Prevalence and Correlates of Eating Disorder Symptoms in Adolescents with Bipolar I Disorder.

Objective: To investigate the prevalence and correlates of eating disorder symptoms in adolescents with bipolar I disorder (BP I). Methods: We retrospectively collected a DSM-IV-TR-based diagnostic assessment of 179 adolescents with BP I and evaluated clinical variables in those with and without eating disorder symptoms. For comparison, we retrospectively evaluated eating disorder symptoms in adolescents with generalized anxiety disorder (GAD). Results: Thirty-six percent of adolescents with BP I experienced lifetime eating disorder symptoms; among comorbid adolescents, 74% reported eating disorder cognitions and 40% reported symptoms related to bingeing, 25% purging, and 17% restricting. BP I adolescents with (vs. without) eating disorder symptoms had higher Children's Depression Rating Scale-Revised scores (40.5 vs. 34.5; p < 0.001; effect size = 0.59) and were more likely to be female (75% vs. 45%; p < 0.001; odds ratio = 3.8). There were no differences in Young Mania Rating Scale scores (p = 0.70); lifetime presence of attention-deficit/hyperactivity disorder (p = 0.86) and alcohol (p = 0.59) or substance (p = 0.89) abuse/dependence symptoms; age of BP I onset (p = 0.14); inpatient hospitalization status at baseline (p = 0.53); presence of lifetime inpatient hospitalization (p = 0.64) or suicide attempt (p = 0.35); seriousness of suicidality (p = 0.86); body mass index (p = 0.48); and second-generation antipsychotic (SGA; p = 0.32) or non-SGA mood stabilizer (p = 0.09) use. Eating disorder cognitions (rather than behaviors) were higher in the GAD group (58%) compared with the BP I group (27%; p = 0.004). Limitations: A retrospective study is subject to recall bias and limits our understanding of the temporal relationship between eating disorder and mood symptoms. Conclusions: Eating disorder symptoms are frequently comorbid in adolescents with BP I. The comorbidity is associated with more severe depression but does not confer a more severe illness course.

A retrospective examination of adjunctive L-methylfolate in children and adolescents with unipolar depression.

BACKGROUND: Adjunctive l-methylfolate is commonly prescribed for children and adolescents with treatment-resistant mood disorders; however, the relationship between l-methylfolate augmentation across methylenetetrahydrofolate reductase (MTHFR) genotypes in youths with depressive symptoms is unclear. METHODS: We retrospectively examined the electronic health records of patients (N = 412) with depressive symptoms associated with unipolar depressive disorders and their MTHFR C677T genotypes from 2013 to 2019. Patients were ≤18 years of age at the time of MTHFR pharmacogenetic testing. Treatment response was assessed with Clinical Global Impression-Improvement (CGI-I) score reported in the medical record. RESULTS: Patients with an MTHFR C677T C/T or T/T genotype were more likely to be prescribed l-methylfolate when the clinician knew their MTHFR genotype (p < 0.0001, OR: 15.1, 95 % CI: [5.1, 44.2]), but not when the clinician did not know their genotype (p = 0.4, OR: 2.1, 95 % CI: [0.4, 11.4]). Change in baseline and endpoint CGI-I scores between patients with an MTHFR C677T variant who were prescribed and not prescribed l-methylfolate did not significantly differ (p = 0.39). Response rate was not associated with l-methylfolate prescription (p = 0.17) or l-methylfolate dose (p = 0.69). LIMITATIONS: This was a retrospective study, which yielded a heterogeneous patient population and limited data availability (e.g., adherence). Patients are severely ill and may have a refractory illness that limits response to adjunctive l-methylfolate. CONCLUSION: Clinicians prescribe l-methylfolate to children and adolescents with depressive symptoms associated with unipolar depressive disorders who have an MTHFR C677T variant, although augmentation may not be associated with treatment response, regardless of MTHFR genotype or dose.

Pharmacogenetically Guided Escitalopram Treatment for Pediatric Anxiety Disorders: Protocol for a Double-Blind Randomized Trial.

Current pharmacologic treatments for pediatric anxiety disorders (e.g., selective serotonin reuptake inhibitors (SSRIs)) frequently use "one size fits all" dosing strategies based on average responses in clinical trials. However, for some SSRIs, including escitalopram, variation in CYP2C19 activity produces substantial variation in medication exposure (i.e., blood medication concentrations). This raises an important question: would refining current SSRI dosing strategies based on CYP2C19 phenotypes increase response and reduce side effect burden? To answer this question, we designed a randomized, double-blind trial of adolescents 12-17 years of age with generalized, separation, and/or social anxiety disorders (N = 132). Patients are randomized (1:1) to standard escitalopram dosing or dosing based on validated CYP2C19 phenotypes for escitalopram metabolism. Using this approach, we will determine whether pharmacogenetically-guided treatment-compared to standard dosing-produces faster and greater reduction in anxiety symptoms (i.e., response) and improves tolerability (e.g., decreased risk of treatment-related activation and weight gain). Secondarily, we will examine pharmacodynamic variants associated with treatment outcomes, thus enhancing clinicians' ability to predict response and tolerability. Ultimately, developing a strategy to optimize dosing for individual patients could accelerate response while decreasing side effects-an immediate benefit to patients and their families. ClinicalTrials.gov Identifier: NCT04623099.

Sex, ethnicity, and antipsychotic medication use in patients with psychosis.

Previous studies suggested that African American patients with psychotic disorders receive higher doses of antipsychotic medication than white patients, are more likely to receive depot antipsychotics, and are less likely to be prescribed second-generation antipsychotics. African-American men in particular may be most likely to receive excessive doses of antipsychotics and depot antipsychotics, although this is less clear. Few studies have examined how sex and ethnicity interactions affect treatment of psychotic disorders. In this study, we examined whether the interaction of sex and ethnicity predicted the use of depot antipsychotics and the dosing of antipsychotics in a sample of inpatients with psychotic disorders. The inpatient records of 167 patients with psychotic disorders were evaluated for type and dose of medication at discharge. African-American men received depot antipsychotic medication more frequently than African-American women and white patients. This difference persisted after controlling for sociodemographic and clinical variables. African-American men and women with psychotic mood disorders were also more likely to be discharged on high antipsychotic doses compared with white patients. There were no ethnic or sex differences in the dosing of antipsychotics for the treatment of schizophrenia spectrum disorders. There were also no ethnic or sex differences in the use of second-generation antipsychotics.