ABSTRACT
OBJECTIVE: To examine the association between antibiotic and acid suppressant prescriptions in the first 2 years of life and subsequent treatment for childhood psychiatric disorders. STUDY DESIGN: This was a retrospective cohort study of children born between October 2001 and September 2012 in the Military Health System enrolled in TRICARE past age 2 years and within 35 days of birth, with an initial hospital stay <7 days, and without psychotropic agents dispensed during the first 2 years of life. Exposure was defined as a filled prescription for an antibiotic or acid suppressant before age 2 years, and the outcome was defined as a filled prescription for a psychotropic agent after age 2 years. RESULTS: For the 804 920 patients (51% males and 49% female) composing the study population, the mean age at first psychotropic prescription was 6.8 years. A total of 24 176 children (3%) were prescribed a proton pump inhibitor (PPI), 79 243 (10%) were prescribed a histamine-2 receptor antagonist (H2RA), and 607 348 (76%) were prescribed an antibiotic during the first 2 years of life. The adjusted hazard ratio (aHR) of a psychotropic prescription was significantly increased in children prescribed any H2RA (1.79; 95% CI, 1.63-1.96), PPI (1.47; 95% CI, 1.26-1.71), or antibiotic (1.71; 95% CI, 1.59-1.84). The aHR of psychotropic prescriptions increased commensurately with each additional antibiotic class added and with each additional class of medication (H2RA, PPI, or antibiotics) prescribed. CONCLUSIONS: Children prescribed antibiotic and acid suppressants in the first 2 years of life have a significant increase in future prescriptions for psychotropics, with a dose-related effect observed. This association represents a potential risk of early exposure to antibiotics and acid suppressants.
Subject(s)
Anti-Bacterial Agents , Histamine H2 Antagonists , Anti-Bacterial Agents/therapeutic use , Child , Child, Preschool , Female , Histamine H2 Antagonists/therapeutic use , Humans , Male , Prescriptions , Proton Pump Inhibitors/therapeutic use , Psychotropic Drugs/therapeutic use , Retrospective StudiesABSTRACT
OBJECTIVE: The potential of clozapine in severe bipolar disorder is suggested by its efficacy in refractory schizophrenia, but the evidence is limited thus far. This report utilizes data from the standard care pathway of the Systematic Treatment Enhancement Program to examine the clinical impact of clozapine in bipolar disorder, comparing it to two groups, one that received olanzapine and an additional group that received neither drug. METHOD: A total of 4,032 outpatients were available for this analysis. Groups for longitudinal analyses are based on the medication used at each visit. Outcomes assessed were clinical status, symptoms subscales, hospitalizations, and death. We utilized mixed models and generalized estimating equations to adjust for baseline differences and investigate longitudinal differences in symptoms, clinical status, and hospitalization rates between groups. RESULTS: During the study, 1.1% (n = 43) of the patients used clozapine at any time. Those on clozapine had significantly fewer manic and depressive symptoms during follow-up as compared with those on neither clozapine nor olanzapine, while those on olanzapine had more symptoms. The use of clozapine was not associated with an increased risk of hospitalization. No deaths were recorded for clozapine group during the trial. CONCLUSIONS: Although prescribed to very few patients, the impact of clozapine was notable, with fewer symptoms in patients who had more severe illnesses at baseline. Clozapine could prove to be as successful an intervention for late-stage bipolar disorder as it has been in schizophrenia.
Subject(s)
Antipsychotic Agents/pharmacology , Bipolar Disorder/drug therapy , Clozapine/pharmacology , Olanzapine/pharmacology , Outcome Assessment, Health Care , Adult , Antipsychotic Agents/administration & dosage , Clozapine/administration & dosage , Female , Hospitalization , Humans , Longitudinal Studies , Male , Middle Aged , Olanzapine/administration & dosage , Outpatients , Program Development , United StatesABSTRACT
OBJECTIVE: Staging models may provide heuristic utility for intervention selection in psychiatry. Although a few proposals have been put forth, there is a need for empirical validation if they are to be adopted. Using data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), we tested a previously elaborated hypothesis on the utility of using the number of previous episodes as a relevant prognostic variable for staging in bipolar disorder. METHODS: This report utilizes data from the multisite, prospective, open-label study 'Standard Care Pathways' and the subset of patients with acute depressive episodes who participated in the randomized trial of adjunctive antidepressant treatment. Outpatients meeting DSM-IV diagnostic criteria for bipolar disorder (n = 3345) were included. For the randomized pathway, patients met criteria for an acute depressive episode (n = 376). The number of previous episodes was categorized as less than 5, 5-10 and more than 10. We used disability at baseline, number of days well in the first year and longitudinal scores of depressive and manic symptoms, quality of life and functioning as validators of models constructed a priori. RESULTS: Patients with multiple previous episodes had consistently poorer cross-sectional and prospective outcomes. Functioning and quality of life were worse, disability more common, and symptoms more chronic and severe. There was no significant effect for staging with regard to antidepressant response in the randomized trial. CONCLUSIONS: These findings confirm that bipolar disorder can be staged with prognostic validity. Stages can be used to stratify subjects in clinical trials and develop specific treatments.