Changes in weight and metabolic parameters during treatment with antipsychotics and metformin: do the data inform as to potential guideline development? A systematic review of clinical studies

Background: Changes in weight and metabolic parameters have been commonly reported in patients with schizophrenia. Metformin has been evaluated in clinical studies to prevent or reduce weight gain and changes in metabolic parameters in non‐diabetic subjects. We undertook a systematic review of the efficacy and safety of metformin in reducing weight gain and metabolic abnormalities in non‐diabetic subjects with schizophrenia or bipolar disorder taking antipsychotic medication to establish if these data could potentially drive guideline development. Methods: Medical databases were searched using terms including ‘antipsychotic’, ‘atypical antipsychotic agent’, ‘antipsychotic agents’, ‘antipsychotic‐drug’ and ‘metformin’ and ‘weight’. Studies reporting weight and/or metabolic outcomes in non‐diabetic subjects with schizophrenia and bipolar disorder were included regardless of methodological type and subject age. Results: Nine randomised double‐blind studies and two open cohort studies evaluating metformin and changes in weight in trials up to 16 weeks were identified. In all, 495 participants received antipsychotics (mostly olanzapine), and three studies were in subjects aged < 18 years. The adult studies predominantly utilised non‐Caucasian subjects with chronic schizophrenia. Weight and lifestyle intervention programmes were provided to all cohorts in eight studies, which confounded interpretation of the data. In ten studies, the addition of metformin to antipsychotic treatment was associated with either significantly attenuated weight gain or weight loss compared with control groups. Nine studies measured various glucose parameters. In four studies, subjects prescribed metformin had significantly improved glucose parameters relative to controls. The two studies of metformin in patients with first‐episode schizophrenia demonstrated the largest improvement in weight and glucose parameters. Conclusions: Metformin may have some value in reducing or preventing weight gain and changes in metabolic parameters during treatment with antipsychotic medication particularly in first‐episode psychosis; however, it has been predominantly studied short‐term and in non‐Caucasian populations. A number of new trials are due to report data 2009–2013 to aid definitive interpretation of the role of metformin. Further longer‐term studies are warranted before definitive guidelines can be established.     

Marine ��-3 Fatty Acid Intake: Associations with cardiometabolic risk and response to weight loss intervention in the Look AHEAD (Action for Health in Diabetes) study

OBJECTIVE

To examine usual marine ω-3 fatty acid (mO-3FA) intake in individuals with diabetes; its association with adiposity, lipid, and glucose control; and its changes with behavioral lifestyle intervention for weight loss.

RESEARCH DESIGN AND METHODS

Cross-sectional and 1-year longitudinal analyses were performed on 2,397 Look AHEAD (Action for Health in Diabetes) participants. Look AHEAD is a cardiovascular outcome trial evaluating the effects of intensive lifestyle intervention for weight loss in overweight/obese subjects with type 2 diabetes.

RESULTS

Baseline mO-3FA intake was 162 ± 138 mg/day. It was inversely associated with triglycerides (β = −0.41, P < 0.001) and weakly with HDL (β = 4.14, P = 0.050), after multiple covariate adjustment. One-year mO-3FA and fried/sandwich fish intake decreased with intensive lifestyle intervention (P < 0.001).

CONCLUSIONS

mO-3FA intake in Look AHEAD participants was low but associated favorably with lipids. These results encourage investigation on the potential benefits of increasing mO-3FA intake in lifestyle interventions for weight loss in individuals with diabetes.Observational studies have suggested that marine ω-3 fatty acid (mO-3FA) intake may decrease coronary atherosclerosis progression in subjects with diabetes (1). However, only a fraction of participants in cardiovascular event studies have had diabetes. Concerns that high-dose mO-3FAs may worsen glucose control have reduced enthusiasm for their use in diabetes (2). Little is known regarding usual dietary mO-3FA intake and its association with metabolic disturbances in diabetes, and much less is known about the effects of weight loss interventions on mO-3FA consumption.     

Adding modeled speech-generating device use to a naturalistic language intervention facilitates generalized communicative spoken utterances immediately after treatment and generalized gains on declarative use 12 weeks after treatment ends in children with ASD who began treatment in the “word combination” stage

This review provides a summary and appraisal commentary on the treatment review by Kasari, C., Kaiser, A., Goods, K., Nietfeld, J., Mathy, P., Landa, R., Murphy, S., & Almirall, D. (2014). Communication interventions for minimally-verbal children with autism: A sequential multiple assignment randomization trial. Journal of the American Academy of Child & Adolescent Psychiatry, 53, 635–646.

Funding: This study was funded by Autism Speaks. Authors reported receiving support from the Health Resources and Services Administration, the National Institutes of Health, Autism Speaks, the Institute of Education Sciences, the Centers for Disease Control and Prevention, the Simons Foundation Autism Research Initiative, and Ride On for Autism. Drs. Kasari and Kaiser are authors of the blended JASPER-EMT model.     

A 58‐year‐old lady presented as an emergency with right upper quadrant pain and loss of 5 stones in weight. What does the X‐ray show?

Renal cell cancers are among the great mimics in surgery as they present with myriad symptoms unrelated to the renal cancer. This patient also interestingly had an incidental finding of porcelain gall bladder.     

Which medical device and/or which local treatment are to be used,as of 2012, in patients with infected pressure sore? Developing French guidelines for clinical practice

IntroductionTaking care of a patient with an infected pressure sore necessitates a diagnosis allowing for a suitable treatment strategy.AimsTo choose the dressings and topical antimicrobial agents that can be used as of 2012 in treatment of an infected pressure sore.MethodsA systematic review of the literature with queries to the databases Pascal Biomed, PubMed and Cochrane Library from 2000 through 2010.ResultsDiagnosis of local infection is essentially clinical. It is subsequently difficult to destroy and/or permeabilize biofilm by means of mechanical wound debridement. Application of an antimicrobial product and a disinfectant solution are of utmost importance in this respect.DiscussionThe studies do not demonstrate that one topical product is better than another in wound cleaning. The papers recommending antimicrobial topics lead to the conclusion that they may be interesting, but show little clinical evidence of their beneficial effects. Dressings including silver, iodine, polyhexamethylene biguanide (PHMB) and negative pressure wound therapy could likewise be of interest, but once again, existing studies present only a low level of evidence (Grade C).ConclusionLocal antimicrobial treatment can be used when there are signs of local infection (Grade C). Systemic antibiotic treatment is to be used when there are general medical signs of infection (Grade B).     

Efficacy and tolerability of intranasal fentanyl spray 50 to 200 μg for breakthrough pain in patients with cancer: A phase III,multinational, randomized,double-blind,placebo-controlled,crossover trial with a 10-month,open-label extension treatment period

Objective: This trial investigated the efficacy and long-term tolerability of intranasal fentanyl spray (INFS) 50 to 200 μg in the treatment of breakthrough pain in opioid-tolerant patients with cancer.Methods: This Phase III, double-blind, randomized, placebo-controlled, crossover trial was conducted at pain centers, anesthesiology departments, palliative care units, and oncology clinics in Austria, Denmark, France, Germany, and Poland. Eligible patients were adults with cancer receiving a stable dose of long-term opioid treatment for the control of background pain. Patients were treated at home with their effective dose of INFS (50, 100, or 200 μg) or inactive spray (placebo) in a randomized sequence for 3 weeks, followed by a 10-month, open-label tolerability phase during which they received their effective dose of INFS. Throughout the study, patients were allowed to use their usual rescue medication, which was recorded in patient diaries. The primary efficacy end point was the pain intensity difference at 10 minutes after study drug administration (PID₁₀), as assessed using an 11-point numeric rating scale (0 = no pain to 10 = worst pain imaginable). An effect size of 0.5 for PID was considered clinically relevant. The rate of response, defined as PID₁₀ >2, was also assessed. Adverse events (AEs) were recorded in patient diaries during the efficacy period and reported in monthly clinic visits and follow-up weekly telephone contacts during the extension period.Results: In all, 120 patients were enrolled and achieved an effective dose; 113 were randomized and 111 were included in the intent-to-treat analysis set (56 men, 55 women; mean [SD] age, 60.6 [9.45] years; mean weight, 70.3 kg [men] and 65.3 kg [women]; white race, 107 [96.4%]; INFS 50 μg, 18; INFS 100 μg, 48; INFS 200 μg, 45; placebo, 110). PID₁₀ with INFS was 2-fold that with placebo (adjusted means, 2.36 vs 1.10; adjusted difference, 1.26 [greater than the clinically relevant difference of 0.5]; P < 0.001). Additional analysis revealed that the mean response rate with all 3 doses of INFS was 51.1% versus 20.9% with placebo. The prevalence of AEs was 22/111 (19.8%) during the efficacy period, during which the most frequently reported AEs were nausea (5 [4.5%]) and vertigo (2 [1.8%]). No serious AEs were considered related to the study drugs. In all, 108 patients entered the extension period, with a mean duration of exposure to INFS of 134.9 days. Progression of underlying malignant disease was the most common AE reported during this period (55 [50.9%]); this event was not considered treatment related.Conclusions: In these opioid-tolerant patients with cancer, INFS at doses of 50, 100, and 200 μg was associated with an onset of activity at 10 minutes and effective treatment of breakthrough pain compared with placebo. All doses were generally well tolerated and clinically efficacious.