Thursday, September 5, 2019

September 2019

Treatments for the Prevention and Management of Suicide: A Systematic Review


Annals of Inernal Medicine

Abstract

Background

Suicide is a growing public health problem, with the national rate in the United States increasing by 30% from 2000 to 2016.

Purpose
To assess the benefits and harms of nonpharmacologic and pharmacologic interventions to prevent suicide and reduce suicide behaviors in at-risk adults.

Data Sources
MEDLINE, EMBASE, PsycINFO, and other databases from November 2011 through May 2018.

Study Selection
Systematic reviews (SRs) and randomized controlled trials (RCTs) that assessed nonpharmacologic or pharmacologic therapies for adults at risk for suicide.

Data Extraction
One investigator abstracted data and assessed study quality, and a second investigator checked abstractions and assessments for accuracy.

Data Synthesis
Eight SRs and 15 RCTs were included. The evidence for psychological interventions suggests that cognitive behavioral therapy (CBT) reduces suicide attempts, suicidal ideation, and hopelessness compared with treatment as usual (TAU). Limited evidence suggests that dialectical behavior therapy (DBT) reduces suicidal ideation compared with wait-list control or crisis planning. The evidence for pharmacologic treatments suggests that ketamine reduces suicidal ideation with minimal adverse events compared with placebo or midazolam. Lithium reduces rates of suicide among patients with unipolar or bipolar mood disorders compared with placebo. However, no differences were observed between lithium and other medications in reducing suicide.

Limitation
Qualitative synthesis of new evidence with existing meta-analyses, methodological shortcomings of studies, heterogeneity of nonpharmacologic interventions, and limited evidence for pharmacologic treatments and harms.

Conclusion
Both CBT and DBT showed modest benefit in reducing suicidal ideation compared with TAU or wait-list control, and CBT also reduced suicide attempts compared with TAU. Ketamine and lithium reduced the rate of suicide compared with placebo, but there was limited information on harms. Limited data are available to support the efficacy of other nonpharmacologic or pharmacologic interventions.
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Source: https://annals.org/

Benzodiazepine Use During Pregnancy Alone or in Combination With an Antidepressant and Congenital Malformations: Systematic Review and Meta-Analysis


The Journal of Clinical Psychiatry

Summary

Objective
To summarize the effects of antenatal benzodiazepine exposure as monotherapy and in combination with antidepressants on the risk of congenital malformations.


Data Sources
MEDLINE, PsycINFO, CINAHL, Embase, and the Cochrane Library were searched from inception to June 30, 2018, using controlled vocabulary and keywords (eg, prenatal, benzodiazepines, malformation).


Study Selection
English-language cohort studies with prospectively collected data on the risk of malformations in benzodiazepine-exposed and -unexposed offspring were evaluated. 23,909 records were screened, 56 studies were assessed for eligibility, and 8 studies were included.


Data Extraction
Quality was assessed by 2 independent reviewers and data extracted. Random-effects models were used for outcomes (≥ 3 studies). Subanalyses examined effect of potential moderators including study quality and timing of exposure, among others.


Results
Prenatal benzodiazepine use was not associated with an increased risk of congenital malformations (odds ratio [OR] = 1.13; 95% CI, 0.99 to 1.30, 8 studies, n = 222/5,195 exposed and 64,335/2,082,467 unexposed), including with first trimester exposure specifically (OR = 1.08; 95% CI, 0.93 to 1.25, P = .33; 5 studies, n = 181/4,331 exposed and 64,308/2,081,463 unexposed). There was no significant association with cardiac malformation following exposure (OR = 1.27; 95% CI, 0.98 to 1.65, P = .07; 4 studies, n = 61/4,414 exposed and 19,260/2,033,402 unexposed). However, concurrent use of benzodiazepine and antidepressants during pregnancy was associated with a significantly increased risk of congenital malformations (OR = 1.40; 95% CI, 1.09 to 1.80, P = .008; 3 studies).


Conclusions
Benzodiazepine exposure during pregnancy does not appear to be associated with congenital malformations or with cardiac malformations specifically. There may be an increased risk of congenital malformations when benzodiazepines are used in conjunction with antidepressants, suggesting that caution with this combination is warranted.
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Effectiveness of a Community‐Based Weight Management Program for Patients Taking Antidepressants and/or Antipsychotic


Obesity
  
Abstract

Objective

This study aimed to compare weight loss (WL) outcomes for patients taking antidepressants and/or antipsychotics with those not taking psychiatric medication.

Methods
A total of 17,519 adults enrolled in a lifestyle WL intervention at the Wharton Medical Clinics in Ontario, Canada, were analyzed. Sex‐stratified multivariable linear regression analysis was used to examine the association of taking antidepressants, antipsychotics, both, or neither with WL when adjusting for age, initial weight, and treatment time.

Results
Twenty‐three percent of patients were taking at least one psychiatric medication. Patients lost a significant amount of weight (P < 0.0001) regardless of psychiatric medication use. Women taking psychiatric medications lost a similar amount of weight as women who were not (P > 0.05). Conversely, men taking antidepressants lost only slightly less weight than men taking both classes or neither class of psychiatric medication (3.2 ± 0.3 kg vs. 5.6 ± 0.9 kg and 4.3 ± 0.1 kg; P < 0.05). However, taking psychiatric medications that cause weight gain was associated with similar significant decreases in weight as taking medications that are weight neutral or associated with WL for both sexes (P > 0.05).

Conclusions
Results of this study suggest that those who participate in a weight management program can lose significant amounts of weight regardless of psychiatric medication use.



A Comparison of Long-Acting Injectable Antipsychotics With Oral Antipsychotics on Time to Rehospitalization Within 1 Year of Discharge in Elderly Patients With Schizophrenia


The American Journal of Geriatric Psychiatry 

Abstract

Objective
The effectiveness of long-acting injectable antipsychotics (LAIs) in elderly patients with schizophrenia remains unclear. This study aimed to compare the effect of LAIs with oral antipsychotics (OAPs) on time to rehospitalization within 1 year of discharge in this population. Other factors potentially associated with time to rehospitalization and trends in LAI prescription rates during the study period were also investigated.

Methods
Patients over 60 years of age with schizophrenia discharged between 2006 and 2017 were followed for 1 year under naturalistic conditions. Survival analysis was used in the comparison between LAIs and OAPs regarding time to rehospitalization. Covariates thought to affect time to rehospitalization were also analyzed. The Cochran-Armitage trend test was used to evaluate whether a time trend existed for LAI prescription rates.

Results
The LAIs group had a significantly lower rehospitalization rate and a significantly longer time to rehospitalization within 1 year of discharge than the OAPs group. Other factors that were associated with a longer time to rehospitalization included a shorter index hospitalization during the time of the study and fewer previous hospitalizations. No significant time trend was found for LAI prescription rates during the study period. However, the prescription rate of second-generation LAIs grew significantly.

Conclusion
LAIs were found superior to OAPs in preventing rehospitalization. A continuous increase in second-generation LAI prescription rate may be due to the better side-effect profile of second-generation LAIs compared to first-generation LAIs. More studies investigating the effectiveness of LAIs in elderly patients with schizophrenia are needed in the future.



Environmental pollution is associated with increased risk of psychiatric disorders


PLOS Biology

Abstract

The search for the genetic factors underlying complex neuropsychiatric disorders has proceeded apace in the past decade. Despite some advances in identifying genetic variants associated with psychiatric disorders, most variants have small individual contributions to risk. By contrast, disease risk increase appears to be less subtle for disease-predisposing environmental insults. In this study, we sought to identify associations between environmental pollution and risk of neuropsychiatric disorders. We present exploratory analyses of 2 independent, very large datasets: 151 million unique individuals, represented in a United States insurance claims dataset, and 1.4 million unique individuals documented in Danish national treatment registers. Environmental Protection Agency (EPA) county-level environmental quality indices (EQIs) in the US and individual-level exposure to air pollution in Denmark were used to assess the association between pollution exposure and the risk of neuropsychiatric disorders. These results show that air pollution is significantly associated with increased risk of psychiatric disorders. We hypothesize that pollutants affect the human brain via neuroinflammatory pathways that have also been shown to cause depression-like phenotypes in animal studies.



Association of Cesarean Delivery With Risk of Neurodevelopmental and Psychiatric Disorders in the Offspring


JAMA Network

Abstract

Importance 
Birth by cesarean delivery is increasing globally, particularly cesarean deliveries without medical indication. Children born via cesarean delivery may have an increased risk of negative health outcomes, but the evidence for psychiatric disorders is incomplete.


Objective 
To evaluate the association between cesarean delivery and risk of neurodevelopmental and psychiatric disorders in the offspring.


Data Sources 
Ovid MEDLINE, Embase, Web of Science, and PsycINFO were searched from inception to December 19, 2018. Search terms included all main mental disorders in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition).


Study Selection 
Two researchers independently selected observational studies that examined the association between cesarean delivery and neurodevelopmental and psychiatric disorders in the offspring.


Data Extraction and Synthesis 
Two researchers independently extracted data according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines and assessed study quality using the Newcastle-Ottawa Scale. Random-effects meta-analyses were used to pool odds ratios (ORs) with 95% CIs for each outcome. Sensitivity and influence analyses tested the robustness of the results.


Main Outcomes and Measures 
The ORs for the offspring with any neurodevelopmental or psychiatric disorder who were born via cesarean delivery compared with those were born via vaginal delivery.


Results 
A total of 6953 articles were identified, of which 61 studies comprising 67 independent samples were included, totaling 20 607 935 deliveries. Compared with offspring born by vaginal delivery, offspring born via cesarean delivery had increased odds of autism spectrum disorders (OR, 1.33; 95% CI, 1.25-1.41; I2 = 69.5%) and attention-deficit/hyperactivity disorder (OR, 1.17; 95% CI, 1.07-1.26; I2 = 79.2%). Estimates were less precise for intellectual disabilities (OR, 1.83; 95% CI, 0.90-3.70; I2 = 88.2%), obsessive-compulsive disorder (OR, 1.49; 95% CI, 0.87-2.56; I2 = 67.3%), tic disorders (OR, 1.31; 95% CI, 0.98-1.76; I2 = 75.6%), and eating disorders (OR, 1.18; 95% CI, 0.96-1.47; I2 = 92.7%). No significant associations were found with depression/affective psychoses or nonaffective psychoses. Estimates were comparable for emergency and elective cesarean delivery. Study quality was high for 82% of the cohort studies and 50% of the case-control studies.


Conclusions and Relevance 
The findings suggest that cesarean delivery births are associated with an increased risk of autism spectrum disorder and attention-deficit/hyperactivity disorder, irrespective of cesarean delivery modality, compared with vaginal delivery. Future studies on the mechanisms behind these associations appear to be warranted.
 




ASSOCIATION OF ANTIPSYCHOTIC TREATMENT WITH RISK OF UNEXPECTED DEATH AMONG CHILDREN AND YOUTHS


JAMA Psychiatry

Abstract

Importance  
Children and youths who are prescribed antipsychotic medications have multiple, potentially fatal, dose-related cardiovascular, metabolic, and other adverse events, but whether or not these medications are associated with an increased risk of death is unknown.


Objective  
To compare the risk of unexpected death among children and youths who are beginning treatment with antipsychotic or control medications.


Design, Setting, and Participants  
This retrospective cohort study was conducted from 1999 through 2014 and included Medicaid enrollees aged 5 to 24 years in Tennessee who had no diagnosis of severe somatic illness, schizophrenia or related psychoses, or Tourette syndrome or chronic tic disorder. Data analysis was performed from January 1, 2017, to August 15, 2018.


Exposures  
Current, new antipsychotic medication use at doses higher than 50 mg (higher-dose group) or 50 mg or lower chlorpromazine equivalents (lower-dose group) as well as control medications (ie, attention-deficit/hyperactivity disorder medications, antidepressants, or mood stabilizers) (control group).


Main Outcomes and Measures  
Deaths during study follow-up while out of hospital or within 7 days after hospital admission, classified as either deaths due to injury or suicide or unexpected deaths. Secondary outcomes were unexpected deaths not due to overdose and death due to cardiovascular or metabolic causes.


Results  
This study included 189 361 children and youths in the control group (mean [SD] age, 12.0 [5.1] years; 43.4% female), 28 377 in the lower-dose group (mean [SD] age, 11.7 [4.4] years; 32.3% female), and 30 120 in the higher-dose group (mean [SD] age, 14.5 [4.8] years; 39.2% female). The unadjusted incidence of death in the higher-dose group was 146.2 per 100 000 person-years (40 deaths per 27 354 person-years), which was significantly greater than that in the control group (54.5 per 100 000 population; 67 deaths per 123 005 person-years) (P < .001). The difference was primarily attributable to the increased incidence of unexpected deaths in the higher-dose group (21 deaths; 76.8 per 100 000 population) compared with the control group (22 deaths; 17.9 per 100 000 population). The propensity score–adjusted hazard ratios were as follows: all deaths (1.80; 95% CI, 1.06-3.07), deaths due to unintentional injury or suicide (1.03; 95% CI, 0.53-2.01), and unexpected deaths (3.51; 95% CI, 1.54-7.96). The hazard ratio was 3.50 (95% CI, 1.35-9.11) for unexpected deaths not due to overdose and 4.29 (95% CI, 1.33-13.89) for deaths due to cardiovascular or metabolic causes. Neither the unadjusted nor adjusted incidence of death in the lower-dose group differed significantly from that in the control group.


Conclusions and Relevance  
The findings suggest that antipsychotic use is associated with increased risk of unexpected death and appear to reinforce recommendations for careful prescribing and monitoring of antipsychotic treatment for children and youths and to underscore the need for larger antipsychotic treatment safety studies in this population.



MITIGATION OF OLANZAPINE-INDUCED WEIGHT GAIN WITH SAMIDORPHAN, AN OPIOID ANTAGONIST: A RANDOMIZED DOUBLE-BLIND PHASE 2 STUDY IN PATIENTS WITH SCHIZOPHRENIA

American Journal of Psychiatry

Objective
Preclinical evidence and data from a proof-of-concept study in healthy volunteers suggest that samidorphan, an opioid antagonist, mitigates weight gain associated with olanzapine. This study prospectively compared combination therapy of olanzapine plus either samidorphan or placebo for the treatment of schizophrenia.

Methods
This was an international, multicenter, randomized phase 2 study of olanzapine plus samidorphan in patients with schizophrenia. The study had a 1-week open-label olanzapine lead-in period followed by a 12-week double-blind treatment phase in which patients were randomly assigned in a 1:1:1:1 ratio to receive olanzapine plus placebo (N=75) or olanzapine plus 5 mg (N=80), 10 mg (N=86), or 20 mg (N=68) of samidorphan. The primary aims were to confirm that the antipsychotic efficacy of olanzapine plus samidorphan was comparable to olanzapine plus placebo, to assess the effect of combining olanzapine with samidorphan on olanzapine-induced weight gain, and to assess the overall safety and tolerability of olanzapine plus samidorphan.

Results
Antipsychotic efficacy, as assessed by total score on the Positive and Negative Syndrome Scale (PANSS), was equivalent across all treatment groups. Treatment with olanzapine plus samidorphan resulted in a statistically significant lower weight gain (37% lower weight gain compared with olanzapine plus placebo). The least square mean percent change from baseline in body weight was 4.1% (2.9 kg) for the olanzapine plus placebo group and 2.6% (1.9 kg) for the olanzapine plus samidorphan group (2.8% [2.1 kg] for the 5 mg group, 2.1% [1.5 kg] for the 10 mg group, and 2.9% [2.2 kg] for the 20 mg group). Adverse events reported at a frequency ≥5% in any of the olanzapine plus samidorphan groups and occurring at a rate ≥2 times greater than in the olanzapine plus placebo group were somnolence, sedation, dizziness, and constipation. Other safety measures were comparable between the olanzapine plus samidorphan groups and the olanzapine plus placebo group.

Conclusions
The antipsychotic efficacy of olanzapine plus samidorphan was equivalent to that of olanzapine plus placebo, and olanzapine plus samidorphan was associated with clinically meaningful and statistically significant mitigation of weight gain compared with olanzapine plus placebo. Olanzapine plus samidorphan was generally well tolerated, with a safety profile similar to olanzapine plus placebo.



MOOD STABILISERS AND RISK OF STROKE IN BIPOLAR DISORDER

The British Journal of Psychiatry

Abstract

Background
Research on the risk of stroke following the use of mood stabilisers specific to patients with bipolar disorder is limited.

Aims
In this study, we investigated the risk of stroke following the exposure to mood stabilisers in patients with bipolar disorder.

Method
Data for this nationwide population-based study were derived from the Taiwan National Health Insurance Research Database. Among a retrospective cohort of patients with bipolar disorder (n = 19 433), 609 new-onset cases of stroke were identified from 1999 to 2012. A case–crossover study design utilising 14-day windows was applied to assess the acute exposure effect of individual mood stabilisers on the risk of ischaemic, haemorrhagic and other types of stroke in patients with bipolar disorder.

Results
Mood stabilisers as a group were significantly associated with the increased risk of stroke in patients with bipolar disorder (adjusted risk ratio, 1.26; P = 0.041). Among individual mood stabilisers, acute exposure to carbamazepine had the highest risk of stroke (adjusted risk ratio, 1.68; P = 0.018), particularly the ischaemic type (adjusted risk ratio, 1.81; P = 0.037). In addition, acute exposure to valproic acid elevated the risk of haemorrhagic stroke (adjusted risk ratio, 1.76; P = 0.022). In contrast, acute exposure to lithium and lamotrigine did not significantly increase the risk of any type of stroke.

Conclusions
Use of carbamazepine and valproic acid, but not lithium and lamotrigine, is associated with increased risk of stroke in patients with bipolar disorder.



PSYCHOSIS WITH METHYLPHENIDATE OR AMPHETAMINE IN PATIENTS WITH ADHD


The New England Journal of Medicine

Abstract

BACKGROUND
The prescription use of the stimulants methylphenidate and amphetamine for the treatment of attention deficit–hyperactivity disorder (ADHD) has been increasing. In 2007, the Food and Drug Administration mandated changes to drug labels for stimulants on the basis of findings of new-onset psychosis. Whether the risk of psychosis in adolescents and young adults with ADHD differs among various stimulants has not been extensively studied.

METHODS
We used data from two commercial insurance claims databases to assess patients 13 to 25 years of age who had received a diagnosis of ADHD and who started taking methylphenidate or amphetamine between January 1, 2004, and September 30, 2015. The outcome was a new diagnosis of psychosis for which an antipsychotic medication was prescribed during the first 60 days after the date of the onset of psychosis. To estimate hazard ratios for psychosis, we used propensity scores to match patients who received methylphenidate with patients who received amphetamine in each database, compared the incidence of psychosis between the two stimulant groups, and then pooled the results across the two databases.

RESULTS
We assessed 337,919 adolescents and young adults who received a prescription for a stimulant for ADHD. The study population consisted of 221,846 patients with 143,286 person-years of follow up; 110,923 patients taking methylphenidate were matched with 110,923 patients taking amphetamines. There were 343 episodes of psychosis (with an episode defined as a new diagnosis code for psychosis and a prescription for an antipsychotic medication) in the matched populations (2.4 per 1000 person-years): 106 episodes (0.10%) in the methylphenidate group and 237 episodes (0.21%) in the amphetamine group (hazard ratio with amphetamine use, 1.65; 95% confidence interval, 1.31 to 2.09).

CONCLUSIONS
Among adolescents and young adults with ADHD who were receiving prescription stimulants, new-onset psychosis occurred in approximately 1 in 660 patients. Amphetamine use was associated with a greater risk of psychosis than methylphenidate. 

Source: https://www.nejm.org/


Online Journals:




Biological Psychiatry - Volume 86, Issue 6, September 2019



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