Which antidepressants have demonstrated superior efficacy? A review of the evidence

A review of published evidence of superior efficacy of a particular antidepressant in major depressive disorder may assist clinicians in making considered treatment choices. To identify such candidates, an international group of experts met to assess published evidence (identified through searches in Medline and Embase databases and discussions with experts in the field) from randomized, controlled trials and meta-analyses comparing two antidepressants under conditions of fair comparison. Criteria were defined to judge the strength of evidence. Two pivotal studies in moderate-to-severe major depressive disorder that demonstrate superiority on the primary efficacy measure, or alternatively one pivotal study supported by consistent results from meta-analyses, was considered to constitute evidence for definite superiority. Three antidepressants met these criteria: clomipramine, venlafaxine, and escitalopram. Three antidepressants were found to have probable superiority: milnacipran, duloxetine, and mirtazapine. Only escitalopram was found to have definite superiority in the treatment of severe depression; probable superiority was identified for venlafaxine and possible superiority for milnacipran and clomipramine. This review of published data found evidence that only a very few antidepressants are shown to be more effective than other

Bacterial Deposition of Gold on Hair: Archeological, Forensic and Toxicological Implications

Trace metal analyses in hair are used in archeological, forensic and toxicological investigations as proxies for metabolic processes. We show metallophilic bacteria mediating the deposition of gold (Au), used as tracer for microbial activity in hair post mortem after burial, affecting results of such analyses. Methodology/Principal Findings Human hair was incubated for up to six months in auriferous soils, in natural soil columns (Experiment 1), soils amended with mobile Au(III)-complexes (Experiment 2) and the Au-precipitating bacterium Cupriavidus metallidurans (Experiment 3), in peptone-meat-extract (PME) medium in a culture of C. metallidurans amended with Au(III)-complexes (Experiment 4), and in non-auriferous soil (Experiment 5). Hair samples were analyzed using scanning electron microscopy, confocal microscopy and inductively coupled plasma-mass spectrometry. In Experiments 1–4 the Au content increased with time (P = 0.038). The largest increase was observed in Experiment 4 vs. Experiment 1 (mean = 1188 vs. 161 µg Kg−1, Fisher's least significance 0.001). The sulfur content, a proxy for hair metabolism, remained unchanged. Notably, the ratios of Au-to-S increased with time (linear trend P = 0.02) and with added Au and bacteria (linear trend, P = 0.005), demonstrating that larger populations of Au-precipitating bacteria and increased availability of Au increased the deposition of Au on the hair. Conclusion/Significance Interactions of soil biota with hair post mortem may distort results of hair analyses, implying that metal content, microbial activities and the duration of burial must be considered in the interpretation of results of archeological, forensic and toxicological hair analyses, which have hitherto been proxies for pre-mortem metabolic processesGenevieve Phillips, Frank Reith, Clifford Qualls, Abdul-Mehdi Ali, Mike Spilde and Otto Appenzelle

Influence of family and friend smoking on intentions to smoke and smoking-related attitudes and refusal self-efficacy among 9-10 year old children from deprived neighbourhoods: a cross-sectional study.

BACKGROUND: Smoking often starts in early adolescence and addiction can occur rapidly. For effective smoking prevention there is a need to identify at risk groups of preadolescent children and whether gender-specific intervention components are necessary. This study aimed to examine associations between mother, father, sibling and friend smoking and cognitive vulnerability to smoking among preadolescent children living in deprived neighbourhoods. METHODS: Cross-sectional data was collected from 9-10 year old children (n =1143; 50.7% girls; 85.6% White British) from 43 primary schools in Merseyside, England. Children completed a questionnaire that assessed their smoking-related behaviour, intentions, attitudes, and refusal self-efficacy, as well as parent, sibling and friend smoking. Data for boys and girls were analysed separately using multilevel linear and logistic regression models, adjusting for individual cognitions and school and deprivation level. RESULTS: Compared to girls, boys had lower non-smoking intentions (P = 0.02), refusal self-efficacy (P = 0.04) and were less likely to agree that smoking is 'definitely' bad for health (P < 0.01). Friend smoking was negatively associated with non-smoking intentions in girls (P < 0.01) and boys (P < 0.01), and with refusal self-efficacy in girls (P < 0.01). Sibling smoking was negatively associated with non-smoking intentions in girls (P < 0.01) but a positive association was found in boys (P = 0.02). Boys who had a smoking friend were less likely to 'definitely' believe that the smoke from other people's cigarettes is harmful (OR 0.57, 95% CI: 0.35 to 0.91, P = 0.02). Further, boys with a smoking friend (OR 0.38, 95% CI: 0.21 to 0.69, P < 0.01) or a smoking sibling (OR 0.45, 95% CI: 0.21 to 0.98) were less likely to 'definitely' believe that smoking is bad for health. CONCLUSION: This study indicates that sibling and friend smoking may represent important influences on 9-10 year old children's cognitive vulnerability toward smoking. Whilst some differential findings by gender were observed, these may not be sufficient to warrant separate prevention interventions. However, further research is needed

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

General practitioners' beliefs about effectiveness and intentions to prescribe smoking cessation medications: qualitative and quantitative studies

BACKGROUND: General practitioners' (GPs) negative beliefs about nicotine dependence medications may act as barriers to prescribing them. METHODS: Study1: Twenty-five GPs from 16 practices across London were interviewed in this qualitative study. Framework analysis was used to identify key themes. Study 2: A convenience sample of 367 GPs completed an internet-based survey. Path-analysis was used to examine the relations between beliefs and intentions to prescribe smoking cessation medications. RESULTS: Study 1: Whilst nicotine replacement therapy (NRT) and bupropion were generally perceived as effective and cost-effective, the effectiveness of NRT was seen as critically dependent on behavioural support for smoking cessation. This dependence appeared to be influenced by perceptions that without support smokers would neglect psychological aspects of smoking and use NRT incorrectly. GPs perceived bupropion as dangerous and were concerned about its side-effects. Study 2: GPs' beliefs had medium (NRT, f(2 )= .23) to large (bupropion, f(2)=.45; NRT without support, f(2)=.59) effects on their intentions to prescribe medications. Beliefs about effectiveness of NRT and bupropion and the perceived danger of bupropion were the key predictors of intentions to prescribe NRT and bupropion, respectively. Beliefs about neglecting psychological aspects of smoking and incorrect use had indirect effects on intentions to prescribe NRT without support, operating via beliefs about effectiveness. CONCLUSION: GPs vary in their beliefs about the effectiveness and safety of smoking cessation medications. Their intentions to prescribe these medications vary in line with these beliefs. Interventions aimed at increasing the likelihood with which GPs prescribe these medications may be more effective if they addressed these beliefs

Benzodiazepine use among adults residing in the urban settlements of Karachi, Pakistan: A cross sectional study

<p>Abstract</p> <p>Background</p> <p>There are hardly any studies carried out in Pakistan on the usage of benzodiazepines at the level of community. This research was aimed to determine the frequency of benzodiazepine use, along with its associations with socio-demographic and clinical characteristics among community dwelling adults, residing in two urban settlements of Karachi, Pakistan.</p> <p>Methods</p> <p>We performed a cross sectional study from August 2008 to December 2009, in 2 areas of Karachi, namely Garden and Sultanabad. We followed the systematic sampling strategy to randomly select the households, with an adult of either sex and of age 18 years or more. Data collection was carried out through interview, using a pre-tested questionnaire, with items on socio-demographic position, medical history and benzodiazepine use. Student's t-test and χ²test was employed to determine the associations between socio-demographic and clinical characteristics, and their relationship with benzodiazepine use was determined using applied logistic regression.</p> <p>Results</p> <p>The overall percentage of benzodiazepine consumption was estimated to be 14%. There were significantly more benzodiazepine users in the peri-urban Sultanabad community to the urban community of Garden (p-value = 0.001). The mean age (± SD) for users was 51.3 (± 15.6) years compared to 37.1 (± 14.4) years among non-users. Bromazepam was the most widely used benzodiazepine (29%); followed by diazepam, with a median duration on primary use being 144 weeks (IQR = 48-240). The adjusted logistic regression model revealed that increasing age, location, female sex, unemployment and psychiatric consultation were associated with increased likelihood of benzodiazepine use.</p> <p>Conclusion</p> <p>We believe the unregulated over-the-counter sales of benzodiazepines and social conditions might be playing a role in this high consumption of benzodiazepines in the community.</p

Relapse according to antipsychotic treatment in schizophrenic patients: a propensity-adjusted analysis

<p>Abstract</p> <p>Objective</p> <p>To compare the rate of relapse as a function of antipsychotic treatment (monotherapy vs. polypharmacy) in schizophrenic patients over a 2-year period.</p> <p>Methods</p> <p>Using data from a multicenter cohort study conducted in France, we performed a propensity-adjusted analysis to examine the association between the rate of relapse over a 2-year period and antipsychotic treatment (monotherapy vs. polypharmacy).</p> <p>Results</p> <p>Our sample consisted in 183 patients; 50 patients (27.3%) had at least one period of relapse and 133 had no relapse (72.7%). Thirty-eight (37.7) percent of the patients received polypharmacy. The most severely ill patients were given polypharmacy: the age at onset of illness was lower in the polypharmacy group (p = 0.03). Patients that received polypharmacy also presented a higher general psychopathology PANSS subscore (p = 0.04) but no statistically significant difference was found in the PANSS total score or the PANSS positive or negative subscales. These patients were more likely to be given prescriptions for sedative drugs (p < 0.01) and antidepressant medications (p = 0.03). Relapse was found in 23.7% of patients given monotherapy and 33.3% given polypharmacy (p = 0.16). After stratification according to quintiles of the propensity score, which eliminated all significant differences for baseline characteristics, antipsychotic polypharmacy was not statistically associated with an increase of relapse: HR = 1.686 (0.812; 2.505).</p> <p>Conclusion</p> <p>After propensity score adjustment, antipsychotic polypharmacy is not statistically associated to an increase of relapse. Future randomised studies are needed to assess the impact of antipsychotic polypharmacy in schizophrenia.</p

Dopaminergic Influences on Emotional Decision Making in Euthymic Bipolar Patients

We recently reported that the D2/D3 agonist pramipexole may have pro-cognitive effects in euthymic patients with bipolar disorder (BPD); however, the emergence of impulse-control disorders has been documented in Parkinson\u27s disease (PD) after pramipexole treatment. Performance on reward-based tasks is altered in healthy subjects after a single dose of pramipexole, but its potential to induce abnormalities in BPD patients is unknown. We assessed reward-dependent decision making in euthymic BPD patients pre- and post 8 weeks of treatment with pramipexole or placebo by using the Iowa Gambling Task (IGT). The IGT requires subjects to choose among four card decks (two risky and two conservative) and is designed to promote learning to make advantageous (conservative) choices over time. Thirty-four BPD patients completed both assessments (18 placebo and 16 pramipexole). Baseline performance did not differ by treatment group (F = 0.63; p = 0.64); however, at week 8, BPD patients on pramipexole demonstrated a significantly greater tendency to make increasingly high-risk, high-reward choices across the five blocks, whereas the placebo group\u27s pattern was similar to that reported in healthy individuals (treatment x time x block interaction,