Changes in energy during treatment of depression: an analysis of duloxetine in double-blind placebo-controlled trials.

AIMS: The aim of this study was to assess how quickly and effectively duloxetine improves energy compared with placebo in patients with major depressive disorder (MDD). METHODS: Data from 10 randomised, double-blind, placebo-controlled clinical trials examining duloxetine (40-60 mg/day) vs. placebo in patients diagnosed with MDD were analysed. Change from baseline at Week 1 through Week 8 in Hamilton Depression Rating Scale (HAM-D) retardation subscale score (Item 1 - depressed mood, Item 7 - work and activities, Item 8 - retardation and Item 14 - genital symptoms) was assessed with mixed model repeated measures analysis. Positive predictive values and negative predictive values were calculated for predictor analysis. RESULTS: Patients treated with duloxetine (N = 1522) experienced statistically significantly (p ≤ 0.05) greater reductions in HAM-D retardation subscale scores vs. placebo (N = 1180) starting at Week 1 throughout Week 8 of treatment. Of the patients with early energy improvement (≥ 20% reduction in HAM-D retardation subscale scores) at Week 1, 48% achieved remission (HAM-D total score ≤ 7) at Week 8; 48% and 46% of patients who experienced early energy improvement at Weeks 2 and 4, respectively, achieved remission at Week 8. DISCUSSION: We demonstrated that treatment with duloxetine, quickly and with increasing magnitude over treatment time, improves low energy symptoms. As early as 1 week after starting treatment with duloxetine, improvement of low energy may serve as a predictor of remission at end-point. CONCLUSIONS: Treatment with duloxetine improves energy in patients with MDD and early response in retardation may serve as a modest predictor of remission at end-point. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov. Study Identifiers: NCT00036335; NCT00073411; NCT00406848 and NCT00536471. Studies HMAQa, HMAQb, HMATa, HMATb, HMBHa and HMBHb predate the registration requirement. DATA POSTING: ClinicalTrials.gov. Study Identifiers: NCT00406848; NCT00536471.

Duloxetine added to oral nonsteroidal anti-inflammatory drugs for treatment of knee pain due to osteoarthritis: results of a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine the efficacy, tolerability, and safety of duloxetine when added to oral nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with osteoarthritis (OA) of the knee with pain of moderate or greater severity. RESEARCH DESIGN AND METHODS: This was a 10-week randomized, double-blind, flexible-dose (duloxetine 60/120 mg/day), placebo-controlled trial that enrolled adult outpatients who had persistent moderate pain (≥4 on a 0-10 numerical rating scale) due to OA of the knee, despite, per protocol, having received optimized oral NSAID therapy (specific drug, dose, and frequency at investigator discretion). CLINICAL TRIALS REGISTRATION: ClinicalTrial.gov identifier: NCT01018680. MAIN OUTCOME MEASURE: Patients entered daily pain ratings in a telephone-based diary. The primary efficacy outcome was the weekly mean of the daily average pain rating at week 8. Safety outcomes were assessed during the entire 10-week study. RESULTS: A total of 524 patients randomly received duloxetine 60/120 mg/day (N = 264) or placebo (N = 260). In total, 74% of the patients completed the study. Mean age was 61 years (SD 9.2), 57% were female, and 81% were white. Duloxetine-treated patients had significantly greater pain reduction at week 8 (p < 0.001) than placebo-treated patients. In addition, relative to placebo at week 8, duloxetine-treated patients had significant improvements in physical function as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (p < 0.001), and Patient Global Impression of Improvement (p < 0.001). Compared to placebo, significantly more nausea, dry mouth, constipation, fatigue and decreased appetite were reported by patients taking duloxetine (each p < 0.05). Discontinuation due to adverse events occurred more commonly in the duloxetine group than the placebo group (p = 0.03). CONCLUSION: Duloxetine added to oral NSAID therapy provided additional significant pain reduction, improved function, and patient-rated impression of improvement. Adverse events were consistent with those seen in previous duloxetine trials. The short duration of the study may not reflect the longer term efficacy and safety of NSAID/duloxetine cotherapy.

Patterns of depressive symptom response in duloxetine-treated outpatients with mild, moderate or more severe depression.

AIMS: This was a post hoc analysis to determine whether baseline severity of depression influenced the efficacy of duloxetine in treating major depressive disorder (MDD) and to better characterise the symptom response profile for duloxetine in patients with mild, moderate or more severe depression. METHODS: Data were pooled from four double-blind, placebo-controlled studies in which outpatients with MDD were randomised to duloxetine (60 mg/day) or placebo for 8-9 weeks. Patients were retrospectively stratified according to baseline 17-item Hamilton Depression Rating scale (HAMD17) total scores: mild=total score

Postpartum emotional illness: recognition and management in primary care.

Recognition and management of postpartum depression and other emotional illnesses in the primary care setting is both possible and desirable. Screening questionnaires and clinical interviews, education of the patient and her family, and appropriate use of medication and support will allow the primary care physician to manage the majority of these cases successfully. Depression is the most common disorder seen in the postpartum period, but several other psychiatric illnesses are also more common in this period. Decisions about pharmacologic management as well as hospitalization must be made in the context of risks and benefits to the patient, her baby, and her family. Although untreated emotional illness in postpartum women can have longterm sequelae for the family, appropriately managed most of these disorders have an excellent prognosis.

Managing agitation in the critical care setting.

Pharmacologic control of the agitated ICU patient requires preliminary assessment of the underlying causes of agitation. Reversal of correctable abnormalities, consideration of drug reaction, withdrawal and pain management should be addressed first. Delirium is the most common cause of agitation in the ICU and often has multiple causes. Pharmacologic management of agitation can be safely accomplished by intravenous haloperidol with or without lorazepam, as outlined above.

Psychiatric aspects of high-risk pregnancy.

The intensity and ramifications of emotional reactions to high-risk pregnancy make liaison work in this field interesting, challenging, and rewarding. The potential benefits include not only improved obstetric patient care, but also risk reduction in the mother-child relationship that follows.