Association of Early Life Prescriptions for Antibiotics and Acid Suppressants with Childhood Psychotropic Prescriptions.

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.

Clozapine and the Course of Bipolar Disorder in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

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.

Cumulative morbidity and prognostic staging of illness in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

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.

Antidepressant treatment-emergent affective switch in bipolar disorder: a prospective case-control study of outcome

OBJECTIVE: Treatment-emergent affective switch has been associated to cycle acceleration and poorer outcome, but there are few studies addressing this issue. The aim of this study was to prospectively compare the outcome of patients presenting treatment-emergent affective switch with patients with spontaneous mania, regarding presence and polarity of a new episode and time to relapse. METHOD: Twenty-four patients with bipolar disorder according to the DSM-IV were followed for 12 months. Twelve patients had treatment-emergent affective switch and twelve had spontaneous mania. Patients were evaluated weekly with the Young Mania Rating Scale and the Hamilton Depression Scale until remission of the index episode, and monthly until completion of the 12-month follow-up. RESULTS: Eleven patients with treatment-emergent affective switch had a recurrence on follow-up, all of them with major depressive episodes. In the group with spontaneous mania, six patients had a recurrence: two had a depressive episode, and four had a manic episode (p = 0.069 for new episode, p = 0.006 for polarity of the episode). Patients with treatment-emergent affective switch relapsed in a shorter period than patients with spontaneous mania (p = 0.016). CONCLUSIONS: In this first prospective study, treatment-emergent affective switch patients were at greater risk of relapses, especially depressive episodes, and presented a shorter duration of remission when compared with patients with spontaneous mania.

OBJETIVO: A ciclagem para mania associada ao antidepressivo tem sido relacionada à aceleração do ciclo e pior evolução, mas há poucos estudos na literatura sobre este assunto. O objetivo deste estudo foi comparar prospectivamente a evolução de pacientes com mania associada a antidepressivo com pacientes com mania espontânea, em relação a tempo para recaída e polaridade do novo episódio. MÉTODO: Vinte e quatro pacientes com transtorno bipolar, de acordo com os critérios diagnósticos do DSM-IV, foram seguidos por 12 meses: 12 pacientes com mania associada a antidepressivo e 12 pacientes com mania espontânea. Os pacientes foram avaliados semanalmente com a Escala para Mania de Young e a Escala para Depressão de Hamilton até remissão do episódio inicial e, mensalmente, até completar o período de seguimento de 12 meses. RESULTADOS: Onze pacientes com mania associada ao antidepressivo tiveram uma recorrência no seguimento, sendo todos os episódios depressivos. No grupo de mania espontânea, seis pacientes apresentaram recorrência, sendo dois episódios depressivos, e quatro episódios de mania (p = 0,069 para novo episódio e p = 0,006 para polaridade do episódio). Pacientes com mania associada a antidepressivo recaíram em um menor período de tempo que os pacientes com mania espontânea (p = 0,016). CONCLUSÕES: Neste estudo prospectivo, os pacientes com mania associada a antidepressivo apresentaram maior risco de recorrência, especialmente episódios depressivos, e com menor duração de remissão quando comparados aos pacientes com mania espontânea.

Antidepressant treatment-emergent affective switch in bipolar disorder: a prospective case-control study of outcome.

OBJECTIVE: Treatment-emergent affective switch has been associated to cycle acceleration and poorer outcome, but there are few studies addressing this issue. The aim of this study was to prospectively compare the outcome of patients presenting treatment-emergent affective switch with patients with spontaneous mania, regarding presence and polarity of a new episode and time to relapse. METHOD: Twenty-four patients with bipolar disorder according to the DSM-IV were followed for 12 months. Twelve patients had treatment-emergent affective switch and twelve had spontaneous mania. Patients were evaluated weekly with the Young Mania Rating Scale and the Hamilton Depression Scale until remission of the index episode, and monthly until completion of the 12-month follow-up. RESULTS: Eleven patients with treatment-emergent affective switch had a recurrence on follow-up, all of them with major depressive episodes. In the group with spontaneous mania, six patients had a recurrence: two had a depressive episode, and four had a manic episode (p = 0.069 for new episode, p = 0.006 for polarity of the episode). Patients with treatment-emergent affective switch relapsed in a shorter period than patients with spontaneous mania (p = 0.016). CONCLUSIONS: In this first prospective study, treatment-emergent affective switch patients were at greater risk of relapses, especially depressive episodes, and presented a shorter duration of remission when compared with patients with spontaneous mania.

El tratamiento de la depresión después de la respuesta inicial a la terapia electrocunvulsiva / Depresion treatment after electroconvulsive therapy

Aunque la terapia electroconvulsiva (TEC) es con frecuencia efectiva para el tratamiento agudo de la depresión mayor (DM), sus efectos benéficos suelen ser de corta duración. La recaída después de la respuesta exitosa a la TEC. continúa siendo un problema de consideración que complica el tratamiento a largo plazo del paciente deprimido. La presente revisión de la literatura publicada en inglés analiza los beneficios de la profilaxis post-TEC, tanto farmacológica como mediante el uso de TEC de mantenimiento (TEC-m) en la prevención de epìsodios depresivos subsecuentes. Durante el primer año posterior al tratamiento exitoso con tec, la recurrencia de depresión fue aproximadamente del 50 por ciento. El uso de farmacoterapia o TEC de mantenimiento reduce significativamante la tasa de recaída. Sin embargo, la evidencia encontrada no fue suficiente para recomendar un tratamiento profiláctico sobre otro. Son necesarios más estudios acerca de posibles predictores y medidas preventivas de la recurrencia de depresión después del tratamiento con TEC.