MDLinx - New Articles

The Effect of Pharmacotherapy on Suicide Rates in Bipolar Patients
CNS Neuroscience & Therapeutics, 08/02/11
Rihmer Z et al. – Several clinical trials provide evidence that effective acute and long–term treatment of bipolar depression provides a strong protection against suicide, suicide attempts, and probably against other complications of this disorder. Current major mood disorder is the most important risk factor of suicide, and bipolar II patients carry the highest risk. In bipolar patients suicidal behavior is most likely to occur during pure or mixed depressive episodes. Since bipolar disorder is a highly recurrent illness, adequate long–term pharmacotherapy is needed to prevent suicidal behavior.





Pregabalin augmentation in treatment-resistant obsessive-compulsive disorder
International Clinical Psychopharmacology, 06/16/11
Oulis P et al. – Despite the several limitations of the study, its results suggest that adjunctive pregabalin might be a safe and efficacious new augmentation agent in the treatment of drug–resistant obsessive?compulsive disorder (OCD). The authors hypothesize that pregabalin's mechanism of action in OCD might consist in its inhibition of glutamatergic neurotransmission.





Life expectancy among persons with schizophrenia or bipolar affective disorder
Schizophrenia Research, 07/12/11
Laursen TM et al. ? Life-expectancy was much shorter in persons with schizophrenia or bipolar disorder. Excess mortality from physical diseases and medical conditions exerts a far greater influence on the curtailed life-expectancy, when compared against the impact of death by external causes. Methods
  • Life-expectancy was calculated by means of survival analysis techniques using entire Danish population as a cohort
  • Life-expectancy 18.7years shorter for schizophrenic men compared to men in general population
  • Corresponding numbers for schizophrenic women 16.3years, for bipolar men 13.6years, and for bipolar women 12.1years





Waist circumference, abdominal obesity, and depression among overweight and obese U.S. adults: National Health and Nutrition Examination Survey 2005-2006
BMC Psychiatry, 08/12/11
Zhao G et al. ? Among overweight and obese U.S. adults, waist circumference or abdominal obesity was significantly associated with increased likelihoods of having major depressive symptoms or moderate-to-severe depressive symptoms. Thus, mental health status should be monitored and evaluated in adults with abdominal obesity, particularly in those who are overweight. Methods
  • Cross-sectional, nationally representative sample from 2005-2006 National Health and Nutrition Examination Survey was used
  • Analyzed data from 2,439 U.S. adults (1,325 men and 1,114 nonpregnant women) aged [greater than or equal to]20 years who were either overweight or obese with BMI of [greater than or equal to]25.0 kg/m2
  • Abdominal obesity defined as waist circumference of >102 cm for men and >88 cm for women
  • Depressive symptoms (defined as having major depressive symptoms or moderate-to-severe depressive symptoms) were assessed by Patient Health Questionnaire-9 diagnostic algorithm
  • Prevalence and ORs with 95% CIs for having major depressive symptoms and moderate-to-severe depressive symptoms were estimated using logistic regression analysis
  • After multivariate adjustment for demographics and lifestyle factors, waist circumference was significantly associated with both major depressive symptoms (OR: 1.03, 95% CI: 1.01-1.05) and moderate-to-severe depressive symptoms (OR: 1.02, 95% CI: 1.01-1.04), and adults with abdominal obesity were significantly more likely to have major depressive symptoms (OR: 2.18, 95% CI: 1.35-3.59) or have moderate-to-severe depressive symptoms (OR: 2.56, 95% CI: 1.34-4.90) than those without
  • These relationships persisted after further adjusting for coexistence of multiple chronic conditions and persisted in participants who were overweight (BMI: 25.0-<30.0 kg/m2) when stratified analyses were conducted by BMI status





Insight in schizophrenia and risk of suicide: a systematic update
Comprehensive Psychiatry, 08/15/11
Lopez–Morinigo JD et al. – There is little evidence to support the suggestion that insight may represent a risk factor for suicide in patients with schizophrenia. If there is an association between such risk and insight, it appears to be mediated by other variables such as depression and, above all, hopelessness. Methods
  • Articles assessing insight and suicidality in patients with schizophrenia spectrum disorders published between 1977 and 2010 were reviewed.
  • A MEDLINE search strategy was used to identify studies using keywords.
  • Application of meta–analytic techniques to selected studies was not possible because of important methodological differences between them.
  • Fifteen studies met predetermined selection criteria.
  • Ten failed to demonstrate a positive association between insight and risk for suicid




Aspirin failure in patients presenting with acute cerebrovascular ischaemia
Thrombosis and Haemostasis, 08/03/11

Halawani SHM et al. – Incomplete platelet inhibition is common around the time of acute cerebrovascular ischaemic events in patients prescribed aspirin. Up to 50% of these observations appear due to incomplete adherence to aspirin therapy. Methods
  • The authors studied 51 adults admitted with suspected ischaemic stroke and already prescribed daily aspirin.
  • Within 48 hours (h) of onset, blood and urine samples were collected to assess platelet aggregation, activation and aspirin response by a range of methods.
  • All tests were then repeated on a second sample taken 24 h after witnessed administration of 75 mg or 150 mg aspirin.
  • At entry to the study, incomplete response to aspirin, measured by arachidonic acid (AA)–stimulated platelet aggregation, was found in 43% of patients.
  • Following in–hospital aspirin administration, there was a significant decrease in AA–aggregation (p=0.001) suggesting poor adherence to therapy prior to admission.
  • However, residual aggregation (10?15%) persisted in 11 subjects ? suggesting alternative causes.
  • In incomplete responders on admission, platelet aggregation with adenosine diphosphate (ADP) was significantly higher compared with responders (p<0.05) but there were no significant differences in collagen aggregation, platelet fibrinogen binding or P–selectin expression, plasma von Willebrand factor, fibrinogen, high–sensitivity C–reactive protein, or the urinary metabolite, 11–dehydro–TxB2.





Sertraline or mirtazapine for depression in dementia (HTA-SADD): A randomised, multicentre, double-blind, placebo-controlled trial
The Lancet - Early Online Publication, 07/25/11
Banerjee S et al. ?Depression is common in dementia but the evidence base for appropriate drug treatment is sparse and equivocal. The authors aimed to assess efficacy and safety of two of the most commonly prescribed drugs, sertraline and mirtazapine, compared with placebo. Because of the absence of benefit compared with placebo and increased risk of adverse events, the present practice of use of these antidepressants, with usual care, for first-line treatment of depression in Alzheimer's disease should be reconsidered. Methods
  • We undertook the parallel-group, double-blind, placebo-controlled, Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) trial in participants from old-age psychiatry services in nine centres in England
  • Participants were eligible if they had probable or possible Alzheimer's disease, depression (lasting &ge4 weeks), and a Cornell scale for depression in dementia (CSDD) score of 8 or more
  • Participants were ineligible if they were clinically critical (eg, suicide risk), contraindicated to study drugs, on antidepressants, in another trial, or had no carer
  • Clinical trials unit at King's College London (UK) randomly allocated participants with computer-generated block randomisation sequence, stratified by centre, with varying block sizes, in a 1:1:1 ratio to receive sertraline (target dose 150 mg per day), mirtazapine (45 mg), or placebo (control group), all with standard care
  • Primary outcome reduction in depression (CSDD score) at 13 weeks (outcomes to 39 weeks were also assessed), assessed with mixed linear-regression model adjusted for baseline CSDD, time, and treatment centre
  • Decreases in depression scores at 13 weeks did not differ between 111 controls and 107 participants allocated to receive sertraline (mean difference 1�17, 95% CI -0�23 to 2�58; p=0�10) or mirtazapine (0�01, -1�37 to 1�38; p=0�99), or between participants in mirtazapine and sertraline groups (1�16, -0�25 to 2�57; p=0�11); these findings persisted to 39 weeks
  • Fewer controls had AE (29 of 111 [26%]) than did participants in sertraline group (46 of 107, 43%; p=0�010) or mirtazapine group (44 of 108, 41%; p=0�031), and fewer serious AE rated as severe (p=0�003)
  • 5 patients in every group died by week 39





Aripiprazole versus placebo for schizophrenia
Cochrane Reviews, 08/15/11
Belgamwar RB et al. – Aripiprazole may be effective for the treatment of schizophrenia. Aripiprazole has a lower risk of raised prolactin and prolongation of the QTc interval. Methods
  • The authors searched the Cochrane Schizophrenia Group Trials Register (January 2008) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO.
  • The authors included all randomised trials comparing aripiprazole with placebo in people with schizophrenia or schizophrenia–like psychosis.
  • The authors extracted data independently.
  • For dichotomous data the authors calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention–to–treat basis based on a fixed–effect model.
  • The authors calculated numbers needed to treat/harm (NNT/NNH) where appropriate.
  • For continuous data, the authors calculated mean differences (MD) again based on a fixed–effect model.
  • Despite the fact that 2585 people participated in nine randomised aripiprazole studies, the authors were unable to extract any usable data on death, service outcomes, general functioning, behaviour, engagement with services, satisfaction with treatment; economic outcomes or cognitive functioning.
  • In general, study attrition was very large for all studies over four weeks' duration.
  • There was high attrition in most of the included studies.
  • Fewer people left the aripiprazole group compared with those in the placebo group (n = 2585, 9 RCTs, RR 0.73 CI 0.60 to 0.87).
  • Compared with placebo, aripiprazole significantly decreased relapse in both the short (n = 310, 1 RCT, RR 0.59 CI 0.45 to 0.77) and medium term (n = 310, 1 RCT, RR 0.66 CI 0.53 to 0.81).
  • It also produced better compliance with study protocol (n = 2275, 8 RCTs, RR 0.74 CI 0.59 to 0.93).
  • Aripiprazole may decrease prolactin levels below those expected from placebo (n = 305, 2 RCT, RR 0.21 CI 0.11 to 0.37).
  • Insomnia (~23%) and headaches (~15%) were commonly reported in both groups, with no significant difference.



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