Evaluation of a multicomponent intervention consisting of education and feedback to reduce benzodiazepine prescriptions by general practitioners: The BENZORED hybrid type 1 cluster randomized controlled trial.

BACKGROUND: Current benzodiazepine (BZD) prescription guidelines recommend short-term use to minimize the risk of dependence, cognitive impairment, and falls and fractures. However, many clinicians overprescribe BZDs and chronic use by patients is common. There is limited evidence on the effectiveness of interventions delivered by general practitioners (GPs) on reducing prescriptions and long-term use of BZDs. We aimed to evaluate the effectiveness of a multicomponent intervention for GPs that seeks to reduce BZD prescriptions and the prevalence of long-term users. METHODS AND FINDINGS: We conducted a multicenter two-arm, cluster randomized controlled trial in 3 health districts in Spain (primary health centers [PHCs] in Balearic Islands, Catalonia, and Valencian Community) from September 2016 to May 2018. The 81 PHCs were randomly allocated to the intervention group (n = 41; 372 GPs) or the control group (n = 40; 377 GPs). GPs were not blinded to the allocation; however, pharmacists, researchers, and trial statisticians were blinded to the allocation arm. The intervention consisted of a workshop about the appropriate prescribing of BZDs and tapering-off long-term BZD use using a tailored stepped dose reduction with monthly BZD prescription feedback and access to a support web page. The primary outcome, based on 700 GPs (351 in the control group and 349 in the intervention group), compared changes in BZD prescriptions in defined daily doses (DDDs) per 1,000 inhabitants per day after 12 months. The 2 secondary outcomes were the proportion of long-term users (≥6 months) and the proportion of long-term users over age 65 years. Intention-to-treat (ITT) analysis was used to assess all clinical outcomes. Forty-nine GPs (21 intervention group and 28 control group) were lost to follow-up. However, all GPs were included in the ITT analysis. After 12 months, there were a statistically significant decline in total BZD prescription in the intervention group compared to the control group (mean difference: -3.24 DDDs per 1,000 inhabitants per day, 95% confidence interval (CI): -4.96, -1.53, p < 0.001). The intervention group also had a smaller number of long-term users. The adjusted absolute difference overall was -0.36 (95% CI: -0.55, -0.16, p > 0.001), and the adjusted absolute difference in long-term users over age 65 years was -0.87 (95% CI: -1.44, -0.30, p = 0.003). A key limitation of this clustered design clinical trial is the imbalance of some baseline characteristics. The control groups have a higher rate of baseline BZD prescription, and more GPs in the intervention group were women, GPs with a doctorate degree, and trainers of GP residents. CONCLUSIONS: A multicomponent intervention that targeted GPs and included educational meeting, feedback about BZD prescriptions, and a support web page led to a statistically significant reduction of BZD prescriptions and fewer long-term users. Although the effect size was small, the high prevalence of BZD use in the general population suggests that large-scale implementation of this intervention could have positive effects on the health of many patients. TRIAL REGISTRATION: ISRCTN ISRCTN28272199.

Evaluating the Implementation of a Multicomponent Intervention Consisting of Education and Feedback on Reducing Benzodiazepine Prescriptions by General Practitioners: BENZORED Hybrid Type I Cluster Randomized Controlled Trial.

BACKGROUND: General practitioners (GPs) in developed countries widely prescribe benzodiazepines (BZDs) for their anxiolytic, hypnotic, and muscle-relaxant effects. Treatment duration, however, is rarely limited, and this results in a significant number of chronic users. Long-term BZD use is associated with cognitive impairment, falls with hip fractures, traffic accidents, and increased mortality. The BENZORED IV trial was a hybrid type-1 trial conducted to evaluate the effectiveness and implementation of an intervention to reduce BZD prescription in primary care. The purpose of this qualitative study was to analyze the facilitators and barriers regarding the implementation of the intervention in primary care settings. METHODS: A qualitative interview study with 40 GPs from three Spanish health districts. Focus group meetings with GPs from the intervention arm of the BENZORED IV trial were held at primary healthcare centers in the three districts. For sampling purposes, the GPs were classified as high or low implementers according to the success of the intervention measured at 12 months. The Consolidated Framework for Implementation Research (CFIR) was used to conduct the meetings and to code, rate, and analyze the data. RESULTS: Three of the 41 CFIR constructs strongly distinguished between high and low implementers: the complexity of the intervention, the individual Stage of Change, and the key stakeholder's engagement. Seven constructs weakly discriminated between the two groups: adaptability in the intervention, external policy and incentives, implementation climate, relative priority, self-efficacy, compatibility, and engaging a formally appointed implementation leader. Fourteen constructs did not discriminate between the two groups, six had insufficient data for evaluation, and eleven had no data for evaluation. CONCLUSIONS: We identified constructs that could explain differences in the efficacy in implementation of the intervention. This information is relevant for the design of successful strategies for implementation of the intervention.

Intervention to reduce benzodiazepine prescriptions in primary care, study protocol of a hybrid type 1 cluster randomised controlled trial: the BENZORED study.

INTRODUCTION: Benzodiazepines (BZDs) are mainly used to treat anxiety and sleep disorders, and are often prescribed for long durations, even though prescription guidelines recommend short-term use due to the risk of dependence, cognitive impairment, and falls and fractures. Education of general practitioners (GPs) regarding the prescription of BZDs may reduce the overuse and of these drugs.The aims of this study are to analyse the effectiveness of an intervention targeted to GPs to reduce BZD prescription and evaluate the implementation process. METHODS AND ANALYSIS: The healthcare centres in three regions of Spain (Balearic Islands, Catalonia and Community of Valencia) will be randomly allocated to receive a multifactorial intervention or usual care (control). GPs in the intervention group will receive a 2-hour workshop about best-practice regarding BZD prescription and BZD deprescribing, monthly feedback about their BZD prescribing practices and access to a support web page. Outcome measures for each GP are the defined daily dosage per 1000 inhabitants per day and the proportion of long-term BZD users at 12 months. Data will be collected from the electronic prescription database of the public health system, and will be subjected to intention-to-treat analysis. Implementation will be evaluated by mixed methods following the five domains of the Consolidated Framework For Implementation Research. ETHICS AND DISSEMINATION: This study was approved by the Balearic Islands Ethical Committee of Clinical Research (IB3065/15), l'IDIAP Jordi Gol Ethical Committee of Clinical Research (PI 15/0148) and Valencia Primary Care Ethical Committee of Clinical Research (P16/024). The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN28272199.

Efficacy of two interventions on the discontinuation of benzodiazepines in long-term users: 36-month follow-up of a cluster randomised trial in primary care.

BACKGROUND: Primary care interventions that promote cessation of benzodiazepine (BZD) use in long-term users are effective at 1 year, but their efficacy at 3 years is uncertain. AIM: To assess the 3-year efficacy of two primary care interventions delivered by GPs on cessation of BZD use in long-term users. DESIGN AND SETTING: Multicentre, three-arm, cluster randomised, controlled trial, with random allocation at the GP level. METHOD: Seventy-five GPs and 532 patients were randomly allocated to three groups: usual care (control), structured intervention with stepped-dose reduction and follow-up visits (SIF), or structured intervention with written stepped-dose reduction (SIW). The primary outcome was BZD use at 36 months. RESULTS: At 36 months, 66/168 patients (39.2%) in the SIW group, 79/191 patients (41.3%) in the SIF group, and 45/173 patients (26.0%) in the control group had discontinued BZD use. The relative risks (RR) adjusted by cluster were 1.51 (95% CI = 1.10 to 2.05; P = 0.009) in the SIW group and 1.59 (95% CI = 1.15 to 2.19; P = 0.005) in the SIF group. A total of 131/188 patients (69.7%) who successfully discontinued BZD use at 12 months remained abstinent at 36 months. The groups showed no significant differences in anxiety, depression, or sleep dissatisfaction at 36 months. CONCLUSION: The interventions were effective on cessation of BZD use; most patients who discontinued at 12 months remained abstinent at 3 years. Discontinuation of BZD use did not have a significant effect on anxiety, depression, or sleep quality.

Effectiveness of a multi-component programme for managing depression in primary care: a cluster randomized trial. The INDI project.

BACKGROUND: There are significant shortcomings in the management and clinical outcomes of depressed patients. The objective is to assess the effectiveness of a multi-component programme to improve the management of depression in primary care. METHODS: This is a cluster-randomized controlled trial, conducted between June 2007 and June 2010. Twenty primary care centres were allocated to intervention group or usual care group. The intervention consisted of a multi-component programme with clinical, educational and organizational procedures including primary care nurses working as case-managers. Outcomes were monitored by a blinded interviewer at 0, 3, 6 and 12 months. TRIAL REGISTRATION: ISRCTN16384353, at http://isrctn.org. RESULTS: In total, 338 adult patients with major depression (DSM-IV) were assessed at baseline. At 12 months, 302 patients were assessed, 172 in the intervention group and 130 in the control group. The severity of depression (mean Patient Health Questionnaire-9 score) was 1.76 points lower in the intervention group [7.15 vs. 8.78, 95% CI=-3.53 to 0.02, p=0.053]. The treatment response rate was 15.4% higher in the intervention group than in the controls [66.9% vs. 51.5%, odds ratio 1.9, 95% CI=1.2 to 3.1, p=0.011)], and the remission rate was 13.4% higher [48.8% vs. 35.4%, odds ratio 1.8, 95% CI=1.1 to 2.9, p=0.026)]. LIMITATIONS: Unblinded physicians diagnosed depression in their patients and decided whether to include them in the study, so we cannot discount a hidden selection bias. CONCLUSIONS: The programme for managing depression leads to better clinical outcomes in patients with major depression in primary care settings.

Comparative efficacy of two primary care interventions to assist withdrawal from long term benzodiazepine use: a protocol for a clustered, randomized clinical trial.

BACKGROUND: Although benzodiazepines are effective, long-term use is not recommended because of potential adverse effects; the risks of tolerance and dependence; and an increased risk of hip fractures, motor vehicle accidents, and memory impairment. The estimated prevalence of long-term benzodiazepine use in the general population is about 2,2 to 2,6%, is higher in women and increases steadily with age. Interventions performed by General Practitioners may help patients to discontinue long-term benzodiazepine use. We have designed a trial to evaluate the effectiveness and safety of two brief general practitioner-provided interventions, based on gradual dose reduction, and will compare the effectiveness of these interventions with that of routine clinical practice. METHODS/DESIGN: In a three-arm cluster randomized controlled trial, general practitioners will be randomly allocated to: a) a group in which the first patient visit will feature a structured interview, followed by visits every 2-3 weeks to the end of dose reduction; b) a group in which the first patient visit will feature a structured interview plus delivery of written instructions to self-reduce benzodiazepine dose, or c) routine care. Using a computerized pharmaceutical prescription database, 495 patients, aged 18-80 years, taking benzodiazepine for at least 6 months, will be recruited in primary care health districts of three regions of Spain (the Balearic Islands, Catalonia, and Valencia). The primary outcome will be benzodiazepine use at 12 months. The secondary outcomes will include measurements of anxiety and depression symptoms, benzodiazepine dependence, quality of sleep, and alcohol consumption. DISCUSSION: Although some interventions have been shown to be effective in reducing benzodiazepine consumption by long-term users, the clinical relevance of such interventions is limited by their complexity. This randomized trial will compare the effectiveness and safety of two complex stepped care interventions with that of routine care in a study with sufficient statistical power to detect clinically relevant differences. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN13024375.

Assessment of an enhanced program for depression management in primary care: a cluster randomized controlled trial. The INDI project (Interventions for Depression Improvement).

BACKGROUND: Most depressed patients are attended at primary care. However, there are significant shortcomings in the diagnosis, management and outcomes of these patients. The aim of this study is to determine whether the implementation of a structured programme for managing depression will provide better health outcomes than usual management. DESIGN: A cluster-randomized controlled trial involving two groups, one of which is the control group consisting of patients who are treated for depression in the usual way and the other is the intervention group consisting of patients on a structured programme for treating depression. SETTING: 20 primary care centres in the province of Tarragona (Spain) SAMPLE: 400 patients over 18 years of age who have experienced an episode of major depression (DSM-IV) and who need to initiate antidepressant treatment INTERVENTION: A multi-component programme with clinical, educational and organisational procedures that includes training for the health care provider and evidence-based clinical guidelines. It also includes primary care nurses working as care-managers who provide educational and emotional support for the patients and who are responsible for active and systematic clinical monitoring. The programme aims to improve the primary care/specialized level interface. MEASUREMENTS: The patients will be monitored by telephone interviews. The interviewer will not know which group the patient belongs to (blind trial). These interviews will be given at 0, 3, 6 and 12 months. MAIN VARIABLES: Severity of the depressive symptoms, response rate and remission rate. ANALYSIS: Outcomes will be analyzed on an intent-to-treat basis and the unit of analysis will be the individual patient. This analysis will take into account the effect of study design on potential lack of independence between observations within the same cluster. DISCUSSION: The effectiveness of caring for depression in primary care can be improved by various strategies. The most effective models involve organisational changes and a greater role of nurses. However, these models are almost exclusively from the USA, and this randomized clinical trial will determine if this approach could be effective to improve the outcomes of depression in primary care in the Spanish health care system. TRIAL REGISTRATION: ISRCTN16384353.

Detection and management of depressive disorders in primary care in Spain.

OBJECTIVE: Many patients with depression who attend primary care are not detected and are unaware of the benefits of therapeutic intervention. Our aim is to evaluate the recognition and management of depressed patients presenting in primary care in Spain. METHODS: This was a two-phase cross-sectional study in primary care centers in Tarragona (Spain). In the first phase, we screened 906 consecutive patients using the Zung's Self-Rating Depression Scale. In the second phase, all 209 patients whose results were positive and 97 patients whose results were negative (1/7 at random) were given the Structured Clinical Interview for DSM-IV Disorders, a series of questionnaires, and the judgment of the physician about the presence of depression was determined. In the 120 patients with major depression and/or dysthymia, predictors of detection and treatment of depression were determined. RESULTS: Seventy-two percent of depressed patients were detected. The detection was associated with educational level, severity of the depression, level of impairment, and the complaint of explicit psychological symptoms. Thirty-four percent were receiving treatment with antidepressants. Antidepressant treatment was associated with marital status, severity of and impairment from the depression, frequency of visits to the family physician, and the patients' complaint of psychological symptoms. CONCLUSION: Many depressed patients are not detected, but these are often the patients who present with the mildest forms of depression and for whom the benefits of detection are far from clear. Although treatment was associated with the severity of depression, most depressed patients, at any level of seriousness, do not receive appropriate treatment.