Friday, June 3, 2016

June 2016

Prenatal Nicotine Exposure and Risk of Schizophrenia Among Offspring in a National Birth Cohort 


The American Journal of Psychiatry

Abstract

Objective:
Cigarette smoking during pregnancy is a major public health problem leading to adverse health outcomes and neurodevelopmental abnormalities among offspring. Its prevalence in the United States and Europe is 12%–25%. This study examined the relationship between prenatal nicotine exposure (cotinine level) in archived maternal sera and schizophrenia in offspring from a national birth cohort.

Method:
The authors conducted a population-based nested case-control study of all live births in Finland from 1983 to 1998. Cases of schizophrenia in offspring (N=977) were identified from a national registry and matched 1:1 to controls on date of birth, sex, and residence. Maternal serum cotinine levels were prospectively measured, using quantitative immunoassay, from early- to mid-gestation serum specimens archived in a national biobank.

Results:
A higher maternal cotinine level, measured as a continuous variable, was associated with an increased odds of schizophrenia (odds ratio=3.41, 95% confidence interval, 1.86–6.24). Categorically defined heavy maternal nicotine exposure was related to a 38% increased odds of schizophrenia. These findings were not accounted for by maternal age, maternal or parental psychiatric disorders, socioeconomic status, and other covariates. There was no clear evidence that weight for gestational age mediated the associations.

Conclusions:
To the authors’ knowledge, this is the first study of the relationship between a maternal smoking biomarker and schizophrenia. It provides the most definitive evidence to date that smoking during pregnancy is associated with schizophrenia. If replicated, these findings suggest that preventing smoking during pregnancy may decrease the incidence of schizophrenia.



Self-harm, Unintentional Injury, and Suicide in Bipolar Disorder During Maintenance Mood Stabilizer Treatment


JAMA Psychiatry

Abstract

Importance  
Self-harm is a prominent cause of morbidity in patients with bipolar disorder and is strongly associated with suicide. There is evolving evidence that lithium use may reduce suicidal behavior, in addition to concerns that the use of anticonvulsants may increase self-harm. Information is limited about the effects of antipsychotics when used as mood stabilizer treatment. Rates of unintentional injury are poorly defined in bipolar disorder, and understanding drug associations with this outcome may shed light on mechanisms for lithium’s potential antisuicidal properties through reduction in impulsive aggression.

Objective  
To compare rates of self-harm, unintentional injury, and suicide in patients with bipolar disorder who were prescribed lithium, valproate sodium, olanzapine, or quetiapine fumarate.

Design, Setting, and Participants  
This investigation was a propensity score (PS)–adjusted and PS-matched longitudinal cohort study in a nationally representative UK sample using electronic health records data collected between January 1, 1995, and December 31, 2013. Participants included all patients diagnosed as having bipolar disorder who were prescribed lithium, valproate, olanzapine, or quetiapine as maintenance mood stabilizer treatment.

Main Outcomes and Measures  
The primary outcome was any form of self-harm. Secondary outcomes were unintentional injury and suicide.

Results  
Of the 14 396 individuals with a diagnosis of BPD, 6671 were included in the cohort, with 2148 prescribed lithium, 1670 prescribed valproate, 1477 prescribed olanzapine, and 1376 prescribed quetiapine as maintenance mood stabilizer treatment. Self-harm rates were lower in patients prescribed lithium (205; 95% CI, 175-241 per 10 000 person-years at risk [PYAR]) compared with those prescribed valproate (392; 95% CI, 334-460 per 10 000 PYAR), olanzapine (409; 95% CI, 345-483 per 10 000 PYAR), or quetiapine (582; 95% CI, 489-692 per 10 000 PYAR). This association was maintained after PS adjustment (hazard ratio [HR], 1.40; 95% CI, 1.12-1.74 for valproate, olanzapine, or quetiapine vs lithium) and PS matching (HR, 1.51; 95% CI, 1.21-1.88). After PS adjustment, unintentional injury rates were lower for lithium compared with valproate (HR, 1.32; 95% CI, 1.10-1.58) and quetiapine (HR, 1.34; 95% CI, 1.07-1.69) but not olanzapine. The suicide rate in the cohort was 14 (95% CI, 9-21) per 10 000 PYAR. Although this rate was lower in the lithium group than for other treatments, there were too few events to allow accurate estimates.

Conclusions and Relevance  
Patients taking lithium had reduced self-harm and unintentional injury rates. This finding augments limited trial and smaller observational study results. It supports the hypothesis that lithium use reduces impulsive aggression in addition to stabilizing mood.



Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder


JAMA Psychiatry 

Abstract

Importance  
Limitations of current antidepressants highlight the need to identify novel treatments for major depressive disorder. A prior open trial found that a single session of whole-body hyperthermia (WBH) reduced depressive symptoms; however, the lack of a placebo control raises the possibility that the observed antidepressant effects resulted not from hyperthermia per se, but from nonspecific aspects of the intervention.

Objective  
To test whether WBH has specific antidepressant effects when compared with a sham condition and to evaluate the persistence of the antidepressant effects of a single treatment.

Design, Setting, and Participants  
A 6-week, randomized, double-blind study conducted between February 2013 and May 2015 at a university-based medical center comparing WBH with a sham condition. All research staff conducting screening and outcome procedures were blinded to randomization status. Of 338 individuals screened, 34 were randomized, 30 received a study intervention, and 29 provided at least 1 postintervention assessment and were included in a modified intent-to-treat efficacy analysis. Participants were medically healthy, aged 18 to 65 years, met criteria for major depressive disorder, were free of psychotropic medication use, and had a baseline 17-item Hamilton Depression Rating Scale score of 16 or greater.

Interventions  
A single session of active WBH vs a sham condition matched for length of WBH that mimicked all aspects of WBH except intense heat.

Main Outcomes and Measures  
Between-group differences in postintervention Hamilton Depression Rating Scale scores.

Results  
The mean (SD) age was 36.7 (15.2) years in the WBH group and 41.47 (12.54) years in the sham group. Immediately following the intervention, 10 participants (71.4%) randomized to sham treatment believed they had received WBH compared with 15 (93.8%) randomized to WBH. When compared with the sham group, the active WBH group showed significantly reduced Hamilton Depression Rating Scale scores across the 6-week postintervention study period (WBH vs sham; week 1: −6.53, 95% CI, −9.90 to −3.16, P < .001; week 2: −6.35, 95% CI, −9.95 to −2.74, P = .001; week 4: −4.50, 95% CI, −8.17 to −0.84, P = .02; and week 6: −4.27, 95% CI, −7.94 to −0.61, P = .02). These outcomes remained significant after evaluating potential moderating effects of between-group differences in baseline expectancy scores. Adverse events in both groups were generally mild.

Conclusions and Relevance  
Whole-body hyperthermia holds promise as a safe, rapid-acting, antidepressant modality with a prolonged therapeutic benefit.



FDA warns about rare but serious skin reactions with mental health drug olanzapine (Zyprexa, Zyprexa Zydis, Zyprexa Relprevv, and Symbyax)


US FDA
  
The U.S. Food and Drug Administration (FDA) is warning that the antipsychotic medicine olanzapine can cause a rare but serious skin reaction that can progress to affect other parts of the body. We are adding a new warning to the drug labels for all olanzapine-containing products that describes this severe condition known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

Health care professionals should immediately stop treatment with olanzapine if DRESS is suspected. When prescribing the medicine, explain the signs and symptoms of severe skin reactions to your patients and tell them when to seek immediate medical care.

Olanzapine is an antipsychotic medicine used to treat mental health disorders schizophrenia and bipolar disorder. It can decrease hallucinations, in which people hear or see things that do not exist, and other psychotic symptoms such as disorganized thinking. Olanzapine is available under the brand names Zyprexa, Zyprexa Zydis, Zyprexa Relprevv, and Symbyax, and also as generics.

DRESS may start as a rash that can spread to all parts of the body. It can include fever and swollen lymph nodes and a swollen face. It causes a higher-than-normal number of infection-fighting white blood cells called eosinophils that can cause inflammation, or swelling. DRESS can result in injury to organs including the liver, kidneys, lungs, heart, or pancreas, and can lead to death.

A search of the FDA Adverse Event Reporting System (FAERS) database identified 23 cases of DRESS reported with olanzapine worldwide since 1996, when the first olanzapine-containing product was approved. FAERS includes only reports submitted to FDA, so there are likely to be additional cases about which we are unaware. One patient taking olanzapine experienced DRESS and died; however, this patient was taking multiple medicines that could also have contributed to death (see Data Summary).

Read More: http://www.fda.gov/


FDA approves first drug to treat hallucinations and delusions associated with Parkinson’s disease 


US FDA

The U.S. Food and Drug Administration today approved Nuplazid (pimavanserin) tablets, the first drug approved to treat hallucinations and delusions associated with psychosis experienced by some people with Parkinson’s disease.

Hallucinations or delusions can occur in as many as 50 percent of patients with Parkinson’s disease at some time during the course of their illness. People who experience them see or hear things that are not there (hallucinations) and/or have false beliefs (delusions). The hallucinations and delusions experienced with Parkinson’s disease are serious symptoms, and can lead to thinking and emotions that are so impaired that the people experiencing them may not relate to loved ones well or take appropriate care of themselves.  

“Hallucinations and delusions can be profoundly disturbing and disabling,” said Mitchell Mathis, M.D., director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research. “Nuplazid represents an important treatment for people with Parkinson’s disease who experience these symptoms.”

Read More: http://www.fda.gov/


FDA warns about new impulse-control problems associated with mental health drug aripiprazole (Abilify, Abilify Maintena, Aristada)


US FDA

The U.S. Food and Drug Administration (FDA) is warning that compulsive or uncontrollable urges to gamble, binge eat, shop, and have sex have been reported with the use of the antipsychotic drug aripiprazole (Abilify, Abilify Maintena, Aristada, and generics). These uncontrollable urges were reported to have stopped when the medicine was discontinued or the dose was reduced. These impulse-control problems are rare, but they may result in harm to the patient and others if not recognized.

Although pathological gambling is listed as a reported side effect in the current aripiprazole drug labels, this description does not entirely reflect the nature of the impulse-control risk that we identified. In addition, we have become aware of other compulsive behaviors associated with aripiprazole, such as compulsive eating, shopping, and sexual actions. These compulsive behaviors can affect anyone who is taking the medicine. As a result, we are adding new warnings about all of these compulsive behaviors to the drug labels and the patient Medication Guides for all aripiprazole products.

Health care professionals should make patients and caregivers aware of the risk of these uncontrollable urges when prescribing aripiprazole, and specifically ask patients about any new or increasing urges while they are being treated with aripiprazole. Closely monitor for new or worsening uncontrollable urges in patients at higher risk for impulse-control problems. These include those with a personal or family history of obsessive-compulsive disorder, impulse-control disorder, bipolar disorder, impulsive personality, alcoholism, drug abuse, or other addictive behaviors. Consider reducing the dose or stopping the medicine if such urges develop.

Read More: http://www.fda.gov/


Long-Term Weight Change after Initiating Second-Generation Antidepressants


Journal of Clinical Medicine

Abstract

Objective
To examine the relationship between the choice of second-generation antidepressant drug treatment and long-term weight change.

Methods 
We conducted a retrospective cohort study to investigate the relationship between choice of antidepressant medication and weight change at two years among adult patients with a new antidepressant treatment episode between January, 2006 and October, 2009 in a large health system in Washington State. Medication use, encounters, diagnoses, height, and weight were collected from electronic databases. We modeled change in weight and BMI at two years after initiation of treatment using inverse probability weighted linear regression models that adjusted for potential confounders. Fluoxetine was the reference treatment.

Results
In intent-to-treat analyses, non-smokers who initiated bupropion treatment on average lost 7.1 lbs compared to fluoxetine users who were non-smokers (95% CI: −11.3, −2.8; p-value < 0.01); smokers who initiated bupropion treatment gained on average 2.2 lbs compared to fluoxetine users who were smokers (95% CI: −2.3, 6.8; p-value = 0.33). Changes in weight associated with all other antidepressant medications were not significantly different than fluoxetine, except for sertraline users, who gained an average of 5.9 lbs compared to fluoxetine users (95% CI: 0.8, 10.9; p-value = 0.02).  

Conclusion
Antidepressant drug therapy is significantly associated with long-term weight change at two years. Bupropion may be considered as the first-line drug of choice for overweight and obese patients unless there are other existing contraindications.



Evidence-based guideline: Treatment of tardive syndromes


Neurology

Abstract

Objective
To make evidence-based recommendations regarding management of tardive syndromes (TDS), including tardive dyskinesias (TDD), by addressing 5 questions: 1) Is withdrawal of dopamine receptor blocking agents (DRBAs) an effective TDS treatment? 2) Does switching from typical to atypical DRBAs reduce TDS symptoms? 3) What is the efficacy of pharmacologic agents in treating TDS? 4) Do patients with TDS benefit from chemodenervation with botulinum toxin? 5) Do patients with TDS benefit from surgical therapy?

Methods
PsycINFO, Ovid MEDLINE, EMBASE, Web of Science, and Cochrane were searched (1966–2011). Articles were classified according to a 4-tiered evidence-rating scheme; recommendations were tied to the evidence.

Results and recommendations
Clonazepam probably improves TDD and ginkgo biloba probably improves TDS (both Level B); both should be considered as treatment. Risperidone may improve TDS but cannot be recommended as treatment because neuroleptics may cause TDS despite masking symptoms. Amantadine and tetrabenazine might be considered as TDS treatment (Level C). Diltiazem should not be considered as TDD treatment (Level B); galantamine and eicosapentaenoic acid may not be considered as treatment (Level C). Data are insufficient to support or refute use of acetazolamide, bromocriptine, thiamine, baclofen, vitamin E, vitamin B6, selegiline, clozapine, olanzapine, melatonin, nifedipine, fluperlapine, sulpiride, flupenthixol, thiopropazate, haloperidol, levetiracetam, quetiapine, ziprasidone, sertindole, aripiprazole, buspirone, yi-gan san, biperiden discontinuation, botulinum toxin type A, electroconvulsive therapy, α-methyldopa, reserpine, and pallidal deep brain stimulation as TDS treatments (Level U). Data are insufficient to support or refute TDS treatment by withdrawing causative agents or switching from typical to atypical DRBA (Level U).



Association Between Genetic Traits for Immune-Mediated Diseases and Alzheimer Disease


JAMA Neurology

Abstract

Importance  
Late-onset Alzheimer disease (AD), the most common form of dementia, places a large burden on families and society. Although epidemiological and clinical evidence suggests a relationship between inflammation and AD, their relationship is not well understood and could have implications for treatment and prevention strategies.

Objective  
To determine whether a subset of genes involved with increased risk of inflammation are also associated with increased risk for AD.

Design, Setting, and Participants  
In a genetic epidemiology study conducted in July 2015, we systematically investigated genetic overlap between AD (International Genomics of Alzheimer’s Project stage 1) and Crohn disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, and psoriasis using summary data from genome-wide association studies at multiple academic clinical research centers. P values and odds ratios from genome-wide association studies of more than 100 000 individuals were from previous comparisons of patients vs respective control cohorts. Diagnosis for each disorder was previously established for the parent study using consensus criteria.

Main Outcomes and Measures  
The primary outcome was the pleiotropic (conjunction) false discovery rate P value. Follow-up for candidate variants included neuritic plaque and neurofibrillary tangle pathology; longitudinal Alzheimer’s Disease Assessment Scale cognitive subscale scores as a measure of cognitive dysfunction (Alzheimer’s Disease Neuroimaging Initiative); and gene expression in AD vs control brains (Gene Expression Omnibus data).

Results  
Eight single-nucleotide polymorphisms (false discovery rate P < .05) were associated with both AD and immune-mediated diseases. Of these, rs2516049 (closest gene HLA-DRB5; conjunction false discovery rate P = .04 for AD and psoriasis, 5.37 × 10−5 for AD, and 6.03 × 10−15 for psoriasis) and rs12570088 (closest gene IPMK; conjunction false discovery rate P = .009 for AD and Crohn disease, P = 5.73 × 10−6 for AD, and 6.57 × 10−5 for Crohn disease) demonstrated the same direction of allelic effect between AD and the immune-mediated diseases. Both rs2516049 and rs12570088 were significantly associated with neurofibrillary tangle pathology (P = .01352 and .03151, respectively); rs2516049 additionally correlated with longitudinal decline on Alzheimer’s Disease Assessment Scale cognitive subscale scores (β [SE], 0.405 [0.190]; P = .03). Regarding gene expression, HLA-DRA and IPMK transcript expression was significantly altered in AD brains compared with control brains (HLA-DRA: β [SE], 0.155 [0.024]; P = 1.97 × 10−10; IPMK: β [SE], −0.096 [0.013]; P = 7.57 × 10−13).

Conclusions and Relevance  
Our findings demonstrate genetic overlap between AD and immune-mediated diseases and suggest that immune system processes influence AD pathogenesis and progression.



Effect of prenatal selective serotonin reuptake inhibitor (SSRI) exposure on birthweight and gestational age: a sibling-controlled cohort study


International Journal of Epidemiology

Abstract

Background
Up to 10% of women are exposed to selective serotonin reuptake inhibitors (SSRIs) during pregnancy. Information on their effect on birthweight and gestational age remains conflicting. The aim of this sibling-controlled prospective cohort study is to address shared geneticand family-level confounding to investigate the effects of prenatal SSRI exposure and maternal depression on birthweight and gestational age.

Methods
We used the Norwegian Mother and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway (MBRN). Our study population consisted of 27 756 siblings; 194 were prenatally exposed to SSRIs and 27 500 were unexposed to any antidepressant medication. Random and fixed effects analysis with propensity score adjustment was used to evaluate the effectson birthweight and gestational age.

Results
SSRI exposure during two or more trimesters was associated with a decrease in birthweight of 205 g [95% confidence interval (CI) −372 to − 38] and a decrease in gestational length of 4.9 days (95% CI − 9.1 to − 1.4). Neither maternal SSRI use in one trimester, lifetime history of major depression nor depressive symptoms during pregnancy were associated with these pregnancy outcomes (for non-pharmacologically treated depression in two periods in pregnancy, +5 g (95% CI − 56 to + 67) and +4.9 days (95% CI − 4.7 to + 14.7), respectively).

Conclusions
Prenatal exposure to SSRIs during two or more trimesters may decrease birthweight and gestational length. Our results indicate that neither maternal depression nor shared genetics and family environment fully explain this association.



Online Journals:




Biological Psychiatry - Volume 79, Issue 12, June 2016



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