Opioid utilization and health-care costs among patients with diabetic peripheral neuropathic pain treated with duloxetine vs. other therapies.

OBJECTIVE: This retrospective cohort study assessed subsequent opioid utilization and health-care costs among patients with diabetic peripheral neuropathic pain (DPNP) who initiated duloxetine vs. other standard of care (SOC) treatments. METHODS: Medical and pharmacy claims were analyzed for commercially-insured individuals aged 18-64. Two study cohorts were constructed from DPNP patients who initiated duloxetine or SOC medications (tricyclic antidepressants, venlafaxine, gabapentin, pregabalin) between March 1, 2005 and December 31, 2005. Initiation was defined as a prior 90-day period without access of the medication. The dispense date of the first initiation was denoted as the index date. Patients with opioids dispensed in the prior 90 days were excluded. Opioid utilization including total days, number of prescriptions filled, and morphine equivalent dosage was assessed for overall, long-acting, and short-acting opioids. Health-care costs and opioid use in the 12-month post-index period were examined via multivariate regression analyses. RESULTS: Four hundred and ninety-nine DPNP patients (272 duloxetine, 227 SOC) were identified. SOC patients had higher prevalence of comorbidities and pre-index health-care costs than duloxetine patients. Controlling for cross-cohort differences, duloxetine patients were significantly less likely to use any opioids than SOC patients. Also, duloxetine patients had 20 fewer adjusted opioid supply days (largely due to the use of short-acting opioids, P < 0.05) and significantly lower adjusted total costs ($8,088, P < 0.05) and diabetes-related costs ($3,092, P < 0.05) in the 12-month post-index period, with most of the cost differences from lower outpatient costs. CONCLUSIONS: DPNP patients who initiated duloxetine therapy were less likely to have subsequent opioid use and had lower health-care costs than SOC patients.

Reduced hedonic capacity in major depressive disorder: evidence from a probabilistic reward task.

OBJECTIVE: Anhedonia, the lack of reactivity to pleasurable stimuli, is a cardinal feature of depression that has received renewed interest as a potential endophenotype of this debilitating disease. The goal of the present study was to test the hypothesis that individuals with major depression are characterized by blunted reward responsiveness, particularly when anhedonic symptoms are prominent. METHODS: A probabilistic reward task rooted within signal-detection theory was utilized to objectively assess hedonic capacity in 23 unmedicated subjects meeting DSM-IV criteria for major depressive disorder (MDD) and 25 matched control subjects recruited from the community. Hedonic capacity was defined as reward responsiveness - i.e., the participants' propensity to modulate behavior as a function of reward. RESULTS: Compared to controls, MDD subjects showed significantly reduced reward responsiveness. Trial-by-trial probability analyses revealed that MDD subjects, while responsive to delivery of single rewards, were impaired at integrating reinforcement history over time and expressing a response bias toward a more frequently rewarded cue in the absence of immediate reward. This selective impairment correlated with self-reported anhedonic symptoms, even after considering anxiety symptoms and general distress. CONCLUSIONS: These findings indicate that MDD is characterized by an impaired tendency to modulate behavior as a function of prior reinforcements, and provides initial clues about which aspects of hedonic processing might be dysfunctional in depression.

Relative antidepressant efficacy of bupropion and the selective serotonin reuptake inhibitors in major depressive disorder: gender-age interactions.

To determine whether age/gender-based differences in efficacy exist between bupropion and the selective serotonin reuptake inhibitors for major depressive disorder, we pooled the findings of 10 double-blind studies comparing bupropion with a selective serotonin reuptake inhibitor. Men (N=943) and women (N=1179) were divided into three age groups (younger than 40, 40-55, older than 55). Improvement in terms of the 17-item Hamilton Depression Rating Scale, as well as the Bech melancholia, anxiety-somatization, and insomnia factors of the Hamilton Depression Rating Scale was compared between the two treatment groups. Of 64 pair-wise comparisons, only one was statistically significant. Specifically, more women treated with a selective serotonin reuptake inhibitor experienced a 50% or greater decrease in Hamilton Depression Rating Scale Anxiety-Somatization scores (58.8 versus 63.8%, P=0.0394). No difference, however, was seen in the degree of resolution of Hamilton Depression Rating Scale Anxiety-Somatization scores (continuous measure) between women treated with bupropion versus a selective serotonin reuptake inhibitor (P=0.114). Bupropion and the selective serotonin reuptake inhibitors, thus, appear to be equally effective in treating depressive symptoms, as well as anxious/somatic symptoms and insomnia in depression. No gender-related or age-related differences were found except that greater improvement was seen in anxious/somatic symptoms of depression among women during selective serotonin reuptake inhibitor treatment. This finding could, however, not be replicated when improvement in anxious/somatic symptoms was defined as a continuous measure.

A survey of five antidepressant properties influencing clinician's treatment choices in MDD.

INTRODUCTION: The goal of the present work was to examine how clinicians' perceptions of the properties of antidepressants may influence their choice of antidepressants when treating major depressive disorder (MDD). METHODS: 273 of 682 (40%) clinicians attending a psychopharmacology review course responded to a questionnaire designed to explore their practices and perceptions with regards to antidepressant pharmacotherapy. RESULTS: Most clinicians ranked efficacy (57.3%) as the most important factor when selecting antidepressants, followed by safety (23.0%), tolerability (9.4%), rapidity of action (5.2%), and cost (4.9%). However, when presented with hypothetical scenarios in which there was a difference in efficacy between two antidepressant agents, the relative safety, tolerability, and cost of the two agents significantly influenced the likelihood of choosing one antidepressant over another. In fact, clinicians required progressively greater differences in efficacy between two agents in order to select one antidepressant over another given a difference in terms of their safety than tolerability, or their tolerability than cost (p < 0.0001 all comparisons). CONCLUSIONS: When selecting an antidepressant, clinicians appear to be most influenced by efficacy, followed by safety. Rapidity of action and cost may be less salient considerations in clinical practice. Further research is necessary to elucidate factors that influence clinicians' choice of antidepressants.

Resolution of sleepiness and fatigue in major depressive disorder: A comparison of bupropion and the selective serotonin reuptake inhibitors.

BACKGROUND: The purpose of this study was to examine whether the treatment of major depressive disorder (MDD) with the norepinephrine-dopamine reuptake inhibitor (NDRI) bupropion results in a greater resolution of sleepiness and fatigue than with the selective serotonin reuptake inhibitors (SSRIs). METHODS: Six double-blind, randomized clinical trials comparing bupropion (n = 662) with an SSRI (n = 655) for the treatment of MDD were pooled. Hypersomnia scores were defined as the sum of scores of the Hamilton Depression Rating Scale (HDRS) items #22, 23, and 24. Fatigue scores were defined as the score of HDRS item #13. RESULTS: There was a greater improvement in hypersomnia scores among bupropion-treated than SSRI-treated (p < .0001) or placebo-treated patients (p = .0008). There was also a greater improvement in fatigue scores among bupropion-treated (p < .0001) and SSRI-treated (p = .0005) than placebo-treated patients as well as a greater improvement in fatigue scores among bupropion-treated than SSRI-treated patients (p = .0078). Fewer bupropion-remitters than SSRI-remitters experienced residual hypersomnia (20.5% vs. 32.1%; p = .0014) or residual fatigue (19.5% vs. 30.2%; p = .0020). CONCLUSION: Treatment of MDD with the NDRI bupropion resulted in a greater resolution of sleepiness and fatigue than SSRIs treatment. Although preliminary, these results warrant prospectively designed studies examining potential differences between bupropion and the SSRIs on these specific depressive symptoms.