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BACKGROUND: The combination of antipsychotics is not well studied among non-psychotic major depressive disorder (MDD). This study aims to explore the antipsychotics use in this population and its associated factors. METHODS: This cross-sectional and multi-site study was conducted in 11 sites of China. one Thousand five hundred three eligible MDD patients after 8-12 weeks of antidepressant treatment were included consecutively. A structured questionnaire was used to obtain socio-demographic data and medical histories. The Chinese version of the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR), the Patient Health Questionnaire-15 (PHQ-15) and the Sheehan Disability Scale (SDS) were used for patient self-rating. Logistic regression model was used to explore the associated factors that could potentially be influential for the use antipsychotic augmentation. RESULTS: Overall, quetiapine (43.4%) was the most commonly used as an adjunct to antidepressants, followed by olanzapine (38.8%). And antipsychotics were commonly combined with escitalopram (23.1%), venlafaxine (21.7%), sertraline (14.8%). The factors influencing the combination of antipsychotics in non-psychotic depressed patients included service setting (OR = 0.444; p < 0.001; 95%CI = 0.338-0.583), comorbidity of physical illness (OR = 1.704; p < 0.001; 95%CI = 1.274-2.278), PHQ level (OR = 0.680; p < 0.001; 95%CI = 0.548-0.844), SDS level (OR = 1.627; p < 0.001; 95%CI = 1.371-1.930) and antidepressants co-treatment (OR = 2.606; p < 0.001; 95%CI = 1.949-3.485). CONCLUSIONS: Antipsychotics use is common among non-psychotic MDD patient. Service setting, comorbidity of physical illness, somatic symptoms, social functioning and engagement, and antidepressants co-treatment could be the factors associated with the antipsychotics use in MDD patients.
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Antipsicóticos , Trastorno Depresivo Mayor , Antidepresivos/uso terapéutico , Antipsicóticos/uso terapéutico , Estudios Transversales , Trastorno Depresivo Mayor/diagnóstico , Humanos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Antipsychotic polypharmacy (APP) is frequently prescribed for schizophrenia-spectrum disorders. Despite the inconsistent findings on efficacy, APP may be beneficial for subgroups of psychotic patients. This meta-analysis of individual patient data investigated moderators of efficacy and tolerability of APP in adult patients with schizophrenia-spectrum disorders. DESIGN: We searched PubMed, EMBASE, and the Cochrane Central Register of Randomized Trials until September 1, 2022, for randomized controlled trials comparing APP with antipsychotic monotherapy. We estimated the effects with a one-stage approach for patient-level moderators and a two-stage approach for study-level moderators, using (generalized) linear mixed-effects models. Primary outcome was treatment response, defined as a reduction of 25 % or more in the Positive and Negative Syndrome Scale (PANSS) score. Secondary outcomes were study discontinuation, and changes from baseline on the PANSS total score, its positive and negative symptom subscale scores, the Clinical Global Impressions Scale (CGI), and adverse effects. RESULTS: We obtained individual patient data from 10 studies (602 patients; 31 % of all possible patients) and included 599 patients in our analysis. A higher baseline PANSS total score increased the chance of a response to APP (OR = 1.41, 95 % CI 1.02; 1.94, p = 0.037 per 10-point increase in baseline PANSS total), mainly driven by baseline positive symptoms. The same applied to changes on the PANSS positive symptom subscale and the CGI severity scale. Extrapyramidal side effects increased significantly where first and second-generation antipsychotics were co-prescribed. Study discontinuation was comparable between both treatment arms. CONCLUSIONS: APP was effective in severely psychotic patients with high baseline PANSS total scores and predominantly positive symptoms. This effect must be weighed against potential adverse effects.
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OBJECTIVE: Pediatric bipolar disorder (PBD) is associated with poor outcomes, including suicidal ideation (SI) and suicide attempt (SA). However, frequencies and risk factors of SI/SA and targeted intervention trials for SI/SA in PBD have not been reviewed systematically. METHODS: We conducted a systematic PubMed review, searching for articles reporting on prevalences/incidences, correlates and intervention studies targeting SI/SA in PBD. Weighted means were calculated, followed by an exploratory meta-regression of SI and SA correlates. RESULTS: Fourteen studies (n = 1595), in which 52.1% of patients were male and the mean age was 14.4 years, reported data on SI/SA prevalence (N = 13, n = 1508) and/or correlates (N = 10, n = 1348) in PBD. Weighted mean prevalences were: past SI = 57.4%, past SA = 21.3%, current SI = 50.4%, and current SA = 25.5%; incidences (mean 42 months of follow-up) were: SI = 14.6% and SA = 14.7%. Regarding significant correlates, SI (N = 3) was associated with a higher percentage of Caucasian race, narrow (as opposed to broad) PBD phenotype, younger age, and higher quality of life than SA. Significant correlates of SA (N = 10) included female sex, older age, earlier illness onset, more severe/episodic PBD, mixed episodes, comorbid disorders, past self-injurious behavior/SI/SA, physical/sexual abuse, parental depression, family history of suicidality, and poor family functioning. Race, socioeconomic status, living situation, and life events were not clearly associated with SA. In a meta-regression analysis, bipolar I disorder and comorbid attention-deficit hyperactivity disorder were significantly associated with SA. Only one open label study targeting the reduction of SI/SA in PBD was identified. CONCLUSIONS: SI and SA are very common but under-investigated in PBD. Exploration of predictors and protective factors is imperative for the establishment of effective preventive and intervention strategies, which are urgently needed.
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Trastorno Bipolar , Ideación Suicida , Intento de Suicidio , Adolescente , Trastorno Bipolar/epidemiología , Trastorno Bipolar/psicología , Trastorno Bipolar/terapia , Niño , Bases de Datos Factuales/estadística & datos numéricos , Femenino , Humanos , Incidencia , Masculino , Prevalencia , Intento de Suicidio/prevención & control , Intento de Suicidio/psicología , Intento de Suicidio/estadística & datos numéricosRESUMEN
Background: This study aims to investigate the factors associated with sexual dysfunction (SD), with a particular focus on the influence of sex on the occurrence and severity of this condition in patients with major depressive disorder (MDD). Method: Sociodemographic and clinical assessments were conducted on 273 patients with MDD (female = 174, male = 99), including the ASEX, QIDS-SR16, GAD-7, and PHQ-15. Univariate analyses, independent samples t-test, Chi-square test, and Fisher's exact test were used as appropriate, and logistic regression analysis was used to identify correlation factors for SD. Statistical analyses were performed using the Statistical Analysis System (SAS 9.4). Result: SD was reported in 61.9% of the participants (ASEX score = 19.6 ± 5.5), and the prevalence of it in females (75.3%, ASEX score = 21.1 ± 5.4) was significantly higher than that in males (38.4%, ASEX score = 17.1 ± 4.6). Factors associated with SD included being female, being aged 45 years or above, having a low monthly income (≤750 USD), feeling more sluggish than usual (a QIDS-SR16 Item 15 score of 1 or above), and having somatic symptoms (evaluated with the total score of PHQ15). Limitation: The use of antidepressants and antipsychotics might be a confounding factor affecting sexual function. Also, the lack of information in the clinical data regarding the number, duration, and time of onset of the episodes limits the richness of the results. Conclusion: Our findings reveal the sex differences in the prevalence and severity of SD in patients with MDD. Evaluated with the ASEX score, female patients showed significantly worse sexual function than male patients. Being female, having a low monthly income, being aged 45 years or above, feeling sluggish, and having somatic symptoms may increase the risk of SD in patients with MDD.
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OBJECTIVE: To evaluate 1) whether early nonresponse to antipsychotics predicts nonresponse and nonremission, 2) patient and illness characteristics as outcome predictors, and 3) response prediction of 30-item Positive and Negative Syndrome Scale (PANSS-30) compared with 6-item PANSS (PANSS-6) and Clinical Global Impressions-Improvement Scale (CGI-I) in youths with first-episode psychosis. METHOD: Post hoc analysis from a 12-week, double-blinded, randomized trial of aripiprazole vs extended-release quetiapine in adolescents (age 12-17 years) with first-episode psychosis was performed. Early nonresponse (week 2 or week 4) was defined as <20% symptom reduction (PANSS-30) (or <20% symptom reduction [PANSS-6] or CGI-I score 4-7 [less than "minimally improved"]). Nonresponse (week 12) was defined as <50% symptom reduction (PANSS-30). Nonremission (week 12) was defined as a score of >3 on 8 selected PANSS-items. Positive/negative predictive values (PPV/NPV) and receiver operating characteristics, binary logistic regression models, and PPV/NPV using PANSS-6 and CGI-I were analyzed. RESULTS: Of 113 randomized patients, 84 were included in post hoc analysis (mean [SD] age = 15.7 [1.3] years; 28.6% male). The 12-week symptom decrease was 31.9% [27.9%], most pronounced within the first 2 weeks (61.1% of total PANSS reduction). Response (27.4%) and remission (22.6%) rates were low. Results indicated that early nonresponse reliably predicted 12-week nonresponse (PPV: week 2, 82.2%; week 4, 90.0%) and nonremission (PPV: week 2, 80.0%; week 4, 90.0%); early nonresponse at week 4 was a statistically significant baseline predictor for 12-week nonresponse; and PANSS-6 had similar predictive significance as PANSS-30. However, outcomes were heterogeneous using CGI-I. CONCLUSION: In youths with first-episode psychosis showing early nonresponse to aripiprazole or extended-release quetiapine, switching antipsychotic drug should be considered. PANSS-6 is a feasible and clinically relevant alternative to PANSS-30 to predict 12-week nonresponse/nonremission. CLINICAL TRIAL REGISTRATION INFORMATION: Tolerance and Effect of Antipsychotics in Children and Adolescents With Psychosis; https://www. CLINICALTRIALS: gov/; NCT01119014.
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Antipsicóticos , Trastornos Psicóticos , Adolescente , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Aripiprazol/farmacología , Niño , Método Doble Ciego , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Trastornos Psicóticos/tratamiento farmacológico , Fumarato de Quetiapina/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: In patients with major depressive disorder (MDD), poor antidepressant treatment response might be associated with an excessive body mass index (BMI). However, the impact of underweight on treatment response is unclear. Moreover, it has not been studied whether a continuous or categorical BMI measure should be used to predict of treatment response. METHODS: Post-hoc analysis of data collected in a clinical trial including adults with MDD (n=202) reporting outcomes of antidepressant medication, i.e. paroxetine, mirtazapine or paroxetine+mirtazapine. Measures included baseline BMI (underweight=BMI <18.5, normal weight:=BMI:18.5-23.9, overweight=BMI≥24) and symptom severity (17-item-Hamilton Depression scale; HAMD-17) assessed at weeks 0, 2, 3, 4, 6 and 8. Univariate analyses were used to explore the effect of baseline BMI on HAMD-17 reduction, response (defined as ≥50% HAMD-17 reduction) and remission (defined as HAMD-17 ≤7) at endpoint. Pearson correlation were used to explore the relationship between body weight, BMI as continuous measure and HAMD-17 reduction. Logistic regression was used to determine the predictors for remission. Multiple linear regression was used to establish the correlation of BMI with change of HAMD-17. RESULTS: 111 (55.0%) patients were normal weight, 20 (9.9%) were underweight, 71 (35.1%) were overweight. Underweight patients showed the best improvement to antidepressant treatment. Non-remitters had greater body weight and BMI than remitters (P<0.05). The reduction of HAMD-17 was correlated with baseline body weight (r=-0.16, P=0.032) and BMI (r=-0.19, P=0.012). Logistic regression found patients with BMI<24 to be 2 times (OR=1.958, 95%CI: 1.015, 3.774) remitters (P=0.045) than overweight patients. The multiple linear regression showed that the change of HAMD-17 total score decreased with increasing BMI (ß=-0.32, P = 0.016). CONCLUSION: We confirmed that BMI can predict treatment outcomes in MDD. For the first time we found that underweight patients benefit most from antidepressant treatment. The findings may be useful to physicians in their decision regarding the choice of antidepressants according to BMI.
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Trastorno Depresivo Mayor , Adulto , Antidepresivos/uso terapéutico , Índice de Masa Corporal , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/epidemiología , Humanos , Paroxetina/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Evidence for the application of transcranial direct current stimulation (tDCS) in the clinical care of attention-deficit/hyperactivity disorder (ADHD) is limited. Therefore, we aimed to summarize study results using meta-analyses of measures of the cardinal symptoms of ADHD. METHODS: We conducted a systematic literature search (PubMed/pubpsych/PsychInfo/WOS) until 01/05/2020 for randomized controlled trials (RCTs) evaluating tDCS vs. control condition in patients with ADHD. A random effects meta-analysis of symptom-related outcomes was performed separately for data on the immediate effect and follow-up. Subgroup- and metaregression analyses for patient characteristics and tDCS parameters were included. RESULTS: Meta-analyzing 13 studies (n=308, age=23.7±13.3), including 20 study arms, tDCS had an immediate effect on overall symptom severity, inattention, and impulsivity, but not on hyperactivity. Results were significant in children and adolescents (8 studies, n=133, age=12.4±3.0). Follow-up data (3 days-4 weeks after stimulation) suggested an ongoing beneficial effect regarding overall symptom severity and a delayed effect on hyperactivity. DISCUSSION: TDCS seems to be a promising method to treat clinical symptoms in ADHD with long-lasting effects. Still, more research considering the individual neuropsychological and anatomical dispositions of the subjects is needed to optimize tDCS protocols and efficacy. Safety issues of tDCS treatment in children and adolescents are addressed.
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Trastorno por Déficit de Atención con Hiperactividad , Estimulación Transcraneal de Corriente Directa , Adolescente , Adulto , Trastorno por Déficit de Atención con Hiperactividad/terapia , Niño , Cognición , Humanos , Conducta Impulsiva , Resultado del Tratamiento , Adulto JovenRESUMEN
RATIONALE: Multiple drugs are known to induce metabolic malfunctions, among them second-generation antipsychotics (SGAs). The pathogenesis of such adverse effects is of multifactorial origin. OBJECTIVES: We investigated whether SGAs drive dysbiosis, assessed whether gut microbiota alterations affect body weight and metabolic outcomes, and looked for the possible mechanism of metabolic disturbances secondary to SGA treatment in animal and human studies. METHODS: A systematic literature search (PubMed/Medline/Embase/ClinicalTrials.gov/PsychInfo) was conducted from database inception until 03 July 2018 for studies that reported the microbiome and weight alterations in SGA-treated subjects. RESULTS: Seven articles reporting studies in mice (experiments = 8) and rats (experiments = 3) were included. Olanzapine was used in five and risperidone in six experiments. Only three articles (experiments = 4) in humans fit our criteria of using risperidone and mixed SGAs. The results confirmed microbiome alterations directly (rodent experiments = 5, human experiments = 4) or indirectly (rodent experiments = 4) with predominantly increased Firmicutes abundance relative to Bacteroidetes, as well as weight gain in rodents (experiments = 8) and humans (experiments = 4). Additionally, olanzapine administration was found to induce both metabolic alterations (adiposity, lipogenesis, plasma free fatty acid, and acetate levels increase) (experiments = 3) and inflammation (experiments = 2) in rodents, whereas risperidone suppressed the resting metabolic rate in rodents (experiments = 5) and elevated fasting blood glucose, triglycerides, LDL, hs-CRP, antioxidant superoxide dismutase, and HOMA-IR in humans (experiment = 1). One rodent study suggested a gender-dependent effect of dysbiosis on body weight. CONCLUSIONS: Antipsychotic treatment-related microbiome alterations potentially result in body weight gain and metabolic disturbances. Inflammation and resting metabolic rate suppression seem to play crucial roles in the development of metabolic disorders.
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Antipsicóticos/efectos adversos , Microbioma Gastrointestinal/efectos de los fármacos , Enfermedades Metabólicas/inducido químicamente , Enfermedades Metabólicas/metabolismo , Aumento de Peso/efectos de los fármacos , Animales , Antipsicóticos/uso terapéutico , Benzodiazepinas/efectos adversos , Benzodiazepinas/uso terapéutico , Microbioma Gastrointestinal/fisiología , Humanos , Hiperglucemia/inducido químicamente , Hiperglucemia/metabolismo , Olanzapina/efectos adversos , Olanzapina/uso terapéutico , Risperidona/efectos adversos , Risperidona/uso terapéutico , Aumento de Peso/fisiologíaRESUMEN
AIM: The Integrated Care in Early Psychosis (ACCESS III) Study examined the efficacy and cost-effectiveness of a combined intervention consisting of strategies to improve early detection and quality of care (integrated care including therapeutic assertive community treatment) in adolescents and young adults in the early phase of a severe psychotic disorder from 2011 to 2014. METHODS: This is a prospective, single-centre, 1-year cohort study comparing an intervention condition (early detection plus integrated care, n = 120) to the historical control condition (standard care, SC, n = 105) for adolescents and young adults aged 12-29 years suffering from a severe, early-phase psychotic disorder (i.e. within 2 years of treatment). RESULTS: Primary outcome is the rate of combined symptomatic (i.e. Positive and Negative Syndrome Scale (PANSS) criteria) and functional (i.e. Global Assessment of Functioning scale (GAF) ≥ 60 points criterion) remission over at least 6 months at study endpoint. Secondary outcome comprises the comparison of the reduction in the duration of untreated psychosis within the 4-year study duration between integrated care and SC, course of psychopathology, functioning, quality of life, satisfaction with care, cost and quality-adjusted life years (QALYs) in comparison to a historical control group. CONCLUSION: To the authors' knowledge, this is the first study assessing the efficacy and cost-effectiveness of a combined intervention consisting of early detection strategies and strategies to improve quality of care in both adolescents and young adults with early-phase psychosis. The results will be published in 2016.
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Prestación Integrada de Atención de Salud , Diagnóstico Precoz , Intervención Médica Temprana/métodos , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/terapia , Adolescente , Adulto , Niño , Estudios de Cohortes , Servicios Comunitarios de Salud Mental , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Satisfacción del Paciente , Estudios Prospectivos , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/psicología , Calidad de la Atención de Salud , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Resultado del Tratamiento , Adulto JovenRESUMEN
Importance: The value of early intervention in psychosis and allocation of public resources has long been debated because outcomes in people with schizophrenia spectrum disorders have remained suboptimal. Objective: To compare early intervention services (EIS) with treatment as usual (TAU) for early-phase psychosis. Data Sources: Systematic literature search of PubMed, PsycINFO, EMBASE, and ClinicalTrials.gov without language restrictions through June 6, 2017. Study Selection: Randomized trials comparing EIS vs TAU in first-episode psychosis or early-phase schizophrenia spectrum disorders. Data Extraction and Synthesis: This systematic review was conducted according to PRISMA guidelines. Three independent investigators extracted data for a random-effects meta-analysis and prespecified subgroup and meta-regression analyses. Main Outcomes and Measures: The coprimary outcomes were all-cause treatment discontinuation and at least 1 psychiatric hospitalization during the treatment period. Results: Across 10 randomized clinical trials (mean [SD] trial duration, 16.2 [7.4] months; range, 9-24 months) among 2176 patients (mean [SD] age, 27.5 [4.6] years; 1355 [62.3%] male), EIS was associated with better outcomes than TAU at the end of treatment for all 13 meta-analyzable outcomes. These outcomes included the following: all-cause treatment discontinuation (risk ratio [RR], 0.70; 95% CI, 0.61-0.80; P < .001), at least 1 psychiatric hospitalization (RR, 0.74; 95% CI, 0.61-0.90; P = .003), involvement in school or work (RR, 1.13; 95% CI, 1.03-1.24; P = .01), total symptom severity (standardized mean difference [SMD], -0.32; 95% CI, -0.47 to -0.17; P < .001), positive symptom severity (SMD, -0.22; 95% CI, -0.32 to -0.11; P < .001), and negative symptom severity (SMD, -0.28; 95% CI, -0.42 to -0.14; P < .001). Superiority of EIS regarding all outcomes was evident at 6, 9 to 12, and 18 to 24 months of treatment (except for general symptom severity and depressive symptom severity at 18-24 months). Conclusions and Relevance: In early-phase psychosis, EIS are superior to TAU across all meta-analyzable outcomes. These results support the need for funding and use of EIS in patients with early-phase psychosis.
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Intervención Médica Temprana/métodos , Trastornos Psicóticos/terapia , Esquizofrenia/terapia , Psicología del Esquizofrénico , Educación/estadística & datos numéricos , Empleo/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Humanos , Trastornos Psicóticos/psicología , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de Regresión , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To meta-analytically examine the trends and correlates of antipsychotic use in youth with mood disorders. METHODS: Systematic literature search without language restriction in PubMed/MEDLINE/PsycINFO from database inception through March 2015 using the following search terms: (antipsychotic* OR neuroleptic* OR "dopamine blocker*" OR antidopaminergic) AND (child* OR adolescen* OR pediatric OR youth) AND (prescription* OR prescrib* OR use OR utilization OR database OR pharmacoepidemiolog* OR frequency OR rate OR rates). Random effects meta-analysis and meta-regression analyses were conducted. STUDY SELECTION: Included were studies reporting on the frequency of (1) mood disorders in antipsychotic-treated youth (≤ 19 years) and (2) antipsychotic use in youth with mood disorders. DATA ABSTRACTION: Two independent investigators abstracted data on study, patient, and treatment characteristics. RESULTS: Forty-one studies were meta-analyzed (N = 518,919, mean ± SD age = 12.8 ± 1.8 years, males = 65.7%). Altogether, 24.2% of antipsychotic-treated youth had a mood disorder diagnosis (studies = 34, depression spectrum disorder = 10.9%, bipolar spectrum disorder = 13.6%). In longitudinal studies, the overall proportion increased significantly from 17.3% in 2000 (range, 1996-2009) to 24.5% in 2006 (range, 2004-2011) (odds ratio [OR] = 1.50; 95% confidence interval [CI], 1.26-1.79; P < .0001). This increase was driven entirely by bipolar spectrum diagnoses (2001 = 11.1%, 2006 = 16.3%, P < .0001), rather than depression spectrum diagnoses (2001 = 9.1%, 2007 = 9.2%, P = .77). Among youth with mood disorders (8 studies), 24.0% received antipsychotics (depression spectrum disorder = 4.6%; bipolar spectrum disorder = 44.0%). CONCLUSIONS: The proportion of youth with mood disorder diagnoses increased significantly among antipsychotic-treated youth, driven entirely by an increase in youth with bipolar spectrum disorders. Progress in understanding the reasons for these trends and for an evaluation of the appropriateness of the observed antipsychotic prescribing requires more detailed information than is available in traditional pharmacoepidemiologic databases.
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Antipsicóticos/uso terapéutico , Trastornos del Humor/tratamiento farmacológico , Adolescente , Antipsicóticos/efectos adversos , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/epidemiología , Trastorno Bipolar/psicología , Niño , Estudios Transversales , Utilización de Medicamentos/tendencias , Femenino , Humanos , Estudios Longitudinales , Masculino , Trastornos del Humor/diagnóstico , Trastornos del Humor/epidemiología , Trastornos del Humor/psicología , Uso Fuera de lo Indicado , Análisis de RegresiónRESUMEN
BACKGROUND: Although caregiver burden is relevant to the outcome for psychiatrically ill youth, most studies have focused on caregiver burden in the community or research settings. Therefore, we aimed at evaluating the subjective caregiver strain (SCS) at the time of presentation of youth to a pediatric psychiatric emergency room (PPER), assessing potential correlates to provide leads for improvements in formal support systems. METHODS: In this retrospective cohort study, the internalized, externalized, and total SCS were assessed in caregivers of youth <18 years of age consecutively evaluated at a PPER during a 1 year period using the Caregiver Strain Questionnaire. Sociodemographic and a broad range of clinical data were collected during the PPER visit using a 12-page semistructured institutional evaluation form. The Appropriateness of Pediatric Psychiatric Emergency Room Contact scale, incorporating acuity, severity and harm potential, was used to rate appropriateness of the visit. RESULTS: In caregivers of 444 youth, the internalized SCS was significantly higher than the externalized SCS (p < 0.001). Multivariable analyses indicated that higher total and externalized SCS were associated with disruptive behavior or substance abuse/dependent disorder diagnosis, presenting complaint of aggression, and discharge plan to the police. Higher total and internalized SCS were associated with lower child functioning, whereas total and internalized SCS were lower in adopted children. In addition, higher externalized SCS was associated with investigator-rated inappropriateness of the emergency visit, presenting complaint of defiance, and a lack of prior psychiatric ER visits. CONCLUSIONS: High levels of CS in PPER highlight the necessity to adhere to existing guidelines regarding the inclusion of caregivers' perceptions into comprehensive psychiatric assessments. The particularly high strain in caregivers of children with externalizing disorders and in families with low-functioning youth may need to prompt PPER staff to provide efficient information on appropriate treatment options for these children and on support facilities for the parents.
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Cuidadores/psicología , Trastornos Mentales/psicología , Padres/psicología , Estrés Psicológico/epidemiología , Adolescente , Niño , Preescolar , Estudios de Cohortes , Servicio de Urgencia en Hospital , Femenino , Adhesión a Directriz , Humanos , Control Interno-Externo , Masculino , Trastornos Mentales/epidemiología , Guías de Práctica Clínica como Asunto , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
Antipsychotic polypharmacy in schizophrenia is much debated, since it is common and costly with unclear evidence for its efficacy and safety. We conducted a systematic literature search and a random effects meta-analysis of randomized trials comparing augmentation with a second antipsychotic vs. continued antipsychotic monotherapy in schizophrenia. Co-primary outcomes were total symptom reduction and study-defined response. Antipsychotic augmentation was superior to monotherapy regarding total symptom reduction (16 studies, N=694, standardized mean difference, SMD=-0.53, 95% CI: -0.87 to -0.19, p=0.002). However, superiority was only apparent in open-label and low-quality trials (both p<0.001), but not in double-blind and high-quality ones (p=0.120 and 0.226, respectively). Study-defined response was similar between antipsychotic augmentation and monotherapy (14 studies, N=938, risk ratio = 1.19, 95% CI: 0.99 to 1.42, p=0.061), being clearly non-significant in double-blind and high-quality studies (both p=0.990). Findings were replicated in clozapine and non-clozapine augmentation studies. No differences emerged regarding all-cause/specific-cause discontinuation, global clinical impression, as well as positive, general and depressive symptoms. Negative symptoms improved more with augmentation treatment (18 studies, N=931, SMD=-0.38, 95% CI: -0.63 to -0.13, p<0.003), but only in studies augmenting with aripiprazole (8 studies, N=532, SMD=-0.41, 95% CI: -0.79 to -0.03, p=0.036). Few adverse effect differences emerged: D2 antagonist augmentation was associated with less insomnia (p=0.028), but more prolactin elevation (p=0.015), while aripiprazole augmentation was associated with reduced prolactin levels (p<0.001) and body weight (p=0.030). These data suggest that the common practice of antipsychotic augmentation in schizophrenia lacks double-blind/high-quality evidence for efficacy, except for negative symptom reduction with aripiprazole augmentation.
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INTRODUCTION: Antipsychotic co-treatment is common in schizophrenia, despite lacking evidence for its efficacy and safety. Areas: We conducted a systematic search of PubMed/PsycInfo/CJN/WangFan/CBM without language restrictions from database inception until 05/25/2015 for randomized trials comparing antipsychotic monotherapy with antipsychotic co-treatment in ≥20 adults with schizophrenia reporting meta-analyzable adverse events (AEs) data. Meta-analyzing 67 studies (n=4,861, duration=10.3±5.2 weeks), antipsychotic co-treatment was similar to monotherapy regarding intolerability-related discontinuation (risk ratio (RR)=0.84, 95% confidence interval (CI)=0.53-1.33, p=0.455). While incidence of ≥1 AE was lower with antipsychotic co-treatment (RR=0.77, 95%CI=0.66-0.90, p=0.001), these results were solely driven by open-label and efficacy-focused studies. Adjunctive D2-antagonists lead to less nausea (RR=0.220, 95%CI=0.06-0.87, p=0.030) and insomnia (RR=0.26, 95%CI=0.08-0.86, p=0.028), but higher prolactin (SMD=2.20, 95%CI=0.43-3.96, p=0.015). Conversely, adjunctive partial D2-agonists (aripiprazole=100%) resulted in lower electrocardiogram abnormalities (RR=0.43, 95%CI=0.25-0.73, p=0.002), constipation (RR=0.45, 95%CI=0.25-0.79, p=0.006), drooling/hypersalivation (RR=0.14, 95%CI=0.07-0.29, p<0.001), prolactin (SMD=-1.77, 95%CI=-2.38, -1.15, p<0.001), total and LDL-cholesterol (SMD=-0.33, 95%CI=-0.55, -0.11, p=0.003; SMD=-0.33, 95%CI=-0.54, -0.10, p=0.004). EXPERT OPINION: No double-blind evidence for altered AE burden associated with antipsychotic co-treatment was found. However, AEs were insufficiently and incompletely reported and follow-up duration was modest. Adjunctive partial D2-agonists might be beneficial for counteracting several AEs. High-quality, long-term studies that comprehensively assess AEs are needed.
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Antipsicóticos/administración & dosificación , Receptores de Dopamina D2/efectos de los fármacos , Esquizofrenia/tratamiento farmacológico , Adulto , Antipsicóticos/efectos adversos , Antipsicóticos/farmacología , Antagonistas de los Receptores de Dopamina D2/administración & dosificación , Antagonistas de los Receptores de Dopamina D2/efectos adversos , Agonismo Parcial de Drogas , Quimioterapia Combinada , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptores de Dopamina D2/metabolismoRESUMEN
OBJECTIVE: Although irritability and aggression are relevant treatment targets in autism spectrum disorders (ASDs) and intellectual disability (ID) that may prompt antipsychotic use, antipsychotic prescribing patterns in such youth have not been systematically reviewed. METHOD: We systematically searched PubMed/MEDLINE/PsycInfo until March 2015 for studies reporting data on the frequency of youth diagnosed with ASDs and/or ID among antipsychotic-treated youth, as well as antipsychotic use in youth with ASD/ID, conducting a meta-analysis and meta-regression analysis of potential moderators, including publication year, study time point, country, setting, sample size, age, sex, and race/ethnicity. RESULTS: A total of 39 studies were meta-analyzed (n = 365,449, age = 11.4 ± 6.2 years, males = 70.0% ± 10.0%). Among 27 studies (n = 273,139, age = 11.9 ± 8.0 years, males = 67.0% ± 12.9%) reporting on antipsychotic-treated youth, 9.5% (95% CI = 7.8%-11.5%) were diagnosed with ASD/ID. In 20 studies (n = 209,756) reporting data separately for ASD, 7.9% (95% CI = 6.2%-9.9%) had an ASD diagnosis. In 5 longitudinal studies, the proportion of antipsychotic-treated youth with ASD did not change significantly from 1996 to 2011 (6.7% to 5.8%, odds ratio = 0.9, 95% CI = 0.8-1.0, p =.17). However, later study time point moderated greater ASD/ID proportions (ß = 0.12, p < .00001). In 13 studies (n = 96,688, age = 9.8 ± 1.2 years, males = 78.6% ± 2.0%) reporting on antipsychotic use in ASD samples, 17.5% (95% CI = 13.7%-22.1%) received antipsychotics. Again, later study time point moderated higher antipsychotic use among patients with ASD (ß = 0.10, p = .004). CONCLUSION: Almost 1 in 10 antipsychotic-treated youth were diagnosed with ASD and/or ID, and 1 in 6 youth with ASD received antipsychotics. Both proportions increased in later years; however, clinical reasons and outcomes of antipsychotic use in ASD/ID require further study.
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Antipsicóticos/uso terapéutico , Trastorno del Espectro Autista/tratamiento farmacológico , Prescripciones de Medicamentos/estadística & datos numéricos , Discapacidad Intelectual/tratamiento farmacológico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adolescente , Niño , Preescolar , Humanos , Pautas de la Práctica en Medicina/tendenciasRESUMEN
Type 2 diabetes mellitus (T2DM) is highly predictive of cardiovascular diseases and can have particularly deleterious health impacts in people with severe mental illness (SMI), i.e. schizophrenia, bipolar disorder or major depressive disorder. This meta-analysis aimed: a) to describe pooled frequencies of T2DM in people with SMI; b) to analyze the influence of demographic, illness and treatment variables as well as T2DM assessment methods; and c) to describe T2DM prevalence in studies directly comparing persons with each specific SMI diagnosis to general population samples. The trim and fill adjusted pooled T2DM prevalence among 438,245 people with SMI was 11.3% (95% CI: 10.0%-12.6%). In antipsychotic-naïve participants, the prevalence of T2DM was 2.9% (95% CI: 1.7%-4.8%). There were no significant diagnostic subgroup differences. A comparative meta-analysis established that multi-episode persons with SMI (N=133,470) were significantly more likely to have T2DM than matched controls (N=5,622,664): relative risk, RR=1.85, 95% CI: 1.45-2.37, p<0.001. The T2DM prevalence was consistently elevated in each of the three major diagnostic subgroups compared to matched controls. Higher T2DM prevalences were observed in women with SMI compared to men (RR=1.43, 95% CI: 1.20-1.69, p<0.001). Multi-episode (versus first-episode) status was the only significant predictor for T2DM in a multivariable meta-regression analysis (r(2) =0.52, p<0.001). The T2DM prevalence was higher in patients prescribed antipsychotics, except for aripriprazole and amisulpride. Routine screening and multidisciplinary management of T2DM is needed. T2DM risks of individual antipsychotic medications should be considered when making treatment choices.
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IMPORTANCE: Antipsychotics are used increasingly in youth for nonpsychotic and off-label indications, but cardiometabolic adverse effects and (especially) type 2 diabetes mellitus (T2DM) risk have raised additional concern. OBJECTIVE: To assess T2DM risk associated with antipsychotic treatment in youth. DATA SOURCES: Systematic literature search of PubMed and PsycINFO without language restrictions from database inception until May 4, 2015. Data analyses were performed in July 2015, and additional analyses were added in November 2015. STUDY SELECTION: Longitudinal studies reporting on T2DM incidence in youth 2 to 24 years old exposed to antipsychotics for at least 3 months. DATA EXTRACTION AND SYNTHESIS: Two independent investigators extracted study-level data for a random-effects meta-analysis and meta-regression of T2DM risk. MAIN OUTCOMES AND MEASURES: The coprimary outcomes were study-defined T2DM, expressed as cumulative T2DM risk or as T2DM incidence rate per patient-years. Secondary outcomes included the comparison of the coprimary outcomes in antipsychotic-treated youth with psychiatric controls not receiving antipsychotics or with healthy controls. RESULTS: Thirteen studies were included in the meta-analysis, including 185,105 youth exposed to antipsychotics and 310,438 patient-years. The mean (SD) age of patients was 14.1 (2.1) years, and 59.5% were male. The mean (SD) follow-up was 1.7 (2.3) years. Among them, 7 studies included psychiatric controls (1,342,121 patients and 2,071,135 patient-years), and 8 studies included healthy controls (298,803 patients and 463,084 patient-years). Antipsychotic-exposed youth had a cumulative T2DM risk of 5.72 (95% CI, 3.45-9.48; P < .001) per 1000 patients. The incidence rate was 3.09 (95% CI, 2.35-3.82; P < .001) cases per 1000 patient-years. Compared with healthy controls, cumulative T2DM risk (odds ratio [OR], 2.58; 95% CI, 1.56-4.24; P < .0001) and incidence rate ratio (IRR) (IRR, 3.02; 95% CI, 1.71-5.35; P < .0001) were significantly greater in antipsychotic-exposed youth. Similarly, compared with psychiatric controls, antipsychotic-exposed youth had significantly higher cumulative T2DM risk (OR, 2.09; 95% CI, 1.50-52.90; P < .0001) and IRR (IRR, 1.79; 95% CI, 1.31-2.44; P < .0001). In multivariable meta-regression analyses of 10 studies, greater cumulative T2DM risk was associated with longer follow-up (P < .001), olanzapine prescription (P < .001), and male sex (P = .002) (r(2) = 1.00, P < .001). Greater T2DM incidence was associated with second-generation antipsychotic prescription (P ≤ .050) and less autism spectrum disorder diagnosis (P = .048) (r(2) = 0.21, P = .044). CONCLUSIONS AND RELEVANCE: Although T2DM seems rare in antipsychotic-exposed youth, cumulative risk and exposure-adjusted incidences and IRRs were significantly higher than in healthy controls and psychiatric controls. Olanzapine treatment and antipsychotic exposure time were the main modifiable risk factors for T2DM development in antipsychotic-exposed youth. Antipsychotics should be used judiciously and for the shortest necessary duration, and their efficacy and safety should be monitored proactively.
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Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/epidemiología , Adolescente , Benzodiazepinas/administración & dosificación , Benzodiazepinas/efectos adversos , Niño , Preescolar , Factores de Confusión Epidemiológicos , Femenino , Humanos , Incidencia , Masculino , Oportunidad Relativa , Olanzapina , Factores de Riesgo , Adulto JovenRESUMEN
INTRODUCTION: Glucose dysregulation and type 2 diabetes mellitus (T2DM) are feared antipsychotic drug adverse effects. Despite increasing utilization, data about antipsychotic risk of T2DM in youth are scarce. AREAS COVERED: We conducted a systematic PubMed/MEDLINE search until 15 May 2014 focusing on studies with ≥ 20 youths aged ≤ 24 years, reporting quantitative data on: i) change in fasting glucose, hemoglobin A1c, insulin or insulin resistance after antipsychotic initiation (studies = 19, n = 2123,age = 13.3 years, follow up = 28.8 weeks); or ii) prevalence (studies = 4) or incidence (studies = 8, follow up = 1.57 years) of T2DM in antipsychotic-exposed youth (studies = 10, n = 65,486, age = 14.2 years) versus healthy controls (studies = 4, n = 246,828), psychiatric controls (studies = 5, n = 61,784) or without control groups (studies = 2). EXPERT OPINION: Antipsychotics are associated with early adverse changes in glucose metabolism that are greater with all analyzable antipsychotics compared to controls, being highest with olanzapine, followed by quetiapine, aripiprazole and risperidone; but data were scarce. Although T2DM is fortunately rare in antipsychotic-treated youth, its prevalence (odds ratio [OR] = 8.176, 95% CI = 7.139 - 9.362) and incidence (OR = 1.450, 95% CI = 1.101 - 1.911, p = 0.006) were higher than in healthy controls. Similarly, T2DM prevalence (OR = 3.475, 95% CI = 3.019 - 4.001, p < 0.0001) and incidence (OR = 5.376, 95% CI = 4.004 - 7.233, p < 0.0001, excluding one outlying study) were higher than in psychiatric controls. Antipsychotics should only be used after lower-risk interventions failed, and inappropriately low clinical metabolic monitoring must be remedied.
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Antipsicóticos/efectos adversos , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/epidemiología , Adolescente , Factores de Edad , Glucemia/efectos de los fármacos , Niño , Hemoglobina Glucada/efectos de los fármacos , Humanos , Insulina/sangre , Resistencia a la Insulina , Factores de RiesgoRESUMEN
INTRODUCTION: Mood stabilizer (MS) plus antipsychotic (AP) co-treatment is common in patients with acute bipolar disorder (BD), but adverse effects (AEs) of this strategy have not been systematically reviewed. AREAS COVERED: We conducted a systematic review searching PubMed/MEDLINE and PsycINFO on April 1, 2015 for randomized trials in ≥ 20 adults with acute manic/mixed or depressed BD comparing MS or AP monotherapy with their combination that reported quantitative AE data. Pooled together, MS+AP versus MS monotherapy (studies = 18, n = 4419) was associated with significantly higher burden regarding 21/53 (39.6%) individual AEs, particularly weight gain-related (5/5 = 100%), extrapyramidal (5/12 = 41.7%) and glucose/lipid-related AEs (3/8 = 37.5%). AP+MS versus AP monotherapy (studies = 3, n = 397) was associated with significantly higher burden regarding 4/21 (19.0%) individual AEs (≥ 1 AE, tremor, sedation/somnolence, vomiting). EXPERT OPINION: Efficacy advantages of AP+MS co-treatment versus monotherapy should be balanced with its greater AE burden. AE risk is higher for adding AP to MS (17 additional AEs) than adding MS to an AP, including the particularly concerning cardiometabolic AEs. More data are needed, as only one or two studies provided data for 21/21 (100%) AEs of MS augmentation of AP, and 13/53 (24.5%) AEs of AP augmentation of MS, and as sparse data suggest clinically relevant AE differences across individual AP+MS combinations.
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Antimaníacos/efectos adversos , Antipsicóticos/efectos adversos , Trastorno Bipolar/tratamiento farmacológico , Enfermedad Aguda , Antimaníacos/administración & dosificación , Antipsicóticos/administración & dosificación , Quimioterapia Combinada , Humanos , Resultado del TratamientoRESUMEN
INTRODUCTION: Although antidepressant (AD) monotherapy is recommended first-line for major depressive disorder (MDD), AD + AD co-treatment is common. AREAS COVERED: We conducted the first systematic review searching PubMed/MEDLINE/PsycInfo/Embase from database inception until 1 June 2015 for acute randomized trials in ≥ 20 adults with MDD comparing AD monotherapy with AD + AD co-treatment that reported quantitative data on adverse events (AEs). Meta-analyzing 23 studies (n = 2435, duration = 6.6 weeks) AD monotherapy and AD + AD co-treatment were similar regarding intolerability-related discontinuation (risk ratio [RR] = 1.38, 95% CI = 0.89 - 1.10) and frequency of ≥ 1 AE (RR = 1.19, 95% CI = 0.95 - 1.49). Nevertheless, AD + AD co-treatment was associated with significantly greater burden regarding 4/25 AEs (tremor: RR = 1.55, 95% CI = 1.01 - 2.38; sweating: RR = 1.95, 95% CI = 1.13 -3.38, ≥ 7% weight gain: RR = 3.15, 95% CI = 1.34 - 7.41; weight gain = 2.17, 95% CI = 0.71 - 3.63 kg), but not more CNS, gastrointestinal, sexual or alertness-related AEs. However, 11/25 AEs (44.0%) were reported in only 1 - 2 studies. Adding noradrenergic and specific serotonergic antidepressants (NaSSA) or tricyclic antidepressants (TCA) to selective serotonin reuptake inhibitors (SSRIs) was specifically associated with more AEs. EXPERT OPINION: The potential for increased AEs with AD + AD co-treatment needs to be considered vis-à-vis unclear efficacy benefits of this strategy. In particular, NaSSAs and TCAs should be added to SSRIs with caution. Clearly, more data on side-effect burden of AD + AD co-treatment are needed.