Treatment resistance in schizophrenia: a meta-analysis of prevalence and correlates

Objectives: To determine the prevalence and correlates of treatment-resistant schizophrenia (TRS) through a systematic review and meta-analysis. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, an electronic search was performed in PubMed and Embase through May 17, 2022. All study designs that assessed a minimum of 20 schizophrenia-spectrum patients and provided data on TRS prevalence or allowed its calculation were included. Estimates were produced using a random-effects model meta-analysis. Results: The TRS prevalence across 50 studies (n = 29,390) was 36.7% (95%CI 33.1-40.5, p < 0.0001). The prevalence ranged from 22% (95%CI 18.4-25.8) in first-episode to 39.5% (95%CI 32.2-47.0) in multiple-episode samples (Q = 18.27, p < 0.0001). Primary treatment resistance, defined as no response from the first episode, was 23.6% (95%CI 20.5-26.8) vs. 9.3% (95%CI 6.8-12.2) for later-onset/secondary (≥ 6 months after initial treatment response). Longer illness duration and recruitment from long-term hospitals or clozapine clinics were associated with higher prevalence estimates. In meta-regression analyses, older age and poor functioning predicted greater TRS. When including only studies with lower bias risk, the TRS prevalence was 28.4%. Conclusion: Different study designs and recruitment strategies accounted for most of the observed heterogeneity in TRS prevalence rates. The results point to early-onset and later-onset TRS as two separate disease pathways requiring clinical attention. Registration number: PROSPERO CRD42018092033.

Appraising the effectiveness of electrical and magnetic brain stimulation techniques in acute major depressive episodes: an umbrella review of meta-analyses of randomized controlled trials

Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of meta-analyses of randomized controlled trials of brain stimulation techniques for managing acute major depressive episodes. A systematic review was performed in the PubMed/MEDLINE databases from inception until March 2020. We included the English language meta-analysis with the most randomized controlled trials on the effects of any brain stimulation technique vs. control in adults with an acute depressive episode. Continuous and dichotomous outcomes were assessed. A Measurement Tool to Assess Systematic Reviews-2 was applied and the credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Seven meta-analyses were included (5,615 patients), providing evidence for different modalities of brain stimulation techniques. Three meta-analyses were evaluated as having high methodological quality, three as moderate, and one as low. The highest quality of evidence was found for high frequency-repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, and bilateral rTMS. There is strong clinical research evidence to guide future clinical use of some techniques. Our results confirm the heterogeneity of the effects across these techniques, indicating that different mechanisms of action lead to different efficacy profiles.

How can we improve antidepressant adherence in the management of depression? A targeted review and 10 clinical recommendations

Adherence to antidepressants is crucial for optimal treatment outcomes when treating depressive disorders. However, poor adherence is common among patients prescribed antidepressants. This targeted review summarizes the main factors associated with poor adherence, interventions that promote antidepressant adherence, pharmacological aspects related to antidepressant adherence, and formulates 10 clinical recommendations to optimize antidepressant adherence. Patient-related factors associated with antidepressant non-adherence include younger age, psychiatric and medical comorbidities, cognitive impairment, and substance use disorders. Prescriber behavior-related factors include neglecting medical and family histories, selecting poorly tolerated antidepressants, or complex antidepressant regimens. Multi-disciplinary interventions targeting both patient and prescriber, aimed at improving antidepressant adherence, include psychoeducation and providing the patient with clear behavioral interventions to prevent/minimize poor adherence. Regarding antidepressant choice, agents with individually tailored tolerability profile should be chosen. Ten clinical recommendations include four points focusing on the patient (therapeutic alliance, adequate history taking, measurement of depressive symptoms, and adverse effects improved access to clinical care), three focusing on prescribing practice (psychoeducation, individually tailored antidepressant choice, simplified regimen), two focusing on mental health services (improved access to mental health care, incentivized adherence promotion and monitoring), and one relating to adherence measurement (adherence measurement with scales and/or therapeutic drug monitoring).

Early stages of bipolar disorder: characterization and strategies for early intervention

Objective: To characterize the early stages of bipolar disorder (BD), defined as the clinical prodrome/subsyndromal stage and first-episode phase, and strategies for their respective treatment. Methods: A selective literature search of the PubMed, Embase, PsycINFO, and ISI databases from inception until March 2014 was performed. Included in this review were articles that a) characterized prodromal and first-episode stages of BD or b) detailed efficacy and safety/tolerability of interventions in patients considered prodromal for BD or those with only one episode of mania/hypomania. Results: As research has only recently focused on characterization of the early phase of BD, there is little evidence for the effectiveness of any treatment option in the early phase of BD. Case management; individual, group, and family therapy; supportive therapy; and group psychoeducation programs have been proposed. Most evidence-based treatment guidelines for BD do not address treatment specifically in the context of the early stages of illness. Evidence for pharmacotherapy is usually presented in relation to illness polarity (i.e., manic/mixed or depressed) or treatment phase. Conclusions: Although early recognition and treatment are critical to preventing unfavorable outcomes, there is currently little evidence for interventions in these stages of BD.

Clinical characteristics and influence of childhood trauma on the prodrome of bipolar disorder

Objectives: To describe the onset pattern, frequency, and severity of the signs and symptoms of the prodrome of the first hypomanic/manic episode and first depressive episode of bipolar disorder (BD) and to investigate the influence of a history of childhood maltreatment on the expression of prodromal symptoms. Methods: Using a semi-structured interview, the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R), information regarding prodromal symptoms was assessed from patients with a DSM-IV diagnosis of BD. History of childhood maltreatment was evaluated using the Childhood Trauma Questionnaire (CTQ). Results: Forty-three individuals with stable BD were included. On average, the prodrome of mania lasted 35.8±68.7 months and was predominantly subacute or insidious, with rare acute presentations. The prodrome of depression lasted 16.6±23.3 months and was also predominantly subacute or insidious, with few acute presentations. The prodromal symptoms most frequently reported prior to the first hypomanic or manic episode were mood lability, depressive mood, and impatience. A history of childhood abuse and neglect was reported by 81.4% of participants. Presence of childhood maltreatment was positively associated with prodromal symptoms, including social withdrawal, decreased functioning, and anhedonia. Conclusions: This study provides evidence of a long-lasting, symptomatic prodrome prior to first hypomanic/manic and depressive episode in BD and suggests that a history of childhood maltreatment influences the manifestations of this prodrome.

Translation and adaptation of the Bipolar Prodrome Symptom Scale-Retrospective: Patient Version to Brazilian portuguese / Tradução e adaptação da Bipolar Prodrome Symptom Scale-Retrospective: Patient Version para português brasileiro

BACKGROUND: Bipolar disorder (BD) is a chronic and often severe mental disease, associated with a significant burden in affected individuals. The characterization of a premorbid (prodromal) period and possible development of preventive interventions are recent advances in this field. Attempts to characterize high-risk stages in BD, identifying symptoms prior to the emergence of a first manic/hypomanic episode, have been limited by a lack of standardized criteria and instruments for assessment. The Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R), developed by Correll and collaborators, retrospectively evaluates symptoms that occur prior to a first full mood episode in individuals with BD. OBJECTIVE: To describe the translation and adaptation process of the BPSS-R to Brazilian Portuguese. METHOD: Translation was conducted as follows: 1) translation of the scale from English to Brazilian Portuguese by authors who have Portuguese as their first language; 2) merging of the two versions by a committee of specialists; 3) back-translation to English by a translator who is an English native speaker; 4) correction of the new version in English by the author of the original scale; 5) finalization of the new version in Brazilian Portuguese. RESULTS: All the steps of the translation process were successfully accomplished, resulting in a final version of the instrument. CONCLUSIONS: The Brazilian Portuguese version of the BPSS-R is a potentially useful instrument to investigate prodromal period of BD in Brazil

INTRODUÇÃO: O transtorno bipolar (TB) é um transtorno mental crônico e muitas vezes grave, associado a um significativo prejuízo psicossocial nos indivíduos afetados. A caracterização de um período pré-mórbido (prodrômico) e o possível desenvolvimento de intervenções preventivas são avanços recentes na área. Tentativas de caracterizar estágios de alto risco para o TB, através da identificação de sintomas antes do aparecimento de um primeiro episódio maníaco/hipomaníaco, têm sido limitadas pela falta de critérios padronizados e instrumentos de avaliação. A Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R), desenvolvida por Correll e colaboradores, avalia retrospectivamente os sintomas que ocorrem antes de um episódio sindrômico de humor em indivíduos com TB. OBJETIVO: Descrever o processo de tradução e adaptação da BPSS-R para português brasileiro. MÉTODO: A tradução foi conduzida como segue: 1) tradução da escala de inglês para português brasileiro por autores que têm o português como língua materna; 2) junção das duas versões por um comitê de especialistas; 3) retrotradução para inglês por um tradutor que tem inglês como língua materna; 4) correção da nova versão em inglês pelo autor do instrumento original; 5) finalização da nova versão em português brasileiro. RESULTADOS: Todos os passos do processo de tradução foram completados com sucesso, resultando em uma versão final do instrumento. CONCLUSÕES: A versão da BPSS-R em português brasileiro é um instrumento potencialmente útil para investigar o período prodrômico do TB no Brasil