Milnacipran is safe and effective for the treatment of multiple symptoms of FM.

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Objective. To assess the efficacy and safety of milnacipran at a dosage of 100 mg/day (50 mg twice daily) for monotherapy treatment of fibromyalgia.Methods. A double-blind, placebo-controlled trial was performed to assess 1,025 patients with fibromyalgia who were randomized to receive milnacipran 100 mg/day (n ‫؍‬ 516) or placebo (n ‫؍‬ 509). Patients underwent 4-6 weeks of flexible dose escalation followed by 12 weeks of stable-dose treatment. Two composite responder definitions were used as primary end points to classify the response to treatment. The 2-measure composite response required achievement of >30% improvement from baseline in the pain score and a rating of "very much improved" or "much improved" on the Patient's Global Impression of Change (PGIC) scale. The 3-measure composite response required satisfaction of these same 2 improvement criteria for pain and global status as well as improvement in physical function on the Short Form 36 (SF-36) physical component summary (PCS) score.Results. After 12 weeks of stable-dose treatment, a significantly greater proportion of milnacipran-treated patients compared with placebo-treated patients showed clinically meaningful improvements, as evidenced by the proportion of patients meeting the 2-measure composite responder criteria (P < 0.001 in the baseline observation carried forward [BOCF] analysis) and 3-measure composite responder criteria (P < 0.001 in the BOCF). Milnacipran-treated patients also demonstrated significantly greater improvements from baseline on multiple secondary outcomes, including 24-hour and weekly recall pain score, PGIC score, SF-36 PCS and mental component summary scores, average pain severity score on the Brief Pain Inventory, Fibromyalgia Impact Questionnaire total score (all P < 0.001 versus placebo), and Multidimensional Fatigue Inventory total score (P ‫؍‬ 0.036 versus placebo). Milnacipran was well tolerated by most patients, with nausea being the most commonly reported adverse event (placebo-adjusted rate of 15.8%).Conclusion. Milnacipran administered at a dosage of 100 mg/day improved pain, global status, fatigue, and physical and mental function in patients with fibromyalgia.

Acquisition of multiresistant A. baumannii was likely multifactorial, related to environmental contamination and contact with transiently colonized healthcare providers. Control measures addressing these potential sources of multiresistant A. baumannii were successful in terminating the outbreak. Ongoing surveillance and continued attention to hand hygiene and adequate environmental cleaning are essential to prevent recurrent outbreaks due to antibiotic-resistant bacteria in burn units.

In addition to confirming that milnacipran safely and effectively improves the multiple symptoms of fibromyalgia, these data indicate that milnacipran provides 1-year durable efficacy in this patient population.

Clinical trials on the treatment of pain syndromes have adopted Patient Global Impression of Change (PGIC) as a primary outcome. However, little is known about how change in clinical status influences these ratings. The present study examined relationships between changes in pain, depressed mood, physical functioning, vitality, sleep disturbance, cognitive complaints, and PGIC ratings among 1260 participants with fibromyalgia (FM) who completed one of two trials examining the safety and efficacy of milnacipran. Many of the relationships between change in clinical status and PGIC ratings were stronger among persons who rated themselves as improved (responders) versus those reporting no change or a worsening of their condition (non-responders). Among non-responders, simultaneous regression analysis revealed that greater degrees of depressed mood and pain, and poorer physical function were significantly associated with worse PGIC ratings. Among responders, improvements in pain were significantly associated with better PGIC ratings, along with improvements in vitality, sleep, physical function, and cognitive complaints. These findings underscore the complexity of global ratings in FM patients, and suggest the association between clinical status and PGIC ratings varies as a function of perceived treatment response. Several domains were associated with PGIC ratings, highlighting the need to assess multiple outcomes in clinical trials of treatments for FM.

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Objective: Abnormal glutamatergic neurotransmission is implicated in the pathophysiology of autism spectrum disorder (ASD). In this study, the safety, tolerability, and efficacy of the glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist memantine (once-daily extended-release [ER]) were investigated in children with autism in a randomized, placebo-controlled, 12 week trial and a 48 week open-label extension.Methods: A total of 121 children 6–12 years of age with Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR)-defined autistic disorder were randomized (1:1) to placebo or memantine ER for 12 weeks; 104 children entered the subsequent extension trial. Maximum memantine doses were determined by body weight and ranged from 3 to 15 mg/day.Results: There was one serious adverse event (SAE) (affective disorder, with memantine) in the 12 week study and one SAE (lobar pneumonia) in the 48 week extension; both were deemed unrelated to treatment. Other AEs were considered mild or moderate and most were deemed not related to treatment. No clinically significant changes occurred in clinical laboratory values, vital signs, or electrocardiogram (ECG). There was no significant between-group difference on the primary efficacy outcome of caregiver/parent ratings on the Social Responsiveness Scale (SRS), although an improvement over baseline at Week 12 was observed in both groups. A trend for improvement at the end of the 48 week extension was observed. No improvements in the active group were observed on any of the secondary end-points, with one communication measure showing significant worsening with memantine compared with placebo (p = 0.02) after 12 weeks.Conclusions: This trial did not demonstrate clinical efficacy of memantine ER in autism; however, the tolerability and safety data were reassuring. Our results could inform future trial design in this population and may facilitate the investigation of memantine ER for other clinical applications.