treatment with atomoxetine, continued treatment over the ensuing 6 months was associated with superior outcomes compared with placebo substitution. However, there was considerable variability between individuals in the magnitude of symptom return after drug discontinuation, suggesting that some subjects treated with atomoxetine for a year with good results may consolidate gains made during drug treatment and could benefit from a medication-free trial to assess the need for ongoing drug treatment. [Copyright &y& Elsevier]

Objective: Attention-deficit/hyperactivity disorder (ADHD) is typically treated over extended periods; however, few placebo-controlled, long-term studies of efficacy have been reported. Method: In a global multicenter study, children and adolescents who responded to an initial 12-week, open-label period of treatment with atomoxetine, a nonstimulant treatment for ADHD, were randomized to continued atomoxetine treatment or placebo for 9 months under double-blind conditions. Results: A total of 416 patients completed acute atomoxetine treatment and were randomized. At end point, atomoxetine was superior to placebo in preventing relapse defined as a return to 90% of baseline symptom severity (proportion relapsing: atomoxetine 65 of 292 [22.3%], placebo 47 of 124 [37.9%], p =.002). The proportion of patients with a 50% worsening in symptoms post-randomization was also lower on atomoxetine (atomoxetine 83 of 292 [28.4%], placebo 59 of 124 [47.6%], p <.001). Compared with patients in the placebo group, atomoxetine-treated patients had superior psychosocial functioning at end point. Discontinuations for adverse events were low in both groups, and tolerability was similar to that observed in acute treatment trials. Conclusions: In patients who responded favorably to 12 weeks of initial treatment, atomoxetine was superior to placebo in maintaining response for the ensuing 9 months. This result supports the value of maintenance treatment with atomoxetine in patients with ADHD who respond to initial treatment. [ABSTRACT FROM AUTHOR]