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6.
Medicine (Baltimore) ; 99(7): e19133, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049832

RESUMO

OBJECTIVES: To compare the therapeutic effect of 6 SSRIs among the Chinese senile depression patients. And drug-induced nausea leads to low compliance in elderly depression patients in China, it is urgent to assess the safety of 6 SSRIs with respect to induced-nausea among the Chinese senile depression patients. METHOD: In the present study, a network of meta-analysis was conducted to assess the efficacy of 6 SSRIs among the Chinese senile depression patients, in addition, the safety of 6 SSRIs with respect to induced-nausea among the Chinese senile depression patients was also evaluated. PubMed, Embase databases, WanFang, CNKI, ChongqingWeiPu were searched for the related articles. The primary outcome of this study were the number of effective cases of SSRIs and the number of cases of nausea caused by SSRIs in Chinese elderly depressed patients. Odds ratios (ORs) and corresponding 95% confidence intervals(95%CIs) were calculated within pairwise and network meta-analysis. RESULTS: Twenty eight trials were identified, including 2246 patients, the network meta-analysis indicated that Escitalopram was associated with a lower risk of nausea compared Paroxetine (odds ratios 0.49, 95%CI = 0.34-0.69) when they were used in Chinese elderly depressed patients. Escitalopram also exhibited distinct advantages compared other SSRIs.In terms of drug efficacy, Escitalopram was significantly superior to Paroxetine (OR = 2.26, 95%CI = 1.55-3.37). CONCLUSION: The rank of SSRIs with respect to induced-nausea was: Combination of EP > Fluoxetine > Paroxetine > Citalopram > Sertraline > Fluvoxamine > Escitalopram, respectively.


Assuntos
Depressão/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Náusea/induzido quimicamente , Inibidores de Captação de Serotonina/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , China , Depressão/complicações , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
PLoS One ; 15(1): e0227364, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31895938

RESUMO

OBJECTIVES: Depression is a common illness with substantial economic consequences for society and a great burden for affected individuals. About 30% of patients with depression do not respond to repeated treatments. Psychiatric comorbidity is known to affect duration, recurrence and treatment outcome of depression. However, there is a lack of knowledge on the extent to which psychiatric comorbidity is identified in the clinical setting for depressed patients in secondary psychiatric care. Therefore, the aim of this study was to compare the agreement between traditional diagnostic assessment (TDA) and a structured and comprehensive diagnostic procedure (SCDP) for identification of personality and anxiety disorder comorbidity in depressed patients in secondary psychiatric care. METHODS: 274 patients aged 18-77 were referred from four secondary psychiatric care clinics in Sweden during 2012-2017. ICD-10 diagnoses according to TDA (mostly unstructured by psychiatric specialist and residents in psychiatry), were retrieved from medical records and compared to diagnoses resulting from the SCDP in the study. This included the Mini International Neuropsychiatric Interview, the Structured Interview for DSM Axis II Personality Disorders and semi-structured questions on psychosocial circumstances, life-events, psychiatric symptoms, psychiatric treatments, substance use, and suicidal and self-harm behaviour. The assessment was carried out by psychiatric specialists or by residents in psychiatry with at least three years of psychiatric training. RESULTS: SCDP identified personality disorder comorbidity in 43% of the patients compared to 11% in TDA (p<0,0001). Anxiety disorder comorbidity was identified in 58% with SCDP compared to 12% with TDA (p<0,0001). CONCLUSIONS: Important psychiatric comorbidity seems to be unrecognized in depressive patients when using TDA, which is routine in secondary psychiatric care. Comorbidities are better identified using the proposed model involving structured and semi-structured interviews together with clinical evaluations by clinical experts.


Assuntos
Transtornos de Ansiedade , Transtorno Depressivo , Entrevista Psicológica/métodos , Transtornos da Personalidade , Atenção Secundária à Saúde/métodos , Adolescente , Adulto , Idoso , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Comorbidade , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Classificação Internacional de Doenças , Masculino , Pessoa de Meia-Idade , Transtornos da Personalidade/diagnóstico , Transtornos da Personalidade/epidemiologia , Escalas de Graduação Psiquiátrica , Psiquiatria , Psicoterapia , Suécia , Adulto Jovem
9.
Drug Saf ; 43(2): 135-145, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31848933

RESUMO

INTRODUCTION: This post-authorization safety study (PASS) was a commitment to the European Medicines Agency. OBJECTIVE: This PASS investigated quetiapine as antidepressant treatment in Swedish registers with regard to the risk for all-cause mortality, self-harm and suicide, acute myocardial infarction, stroke, diabetes mellitus, extrapyramidal disorders, and somnolence. METHODS: Users of quetiapine and antidepressants (2011‒2014) who had changed treatment in the past year were included. Conditional logistic regression models were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) for each outcome in nested case-control studies for quetiapine as combination therapy and monotherapy, monotherapy with antidepressants, and no medication, versus the use of combinations of antidepressants (reference group). RESULTS: Overall, 7421 quetiapine users and 281,303 antidepressant users were included. For quetiapine in combination, risks were increased for all-cause mortality [adjusted OR (aOR) 1.31, 95% CI 1.12-1.54] compared with combinations of antidepressants; however, when stratified by age, only patients ≥ 65 years of age had an increased mortality, and, in a post hoc analysis excluding patients with Parkinson's disease, no mortality increase remained. Furthermore, the risk for self-harm and suicide was increased (aOR 1.53, 95% CI 1.31-1.79), but when stratified by age, the risk increase was found only among patients aged 18-64 years. Risks were also increased for stroke among patients ≥ 65 years of age (aOR 1.47, 95% CI 1.01-2.12), for extrapyramidal disorder (aOR 6.15, 95% CI 3.57-10.58), and for somnolence (aOR 2.41, 95% CI 1.42-4.11). CONCLUSION: Risks for all-cause mortality, self-harm and suicide, and stroke in older patients may be higher among patients treated with quetiapine and antidepressant combination therapy.


Assuntos
Antidepressivos/administração & dosagem , Transtorno Depressivo/tratamento farmacológico , Fumarato de Quetiapina/administração & dosagem , Comportamento Autodestrutivo/epidemiologia , Suicídio/estatística & dados numéricos , Adolescente , Adulto , Idoso , Antidepressivos/efeitos adversos , Estudos de Casos e Controles , Transtorno Depressivo/mortalidade , Transtorno Depressivo/psicologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fumarato de Quetiapina/efeitos adversos , Estudos Retrospectivos , Comportamento Autodestrutivo/induzido quimicamente , Comportamento Autodestrutivo/mortalidade , Comportamento Autodestrutivo/psicologia , Suicídio/psicologia , Suécia/epidemiologia , Resultado do Tratamento , Adulto Jovem
10.
Zh Nevrol Psikhiatr Im S S Korsakova ; 119(9. Vyp. 2): 60-67, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31825392

RESUMO

Depression often complicates the course of the post-stroke period, adversely affecting the functional recovery and quality of life of patients, and is associated with an increased risk of mortality. Over the recent years, the role of inflammatory processes, genetics, white matter damage, cerebrovascular reactivity disorders, changes in the level of monoamines and cortisol, impaired neuroplasticity and glutamate neurotransmission in the pathophysiological mechanisms of post-stroke depression (PSD) is increasingly discussed. Randomized clinical trials (RCTs) have shown that antidepressants are highly effective in the treatment and prevention of PSD. The action of antidepressants, in particular selective serotonin reuptake inhibitors (SSRIs), can be directed to the main pathophysiological processes of post-stroke depression. Treatment of PSD with antidepressants not only reduces the severity of depression, but also improves the functional state, rehabilitation and quality of life of patients.


Assuntos
Transtorno Depressivo , Acidente Vascular Cerebral , Antidepressivos/uso terapêutico , Depressão , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/terapia , Humanos , Qualidade de Vida , Inibidores de Captação de Serotonina , Acidente Vascular Cerebral/complicações
12.
Int J Mol Sci ; 21(1)2019 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-31881712

RESUMO

Depression is a common and severe neuropsychiatric disorder that is one of the leading causes of global disease burden. Although various anti-depressants are currently available, their efficacies are barely adequate and many have side effects. Hericium erinaceus, also known as Lion's mane mushroom, has been shown to have various health benefits, including antioxidative, antidiabetic, anticancer, anti-inflammatory, antimicrobial, antihyperglycemic, and hypolipidemic effects. It has been used to treat cognitive impairment, Parkinson's disease, and Alzheimer's disease. Bioactive compounds extracted from the mycelia and fruiting bodies of H. erinaceus have been found to promote the expression of neurotrophic factors that are associated with cell proliferation such as nerve growth factors. Although antidepressant effects of H. erinaceus have not been validated and compared to the conventional antidepressants, based on the neurotrophic and neurogenic pathophysiology of depression, H. erinaceus may be a potential alternative medicine for the treatment of depression. This article critically reviews the current literature on the potential benefits of H. erinaceus as a treatment for depressive disorder as well as its mechanisms underlying the antidepressant-like activities.


Assuntos
Basidiomycota/química , Produtos Biológicos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Basidiomycota/metabolismo , Produtos Biológicos/química , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ensaios Clínicos como Assunto , Transtorno Depressivo/patologia , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/uso terapêutico , Humanos , Indóis/química , Indóis/isolamento & purificação , Indóis/uso terapêutico , Micélio/química , Micélio/metabolismo , Fatores de Crescimento Neural/metabolismo
13.
Cochrane Database Syst Rev ; 12: CD013299, 2019 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-31868236

RESUMO

BACKGROUND: It is common for peoples not to take antidepressant medication as prescribed, with around 50% of people likely to prematurely discontinue taking their medication after six months. Community pharmacists may be well placed to have a role in antidepressant management because of their unique pharmacotherapeutic knowledge and ease of access for people. Pharmacists are in an ideal position to offer proactive interventions to people with depression or depressive symptoms. However, the effectiveness and acceptability of existing pharmacist-based interventions is not yet well understood. The degree to which a pharmacy-based management approach might be beneficial, acceptable to people, and effective as part of the overall management for those with depression is, to date, unclear. A systematic review of randomised controlled trials (RCTs) will help answer these questions and add important knowledge to the currently sparse evidence base. OBJECTIVES: To examine the effects of pharmacy-based management interventions compared with active control (e.g. patient information materials or any other active intervention delivered by someone other than the pharmacist or the pharmacy team), waiting list, or treatment as usual (e.g. standard pharmacist advice or antidepressant education, signposting to support available in primary care services, brief medication counselling, and/or (self-)monitoring of medication adherence offered by a healthcare professional outside the pharmacy team) at improving depression outcomes in adults. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMD-CTR) to June 2016; the Cochrane Library (Issue 11, 2018); and Ovid MEDLINE, Embase, and PsycINFO to December 2018. We searched theses and dissertation databases and international trial registers for unpublished/ongoing trials. We applied no restrictions on date, language, or publication status to the searches.  SELECTION CRITERIA: We included all RCTs and cluster-RCTs where a pharmacy-based intervention was compared with treatment as usual, waiting list, or an alternative intervention in the management of depression in adults over 16 years of age. Eligible studies had to report at least one of the following outcomes at any time point: depression symptom change, acceptability of the intervention, diagnosis of depression, non-adherence to medication, frequency of primary care appointments, quality of life, social functioning, or adverse events.  DATA COLLECTION AND ANALYSIS: Two authors independently, and in duplicate, conducted all stages of study selection, data extraction, and quality assessment (including GRADE). We discussed disagreements within the team until we reached consensus. Where data did not allow meta-analyses, we synthesised results narratively.  MAIN RESULTS: Twelve studies (2215 participants) met the inclusion criteria and compared pharmacy-based management with treatment as usual. Two studies (291 participants) also included an active control (both used patient information leaflets providing information about the prescribed antidepressant). Neither of these studies reported depression symptom change. A narrative synthesis of results on acceptability of the intervention was inconclusive, with one study reporting better acceptability of pharmacy-based management and the other better acceptability of the active control. One study reported that participants in the pharmacy-based management group had better medication adherence than the control participants. One study reported adverse events with no difference between groups. The studies reported no other outcomes. Meta-analyses comparing pharmacy-based management with treatment as usual showed no evidence of a difference in the effect of the intervention on depression symptom change (dichotomous data; improvement in symptoms yes/no: risk ratio (RR), 0.95, 95% confidence interval (CI) 0.86 to 1.05; 4 RCTs, 475 participants; moderate-quality evidence; continuous data: standard mean difference (SMD) -0.04, 95% CI -0.19 to 0.10; 5 RCTs, 718 participants; high-certainty evidence), or acceptability of the intervention (RR 1.09, 95% CI 0.81 to 1.45; 12 RCTs, 2072 participants; moderate-certainty evidence). The risk of non-adherence was reduced in participants receiving pharmacy-based management (RR 0.73, 95% CI 0.61 to 0.87; 6 RCTs, 911 participants; high-certainty evidence). We were unable to meta-analyse data on diagnosis of depression, frequency of primary care appointments, quality of life, or social functioning. AUTHORS' CONCLUSIONS: We found no evidence of a difference between pharmacy-based management for depression in adults compared with treatment as usual in facilitating depression symptom change. Based on numbers of participants leaving the trials early, there may be no difference in acceptability between pharmacy-based management and controls. However, there was uncertainty due to the low-certainty evidence.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Adesão à Medicação , Antidepressivos/efeitos adversos , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
14.
Artigo em Russo | MEDLINE | ID: mdl-31626168

RESUMO

AIM: To evaluate the efficacy of alimemazine in the form of a solution for intramuscular injections in the treatment of anxiety and depressive disorders. MATERIAL AND METHODS: Twenty patients, who met ICD-10 criteria for anxiety and depressive disorders, participated in the clinical observation. Alimemazine was used in the form of a solution for intramuscular injection (5 mg/ml) along with SSRIs and SNRIs. RESULTS: The significant positive dynamics in the reduction of anxiety-depressive disorders, sleep disorders and vegetative symptoms was observed in patients treated with alimemazine (solution) and antidepressants from the group of SSRIs and SSRIs. CONCLUSION: The drug has demonstrated efficacy and a favorable tolerability profile.


Assuntos
Antidepressivos , Transtorno Depressivo , Trimeprazina , Antidepressivos/administração & dosagem , Ansiedade , Transtorno Depressivo/tratamento farmacológico , Humanos , Injeções Intramusculares , Inibidores de Captação de Serotonina/uso terapêutico , Trimeprazina/administração & dosagem
15.
Artigo em Russo | MEDLINE | ID: mdl-31626232

RESUMO

Depression is a frequent complication of stroke and occurs in approximately one in three surviving patients. Depression worsens the course of post-stroke neurological disorders, enhances the physical helplessness of patients, further reduces their quality of life, significantly decreases the effectiveness of therapeutic and rehabilitation measures and increases the risk of death. Antidepressants eliminate or relieve depressive symptoms, mitigate neurological disorders, improve cognitive functions and the general condition of patients, increase the effectiveness of treatment and rehabilitation, diminish the risk of recurrent stroke and decrease mortality. Selective serotonin reuptake inhibitors are the first line antidepressants for post-stroke patients; there is evidence of the effectiveness of other modern antidepressants, as well as tricyclic drugs. Unresolved aspects of this problem that require further well-designed controlled studies include tolerability of antidepressants by patients of late age, the choice of optimal drugs and the duration of therapy.


Assuntos
Antidepressivos Tricíclicos , Depressão , Transtorno Depressivo , Acidente Vascular Cerebral , Antidepressivos Tricíclicos/uso terapêutico , Depressão/complicações , Depressão/tratamento farmacológico , Transtorno Depressivo/complicações , Transtorno Depressivo/tratamento farmacológico , Humanos , Qualidade de Vida , Inibidores de Captação de Serotonina/uso terapêutico , Acidente Vascular Cerebral/complicações
16.
Biomed Res Int ; 2019: 5705232, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612144

RESUMO

Postmenopausal depression is closely associated with depletion of estrogen which modulates transmission of 5-HT, a key neurotransmitter that regulates stress-managing circuits in the brain. In this study, antidepressive efficacy of white ginseng (Panax gingseng Meyer, WG) was evaluated in stressed ovariectomized rats. Female Sprague Dawley rats were ovariectomized and repeatedly restraint stressed for 2 weeks (2h/day). Thirty minutes before restraint stress, rats were administered saline (control), WG 200 mg/kg (p.o.), WG 400 mg/kg (p.o.), or fluoxetine (PC, 10 mg/kg, i.p.). Tail suspension test (TST) and forced swimming test (FST) were performed to assess antidepressant effect of WG. After behavioral tests, levels of serum corticosterone (CORT) and hippocampal 5-HT were measured. Significant decrease of immobility time in TST and FST was shown in rats administered with PC or WG 400 compared to the control. WG200-treated rats showed remarkable reduction in immobility time of TST. PC, WG 200, or WG 400-administred group exhibited significant reduction of CORT compared to the control. PC or WG-treated rats exhibited remarkable increase in hippocampal 5-HT concentration compared to the control. Hippocampal 5-HT levels in WG groups were higher than those in the PC group. The present study demonstrated that WG had antidepressant efficacy in an animal model of menopausal depression. Treatment with WG enhanced hippocampal 5-HT level while suppressing depressive symptom and serum CORT level. These results provide evidence that WG plays an important role in activating serotonergic neurons in stressful situation, suggesting that WG might be a reliable natural alternative of antidepressant drugs to treat menopausal depression.


Assuntos
Depressão/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Panax/química , Serotonina/metabolismo , Animais , Antidepressivos/química , Antidepressivos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Depressão/genética , Depressão/fisiopatologia , Transtorno Depressivo/genética , Transtorno Depressivo/fisiopatologia , Modelos Animais de Doenças , Elevação dos Membros Posteriores/métodos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Ratos , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/genética , Estresse Psicológico/fisiopatologia , Natação
17.
Tijdschr Psychiatr ; 61(9): 635-643, 2019.
Artigo em Holandês | MEDLINE | ID: mdl-31560783

RESUMO

BACKGROUND: Antidepressants remain controversial, partly due to allegations that disappointing results were buried and because of their modest average efficacy.
AIM: To investigate bias in the antidepressant literature and the possibilities for predicting which patients with depression or anxiety do receive significant benefits from antidepressants.
METHOD: We investigated bias by comparing information from the US Food and Drug Administration with the published literature. To predict response, we used patient data from randomized trials.
RESULTS: Of all studies on depression or anxiety, 50% and 72% were positive, compared to 95% and 96% of all published studies. Safety outcomes were poorly reported in published articles and unpublished studies were often 'bundled' into pooled-trials publications with positive conclusions. We found an association between severity and antidepressant efficacy for some, but not all, anxiety disorders; previous research has found inconsistent evidence for this association for depression. Furthermore, patients with depression that showed early improvement were more likely to attain a good response, irrespective of which symptoms improved.
CONCLUSION: These results demonstrate the severe impact of bias on the antidepressant literature. Severity and early improvement predicted a good response, but more information is needed to improve predictions. The increased accessibility of individual patient data will hopefully soon enable further progress in this area.


Assuntos
Antidepressivos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Transtornos de Ansiedade/complicações , Transtorno Depressivo/complicações , Diagnóstico Duplo (Psiquiatria) , Medicina Baseada em Evidências , Humanos , Resultado do Tratamento
18.
Turk Psikiyatri Derg ; 30(2): 145-148, 2019.
Artigo em Turco | MEDLINE | ID: mdl-31487381

RESUMO

Bupropion is a selective norepinephrine and dopamine reuptakeinhibitor. It is used in the treatment of depression and nicotineaddiction. When compared to the other antidepressants, bupropion hasa relatively lower risk of triggering shift to hypomania or mania in bipolardepression treatment. Here we report two cases of bipolar depressionpatients with manic shift when bupropion was used as an adjunct tomood stabilizer treatment. The first was a 43-year old female patient.Manic symptoms occurred after bupropion was added to lithium andquetiapine treatment for bipolar disorder (BD) depressive episode.Her manic symptoms regressed rapidly after discontinuing bupropiontreatment. The second patient was a 26-year old male on lithium andvalproate therapy with a BD diagnosis. After bupropion was added tohis treatment for depressive symptoms, psychotic mania ensued and hehad to be admitted to the hospital. Significant improvement was notedshortly after bupropion was discontinued and antipsychotic treatmentwas initiated.


Assuntos
Antidepressivos de Segunda Geração/efeitos adversos , Antipsicóticos/administração & dosagem , Transtorno Bipolar/psicologia , Bupropiona/efeitos adversos , Transtorno Depressivo/psicologia , Adulto , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo/complicações , Transtorno Depressivo/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Masculino
19.
Expert Opin Drug Metab Toxicol ; 15(10): 831-847, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31526279

RESUMO

Introduction: Nowadays, the first-line medications in depression include SSRIs, SNRIs, NDRIs, NaSSAs, SMSs, or a melatonin (M1/M2) receptor agonist and a 5-HT2C receptor antagonist. These drugs have quite similar antidepressant efficacy and safety profiles, but they differ in chemical structure, receptor affinity, and pharmacokinetics. Areas covered: Pharmacokinetic properties of first-line antidepressant drugs and factors influencing their pharmacokinetic processes are presented. Alterations in pharmacokinetics of newer antidepressants in special populations are summarized. In addition, the significance of therapeutic drug monitoring (TDM) and pharmacogenetic testing in dose optimization for the treatment of depressive disorders using newer antidepressants is discussed. Expert opinion: Due to the fact that 30-40% of depressive patients do not respond to the therapy and that the incidence of depression is constantly growing, the search for new more effective and safer antidepressant therapies is becoming an urgent need. More well-designed clinical studies under naturalistic conditions are needed to establish/refine therapeutic ranges for older and current state-of-the-art antidepressant drugs. The pharmacogenetic testing with concomitant application of TDM seems to be the best way for implementing personalized dosing of current state-of-the-art antidepressants metabolized by polymorphic CYPs, especially when co-administered with strong inhibitors or other substrates of CYP2D6 or CYP2C19.


Assuntos
Antidepressivos/administração & dosagem , Depressão/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Animais , Antidepressivos/farmacocinética , Antidepressivos/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Humanos , Farmacogenética
20.
Lancet Psychiatry ; 6(11): 903-914, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31543474

RESUMO

BACKGROUND: Depression is usually managed in primary care, but most antidepressant trials are of patients from secondary care mental health services, with eligibility criteria based on diagnosis and severity of depressive symptoms. Antidepressants are now used in a much wider group of people than in previous regulatory trials. We investigated the clinical effectiveness of sertraline in patients in primary care with depressive symptoms ranging from mild to severe and tested the role of severity and duration in treatment response. METHODS: The PANDA study was a pragmatic, multicentre, double-blind, placebo-controlled randomised trial of patients from 179 primary care surgeries in four UK cities (Bristol, Liverpool, London, and York). We included patients aged 18 to 74 years who had depressive symptoms of any severity or duration in the past 2 years, where there was clinical uncertainty about the benefit of an antidepressant. This strategy was designed to improve the generalisability of our sample to current use of antidepressants within primary care. Patients were randomly assigned (1:1) with a remote computer-generated code to sertraline or placebo, and were stratified by severity, duration, and site with random block length. Patients received one capsule (sertraline 50 mg or placebo orally) daily for one week then two capsules daily for up to 11 weeks, consistent with evidence on optimal dosages for efficacy and acceptability. The primary outcome was depressive symptoms 6 weeks after randomisation, measured by Patient Health Questionnaire, 9-item version (PHQ-9) scores. Secondary outcomes at 2, 6 and 12 weeks were depressive symptoms and remission (PHQ-9 and Beck Depression Inventory-II), generalised anxiety symptoms (Generalised Anxiety Disorder Assessment 7-item version), mental and physical health-related quality of life (12-item Short-Form Health Survey), and self-reported improvement. All analyses compared groups as randomised (intention-to-treat). The study is registered with EudraCT, 2013-003440-22 (protocol number 13/0413; version 6.1) and ISRCTN, ISRCTN84544741, and is closed to new participants. FINDINGS: Between Jan 1, 2015, and Aug 31, 2017, we recruited and randomly assigned 655 patients-326 (50%) to sertraline and 329 (50%) to placebo. Two patients in the sertraline group did not complete a substantial proportion of the baseline assessment and were excluded, leaving 653 patients in total. Due to attrition, primary outcome analyses were of 550 patients (266 in the sertraline group and 284 in the placebo group; 85% follow-up that did not differ by treatment allocation). We found no evidence that sertraline led to a clinically meaningful reduction in depressive symptoms at 6 weeks. The mean 6-week PHQ-9 score was 7·98 (SD 5·63) in the sertraline group and 8·76 (5·86) in the placebo group (adjusted proportional difference 0·95, 95% CI 0·85-1·07; p=0·41). However, for secondary outcomes, we found evidence that sertraline led to reduced anxiety symptoms, better mental (but not physical) health-related quality of life, and self-reported improvements in mental health. We observed weak evidence that depressive symptoms were reduced by sertraline at 12 weeks. We recorded seven adverse events-four for sertraline and three for placebo, and adverse events did not differ by treatment allocation. Three adverse events were classified as serious-two in the sertraline group and one in the placebo group. One serious adverse event in the sertraline group was classified as possibly related to study medication. INTERPRETATION: Sertraline is unlikely to reduce depressive symptoms within 6 weeks in primary care but we observed improvements in anxiety, quality of life, and self-rated mental health, which are likely to be clinically important. Our findings support the prescription of SSRI antidepressants in a wider group of participants than previously thought, including those with mild to moderate symptoms who do not meet diagnostic criteria for depression or generalised anxiety disorder. FUNDING: National Institute for Health Research.


Assuntos
Transtorno Depressivo/tratamento farmacológico , Atenção Primária à Saúde/métodos , Inibidores de Captação de Serotonina/uso terapêutico , Sertralina/uso terapêutico , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Reino Unido , Adulto Jovem
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