Our objective was to examine the association between antipsychotic receptor binding profiles and the magnitude of common side-effects. We used regression analysis to examine the association between ...the receptor binding affinities of antipsychotic agents (log Ki) and degree of specific antipsychotic side-effects. Data on magnitude of weight gain, prolactin increase and QTc prolongation (in Standardized Mean Difference) and risk of sedation and extrapyramidal symptoms (in Odds Ratio) between individual antipsychotic medications as compared to placebo was based on a recent network meta-analysis examining the treatment of schizophrenia. Receptor affinities (in log Ki) were examined for the D2, 5-HT1A, 5-HT2A, 5-HT2C, H1, alpha1, alpha2, M1, M3 and M4 receptors. Medications were weighted in the analysis using the generic inverse variance method utilizing variance estimates from the previous meta-analysis.
Magnitude of weight gain was significantly associated with the affinity of antipsychotic medications to M1, M3, 5-HT2C and H1 receptors. Risk of sedation was significantly associated with the affinity to the M1 and M4 receptors. Magnitude of hyperprolactinemia was significantly associated with the affinity to M1 and M4 receptors. Risk of extrapyramidal side effects was associated with the affinity to 5-HT2C and M1 receptors. QT prolongation was not significantly associated with antipsychotic receptor affinities. Our meta-analysis demonstrated that increased affinity of antipsychotics for certain receptors are significantly associated with higher risk of sedation, hyperprolactinemia, extrapyramidal side effects and weight gain.
•Increased M1 and M4 affinity of antipsychotics wereassociated with increased risk of sedation.•Increased H1, 5-HT2C, M1 and M3 affinity of antipsychotics were associated with increased risk of weight gain.•Decreased M1 and M4 affinity of antipsychotics were associated with increased prolactin levels.•Decreased 5-HT2C and M1 affinity of antipsychotics wereassociated with increased relative risk of extrapyramidal side effects.•We failed to demonstrate any significant association between the receptor affinities and QT prolongation among antipsychotic agents.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Obsessive-compulsive disorder (OCD) affects up to 2.5% of the population of the course of a lifetime and produces substantial morbidity. Approximately 70% of patients can experience significant ...symptomatic relief with appropriate pharmacotherapy. Selective serotonin reuptake inhibitors are the mainstay of pharmacological treatment. These drugs are typically used at higher doses and for longer periods than in depression. Proven second-line treatments include the tricyclic clomipramine and the addition of low-dose neuroleptic medications. OCD refractory to available treatments remains a profound clinical challenge.
Family accommodation describes changes that individuals make to their behavior, to help their relative who is dealing with a psychiatric and/or psychological disorder(s), avoid or alleviate distress ...related to the disorder. Research on family accommodation has advanced rapidly. In this update we aim to provide a synthesis of findings from the past five years. A search of available, peer-reviewed, English language papers was conducted through PubMed and PsycINFO, cross referencing psychiatric disorders with accommodation and other family-related terms. The resulting 121 papers were individually reviewed and evaluated and the main findings were discussed. Family accommodation is common in obsessive-compulsive disorder (OCD) and in anxiety disorders, and manifests similarly across these disorders. Family accommodation is associated with more severe psychopathology and poorer clinical outcomes. Treatments have begun to focus on the reduction of family accommodation as a primary therapeutic goal and finally, neurobiological underpinnings of family accommodation are beginning to be investigated.
Anxiety is a common and impairing problem in children and adolescents with autism spectrum disorder (ASD). There is emerging evidence that cognitive-behavioral therapy (CBT) could reduce anxiety in ...children with high-functioning ASD.
To systematically review the evidence of using CBT to treat anxiety in children and adolescents with ASD. Methods for this review were registered with PROSPERO (CRD42012002722).
We included randomized controlled trials published in English in peer-reviewed journals comparing CBT with another treatment, no treatment control, or waitlist control. Two authors independently screened 396 records obtained from database searches and hand searched relevant journals. Two authors independently extracted and reconciled all data used in analyses from study reports.
Eight studies involving 469 participants (252 treatment, 217 comparison) met our inclusion criteria and were included in meta-analyses. Overall effect sizes for clinician- and parent-rated outcome measures of anxiety across all studies were d = 1.19 and d = 1.21, respectively. Five studies that included child self-report yielded an average d = 0.68 across self-reported anxiety.
Parent ratings and clinician ratings of anxiety are sensitive to detecting treatment change with CBT for anxiety relative to waitlist and treatment-as-usual control conditions in children with high-functioning ASD. Clinical studies are needed to evaluate CBT for anxiety against attention control conditions in samples of children with ASD that are well characterized with regard to ASD diagnosis and co-occurring anxiety symptoms.
Objective:
OCD is a clinically heterogeneous condition. This heterogeneity has the potential to reduce power in genetic, neuroimaging, and clinical trials. Despite a mounting number of studies, there ...remains debate regarding the exact factor structure of OCD symptoms. The authors conducted a meta-analysis to determine the factor structure of the Yale-Brown Obsessive Compulsive Scale Symptom Checklist.
Method:
Studies were included if they involved subjects with OCD and included an exploratory factor analysis of the 13 Yale-Brown Obsessive Compulsive Scale Symptom Checklist categories or the items therein. A varimax-rotation was conducted in SAS 9.1 using the PROC FACTOR CORR to extract factors from sample-size weighted co-occurrence matrices. Stratified meta-analysis was conducted to determine the factor structure of OCD in studies involving children and adults separately.
Results:
Twenty-one studies involving 5,124 participants were included. The four factors generated were 1) symmetry: symmetry obsessions and repeating, ordering, and counting compulsions; 2) forbidden thoughts: aggression, sexual, religious, and somatic obsessions and checking compulsions, 3) cleaning: cleaning and contamination, and 4) hoarding: hoarding obsessions and compulsions. Factor analysis of studies including adults yielded an identical factor structure compared to the overall meta-analysis. Factor analysis of child-only studies differed in that checking loaded highest on the symmetry factor and somatic obsessions, on the cleaning factor.
Conclusions:
A four-factor structure explained a large proportion of the heterogeneity in the clinical symptoms of OCD. Further item-level factor analyses are needed to determine the appropriate placement of miscellaneous somatic and checking OCD symptoms.
To review the assessment and treatment of treatment-refractory pediatric obsessive-compulsive disorder (OCD).
A PubMed search was conducted to identify controlled trials in pediatric OCD. In ...addition, practice guidelines for the treatment of adults and children were further reviewed for references in treatment-refractory OCD across the lifespan.
Pharmacotherapy with selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT) were found to be effective treatments for pediatric OCD. Evidence suggests that CBT is also effective even in pediatric patients with refractory OCD symptoms. Antipsychotic augmentation, raising SSRI dosage, and several glutamate-modulating agents have some evidence of efficacy in adults with treatment-refractory OCD but have not been studied in pediatric populations.
Several pharmacological treatment options exist for children with refractory OCD symptoms. However, little evidence-based data exist to guide treatment for our most challenging pediatric OCD patients. Further research is needed to evaluate the efficacy/side effect profile of commonly used interventions in treatment-refractory pediatric OCD.
We conducted a meta-analysis to examine the following: the time course of response to selective serotonin reuptake inhibitors (SSRIs) and clomipramine in pediatric obsessive-compulsive disorder ...(OCD); whether higher doses of SSRIs are associated with an improved response in pediatric OCD; differences in efficacy among SSRI agents; differences in efficacy between SSRIs and clomipramine; and whether the time course and magnitude of response to SSRIs are different in pediatric and adult patients with OCD.
We searched PubMed and CENTRAL for randomized controlled trials comparing SSRIs (or clomipramine) to placebo for the treatment of pediatric OCD and using the Children's Yale-Brown Obsessive-Compulsive Scale as an outcome. We extracted weekly symptom data from trials to characterize the trajectory of pharmacological response to SSRIs. Pooled estimates of treatment effect were calculated based on weighted mean differences between the treatment and placebo groups.
Nine trials involving 801 children with OCD were included in this meta-analysis. A logarithmic model indicating that the greatest benefits occurred early in treatment best fit the longitudinal data for both clomipramine and SSRIs. Clomipramine was associated with a greater measured benefit compared to placebo than SSRIs. There was no evidence for a relationship between SSRI dosing and treatment effect, although data were limited. Adults and children with OCD demonstrated a similar degree and time course of response to SSRIs in OCD.
These results suggest that the greatest incremental treatment gains in pediatric OCD occur early in SSRI treatment (similar to adults with OCD and children and adults with major depression).
To evaluate the efficacy and tolerability of pharmacotherapy in pediatric anxiety disorders using network meta-analysis.
PubMed, Cochrane Database, Web of Science, PsycNET, and ClinicalTrials.gov ...were searched for double-blind, controlled pharmacotherapy trials in youth with anxiety disorders from 1966 to September 2017.
All double-blind, placebo-controlled trials of pharmacotherapy in the treatment of pediatric patients with generalized, social, and/or separation anxiety disorders were included.
We extracted demographic, symptom severity, global improvement, discontinuation, and suicidality data. Risk of bias was assessed with the Cochrane risk-of-bias tool, and a network meta-analysis comparing the efficacy and tolerability of medications and medication classes was performed using the gemtc package (R).
We identified 20 citations (22 RCTs, 24 treatment arms) with 2,623 patients. Selective serotonin reuptake inhibitors (SSRIs) were the only class that was superior in reducing anxiety (standardized mean difference: 5.2; credible interval CrI: 2.8 to 8.8) and in likelihood of treatment response compared to placebo (odds ratio OR: 4.6; CrI: 3.1 to 7.5). Serotonin-norepinephrine reuptake inhibitor (SNRI) and α₂ agonist treatment were associated with more frequent treatment response compared to placebo. The likelihood of treatment response was greater for SSRIs compared to SNRIs (OR: 1.9; CrI: 1.1 to 3.5). All-cause discontinuation and treatment-emergent suicidality significantly differed among medications but not medication class.
Although multiple medications reduce anxiety in children and adolescents, treatment response, tolerability, and treatment-emergent suicidality differ among these medications and medication classes. Determining whether efficacy and tolerability differences represent true differences (or reflect differences in trial design) requires additional head-to-head medication trials and-to exclude the impact of missing treatment interventions-requires trials of medications that successfully treat anxiety in adults but that have not been evaluated in youth.
The deleterious impact of the COVID‐19 pandemic on youth mental health has garnered much attention (Newlove‐Delgado et al., 2023). It has been a topic of interest in both research and academic ...writing, as well as in the public press (e.g., Tanner, 2023). Disorders and mental health concerns of focus have been wide‐ranging, with some of the most severe presentations, such as suicidality, highlighted (Asarnow and Chung, 2021). Eating disorders are among the most life‐threatening and prominent mental health concerns that have been exacerbated by the pandemic, and our current models of youth mental health care cannot keep up. Given this context, our team read and reviewed the manuscript, ‘Shifting age of child eating disorder hospitalizations during the Covid‐19 pandemic’ (Auger et al., 2023), eagerly. While the increasing severity of eating disorder presentations and increase in pediatric hospitalization has been an area of research (Asch et al., 2021), including at our own institution (Shum et al., 2022), the impact of age of onset, and the consequential impact on current systems of care, requires much greater attention.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Suicide is currently the second leading cause of death in young people ages 10–19 (CDC, 2015). Current statistics suggest that in the US one in every seven youths has seriously considered or made a ...plan to commit suicide and one in every 13 youths has attempted suicide in the previous year (CDC, 2015). Suicide represents a – if not the – major public health problem in adolescents.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
PDF
