RESUMEN
In July 2015, the Canadian Agency for Drugs and Technologies in Health (CADTH) released a Rapid Response report summary, with a critical appraisal, on discontinuation strategies for patients with long-term benzodiazepines (BDZ) use. The CADTH document is a review of the literature. It includes studies whose intervention is BDZ discontinuation. Also, clinical guidelines, systematic reviews and meta-analyses are included. What emerges from the CADTH guidelines is that the best strategy remains gradual tapering of BDZ with little evidence for the use of adjunctive medications. The results show that simple interventions such as discontinuation letters from clinicians, self-help information and support in general, added to gradual tapering may be associated with a two- to three-fold higher chance of successful withdrawal, compared with treatment as usual. We suggest possible implications for day-to-day clinical practice.
Asunto(s)
Benzodiazepinas/administración & dosificación , Trastornos Mentales/tratamiento farmacológico , Canadá , HumanosRESUMEN
BACKGROUND: For many years amitriptyline has been considered one of the reference compounds for the pharmacological treatment of depression. However, new tricyclic drugs, heterocyclic compounds and selective serotonin reuptake inhibitors have been introduced on the market with the claim of a more favourable tolerability/efficacy profile. OBJECTIVES: The aim of the present systematic review was to investigate the tolerability and efficacy of amitriptyline in comparison with the other tricyclic/heterocyclic antidepressants and with the selective serotonin reuptake inhibitors. SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR-Studies) was searched on 28-11-2005. Reference lists of all included studies were checked. SELECTION CRITERIA: Only randomised controlled trials were included. Study participants were of either sex and any age with a primary diagnosis of depression. Included trials compared amitriptyline with another tricyclic/heterocyclic antidepressant or with one of the selective serotonin reuptake inhibitors. DATA COLLECTION AND ANALYSIS: Data were extracted using a standardised form. The number of patients undergoing the randomisation procedure, the number of patients who completed the study and the number of improved patients were extracted. In addition, group mean scores at the end of the trial on Hamilton Depression Scale or any other depression scale were extracted. In the tolerability analysis, the number of patients failing to complete the study and the number of patients complaining of side-effects were extracted. MAIN RESULTS: A total number of 194 studies were included in the review. The estimate of the overall odds ratio (OR) for responders showed that more subjects responded to amitriptyline in comparison with the control antidepressant group (OR 1.12 to 95% confidence interval (CI) 1.02 to 1.23, number needed to treat to benefit (NNTB) = 50). The estimate of the efficacy of amitriptyline and control agents on a continuous outcome revealed an effect size which also significantly favoured amitriptyline (Standardised Mean Difference (SMD) 0.13, 95% CI 0.04 to 0.23). Whilst these differences are statistically significant, their clinical significance is less clear. When the efficacy analysis was stratified by drug class, no difference in outcome emerged between amitriptyline and either tricyclic or selective serotonin reuptake inhibitor comparators. The dropout rate in patients taking amitriptyline and control agents was similar; however, the estimate of the proportion of patients who experienced side-effects significantly favoured control agents in comparison with amitriptyline (OR 0.66, 95% CI 0.59 to 0.74). When the tolerability analysis was stratified by drug class, the dropout rate in patients taking amitriptyline and the selective serotonin reuptake inhibitors significantly favoured the latter (OR 0.84, 95% CI 0.75 to 0.95, number needed to treat to harm (NNTH) = 40). When the responder analysis was stratified by study setting amitriptyline was more effective than control antidepressants in inpatients (OR 1.22, 95% CI 1.04 to 1.42, NNTB = 24), but not in outpatients (OR 1.01, 95%CI 0.88 to 1.17, NNTB = 200). AUTHORS' CONCLUSIONS: This present systematic review indicates that amitriptyline is at least as efficacious as other tricyclics or newer compounds. However, the burden of side-effects in patients receiving it was greater. In comparison with selective serotonin reuptake inhibitors amitriptyline was less well tolerated, and although counterbalanced by a higher proportion of responders, the difference was not statistically significant.
Asunto(s)
Amitriptilina/uso terapéutico , Antidepresivos Tricíclicos/uso terapéutico , Depresión/tratamiento farmacológico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
BACKGROUND: Although the selective serotonin reuptake inhibitors (SSRIs) are widely used as first-line agents in depression, amitriptyline, a reference tricyclic (TCA) agent, has the edge in terms of efficacy over control antidepressants (ADs), but it is not clear whether this advantage can be attributed to a more favourable profile in inpatients, but not in outpatients, with depression. The aim of this study was to investigate the contribution of study setting on outcome in clinical trials comparing amitriptyline with any other AD. METHODS: A systematic review and meta-regression analysis of amitryptiline randomised clinical trials was carried out. The electronic search yielded 181 randomised clinical trials, 47% enrolling inpatients and 53% outpatients with depression. RESULTS: Both on a dichotomous and continuous out-come, amitriptyline was more effective than control agents in in-patients [Peto odds ratio (OR): 1.22, 95%, Confidence Interval (CI): 1.04, 1.42; Standardised Mean Difference (SMD): 0.28, 95 %,Cl: 0.08, 0.46], but not in outpatients (Peto OR: 1.01, 95%, CI: 0.88,1.17; SMD: 0.10,95% CI: -0.02,0.23). Among inpatients amitriptyline was significantly more effective than TCA and nonsignificantly more effective than the SSRIs. Among outpatients no statistically significant differences emerged between amitriptyline and TCA and between amitriptyline and the SSRIs. Amitriptylinewas less well tolerated than control agents in outpatients (Peto OR: 0.90, 95%, CI: 0.81, 0.99), but not in inpatients (Peto OR:1.09, 95% CI: 0.95, 1.25). CONCLUSIONS: These data suggest that a reasonable approach could be the first-line prescription of newer agents in the routine outpatient care of depressive subjects, and the use of amitriptyline in inpatients with severe depression.
Asunto(s)
Inhibidores de Captación Adrenérgica/uso terapéutico , Amitriptilina/uso terapéutico , Depresión/tratamiento farmacológico , Pacientes Internos , Pacientes Ambulatorios , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Evaluación de Medicamentos , Humanos , Escalas de Valoración Psiquiátrica , Análisis de RegresiónRESUMEN
BACKGROUND: For many years amitriptyline has been considered one of the reference compounds for the pharmacological treatment of depression. However, new tricyclic drugs, heterocyclic compounds and the selective serotonin reuptake inhibitors have been introduced on the market with the claim of a more favourable tolerability/efficacy profile. OBJECTIVES: The aim of the present systematic review was to investigate the tolerability and efficacy of amitriptyline in comparison with the other tricyclic/heterocyclic antidepressants and with the selective serotonin reuptake inhibitors. SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (2002-3) and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Key journals and conference abstracts were handsearched. Pharmaceutical companies were contacted for information on unpublished materials. SELECTION CRITERIA: Only randomised controlled trials were included. Study participants were of either sex and any age with a primary diagnosis of depression. Included trials compared amitriptyline with another tricyclic/heterocyclic antidepressant or with one of the selective serotonin reuptake inhibitors. DATA COLLECTION AND ANALYSIS: Data were extracted using a standardised form. The number of patients undergoing the randomisation procedure, the number of patients who completed the study and the number of improved patients were extracted. In addition, group mean scores at the end of the trial on Hamilton Depression Scale or any other depression scale were extracted. In the tolerability analysis, the number of patients failing to complete the study and the number of patients complaining of side-effects was extracted. MAIN RESULTS: The estimate of the overall odds ratio for responders showed that more subjects responded to amitriptyline in comparison with the control antidepressant group (odds ratio 1.12, 95% confidence interval 1.01, 1.23, number needed to treat 50). The estimate of the efficacy of amitriptyline and control agents on a continuous outcome revealed an effect size which also significantly favoured amitriptyline (Standardised Mean Difference 0.13, 95% confidence interval 0.04, 0.23). Whilst these differences are statistically significant, their clinical significance is less clear. When the efficacy analysis was stratified by drug class, no difference in outcome emerged between amitriptyline and either tricyclic or selective serotonin reuptake inhibitor comparators. The dropout rate in patients taking amitriptyline and control agents was similar; however, the estimate of the proportion of patients who experienced side-effects significantly favoured control agents in comparison with amitriptyline (odds ratio 0.63, 95% confidence interval 0.56, 0.71). When the tolerability analysis was stratified by drug class, the dropout rate in patients taking amitriptyline and the selective serotonin reuptake inhibitors significantly favoured the latter (odds ratio 0.84, 95% confidence interval 0.75,0.95, number needed to harm 40). When the responder analysis was stratified by study setting amitriptyline was more effective than control ADs in inpatients (odds ratio 1.22, 95% confidence interval 1.04, 1.42, number needed to treat 24), but not in outpatients (odds ratio 1.01, 95% confidence interval 0.88, 1.17, number needed to treat = 200). REVIEWER'S CONCLUSIONS: This present systematic review indicates that amitriptyline is at least as efficacious as other tricyclics or newer compounds. However, the burden of side-effects in patients receiving it was greater. In comparison with the selective serotonin reuptake inhibitors amitriptyline was less well tolerated, and although counterbalanced by a higher proportion of responders, the difference was not statistically significant.
Asunto(s)
Amitriptilina/uso terapéutico , Antidepresivos Tricíclicos/uso terapéutico , Depresión/tratamiento farmacológico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
The present study was carried out to investigate the routine use of second-generation antipsychotic drugs in the Italian psychiatric care system. Seven outpatient psychiatric services enrolled a consecutive case series of patients who were being treated, or had started treatment, with clozapine, olanzapine, risperidone, or quetiapine. Information on sociodemographic and clinical variables, current psychotropic drug use, side-effects and past use of typical drugs was collected. In addition, patient symptoms and functional status were evaluated by the Health of the Nation Outcome Scale. Patients receiving off-label prescribing of second-generation antipsychotics were identified. A total of 209 patients were collected. In comparison with patients receiving other second-generation antipsychotics, living in residential facilities, unemployment, long psychiatric histories, and problems with activities of daily living and living conditions were more common in clozapine-treated patients. Nearly 80 % of patients receiving clozapine had schizophrenia compared to less than 50 % of those receiving other second-generation antipsychotics. Overall, 109 patients (52 %) received off-label prescriptions of second-generation antipsychotic drugs. This survey indicates that clozapine was mostly reserved for severe cases and poor responders; the high rate of off-label prescriptions highlights the gap existing between recommendations derived from randomised clinical trials and the current use of drugs.
Asunto(s)
Antidepresivos de Segunda Generación/uso terapéutico , Servicios Comunitarios de Salud Mental/tendencias , Pirenzepina/análogos & derivados , Esquizofrenia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Benzodiazepinas , Escalas de Valoración Psiquiátrica Breve , Clozapina/uso terapéutico , Dibenzotiazepinas/uso terapéutico , Quimioterapia Combinada , Utilización de Medicamentos/tendencias , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Olanzapina , Pacientes Ambulatorios , Farmacoepidemiología , Pirenzepina/uso terapéutico , Escalas de Valoración Psiquiátrica , Fumarato de Quetiapina , Risperidona/uso terapéutico , Esquizofrenia/diagnóstico , Resultado del TratamientoRESUMEN
A rare case of cholostasis from tuberculotic infiltration of the Vater's ampulla is described and was observed in a patient 83 years old. The diagnosis was made at operation after a positive radiologic evidence of an oddian stenosis with cholostasis and an important dilatation of the bile ducts. The surgical operation and the antituberculotic therapy allowed to overcome the cholostasis and the specific infection of the patient and to improve his quality of life and to prolong his survival. The description of this case, in our opinion, is important to underline that tuberculosis of the biliary papilla should be kept in mind as a possible, but rare cause, of obstructive jaundice, during the differential diagnosis.