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1.
Psychiatr Danub ; 33(2): 147-151, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34185734

RESUMO

Depression is the most prevalent mood disorder among pregnant women. Only 50% of women seek intervention during gestation. Untreated during pregnancy, depression can induce obstetric and neonatal complications, most commonly, anhedonia, suboptimal weight gain, suicidal behavior, pre-term birth, and/or spontaneous miscarriage. The babies more often suffer cognitive deficits, low birth weight, and growth delay. The mothers subsequently also experience an increased risk for significant degrees of postpartum depression. Those with relatively milder cases of depression should initially receive psychotherapy. Otherwise, there are many antidepressant medications available for the pharmacotherapy of depression. However, treating pregnant females with depression is a challenge because of potential teratogenic effects caused by many pharmaceuticals. Physicians should know the recommended guidelines for treating depressed women during a time of gestation. It is crucial to identify women suffering from depression during pregnancy, and electing those that warrant pharmacotherapy while picking the best and safest medication is a complex process with paramount significance. Before prescribing an antidepressant drug, explain the advantages and disadvantages of the interventions. Whenever prescribing during these circumstances, more than conventionally close obstetric, emotional, and medication monitoring is to be provided. This would also include an emphasis on diet, exercise, psychotherapy, and avoidance of any non-critical medicinal or other substance exposures.


Assuntos
Depressão Pós-Parto , Complicações na Gravidez , Antidepressivos/efeitos adversos , Exercício Físico , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Gestantes
2.
Syst Rev ; 10(1): 171, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108032

RESUMO

BACKGROUND: Major depression significantly impairs quality of life, increases the risk of suicide, and poses tremendous economic burden on individuals and societies. Duloxetine, a serotonin norepinephrine reuptake inhibitor, is a widely prescribed antidepressant. The effects of duloxetine have, however, not been sufficiently assessed in earlier systematic reviews and meta-analyses. METHODS/DESIGN: A systematic review will be performed including randomised clinical trials comparing duloxetine with 'active' placebo, placebo or no intervention for adults with major depressive disorder. Bias domains will be assessed, an eight-step procedure will be used to assess if the thresholds for clinical significance are crossed. We will conduct meta-analyses. Trial sequential analysis will be conducted to control random errors, and the certainty of the evidence will be assessed using GRADE. To identify relevant trials, we will search Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, PsycINFO, Science Citation Index Expanded, Social Sciences Citation Index, Conference Proceedings Citation Index-Science and Conference Proceedings Citation Index-Social Science & Humanities. We will also search Chinese databases and Google Scholar. We will search all databases from their inception to the present. Two review authors will independently extract data and perform risk of bias assessment. Primary outcomes will be the difference in mean depression scores on Hamilton Depression Rating Scale between the intervention and control groups and serious adverse events. Secondary outcomes will be suicide, suicide-attempts, suicidal ideation, quality of life and non-serious adverse events. DISCUSSION: No former systematic review has systematically assessed the beneficial and harmful effects of duloxetine taking into account both the risks of random errors and the risks of systematic errors. Our review will help clinicians weigh the benefits of prescribing duloxetine against its adverse effects and make informed decisions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2016 CRD42016053931.


Assuntos
Transtorno Depressivo Maior , Adulto , Antidepressivos/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Cloridrato de Duloxetina/uso terapêutico , Humanos , Metanálise como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Ideação Suicida , Revisões Sistemáticas como Assunto
3.
Cochrane Database Syst Rev ; 5: CD013674, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34029378

RESUMO

BACKGROUND: Major depressive disorders have a significant impact on children and adolescents, including on educational and vocational outcomes, interpersonal relationships, and physical and mental health and well-being. There is an association between major depressive disorder and suicidal ideation, suicide attempts, and suicide. Antidepressant medication is used in moderate to severe depression; there is now a range of newer generations of these medications. OBJECTIVES: To investigate, via network meta-analysis (NMA), the comparative effectiveness and safety of different newer generation antidepressants in children and adolescents with a diagnosed major depressive disorder (MDD) in terms of depression, functioning, suicide-related outcomes and other adverse outcomes. The impact of age, treatment duration, baseline severity, and pharmaceutical industry funding was investigated on clinician-rated depression (CDRS-R) and suicide-related outcomes. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Library (Central Register of Controlled Trials (CENTRAL) and Cochrane Database of Systematic Reviews (CDSR)), together with Ovid Embase, MEDLINE and PsycINFO till March 2020. SELECTION CRITERIA: Randomised trials of six to 18 year olds of either sex and any ethnicity with clinically diagnosed major depressive disorder were included. Trials that compared the effectiveness of newer generation antidepressants with each other or with a placebo were included. Newer generation antidepressants included: selective serotonin reuptake inhibitors; selective norepinephrine reuptake inhibitors (SNRIs); norepinephrine reuptake inhibitors; norepinephrine dopamine reuptake inhibitors; norepinephrine dopamine disinhibitors (NDDIs); and tetracyclic antidepressants (TeCAs). DATA COLLECTION AND ANALYSIS: Two reviewers independently screened titles/abstracts and full texts, extracted data, and assessed risk of bias. We analysed dichotomous data as Odds Ratios (ORs), and continuous data as Mean Difference (MD) for the following outcomes: depression symptom severity (clinician rated), response or remission of depression symptoms, depression symptom severity (self-rated), functioning, suicide related outcomes and overall adverse outcomes. Random-effects network meta-analyses were conducted in a frequentist framework using multivariate meta-analysis. Certainty of evidence was assessed using Confidence in Network Meta-analysis (CINeMA). We used "informative statements" to standardise the interpretation and description of the results. MAIN RESULTS: Twenty-six studies were included. There were no data for the two primary outcomes (depressive disorder established via clinical diagnostic interview and suicide), therefore, the results comprise only secondary outcomes. Most antidepressants may be associated with a "small and unimportant" reduction in depression symptoms on the CDRS-R scale (range 17 to 113) compared with placebo (high certainty evidence: paroxetine: MD -1.43, 95% CI -3.90, 1.04; vilazodone: MD -0.84, 95% CI -3.03, 1.35; desvenlafaxine MD -0.07, 95% CI -3.51, 3.36; moderate certainty evidence: sertraline: MD -3.51, 95% CI -6.99, -0.04; fluoxetine: MD -2.84, 95% CI -4.12, -1.56; escitalopram: MD -2.62, 95% CI -5.29, 0.04; low certainty evidence: duloxetine: MD -2.70, 95% CI -5.03, -0.37; vortioxetine: MD 0.60, 95% CI -2.52, 3.72; very low certainty evidence for comparisons between other antidepressants and placebo). There were "small and unimportant" differences between most antidepressants in reduction of depression symptoms (high- or moderate-certainty evidence). Results were similar across other outcomes of benefit. In most studies risk of self-harm or suicide was an exclusion criterion for the study. Proportions of suicide-related outcomes were low for most included studies and 95% confidence intervals were wide for all comparisons. The evidence is very uncertain about the effects of mirtazapine (OR 0.50, 95% CI 0.03, 8.04), duloxetine (OR 1.15, 95% CI 0.72, 1.82), vilazodone (OR 1.01, 95% CI 0.68, 1.48), desvenlafaxine (OR 0.94, 95% CI 0.59, 1.52), citalopram (OR 1.72, 95% CI 0.76, 3.87) or vortioxetine (OR 1.58, 95% CI 0.29, 8.60) on suicide-related outcomes compared with placebo. There is low certainty evidence that escitalopram may "at least slightly" reduce odds of suicide-related outcomes compared with placebo (OR 0.89, 95% CI 0.43, 1.84). There is low certainty evidence that fluoxetine (OR 1.27, 95% CI 0.87, 1.86), paroxetine (OR 1.81, 95% CI 0.85, 3.86), sertraline (OR 3.03, 95% CI 0.60, 15.22), and venlafaxine (OR 13.84, 95% CI 1.79, 106.90) may "at least slightly" increase odds of suicide-related outcomes compared with placebo. There is moderate certainty evidence that venlafaxine probably results in an "at least slightly" increased odds of suicide-related outcomes compared with desvenlafaxine (OR 0.07, 95% CI 0.01, 0.56) and escitalopram (OR 0.06, 95% CI 0.01, 0.56). There was very low certainty evidence regarding other comparisons between antidepressants. AUTHORS' CONCLUSIONS: Overall, methodological shortcomings of the randomised trials make it difficult to interpret the findings with regard to the efficacy and safety of newer antidepressant medications. Findings suggest that most newer antidepressants may reduce depression symptoms in a small and unimportant way compared with placebo. Furthermore, there are likely to be small and unimportant differences in the reduction of depression symptoms between the majority of antidepressants. However, our findings reflect the average effects of the antidepressants, and given depression is a heterogeneous condition, some individuals may experience a greater response. Guideline developers and others making recommendations might therefore consider whether a recommendation for the use of newer generation antidepressants is warranted for some individuals in some circumstances. Our findings suggest sertraline, escitalopram, duloxetine, as well as fluoxetine (which is currently the only treatment recommended for first-line prescribing) could be considered as a first option. Children and adolescents considered at risk of suicide were frequently excluded from trials, so that we cannot be confident about the effects of these medications for these individuals. If an antidepressant is being considered for an individual, this should be done in consultation with the child/adolescent and their family/caregivers and it remains critical to ensure close monitoring of treatment effects and suicide-related outcomes (combined suicidal ideation and suicide attempt) in those treated with newer generation antidepressants, given findings that some of these medications may be associated with greater odds of these events. Consideration of psychotherapy, particularly cognitive behavioural therapy, as per guideline recommendations, remains important.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Adolescente , Antidepressivos/efeitos adversos , Viés , Criança , Citalopram/uso terapêutico , Transtorno Depressivo Maior/psicologia , Succinato de Desvenlafaxina/uso terapêutico , Cloridrato de Duloxetina/uso terapêutico , Feminino , Fluoxetina/uso terapêutico , Humanos , Masculino , Mirtazapina/uso terapêutico , Metanálise em Rede , Paroxetina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Sertralina/uso terapêutico , Ideação Suicida , Cloridrato de Venlafaxina/uso terapêutico , Cloridrato de Vilazodona/uso terapêutico , Vortioxetina/uso terapêutico
4.
J Affect Disord ; 290: 254-260, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34010750

RESUMO

BACKGROUND: Several national guidelines include recommendations for a minimum duration of antidepressant treatment, but these vary from 4-9 months after remission. We aimed to investigate whether there is an optimal minimum duration of antidepressant treatment to reduce relapse risk. METHODS: A Danish population-based cohort study among 89,442 adults who initiated antidepressants for depression treatment aged 18-60 years, from 2006-2015. We defined antidepressant discontinuation as ≥30 days without treatment. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) to indicate the risk of restarting antidepressants among those who discontinued antidepressants with <4, 4-6, and 7-9 months of use compared with discontinuation after 10-12 months. RESULTS: For individuals on antidepressant treatment <4, 4-6, 7-9 and 10-12 months, cumulative incidence of restarting treatment within one year was 37.4% (95% CI: 36.9-37.8%), 35.1% (95% CI: 34.6-35.7%), 35.0% (95% CI: 34.2-35.8%) and 32.8% (95% CI: 31.7-34.0%), respectively. Individuals on antidepressants <10 months versus 10-12 months had higher risk of restarting antidepressants: the HR for antidepressant treatment <4 months was 1.21 (95% CI: 1.16-1.27), 4-6 months 1.11 (95% CI: 1.06-1.17), and 7-9 months 1.09 (95% CI: 1.04-1.15). LIMITATIONS: We were not able to ascertain the reasons why individuals discontinued antidepressants, and systematic errors from unmeasured confounders cannot be ruled out. CONCLUSIONS: Based on our findings, a minimum of 10-12 months of treatment appears to be preferable if there is concern about relapse after discontinuation.


Assuntos
Antidepressivos , Depressão/tratamento farmacológico , Adulto , Antidepressivos/efeitos adversos , Doença Crônica , Estudos de Coortes , Humanos , Recidiva
5.
Intern Med J ; 51(5): 793-796, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34047027

RESUMO

Antidepressant drugs, which are widely used in palliative care patients for both management of psychiatric disorders and non-psychiatric symptoms, may cause a cluster of distressing symptoms on discontinuation. In dying patients, cessation of oral intake may occur either temporarily or permanently for reasons related to disease or its treatment, as well as in the days before death. We examined antidepressant use in palliative care patients by risk of antidepressant discontinuation syndrome (ADDS). Strategies for reducing the risk of ADDS, and for managing it that should occur, are discussed.


Assuntos
Antidepressivos , Cuidados Paliativos , Antidepressivos/efeitos adversos , Humanos
6.
J Affect Disord ; 289: 167-176, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33989969

RESUMO

There is significant association between obesity and depression. Naltrexone/Bupropion (NB) is indicated for treatment of overweight and obesity (BMI ≥27 kg/m2 with a comorbidity or ≥30 kg/m2). This post-hoc analysis examines safety and efficacy of NB and placebo among individuals with overweight or obesity who were also taking antidepressant therapy during the LIGHT trial (N=8910). Subjects were divided into four subgroups: NB + antidepressants (n=1150), NB without antidepressants (n=3300), placebo + antidepressants (n=1127) and placebo without antidepressants (n=3317). Among subjects taking NB, the combined incidence of serious adverse events (AEs) and AEs leading to treatment discontinuation was not significantly different between those on antidepressants and those who were not. The key weight-loss efficacy analyses were performed on NB or placebo-treated subjects who remained on study therapy through 104 weeks and who did or did not have documented antidepressant use at each of the baseline, week 52 and week 104 visits (Completers: N=1811; 47.0% female, 86.9% white, mean age of 61 years, mean baseline BMI 37.4 kg/m2). The mean adjusted weight change in subjects taking antidepressants was numerically, but not significantly greater for NB vs. placebo (-6.3% vs. -4.3%). For those subjects not on antidepressants, weight loss was significantly greater for NB vs. PL (-6.8% vs. -3.6%). NB is generally well tolerated in patients with overweight or obesity who are on antidepressants and is effective in promoting weight loss regardless of antidepressant use. These results show that for patients on antidepressant therapy, NB may be an effective option for obesity management.


Assuntos
Bupropiona , Naltrexona , Antidepressivos/efeitos adversos , Bupropiona/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Naltrexona/efeitos adversos , Obesidade/tratamento farmacológico , Sobrepeso/complicações , Perda de Peso
7.
J Psychiatr Res ; 138: 576-583, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33991996

RESUMO

Dissociative symptoms are common, possibly severe, side effects associated with the use of ketamine and esketamine in depression. We investigated the relationship between trait dissociation and dissociation induced by ketamine and esketamine used as augmentation therapy in treatment-resistant depression (TRD). Adults with TRD were randomly assigned to receive a single intravenous infusion, with a duration of 40 min, of either esketamine 0.25 mg/kg or ketamine 0.5 mg/kg. We assessed trait dissociation with the Dissociative Experience Scale (DES) and, to evaluate induced dissociation, the Clinician-Administered Dissociative States Scale (CADSS) was used. Thirty-two subjects received esketamine and 29 received ketamine. The groups had similar median DES scores (p = 0.26). More than 30% of the patients in both groups had DES scores ≥30 points. The median CADSS score in the esketamine group was equivalent to that in the ketamine group (p = 0.40). Every 5 points increment in the DES was associated with a 10.9% (95% CI 4.5-17.8%) increase in the CADSS, in an exponential fashion when the two groups were pooled together. Subjects with high trait dissociation had a higher risk of induced dissociation state (relative risk [RR] 1.41, 95% CI 1.11-1.78) and very high induced dissociation (RR 3.05, 95% CI 1.14-8.15). Induced dissociation was not a serious adverse effect. The findings suggest that trait dissociation is a predictor of induced dissociation by Ketamine or Esketamine in TRD subjects. Screening for trait dissociation and counseling patients with high trait dissociation on the risks of dissociation by these drugs are recommended.


Assuntos
Transtorno Depressivo Resistente a Tratamento , Ketamina , Adulto , Antidepressivos/efeitos adversos , Depressão , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Humanos , Ketamina/efeitos adversos
8.
Syst Rev ; 10(1): 154, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34034811

RESUMO

BACKGROUND: Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide. Antidepressants are frequently used to treat major depressive disorder. It has been shown repeatedly that antidepressants seem to reduce depressive symptoms with a statistically significant effect, but the clinical importance of the effect sizes seems questionable. Both beneficial and harmful effects of antidepressants have not previously been sufficiently assessed. The main objective of this review will be to evaluate the beneficial and harmful effects of antidepressants versus placebo, 'active placebo', or no intervention for adults with major depressive disorder. METHODS/DESIGN: A systematic review with meta-analysis will be reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), bias will be assessed with the Cochrane Risk of Bias tool-version 2 (ROB2), our eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, Trial Sequential Analysis will be conducted to control for random errors, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. To identify relevant trials, we will search both for published and unpublished trials in major medical databases from their inception to the present. Clinical study reports will be obtained from regulatory authorities and pharmaceutical companies. Two review authors will independently screen the results of the literature searches, extract data, and perform risk of bias assessment. We will include any published or unpublished randomised clinical trial comparing one or more antidepressants with placebo, 'active placebo', or no intervention for adults with major depressive disorder. The following active agents will be included: agomelatine, amineptine, amitriptyline, bupropion, butriptyline, cianopramine, citalopram, clomipramine, dapoxetine, demexiptiline, desipramine, desvenlafaxine, dibenzepin, dosulepin, dothiepin, doxepin, duloxetine, escitalopram, fluoxetine, fluvoxamine, imipramine, iprindole, levomilnacipran, lofepramine, maprotiline, melitracen, metapramine, milnacipran, mirtazapine, nefazodone, nortriptyline, noxiptiline, opipramol, paroxetine, protriptyline, quinupramine, reboxetine, sertraline, trazodone, tianeptine, trimipramine, venlafaxine, vilazodone, and vortioxetine. Primary outcomes will be depressive symptoms, serious adverse events, and quality of life. Secondary outcomes will be suicide or suicide attempt, suicidal ideation, and non-serious adverse events. DISCUSSION: As antidepressants are commonly used to treat major depressive disorder in adults, a systematic review evaluating their beneficial and harmful effects is urgently needed. This review will inform best practice in treatment and clinical research of this highly prevalent and burdensome disorder. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020220279.


Assuntos
Transtorno Depressivo Maior , Adulto , Antidepressivos/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Metanálise como Assunto , Qualidade de Vida , Revisões Sistemáticas como Assunto , Vortioxetina/uso terapêutico
9.
Transl Psychiatry ; 11(1): 249, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33907188

RESUMO

The Hamilton Depression Rating Scale (HDRS-17) measures symptoms that may overlap with common antidepressant side effects (e.g., sexual dysfunction), thus making it possible that side effects of antidepressant treatment are erroneously rated as symptoms of depression, and vice versa. This study uses patient-level data from previously conducted antidepressant treatment trials to assess whether side effect ratings co-vary with HDRS-17 ratings. Data from all HDRS-17-rated, industry-sponsored pre- and post-marketing trials (n = 4647) comparing the serotonin and noradrenaline reuptake inhibitor, duloxetine, to placebo and/or to a selective serotonin reuptake inhibitor were pooled; three studies, which utilised sub-therapeutic doses, did not have symptom-level ratings available and could not be included. Severity was assessed for side effects related to sleep, somatic anxiety, gastrointestinal function, and sexual dysfunction. Analysis of covariance was used to assess the relation between these side effects and ratings of relevant HDRS-17-derived outcome parameters. Side effects related to sleep, somatic anxiety and sexual dysfunction significantly and exclusively associated with higher scores on HDRS-17 items measuring the corresponding domains. Side effects related to gastrointestinal function associated with higher HDRS-17 item scores on all assessed domains. Treatment outcome was significantly related to side effect severity when assessed using HDRS-17-sum (beta 0.32 (0.074), p < 0.001), but not when the HDRS-6-sum-score (beta 0.035 (0.043), p = 0.415) or the depressed mood item (beta 0.007 (0.012), p = .527) were used as effect parameters. That some HDRS-17 items co-vary with common antidepressant side effects suggests some of these adverse events are counted twice, potentially leading to an underestimation of antidepressant efficacy.


Assuntos
Depressão , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Antidepressivos/efeitos adversos , Humanos , Inibidores de Captação de Serotonina/efeitos adversos , Resultado do Tratamento
12.
Neuropsychopharmacology ; 46(8): 1518-1525, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33820955

RESUMO

To investigate the association between intrauterine antidepressant exposure and offspring affective disorders over an 18-year follow-up period using Danish national registers. We included 42,988 singletons born during 1998-2011 and followed-up until 2016, death, emigration, or date of first affective disorder diagnosis. Children were categorised into two groups according to maternal antidepressant use within 2 years before and during pregnancy: continuation (use before and during pregnancy) or discontinuation (use before but not during pregnancy). The outcome was an affective disorders diagnosis in the offspring based on secondary/tertiary care records and primary care prescription data. Hazard ratios (HR) of affective disorders were estimated using Cox regression models. To consider confounding by shared environmental or genetic factors, we investigated the effect of paternal antidepressant use on the risk for affective disorders. Affective disorders were diagnosed in 1538 children. Children whose mothers continued antidepressants during pregnancy had an increased risk of affective disorders (HR = 1.20, 95% CI = 1.08-1.34), compared with children whose mothers discontinued before pregnancy. Similarly, continued paternal antidepressant use during pregnancy was associated with higher risk for offspring affective disorders (HR = 1.29, 95% CI = 1.12-1.49), compared to discontinuation. Based on data from primary and secondary/tertiary care, maternal antidepressant use during pregnancy was associated with an increased risk of affective disorders in the offspring. As similar associations were observed in children whose fathers continued antidepressant use across the pregnancy period, the observed association may be attributable to the underlying parental psychopathology, rather than the direct intrauterine exposure to antidepressants.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Antidepressivos/efeitos adversos , Criança , Estudos de Coortes , Feminino , Humanos , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/epidemiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Modelos de Riscos Proporcionais , Fatores de Risco
14.
Cochrane Database Syst Rev ; 4: CD010682, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33860531

RESUMO

BACKGROUND: Depressive disorders are the most common psychiatric comorbidity in people with epilepsy, affecting around one-third, with a significant negative impact on quality of life. There is concern that people may not be receiving appropriate treatment for their depression because of uncertainty regarding which antidepressant or class works best, and the perceived risk of exacerbating seizures. This review aimed to address these issues, and inform clinical practice and future research. This is an updated version of the original Cochrane Review published in Issue 12, 2014. OBJECTIVES: To evaluate the efficacy and safety of antidepressants in treating depressive symptoms and the effect on seizure recurrence, in people with epilepsy and depression. SEARCH METHODS: For this update, we searched CRS Web, MEDLINE, SCOPUS, PsycINFO, and ClinicalTrials.gov (February 2021). We searched the World Health Organization Clinical Trials Registry in October 2019, but were unable to update it because it was inaccessible. There were no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and prospective non-randomised studies of interventions (NRSIs), investigating children or adults with epilepsy, who were treated with an antidepressant and compared to placebo, comparative antidepressant, psychotherapy, or no treatment for depressive symptoms.  DATA COLLECTION AND ANALYSIS: The primary outcomes were changes in depression scores (proportion with a greater than 50% improvement, mean difference, and proportion who achieved complete remission) and change in seizure frequency (mean difference, proportion with a seizure recurrence, or episode of status epilepticus). Secondary outcomes included the number of participants who withdrew from the study and reasons for withdrawal, quality of life, cognitive functioning, and adverse events. Two review authors independently extracted data for each included study. We then cross-checked the data extraction. We assessed risk of bias using the Cochrane tool for RCTs, and the ROBINS-I for NRSIs. We presented binary outcomes as risk ratios (RRs) with 95% confidence intervals (CIs) or 99% CIs for specific adverse events. We presented continuous outcomes as standardised mean differences (SMDs) with 95% CIs, and mean differences (MDs) with 95% CIs.  MAIN RESULTS: We included 10 studies in the review (four RCTs and six NRSIs), with 626 participants with epilepsy and depression, examining the effects of antidepressants. One RCT was a multi-centre study comparing an antidepressant with cognitive behavioural therapy (CBT). The other three RCTs were single-centre studies comparing an antidepressant with an active control, placebo, or no treatment. The NRSIs reported on outcomes mainly in participants with focal epilepsy before and after treatment for depression with a selective serotonin reuptake inhibitor (SSRI); one NRSI compared SSRIs to CBT.  We rated one RCT at low risk of bias, three RCTs at unclear risk of bias, and all six NRSIs at serious risk of bias. We were unable to conduct any meta-analysis of RCT data due to heterogeneity of treatment comparisons. We judged the certainty of evidence to be moderate to very low across comparisons, because single studies contributed limited outcome data, and because of risk of bias, particularly for NRSIs, which did not adjust for confounding variables. More than 50% improvement in depressive symptoms ranged from 43% to 82% in RCTs, and from 24% to 97% in NRSIs, depending on the antidepressant given. Venlafaxine improved depressive symptoms by more than 50% compared to no treatment (mean difference (MD) -7.59 (95% confidence interval (CI) -11.52 to -3.66; 1 study, 64 participants; low-certainty evidence); the results between other comparisons were inconclusive. Two studies comparing SSRIs to CBT reported inconclusive results for the proportion of participants who achieved complete remission of depressive symptoms.  Seizure frequency data did not suggest an increased risk of seizures with antidepressants compared to control treatments or baseline. Two studies measured quality of life; antidepressants did not appear to improve quality of life over control. No studies reported on cognitive functioning. Two RCTs and one NRSI reported comparative data on adverse events; antidepressants did not appear to increase the severity or number of adverse events compared to controls. The NSRIs reported higher rates of withdrawals due to adverse events than lack of efficacy. Reported adverse events for antidepressants included nausea, dizziness, sedation, headache, gastrointestinal disturbance, insomnia, and sexual dysfunction.  AUTHORS' CONCLUSIONS: Existing evidence on the effectiveness of antidepressants in treating depressive symptoms associated with epilepsy is still very limited. Rates of response to antidepressants were highly variable. There is low certainty evidence from one small RCT (64 participants) that venlafaxine may improve depressive symptoms more than no treatment; this evidence is limited to treatment between 8 and 16 weeks, and does not inform longer-term effects. Moderate to low evidence suggests neither an increase nor exacerbation of seizures with SSRIs.  There are no available comparative data to inform the choice of antidepressant drug or classes of drug for efficacy or safety for treating people with epilepsy and depression. RCTs of antidepressants utilising interventions from other treatment classes besides SSRIs, in large samples of patients with epilepsy and depression, are needed to better inform treatment policy. Future studies should assess interventions across a longer treatment duration to account for delayed onset of action, sustainability of treatment responses, and to provide a better understanding of the impact on seizure control.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Epilepsia/tratamento farmacológico , Adolescente , Adulto , Antidepressivos/efeitos adversos , Viés , Criança , Terapia Cognitivo-Comportamental , Depressão/etiologia , Epilepsia/induzido quimicamente , Epilepsia/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Captação de Serotonina/efeitos adversos , Inibidores de Captação de Serotonina/uso terapêutico , Adulto Jovem
15.
Biomed Res Int ; 2021: 6699028, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791379

RESUMO

Introduction: Depression is a major global health problem with a relatively high lifetime prevalence and significant disability. Antidepressants are the most effective medications used for the treatment of depression. Hence, this study is aimed at summarizing the studies on antidepressant use among patients diagnosed with depression. Method: PubMed, Embase, Web of Science, Scopus, and Google Scholar were searched for literature (2000-2019) using keywords such as depression, drug utilization, antidepressants, prescription, serotonin reuptake inhibitor, serotonin and norepinephrine reuptake inhibitor, tricyclic antidepressants, and atypical antidepressants. Results: Antidepressant users were mostly females, married people, housewives, lower-income people, employees, and highly educated people, as they were found to be more prone to develop depression than their counterparts. Selective serotonin reuptake inhibitors (SSRIs), such as sertraline, were most commonly prescribed among depressive patients. Conclusion: Our study suggested that out of five major antidepressant drugs available for the treatment of depression, selective serotonin reuptake inhibitors are preferred over others because of their better side effects and tolerability profile.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Antidepressivos/efeitos adversos , Depressão/metabolismo , Humanos , Inibidores de Captação de Serotonina/efeitos adversos
16.
N Engl J Med ; 384(15): 1402-1411, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33852780

RESUMO

BACKGROUND: Psilocybin may have antidepressant properties, but direct comparisons between psilocybin and established treatments for depression are lacking. METHODS: In a phase 2, double-blind, randomized, controlled trial involving patients with long-standing, moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, a selective serotonin-reuptake inhibitor, over a 6-week period. Patients were assigned in a 1:1 ratio to receive two separate doses of 25 mg of psilocybin 3 weeks apart plus 6 weeks of daily placebo (psilocybin group) or two separate doses of 1 mg of psilocybin 3 weeks apart plus 6 weeks of daily oral escitalopram (escitalopram group); all the patients received psychological support. The primary outcome was the change from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16; scores range from 0 to 27, with higher scores indicating greater depression) at week 6. There were 16 secondary outcomes, including QIDS-SR-16 response (defined as a reduction in score of >50%) and QIDS-SR-16 remission (defined as a score of ≤5) at week 6. RESULTS: A total of 59 patients were enrolled; 30 were assigned to the psilocybin group and 29 to the escitalopram group. The mean scores on the QIDS-SR-16 at baseline were 14.5 in the psilocybin group and 16.4 in the escitalopram group. The mean (±SE) changes in the scores from baseline to week 6 were -8.0±1.0 points in the psilocybin group and -6.0±1.0 in the escitalopram group, for a between-group difference of 2.0 points (95% confidence interval [CI], -5.0 to 0.9) (P = 0.17). A QIDS-SR-16 response occurred in 70% of the patients in the psilocybin group and in 48% of those in the escitalopram group, for a between-group difference of 22 percentage points (95% CI, -3 to 48); QIDS-SR-16 remission occurred in 57% and 28%, respectively, for a between-group difference of 28 percentage points (95% CI, 2 to 54). Other secondary outcomes generally favored psilocybin over escitalopram, but the analyses were not corrected for multiple comparisons. The incidence of adverse events was similar in the trial groups. CONCLUSIONS: On the basis of the change in depression scores on the QIDS-SR-16 at week 6, this trial did not show a significant difference in antidepressant effects between psilocybin and escitalopram in a selected group of patients. Secondary outcomes generally favored psilocybin over escitalopram, but the analyses of these outcomes lacked correction for multiple comparisons. Larger and longer trials are required to compare psilocybin with established antidepressants. (Funded by the Alexander Mosley Charitable Trust and Imperial College London's Centre for Psychedelic Research; ClinicalTrials.gov number, NCT03429075.).


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Antidepressivos/uso terapêutico , Citalopram/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Alucinógenos/uso terapêutico , Psilocibina/uso terapêutico , Adulto , Antidepressivos/efeitos adversos , Antidepressivos de Segunda Geração/efeitos adversos , Citalopram/efeitos adversos , Transtorno Depressivo Maior/psicologia , Método Duplo-Cego , Feminino , Alucinógenos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Psilocibina/efeitos adversos , Autorrelato , Inquéritos e Questionários , Adulto Jovem
17.
Sr Care Pharm ; 36(5): 228-237, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33879283

RESUMO

Every drug review for older people should consider which medicines to continue, but equally important, which medicines can be discontinued. As we age, the balance between potential benefits and potential risks of medications often shifts towards more harm. For example, antidepressants are commonly prescribed in general, but in the older person, they carry specific potential harms. Further, there is data indicating that a substantial proportion of users have no evidence-based indications to continue antidepressants and could be candidates to try stopping treatment. We outline first the imperatives and evidence for deprescribing antidepressants and then finally the practical approaches to deprescribing.


Assuntos
Desprescrições , Idoso , Idoso de 80 Anos ou mais , Antidepressivos/efeitos adversos , Humanos
18.
Eur J Pharmacol ; 899: 173998, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33676942

RESUMO

Various antidepressants are commonly used to treat depression and anxiety disorders, and sex differences have been identified in their efficacy and side effects. Steroids, such as estrogens and testosterone, both in the periphery and locally in the brain, are regarded as important modulators of these sex differences. This review presents published data from preclinical and clinical studies that measure testosterone and estrogen level changes during and/or after acute or chronic administration of different antidepressants. The majority of studies show an interaction between sex hormones and antidepressants on sexual function and behavior, or in depressive symptom alleviation. However, most of the studies omit to investigate antidepressants' effects on circulating levels of gonadal hormones. From data reviewed herein, it is evident that most antidepressants can influence testosterone and estrogen levels. Still, the evidence is conflicting with some studies showing an increase, others decrease or no effect. Most studies are conducted in male animals or humans, underscoring the importance of considering sex as an important variable in such investigations, especially as depression and anxiety disorders are more common in women than men. Therefore, research is needed to elucidate the extent to which antidepressants can influence both peripheral and brain levels of testosterone and estrogens, in males and females, and whether this impacts the effectiveness or side effects of antidepressants.


Assuntos
Afeto/efeitos dos fármacos , Antidepressivos/uso terapêutico , Encéfalo/efeitos dos fármacos , Depressão/tratamento farmacológico , Estrogênios/metabolismo , Testosterona/metabolismo , Animais , Antidepressivos/efeitos adversos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Depressão/metabolismo , Depressão/fisiopatologia , Depressão/psicologia , Estrogênios/sangue , Feminino , Humanos , Masculino , Medição de Risco , Fatores de Risco , Fatores Sexuais , Testosterona/sangue , Resultado do Tratamento
19.
J Psychiatr Res ; 137: 319-327, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33744511

RESUMO

High doses of antidepressants, particularly clomipramine and selective serotonin reuptake inhibitors (SSRIs), are the well-established treatment for obsessive-compulsive disorder (OCD), but manic/hypomanic episodes are potential adverse events associated with this treatment. A systematic literature review was performed on manic/hypomanic episodes in non-bipolar OCD patients. Clinical, sociodemographic and antidepressant characteristics during the manic/hypomanic switch were extracted using descriptive statistics. Data were obtained from 20 case reports and case series. Switching episodes mostly appeared in the first 12 weeks after antidepressant initiation and took place more frequently during SSRI use (mostly fluoxetine) in 64.3% of cases. Clomipramine and SSRI use differed non-significantly between the switching episodes that appeared during the first 12 weeks of antidepressant treatment and the episodes that appeared beyond 12 weeks. Switching episodes emerging before 12 weeks were associated with a lower defined daily dose of antidepressants than episodes emerging after 12 weeks. These findings suggest that there are two independent characteristics involved in manic/hypomanic switch in OCD: a) they appeared most frequently with SSRI use (fluoxetine) regardless of the time of it use, and b) episodes appeared in the first 12 weeks after SSRI or clomipramine initiation had a lower dose of antidepressant than episodes appeared after 12 weeks.


Assuntos
Mania , Transtorno Obsessivo-Compulsivo , Antidepressivos/efeitos adversos , Clomipramina/uso terapêutico , Humanos , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Inibidores de Captação de Serotonina/efeitos adversos
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