RESUMO
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention or impulsivity or both, and hyperactivity, which affect children, adolescents, and adults. In some countries, methylphenidate is the first option to treat adults with moderate or severe ADHD. However, evidence on the efficacy and adverse events of immediate-release (IR) methylphenidate in the treatment of ADHD in adults is limited and controversial. OBJECTIVES: To evaluate the efficacy and harms (adverse events) of IR methylphenidate for treating ADHD in adults. SEARCH METHODS: In January 2020, we searched CENTRAL, MEDLINE, Embase, eight additional databases and three trial registers. We also searched internal reports on the European Medicines Agency and the US Food and Drug Administration websites. We checked citations of included trials to identify additional trials not captured by the electronic searches. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing IR methylphenidate, at any dose, with placebo or other pharmacological interventions (including extended-release formulations of methylphenidate) for ADHD in adults. Primary outcomes comprised changes in the symptoms of ADHD (efficacy) and harms. Secondary outcomes included changes in the clinical impression of severity and improvement, level of functioning, depression, anxiety and quality of life. Outcomes could have been rated by investigators or participants. DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently on the characteristics of the trials, participants, interventions; outcomes and financial conflict of interests. We resolved disagreements by discussion or consulting a third review author. We obtained additional, unpublished information from the authors of one included trial that had reported efficacy data in a graph. We calculated mean differences (MDs) or standardized MDs (SMDs) with 95% confidence intervals (CIs) for continuous data reported on the same or different scales, respectively. We summarized dichotomous variables as risk ratios (RRs) with 95% CI. MAIN RESULTS: We included 10 trials published between 2001 and 2016 involving 497 adults with ADHD. Three trials were conducted in Europe and one in Argentina; the remaining trials did not report their location. The RCTs compared IR methylphenidate with placebo, an osmotic-release oral system (OROS) of methylphenidate (an extended-release formulation), an extended-release formulation of bupropion, lithium, and Pycnogenol® (maritime pine bark extract). Participants comprised outpatients, inpatients in addiction treatment, and adults willing to attend an intensive outpatient program for cocaine dependence. The duration of the follow-up ranged from 6 to 18 weeks. IR methylphenidate versus placebo We found very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce symptoms of ADHD when measured with investigator-rated scales (MD -20.70, 95% CI -23.97 to -17.43; 1 trial, 146 participants; end scores; Adult ADHD Investigator Symptom Report Scale (AISRS), scored from 0 to 54), but the evidence is uncertain. The effect of IR methylphenidate on ADHD symptoms when measured with participant-rated scales was moderate, but the certainty of the evidence is very low (SMD -0.59, 95% CI -1.25 to 0.06; I2 = 69%; 2 trials, 138 participants; end scores). There is very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce the clinical impression of the severity of ADHD symptoms (MD -0.57, 95% CI -0.85 to -0.28; 2 trials, 139 participants; I2 = 0%; change and end scores; Clinical Global Impression (CGI)-Severity scale (scored from 1 (very much improved) to 7 (very much worse))). There is low-certainty evidence that, compared with placebo, IR methylphenidate may slightly impact the clinical impression of an improvement in symptoms of ADHD (MD -0.94, 95% CI -1.37 to -0.51; 1 trial, 49 participants; end scores; CGI-Improvement scale (scored from 1 (very much improved) to 7 (very much worse))). There is no clear evidence of an effect on anxiety (MD -0.20, 95% CI -4.84 to 4.44; 1 trial, 19 participants; change scores; Hamilton Anxiety Scale (HAM-A; scored from 0 to 56); very low-certainty evidence) or depression (MD 2.80, 95% CI -0.09 to 5.69; 1 trial, 19 participants; change scores; Hamilton Depression Scale (HAM-D; scored from 0 to 52); very low-certainty evidence) in analyses comparing IR methylphenidate with placebo. IR methylphenidate versus lithium Compared with lithium, it is uncertain whether IR methylphenidate increases or decreases symptoms of ADHD (MD 0.60, 95% CI -3.11 to 4.31; 1 trial, 46 participants; end scores; Conners' Adult ADHD Rating Scale (scored from 0 to 198); very low-certainty evidence); anxiety (MD -0.80, 95% CI -4.49 to 2.89; 1 trial, 46 participants; end scores; HAM-A; very low-certainty evidence); or depression (MD -1.20, 95% CI -3.81 to 1.41, 1 trial, 46 participants; end scores; HAM-D scale; very low-certainty evidence). None of the included trials assessed participant-rated changes in symptoms of ADHD, or clinical impression of severity or improvement in participants treated with IR methylphenidate compared with lithium. Adverse events were poorly assessed and reported. We rated all trials at high risk of bias due to selective outcome reporting of harms and masking of outcome assessors (failure to blind outcome assessor to measure adverse events). Overall, four trials with 203 participants who received IR methylphenidate and 141 participants who received placebo described the occurrence of harms. The use of IR methylphenidate in these trials increased the risk of gastrointestinal complications (RR 1.96, 95% CI 1.13 to 2.95) and loss of appetite (RR 1.77, 95% CI 1.06 to 2.96). Cardiovascular adverse events were reported inconsistently, preventing a comprehensive analysis. One trial comparing IR methylphenidate to lithium reported five and nine adverse events, respectively. We considered four trials to have notable concerns of vested interests influencing the evidence, and authors from two trials omitted information related to the sources of funding and conflicts of interest. AUTHORS' CONCLUSIONS: We found no certain evidence that IR methylphenidate compared with placebo or lithium can reduce symptoms of ADHD in adults (low- and very low-certainty evidence). Adults treated with IR methylphenidate are at increased risk of gastrointestinal and metabolic-related harms compared with placebo. Clinicians should consider whether it is appropriate to prescribe IR methylphenidate, given its limited efficacy and increased risk of harms. Future RCTs should explore the long-term efficacy and risks of IR methylphenidate, and the influence of conflicts of interest on reported effects.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/administração & dosagem , Metilfenidato/administração & dosagem , Adulto , Antidepressivos de Segunda Geração/administração & dosagem , Ansiedade/tratamento farmacológico , Viés , Bupropiona/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Depressão/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Feminino , Flavonoides/administração & dosagem , Humanos , Compostos de Lítio/administração & dosagem , Masculino , Metilfenidato/efeitos adversos , Pessoa de Meia-Idade , Placebos/administração & dosagem , Extratos Vegetais/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: The hospitalization for ambulatory care sensitive conditions (ACSC) has been used to assess the effectiveness of primary health care (PHC). Due to the existence of different models of organization of PHC in Brazil, it is important to develop indicators and tools for their assessment. OBJECTIVE: Assessment PHC from the perspective of patients hospitalized for ACSC. METHODS: A cross-sectional study was carried out. The patients were interviewed for assessment of PHC quality using the primary care assessment tool and a questionnaire. Descriptive analyses were performed and the Primary Health Care Index (PHCI) was calculated according to the health service modality, either the traditional primary health care (TPHC) or the Family Health Program (FHP). The PHCI of the two health care models were compared. RESULTS: A total of 314 ACSC patients were interviewed 26.4% from the FHP and 73.6% from the TPHC. In general, the PHCI dimension with the lowest score was health service access. There was no significant difference in the general PHCI for the two modalities of services (P = 0.16); however, comprehensiveness was better assessed in the TPHC, while longitudinality, family focus and community orientation were better evaluated by FHP users (P ≤ 0.05). CONCLUSION: The FHP was found to be better qualified to establish longitudinality in the community, an important dimension for continued care. However, promoting access to and consolidating a proactive care model focussed on family shows to be a great challenge for the implementation of a quality and resolutive PHC in large urban centres.
Assuntos
Assistência Ambulatorial , Saúde da Família , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Atenção Primária à Saúde , Qualidade da Assistência à Saúde/normas , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Fatores Socioeconômicos , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: Although not designed for research purposes, medical charts can be a unique source for obtaining information on long-term adverse drug reactions. This study aimed to assess the availability of key information on paper-based patient medical records needed to detect long-term adverse reactions to antiretroviral therapy (ART). METHODS: This is an ongoing historical cohort study carried out in three public HIV/AIDS referral centers in Belo Horizonte, Brazil. Medical charts of treatment-naïve HIV-infected adult patients initiating ART between 2001 and 2005 were reviewed for a follow-up period of up to 5 years after the first ART prescription. Descriptive analysis was performed by estimating the absolute and relative frequencies of selected variables. The Naranjo algorithm was employed to assess the availability of data on long-term adverse outcomes in medical charts. RESULTS: A total of 233 medical charts were eligible for study and 26.1% contained at least one long-term adverse reaction, corresponding to 45 cases of dyslipidemia (19.3%), 16 (6.9%) of lipodystrophy and 5 of type 2 diabetes mellitus (2.1%). Temporal relationship and ART switch could be better documented from medical charts. Information on reasons for ART switching and alternative causes for adverse reactions was very lacking. CONCLUSIONS: Specific tools should be developed and included in medical routines to improve adverse reaction reporting by physicians and other health professionals. This could be implemented simultaneously with the transition from paper to electronic medical charts in Brazil, facilitating the identification of long-term adverse reactions to antiretroviral drugs in epidemiological studies and in clinical practice.