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OBJECTIVES: Binge spectrum disorders are prevalent worldwide. Psychiatric and medical comorbidities are common, and societal costs are significant. Evidence-based treatment remains underutilized. Cognitive behavioral therapy is the recommended first-line treatment, but pharmacotherapy may be easier to access. INTERVENTIONS: Meta-analytic evidence directly comparing cognitive behavioral therapy with pharmacotherapy is lacking. We aimed to compare the effects of cognitive behavioral therapy interventions with any pharmacological treatment for binge spectrum disorders. We searched PubMed, Embase, CENTRAL, ClinicalTrials.gov and reference lists for randomized controlled trials comparing cognitive behavioral therapy with any pharmacotherapy for bulimia nervosa/binge eating disorder and performed pairwise meta-analytic evaluations. PRIMARY OUTCOMES: Primary outcomes are remission and frequency of binges. Secondary outcomes are frequency of purges, response, eating disorder psychopathology, weight/body mass index, depression, anxiety, quality of life and dropouts. RESULTS: Eleven randomized controlled trials comparing cognitive behavioral therapy with fluoxetine/imipramine/desipramine/methylphenidate/sibutramine were identified (N = 531). Cognitive behavioral therapy was superior to antidepressants in terms of remission, frequency of binges and eating disorder psychopathology. There were no statistically significant differences for any of the individual cognitive behavioral therapy vs drug comparisons in terms of response/depression/anxiety/weight/quality of life/dropouts. Cognitive behavioral therapy was not superior to sibutramine/methylphenidate for the primary outcomes. CONCLUSIONS: Data are scarce, comparisons underpowered and, considering the inherent methodological limitations of psychotherapy trials, questions arise regarding the presumed superiority of cognitive behavioral therapy. Further research is needed.
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Trastorno por Atracón , Terapia Cognitivo-Conductual , Humanos , Antidepresivos/uso terapéutico , Trastorno por Atracón/tratamiento farmacológico , Trastorno por Atracón/terapia , Terapia Cognitivo-Conductual/métodosRESUMEN
INTRODUCTION: The Young Mania Rating Scale (YMRS) is the gold standard to assess manic symptoms of bipolar disorder, yet the clinical meaning of scores is unknown. To clinically understand and interpret YMRS scores, we examined linkages between the total and change scores of YMRS with the Clinical Global Impression (CGI) ratings. METHODS: Individual participant data (N=2,988) from eight randomized, double-blind, placebo-controlled trials were included. Data were collected at baseline and subsequent visits. Spearman's correlation coefficients ρ were computed, and equipercentile linking was implemented. RESULTS: A YMRS score of 6 points corresponded approximately to 'borderline mentally ill,' 12 points to 'mildly ill,' 20 points to 'moderately ill,' 30 points to 'markedly ill,' 40 points to 'severely ill,' and 52 points to 'among the most extremely ill' patients on the CGI-S. A reduction of CGI-S by one point as well as 'minimally improved' on the CGI-I corresponded approximately to an absolute decrease of 4 to 8 YMRS points or a 21% to 29% reduction of YMRS baseline score whereas a reduction of CGI-S by two points and 'much improved' on the CGI-I corresponded to an absolute decrease of 10 to 15 points or a 42% to 53% reduction of YMRS baseline score. DISCUSSION: The current study findings offer clinicians meaningful cutoff values to interpret YMRS scores. Moreover, these values contribute to the definition of treatment targets, response, remission, and entry criteria in mania trials.
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Trastorno Bipolar , Manía , Humanos , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/tratamiento farmacológico , Método Doble Ciego , Escalas de Valoración Psiquiátrica , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: In clinical practice, different antipsychotics can be combined in the treatment of people with schizophrenia (polypharmacy). This strategy can aim at increasing efficacy, but might also increase the adverse effects due to drug-drug interactions. Reducing polypharmacy by withdrawing one or more antipsychotics may reduce this problem, but must be done carefully, in order to maintain efficacy. OBJECTIVES: To examine the effects and safety of reducing antipsychotic polypharmacy compared to maintaining people with schizophrenia on the same number of antipsychotics. SEARCH METHODS: On 10 February 2021, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, CINAHL, ClinicalTrials.Gov, Embase, ISRCTN, MEDLINE, PsycINFO, PubMed and WHO ICTRP. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared reduction in the number of antipsychotics to continuation of the current number of antipsychotics. We included adults with schizophrenia or related disorders who were receiving more than one antipsychotic and were stabilised on their current treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all the identified references for inclusion, and all the full papers. We contacted study authors if we needed any further information. Two review authors independently extracted the data, assessed the risk of bias using RoB 2 and the certainty of the evidence using the GRADE approach. The primary outcomes were: quality of life assessed as number of participants with clinically important change in quality of life; service use assessed as number of participants readmitted to hospital and adverse effects assessed with number of participants leaving the study early due to adverse effects. MAIN RESULTS: We included five RCTs with 319 participants. Study duration ranged from three months to one year. All studies compared polypharmacy continuation with two antipsychotics to polypharmacy reduction to one antipsychotic. We assessed the risk of bias of results as being of some concern or at high risk of bias. A lower number of participants left the study early due to any reason in the polypharmacy continuation group (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.29 to 0.68; I2 = 0%; 5 RCTs, n = 319; low-certainty evidence), and a lower number of participants left the study early due to inefficacy (RR 0.21, 95% CI 0.07 to 0.65; I2 = 0%; 3 RCTs, n = 201). Polypharmacy continuation resulted in more severe negative symptoms (MD 3.30, 95% CI 1.51 to 5.09; 1 RCT, n = 35). There was no clear difference between polypharmacy reduction and polypharmacy continuation on readmission to hospital, leaving the study early due to adverse effects, functioning, global state, general mental state and positive symptoms, number of participants with at least one adverse effect, weight gain and other specific adverse effects, mortality and cognition. We assessed the certainty of the evidence as very low or low across measured outcomes. No studies reported quality of life, days in hospital, relapse, depressive symptoms, behaviour and satisfaction with care. Due to lack of data, it was not possible to perform some planned sensitivity analyses, including one controlling for increasing the dose of the remaining antipsychotic. As a result, we do not know if the observed results might be influenced by adjustment of dose of remaining antipsychotic compound. AUTHORS' CONCLUSIONS: This review summarises the latest evidence on polypharmacy continuation compared with polypharmacy reduction. Our results show that polypharmacy continuation might be associated with a lower number of participants leaving the study early, especially due to inefficacy. However, the evidence is of low and very low certainty and the data analyses based on few study only, so that it is not possible to draw strong conclusions based on the results of the present review. Further high-quality RCTs are needed to investigate this important topic.
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Antipsicóticos , Esquizofrenia , Adulto , Antipsicóticos/efectos adversos , Humanos , Polifarmacia , Esquizofrenia/tratamiento farmacológico , Aumento de PesoRESUMEN
BACKGROUND: Antipsychotic drugs are the mainstay treatment for schizophrenia, yet they are associated with diverse and potentially dose-related side effects which can reduce quality of life. For this reason, the lowest possible doses of antipsychotics are generally recommended, but higher doses are often used in clinical practice. It is still unclear if and how antipsychotic doses could be reduced safely in order to minimise the adverse-effect burden without increasing the risk of relapse. OBJECTIVES: To assess the efficacy and safety of reducing antipsychotic dose compared to continuing the current dose for people with schizophrenia. SEARCH METHODS: We conducted a systematic search on 10 February 2021 at the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, ISRCTN, and WHO ICTRP. We also inspected the reference lists of included studies and previous reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing any dose reduction against continuation in people with schizophrenia or related disorders who were stabilised on their current antipsychotic treatment. DATA COLLECTION AND ANALYSIS: At least two review authors independently screened relevant records for inclusion, extracted data from eligible studies, and assessed the risk of bias using RoB 2. We contacted study authors for missing data and additional information. Our primary outcomes were clinically important change in quality of life, rehospitalisations and dropouts due to adverse effects; key secondary outcomes were clinically important change in functioning, relapse, dropouts for any reason, and at least one adverse effect. We also examined scales measuring symptoms, quality of life, and functioning as well as a comprehensive list of specific adverse effects. We pooled outcomes at the endpoint preferably closest to one year. We evaluated the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 25 RCTs, of which 22 studies provided data with 2635 participants (average age 38.4 years old). The median study sample size was 60 participants (ranging from 18 to 466 participants) and length was 37 weeks (ranging from 12 weeks to 2 years). There were variations in the dose reduction strategies in terms of speed of reduction (i.e. gradual in about half of the studies (within 2 to 16 weeks) and abrupt in the other half), and in terms of degree of reduction (i.e. median planned reduction of 66% of the dose up to complete withdrawal in three studies). We assessed risk of bias across outcomes predominantly as some concerns or high risk. No study reported data on the number of participants with a clinically important change in quality of life or functioning, and only eight studies reported continuous data on scales measuring quality of life or functioning. There was no difference between dose reduction and continuation on scales measuring quality of life (standardised mean difference (SMD) -0.01, 95% confidence interval (CI) -0.17 to 0.15, 6 RCTs, n = 719, I2 = 0%, moderate certainty evidence) and scales measuring functioning (SMD 0.03, 95% CI -0.10 to 0.17, 6 RCTs, n = 966, I2 = 0%, high certainty evidence). Dose reduction in comparison to continuation may increase the risk of rehospitalisation based on data from eight studies with estimable effect sizes; however, the 95% CI does not exclude the possibility of no difference (risk ratio (RR) 1.53, 95% CI 0.84 to 2.81, 8 RCTs, n = 1413, I2 = 59% (moderate heterogeneity), very low certainty evidence). Similarly, dose reduction increased the risk of relapse based on data from 20 studies (RR 2.16, 95% CI 1.52 to 3.06, 20 RCTs, n = 2481, I2 = 70% (substantial heterogeneity), low certainty evidence). More participants in the dose reduction group in comparison to the continuation group left the study early due to adverse effects (RR 2.20, 95% CI 1.39 to 3.49, 6 RCTs with estimable effect sizes, n = 1079, I2 = 0%, moderate certainty evidence) and for any reason (RR 1.38, 95% CI 1.05 to 1.81, 12 RCTs, n = 1551, I2 = 48% (moderate heterogeneity), moderate certainty evidence). Lastly, there was no difference between the dose reduction and continuation groups in the number of participants with at least one adverse effect based on data from four studies with estimable effect sizes (RR 1.03, 95% CI 0.94 to 1.12, 5 RCTs, n = 998 (4 RCTs, n = 980 with estimable effect sizes), I2 = 0%, moderate certainty evidence). AUTHORS' CONCLUSIONS: This review synthesised the latest evidence on the reduction of antipsychotic doses for stable individuals with schizophrenia. There was no difference between dose reduction and continuation groups in quality of life, functioning, and number of participants with at least one adverse effect. However, there was a higher risk for relapse and dropouts, and potentially for rehospitalisations, with dose reduction. Of note, the majority of the trials focused on relapse prevention rather potential beneficial outcomes on quality of life, functioning, and adverse effects, and in some studies there was rapid and substantial reduction of doses. Further well-designed RCTs are therefore needed to provide more definitive answers.
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Antipsicóticos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Esquizofrenia , Humanos , Adulto , Antipsicóticos/efectos adversos , Reducción Gradual de Medicamentos , Esquizofrenia/tratamiento farmacológico , Calidad de Vida , RecurrenciaRESUMEN
BACKGROUND: Many people with schizophrenia do not respond to an initially prescribed antipsychotic drug. In such cases, one treatment strategy could be to increase the antipsychotic dose; and another strategy could be to switch to a different antipsychotic drug. OBJECTIVES: To examine the efficacy of increasing the antipsychotic dose versus switching the antipsychotic drug in the treatment of non-responsive people with schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (10 June 2014, 6 October 2015, and 30 March 2017). We examined references of all included studies for further trials. SELECTION CRITERIA: All relevant randomised controlled trials (RCTs) comparing increasing the antipsychotic dose versus switching to a different antipsychotic drug for people with schizophrenia who have not responded to their initial antipsychotic treatment. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data. We analysed dichotomous data using relative risks (RR) and their 95% confidence intervals (CIs). We analysed continuous data using mean differences (MD) and their 95% CIs. We assessed risk of bias for included studies and used GRADE to create a 'Summary of findings' table. MAIN RESULTS: We include one RCT with relevant data on 29 participants in this review. The trial had a parallel design and was double-blind, but blinding procedures were not described. The trial included people who were non-responsive to fluphenazine 20 mg/day administered for 4 weeks. Participants were randomly assigned to continuing treatment with fluphenazine 20 mg/day, increasing the dose to fluphenazine 80 mg/day or switching to haloperidol 20 mg/day for four additional weeks. Data were reported only for 47 out of 58 initially randomised participants. The trial was published in 1993. The fact that only one RCT with a small sample size (N = 29) was included in the analysis limits the quality of the evidence. Overall, no clear difference was found between groups in terms of the three available outcomes: global state (number of participants with clinically relevant response (RR 1.63, 95% CI 0.17 to 15.99, very low quality evidence); general mental state (endpoint score, BPRS total) (MD 2.00, 95% CI -4.20 to 8.20, very low quality evidence); and negative symptoms (endpoint score, SANS) (MD 3.40, 95% CI -12.56 to 19.36). No data were reported for leaving the study early, adverse effects, time in hospital, quality of life, satisfaction with care and functioning. AUTHORS' CONCLUSIONS: There is extremely limited evidence and no clear conclusions can be drawn. There is an urgent need for further trials in order to determine the optimal treatment strategy for people with schizophrenia who do not respond to their initial antipsychotic treatment.
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Antipsicóticos/administración & dosificación , Sustitución de Medicamentos , Flufenazina/administración & dosificación , Haloperidol/administración & dosificación , Humanos , Esquizofrenia/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Many people with schizophrenia do not reach a satisfactory clinical response with a standard dose of an initially prescribed antipsychotic drug. In such cases, clinicians face the dilemma of increasing the antipsychotic dose in order to enhance antipsychotic efficacy. OBJECTIVES: To examine the efficacy of increasing antipsychotic dose compared to keeping the same dose in the treatment of people with schizophrenia who have not responded (as defined in the individual studies) to an initial antipsychotic drug trial. We also examine the adverse effects associated with such a procedure. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (10 June 2014, 6 October 2015, and 30 March 2017). We examined references of all included studies for further trials. SELECTION CRITERIA: All relevant randomised controlled trials (RCTs), reporting useable data, comparing increasing the antipsychotic dose rather than maintaining the original dose for people with schizophrenia who do not respond to their initial antipsychotic treatment. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data . We analysed dichotomous data using relative risks (RR) and the 95% confidence intervals (CI). We analysed continuous data using mean differences (MD) and their 95% CI. We assessed risk of bias for included studies and used GRADE to create a 'Summary of findings' table. MAIN RESULTS: Ten relevant RCTs with 675 participants are included in this review. All trials were double blind except one single blind. All studies had a run-in phase to confirm they did not respond to their initial antipsychotic treatment. The trials were published between 1980 and 2016. In most studies the methods of randomisation, allocation and blinding were poorly reported. In addition sample sizes were often small, limiting the overall quality of the evidence. Overall, no clear difference was found between groups in terms of the number of participants who showed clinically relevant response (RR 1.09, 95% CI 0.86 to 1.40, 9 RCTs, N = 533, low-quality evidence), or left the study early due to adverse effects (RR 1.63, 95% CI 0.52 to 5.07, very low quality evidence), or due to any reason (RR 1.30, 95% CI 0.89 to 1.90, 5 RCTs, N = 353, low-quality evidence). Similarly, no clear difference was found in general mental state as measured by PANSS total score change (MD -1.44, 95% CI -6.85 to 3.97, 3 RCTs, N = 258, very low quality evidence). At least one adverse effect was equivocal between groups (RR 0.91, 95% CI 0.55 to 1.50, 2 RCTs, N = 191, very low quality evidence). Data were not reported for time in hospital or quality-of-life outcomes. Finally, subgroup and sensitivity analyses did not show any effect on the primary outcome but these analyses were clearly underpowered. AUTHORS' CONCLUSIONS: Current data do not show any clear differences between increasing or maintaining the antipsychotic dose for people with schizophrenia who do not respond to their initial antipsychotic treatment. Adverse effect reporting was limited and poor. There is an urgent need for further trials in order to determine the optional treatment strategy in such cases.
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Antipsicóticos/administración & dosificación , Esquizofrenia/tratamiento farmacológico , Antipsicóticos/efectos adversos , Método Doble Ciego , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Método Simple Ciego , Resultado del TratamientoRESUMEN
BACKGROUND: As the number of systematic reviews is growing rapidly, we systematically investigate whether meta-analyses published in leading medical journals present an outline of available evidence by referring to previous meta-analyses and systematic reviews. METHODS: We searched PubMed for recent meta-analyses of pharmacological treatments published in high impact factor journals. Previous systematic reviews and meta-analyses were identified with electronic searches of keywords and by searching reference sections. We analyzed the number of meta-analyses and systematic reviews that were cited, described and discussed in each recent meta-analysis. Moreover, we investigated publication characteristics that potentially influence the referencing practices. RESULTS: We identified 52 recent meta-analyses and 242 previous meta-analyses on the same topics. Of these, 66% of identified previous meta-analyses were cited, 36% described, and only 20% discussed by recent meta-analyses. The probability of citing a previous meta-analysis was positively associated with its publication in a journal with a higher impact factor (odds ratio, 1.49; 95% confidence interval, 1.06 to 2.10) and more recent publication year (odds ratio, 1.19; 95% confidence interval 1.03 to 1.37). Additionally, the probability of a previous study being described by the recent meta-analysis was inversely associated with the concordance of results (odds ratio, 0.38; 95% confidence interval, 0.17 to 0.88), and the probability of being discussed was increased for previous studies that employed meta-analytic methods (odds ratio, 32.36; 95% confidence interval, 2.00 to 522.85). CONCLUSIONS: Meta-analyses on pharmacological treatments do not consistently refer to and discuss findings of previous meta-analyses on the same topic. Such neglect can lead to research waste and be confusing for readers. Journals should make the discussion of related meta-analyses mandatory.
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Metaanálisis como Asunto , Literatura de Revisión como Asunto , HumanosRESUMEN
BACKGROUND: Haloperidol is worldwide one of the most frequently used antipsychotic drugs with a very high market share. Previous narrative, unsystematic reviews found no differences in terms of efficacy between the various first-generation ("conventional", "typical") antipsychotic agents. This established the unproven psychopharmacological assumption of a comparable efficacy between the first-generation antipsychotic compounds codified in textbooks and treatment guidelines. Because this assumption contrasts with the clinical impression, a high-quality systematic review appeared highly necessary. OBJECTIVES: To compare the efficacy, acceptability, and tolerability of haloperidol with other first-generation antipsychotics in schizophrenia and schizophrenia-like psychosis. SEARCH METHODS: In October 2011 and July 2012, we searched the Cochrane Schizophrenia Group's Trials Register, which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. To identify further relevant publications, we screened the references of all included studies and contacted the manufacturers of haloperidol for further relevant trials and missing information on identified studies. Furthermore, we contacted the corresponding authors of all included trials for missing data. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared oral haloperidol with another oral first-generation antipsychotic drug (with the exception of the low-potency antipsychotics chlorpromazine, chlorprothixene, levopromazine, mesoridazine, perazine, prochlorpromazine, and thioridazine) in schizophrenia and schizophrenia-like psychosis. Clinically important response to treatment was defined as the primary outcome. Secondary outcomes were global state, mental state, behaviour, overall acceptability (measured by the number of participants leaving the study early due to any reason), overall efficacy (attrition due to inefficacy of treatment), overall tolerability (attrition due to adverse events), and specific adverse effects. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data from the included trials. The methodological quality of the included studies was assessed using The Cochrane Collaboration`s 'Risk of bias' tool.We analysed dichotomous outcomes with risk ratios (RR) and continuous outcomes with mean differences (MD), both with the associated 95% confidence intervals (CI). All analyses were based on a random-effects model and we preferably used data on an intention-to-treat basis where possible. MAIN RESULTS: The systematic review currently includes 63 randomised trials with 3675 participants. Bromperidol (n = 9), loxapine (n = 7), and trifluoperazine (n = 6) were the most frequently administered antipsychotics comparator to haloperidol. The included studies were published between 1962 and 1993, were characterised by small sample sizes (mean: 58 participants, range from 18 to 206) and the predefined outcomes were often incompletely reported. All results for the main outcomes were based on very low or low quality data. In many trials the mechanism of randomisation, allocation, and blinding was frequently not reported. In short-term studies (up to 12 weeks), there was no clear evidence of a difference between haloperidol and the pooled group of the other first-generation antipsychotic agents in terms of the primary outcome "clinically important response to treatment" (40 RCTs, n = 2132, RR 0.93 CI 0.87 to 1.00). In the medium-term trials, haloperidol may be less effective than the other first-generation antipsychotic group but this evidence is based on only one trial (1 RCT, n = 80, RR 0.51 CI 0.37 to 0.69).Based on limited evidence, haloperidol alleviated more positive symptoms of schizophrenia than the other antipsychotic drugs. There were no statistically significant between-group differences in global state, other mental state outcomes, behaviour, leaving the study early due to any reason, due to inefficacy, as well as due to adverse effects. The only statistically significant difference in specific side effects was that haloperidol produced less akathisia in the medium term. AUTHORS' CONCLUSIONS: The findings of the meta-analytic calculations support the statements of previous narrative, unsystematic reviews suggesting comparable efficacy of first-generation antipsychotics. In efficacy-related outcomes, there was no clear evidence of a difference between the prototypal drug haloperidol and other, mainly high-potency first-generation antipsychotics. Additionally, we demonstrated that haloperidol is characterised by a similar risk profile compared to the other first-generation antipsychotic compounds. The only statistically significant difference in specific side effects was that haloperidol produced less akathisia in the medium term. The results were limited by the low methodological quality in many of the included original studies. Data for the main results were low or very low quality. Therefore, future clinical trials with high methodological quality are required.
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Antipsicóticos/uso terapéutico , Haloperidol/uso terapéutico , Trastornos Psicóticos/tratamiento farmacológico , Esquizofrenia/tratamiento farmacológico , Administración Oral , Antipsicóticos/efectos adversos , Haloperidol/efectos adversos , Haloperidol/análogos & derivados , Humanos , Loxapina/efectos adversos , Loxapina/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Trifluoperazina/efectos adversos , Trifluoperazina/uso terapéuticoRESUMEN
BACKGROUND AND OBJECTIVES: Sleep problems and insomnia are common, challenging to treat, and transcend specific diagnoses. Although trazodone is a popular choice, robust meta-analytic evidence is lacking. This systematic review and meta-analysis investigates the efficacy and safety of trazodone for sleep disturbances, reflecting recent updates in insomnia diagnosis and treatment. METHODS: We searched Medline, Embase, APA PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to 1 May 2024, for Randomized Controlled Trials (RCTs) comparing trazodone with placebo and reporting sleep-related outcomes. The minimum pharmacotherapy duration was 5 days. Included were all RCTs regardless of blinding (open-label or single- or double-blind), while quasi-randomized studies were excluded. The Cochrane Risk of Bias Tool for Randomized Trials assessed bias. Analyses used a random-effects model on an intention-to-treat (ITT) basis. Risk ratio (RR) was used for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes. When different units or scales were used, Hedge's adjusted g standardized mean difference (SMD) was calculated. Subgroup and preplanned sensitivity analyses explored heterogeneity and evaluated findings' strength and consistency. RESULTS: In total, 44 RCTs with 3935 participants were included. Trazodone did not significantly impact subjective total sleep time (TST) [WMD = 0.73 min, 95% confidence interval (CI) - 24.62; 26.07, p = 0.96] but improved sleep quality (SQ) (SMD = - 0.58, 95% CI - 0.87; - 0.28, p < 0.01) and secondary outcomes. These included the number of nocturnal awakenings (SMD = - 0.57, 95% CI - 0.85; - 0.30], p < 0.01), nocturnal time awake after sleep onset (WMD = - 13.47 min, 95% CI - 23.09; - 3.86], p < 0.01), objective TST by polysomnography (WMD = 27.98 min, 95% CI 4.02; 51.95, p = 0.02), and sleep efficiency (WMD = 3.32, 95% CI 0.53; 1.57, p = 0.02). Tolerability issues included more dropouts owing to adverse effects (RR = 2.30, 95% CI 1.45; 3.64, p < 0.01), any sleep-related adverse effects (RR = 3.67, 95% CI 1.07; 12.47, p = 0.04), more adverse effects in general (RR = 1.18, 95% CI 1.03; 1.33, p = 0.02), and more sleep-related adverse effects (RR = 4.31, 95% CI 2.29; 8.13, p < 0.01). CONCLUSION: Trazodone extends total sleep time but does not affect perceived sleep duration. It may improve sleep quality and continuity but has minor effects on sleep latency, efficiency, and daytime impairment. Trazodone is associated with adverse effects, necessitating a careful risk-benefit assessment. Limited data restrict generalizability, underscoring the need for more research. REGISTRATION: PROSPERO registration number,CRD42022383121.
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Antidepressants are a commonly used, easily accessible, and overall safe treatment option for post-traumatic stress disorder (PTSD). The present review aims to evaluate the efficacy and safety of antidepressants in treating sleep disturbances in patients with PTSD. PubMed and the Cochrane Library were searched (July 2022) for systematic reviews and meta-analyses on the treatment of PTSD. Moreover, PubMed and ClinicalTrials.gov were searched for individual trials investigating the antidepressant treatment of PTSD (up to September 2022), and reference lists of all possibly relevant identified studies were screened. Sleep-related outcomes, i.e., total sleep time, sleep quality, dreams/ nightmares, insomnia, and somnolence, were extracted independently by at least two reviewers. Metaanalytic evaluations were performed wherever possible. 39 randomised controlled trials (RCTs) were identified; data from pooled analyses, reviews, and observational studies were used for antidepressants with a weak evidence base or when their findings were deemed important. Overall, scarce data exist on the effects of antidepressants on sleep outcomes among patients with PTSD. Some evidence may support the use of amitriptyline, nefazodone, paroxetine, and sertraline for improving sleep in patients with PTSD. Τhere was a meta-analytical trend indicating improvement of nightmares with fluoxetine, less insomnia with amitriptyline and more with brofaromine, as well as more somnolence with paroxetine vs. placebo, respectively. However, data from more than 1 RCT with a considerable number of patients were only available for paroxetine. Evidence is insufficient to draw safe conclusions. More and better-designed RCTs, with consistent reporting of sleep-related outcomes, are needed.
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Trastornos del Inicio y del Mantenimiento del Sueño , Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/complicaciones , Trastornos por Estrés Postraumático/tratamiento farmacológico , Paroxetina/efectos adversos , Amitriptilina/uso terapéutico , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Trastornos del Inicio y del Mantenimiento del Sueño/inducido químicamente , Somnolencia , Revisiones Sistemáticas como Asunto , Antidepresivos/uso terapéuticoRESUMEN
BACKGROUND: Sleep disturbances are an important symptom dimension of post-traumatic-stress-disorder (PTSD). There is no meta-analytic evidence examining the effects of all types of pharmacotherapy on sleep outcomes among patients with PTSD. METHODS: Medline/Embase/PsychInfo/CENTRAL/clinicaltrials.gov/ICTRP, reference lists of published reviews and all included studies were searched for Randomised Controlled Trials (RCTs) examining any pharmacotherapy vs. placebo or any other drug among patients with PTSD. PRIMARY OUTCOMES: total sleep time, nightmares, sleep quality. SECONDARY OUTCOMES: sleep onset latency, number of nocturnal awakenings, time spent awake following sleep onset, dropouts due to sleep-related adverse-effects, insomnia/somnolence/vivid-dreams as adverse-effects. Pairwise and network meta-analyses were performed. RESULTS: 99 RCTs with 10,481 participants were included. Prazosin may be the most effective treatment for insomnia (SMD = -0.88, 95%CI = [-1.22;-0.54], nightmares (SMD = -0.44, 95%CI = [-0.84;-0.04]) and poor sleep quality (SMD = -0.55, 95%CI = [-1.01;-0.10]). Evidence is scarce and indicates lack of efficacy for SSRIs, Mirtazapine, z-drugs and benzodiazepines, which are widely used in daily practice. Risperidone and Quetiapine carry a high risk of causing somnolence without having a clear therapeutic benefit. Hydroxyzine, Trazodone, Nabilone, Paroxetine and MDMA-assisted psychotherapy may be promising options, but more research is needed. CONCLUSIONS: Underpowered individual comparisons and very-low to moderate confidence in effect estimates hinder the generalisability of the results. More RCTs, specifically reporting on sleep-related outcomes, are urgently needed.
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Metaanálisis en Red , Trastornos del Sueño-Vigilia , Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/tratamiento farmacológico , Trastornos por Estrés Postraumático/complicaciones , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Prazosina/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Sueños/efectos de los fármacos , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológicoRESUMEN
BACKGROUND: Alzheimer's disease (AD) is highly intertwined with sleep disturbances throughout its whole natural history. Sleep consists of a major compound of the functionality of the glymphatic system, as the synchronized slow-wave activity during NREM facilitates cerebrospinal and interstitial long-distance mixing. OBJECTIVE: The present study undertakes a scoping review of research on the involvement of the glymphatic system in AD-related sleep disturbances. DESIGN: we searched Medline, Embase, PsychInfo and HEAL-link databases, without limitations on date and language, along with reference lists of relevant reviews and all included studies. We included in vivo, in vitro and post-mortem studies examining glymphatic implications of sleep disturbances in human populations with AD spectrum pathology. A thematic synthesis of evidence based on the extracted content was applied and presented in a narrative way. RESULTS: In total, 70 original research articles were included and were grouped as following: a) Protein aggregation and toxicity, after sleep deprivation, along with its effects on sleep architecture, b) Glymphatic Sequalae in SDB, yielding potential glymphatic markers c) Circadian Dysregulation, d) Possible Interventions. CONCLUSIONS: this review sought to provide insight into the role of sleep disturbances in AD pathogenesis, in the context of the glymphatic disruption.
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Enfermedad de Alzheimer , Sistema Glinfático , Trastornos del Sueño-Vigilia , Humanos , Enfermedad de Alzheimer/metabolismo , Sistema Glinfático/metabolismo , Trastornos del Sueño-Vigilia/metabolismo , Privación de Sueño , Sueño/fisiología , Encéfalo/metabolismoRESUMEN
(1) Background: The use of benzodiazepines for the treatment of acute mania remains prevalent. This systematic review and meta-analysis provides an updated assessment of Clonazepam's antimanic efficacy, tolerability, and acceptability. (2) Methods: A systematic search of multiple databases and clinical trial registries was conducted, aiming to identify any controlled studies of Clonazepam vs. placebo or any other pharmacotherapy for the treatment of acute mania. Pairwise meta-analytic evaluations were performed. (3) Results: Six studies were included with a total number of 192 participants, all of which were randomized controlled trials. Clonazepam may be superior to a placebo in the acute phase of treatment and no different to Lithium and Haloperidol in terms of efficacy, both acutely and in the medium to long term. Clonazepam may be an acceptable and well-tolerated treatment for acute mania, especially when used as an augmentation strategy. Comparisons were underpowered, with minimal sample sizes and only one study per comparison in many cases, thus limiting the generalizability of our findings and hindering firm clinical conclusions. (4) Conclusions: Given the prevalence of benzodiazepine use in current practice, more and larger studies are urgently needed.
RESUMEN
Bulimia Nervosa is a disorder with high rates of psychiatric and medical comorbidity and substantial societal costs. Cognitive Behavioural Therapy is considered the preferred treatment, but access can be problematic. Pharmacotherapy is more accessible but remains significantly underutilised. We aimed to assess the efficacy, tolerability, and safety of all available forms of pharmacotherapy for the treatment of bulimia nervosa. We conducted a comprehensive search of PubMed, EMBASE, CENTRAL, ClinicalTrials.gov, and reference lists of relevant articles up until April 2023. The primary outcomes were remission and binge frequency. 52 randomised controlled trials (RCTs) involving 3313 participants were included in the meta-analysis. Overall, no significant difference was observed between drugs and placebo in terms of remission; however, the available data were limited. Notably, drugs, particularly antidepressants, demonstrated a significant reduction in the frequency of binge episodes compared to placebo. Antidepressants were also found to be more effective than placebo in terms of treatment response and other clinically meaningful outcomes. An important limitation is that few RCTs were available for individual drugs. Our findings provide evidence supporting the increased utilisation of pharmacotherapy in clinical practice and underscore the need for further research involving larger populations and a broader range of outcomes.
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Bulimia Nerviosa , Terapia Cognitivo-Conductual , Humanos , Bulimia Nerviosa/tratamiento farmacológico , Antidepresivos/uso terapéutico , Comorbilidad , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The impact of the COVID-19 pandemic on the mental health of healthcare professionals is currently under research and prevalence of mental health symptoms across the world vary a lot. Moreover, knowledge and perceptions of healthcare professionals towards the new coronavirus is yet to be explored since very few data have been published to date. Thus, we decided to conduct a cross-sectional, web-based survey to measure the levels of depressive, anxiety and stress symptoms using the Depression, Anxiety and Stress Scale-21. The knowledge and perceptions of healthcare professionals towards the new coronavirus were also examined with a self-constructed questionnaire. Data were collected between April 19th and May 31st 2020. In total, 1484 professionals participated in the survey and 1064 completed it in full; 60.8% were females, 66.5% were physicians and 24.3% were first-line healthcare workers. The prevalence of at least moderate symptoms was 13% for depression, 11.9% for anxiety, and 11.3% for stress. Women, younger participants, residents in urban areas, having lower income and worse self-reported health status had higher scores in all outcomes. First-line healthcare workers also indicated higher anxiety scores compared to those who were not first responders. Regarding knowledge and perceptions, most participants agreed with the asymptomatic nature of the virus and its heightened danger for older individuals and those with underlying health conditions. Different views were expressed regarding the possibility of airborne transmission, its similarity to common flu, and the statements that the new coronavirus is manufactured and serves a specific purpose and that it is out of control. In conclusion, the results of our study suggest that the prevalence of depressive, anxiety and stress symptoms in Greek healthcare professionals is placed in the lower end of the range reported from various recent studies across the world. Nevertheless, professionals at risk should be monitored closely and supported when needed.airborne transmission, its similarity to common flu, and the statements that the new coronavirus is manufactured and serves a specific purpose and that it is out of control. In conclusion, the results of our study suggest that the prevalence of depressive, anxiety and stress symptoms in Greek healthcare professionals is placed in the lower end of the range reported from various recent studies across the world. Nevertheless, professionals at risk should be monitored closely and supported when needed.
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COVID-19 , Ansiedad/epidemiología , Estudios Transversales , Atención a la Salud , Depresión/epidemiología , Femenino , Grecia/epidemiología , Personal de Salud , Humanos , Pandemias , SARS-CoV-2 , Estrés Psicológico/epidemiologíaRESUMEN
The objective of this cross-sectional survey was to estimate the association between multiple socioeconomic, and health-related characteristics, COVID-19 related attitudes and adoption of public health preventive behaviors. A national cross-sectional survey among 1205 adults was conducted in April 2020 in Greece. Multivariable ordered logistic regression models were used to estimate the association between COVID-19 related attitudes and knowledge and adoption of preventive behaviors, controlling for socioeconomic and health-related characteristics. A total of 923 individuals fully completed the survey. Individuals who believed that the virus is out of control, is transmitted through the air, and is not similar to the common flu were more likely to adopt public health preventive behaviors more frequently, particularly wearing masks in public spaces, washing their hands, and spending fewer hours out of their homes. Uncertainty about the virus symptomatology was associated with less frequent mask-wearing and handwashing. Increased social support, frequent media use for COVID-19 updates, trust to authorities, older age, worse health status, female gender and being a healthcare professional were also associated with uptake of some preventive health behaviors. Attitudinal and socioeconomic determinants critically affect public engagement in preventive behaviors. Health policy initiatives should focus on community outreach approaches to raise awareness and to strengthen social support mechanisms by integrating multiple stakeholders.
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COVID-19/prevención & control , Conductas Relacionadas con la Salud , Salud Pública , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Grecia , Conocimientos, Actitudes y Práctica en Salud , Política de Salud , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pandemias , SARS-CoV-2 , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVE: An important clinical question is how many patients with acute schizophrenia do not respond to antipsychotics despite being treated for adequate time and with an effective dose. However, up to date, the exact extent of the phenomenon remains unclear. METHODS: We calculated the nonresponse and nonremission percentages using individual patient data from 16 randomized controlled trials (RCTs). Six thousand two hundred twenty-one patients were assigned to one antipsychotic (amisulpride, flupenthixol, haloperidol, olanzapine, quetiapine, risperidone, or ziprasidone) at an adequate dose; the response was assessed at 4-6 weeks. As various definitions of nonresponse have been used in the literature, we applied 4 different cut-offs covering the whole range of percent Positive and Negative Syndrome Scale (PANSS)/Brief Psychiatric Rating Scale (BPRS) reduction (≤0%, <25%, <50%, <75%).For symptomatic remission, we used the definition proposed by Andreasen without employing the time criterion. RESULTS: The overall nonresponse for the cut-off of ≤0% PANSS/BPRS reduction was 19.8% (18.8%-20.8%); for the cut-off of <25% reduction it was 43% (41.7%-44.3%); for the cut-off of <50% reduction it was 66.5% (65.3%-67.8%); and for the cut-off of <75% reduction it was 87% (86%-87.9%). The overall percentage of no symptomatic remission was 66.9% (65.7%-68.1%). Earlier onset of illness, lower baseline severity and the antipsychotic used were significantly associated with higher nonresponse percentages. CONCLUSIONS: Nonresponse and nonremission percentages were notably high. Nevertheless, the patients in our analysis could represent a negative selection since they came from short-term RCTs and could have been treated before study inclusion; thus, further response may not have been observed. Observational studies on this important question are needed.
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Antipsicóticos/farmacología , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Esquizofrenia/tratamiento farmacológico , Adulto , HumanosRESUMEN
BACKGROUND: The efficacy of antipsychotics across the initial severity range in patients with acute mania remains unclear. Therefore, we examined the influence of baseline severity on the efficacy of olanzapine. METHODS: We did an individual participant data meta-analysis of double-blind, randomised controlled trials that compared olanzapine with placebo, identified through searches of the ClinicalStudyRequest.com database on Feb 2, 2016. We included patients with acute mania associated with bipolar I disorder. We examined the association between baseline and change scores on the Young Mania Rating Scale (YMRS; range 0-60) up to 3 weeks for olanzapine versus placebo groups using eight increasingly complex competing mixed-effects models for repeated measures. FINDINGS: We identified 33 reports, five (15%) of which were eligible and contained data for 939 patients (552 received olanzapine; 387 received placebo). The interaction between baseline severity and treatment was significant (ß=0·22, 95% CI 0·05-0·39; p=0·013). The greater the baseline severity, the greater the magnitude of the differences between olanzapine and placebo was expected. The mean estimated YMRS scores were reduced at 3 weeks in both groups, but were greater with olazapine than placebo by 2·56 points for patients with a baseline score of 20-25 (9·26 for olanzapine vs 6·70 for placebo; effect size 0·35, 95% CI 0·11-0·60), by 4·74 points for a baseline score of 25-35 (14·25 vs 9·51; 0·58, 0·34-0·86), and by 8·01 points for a baseline score of 35-60 (21·72 vs 13·71; 0·70, 0·31-1·23). INTERPRETATION: Benefits of olanzapine can be expected for patients across the full spectrum of symptom severity who are likely to be treated for acute mania. Less severely ill patients seem to benefit less in terms of olanzapine efficacy, but still experience the same side-effects as more severely ill patients. Thus, clinicians and patients should carefully consider the benefit-to-risk ratio of olanzapine and its additional, prophylactic effect against relapse in the long term. The generalisability of these results to other antipsychotics, trial designs, and medical conditions remains to be established. FUNDING: None.
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Antipsicóticos/farmacología , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/fisiopatología , Olanzapina/farmacología , Evaluación de Resultado en la Atención de Salud , Índice de Severidad de la Enfermedad , HumanosRESUMEN
IMPORTANCE: In treatment-resistant schizophrenia, clozapine is considered the standard treatment. However, clozapine use has restrictions owing to its many adverse effects. Moreover, an increasing number of randomized clinical trials (RCTs) of other antipsychotics have been published. OBJECTIVE: To integrate all the randomized evidence from the available antipsychotics used for treatment-resistant schizophrenia by performing a network meta-analysis. DATA SOURCES: MEDLINE, EMBASE, Biosis, PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, World Health Organization International Trial Registry, and clinicaltrials.gov were searched up to June 30, 2014. STUDY SELECTION: At least 2 independent reviewers selected published and unpublished single- and double-blind RCTs in treatment-resistant schizophrenia (any study-defined criterion) that compared any antipsychotic (at any dose and in any form of administration) with another antipsychotic or placebo. DATA EXTRACTION AND SYNTHESIS: At least 2 independent reviewers extracted all data into standard forms and assessed the quality of all included trials with the Cochrane Collaboration's risk-of-bias tool. Data were pooled using a random-effects model in a Bayesian setting. MAIN OUTCOMES AND MEASURES: The primary outcome was efficacy as measured by overall change in symptoms of schizophrenia. Secondary outcomes included change in positive and negative symptoms of schizophrenia, categorical response to treatment, dropouts for any reason and for inefficacy of treatment, and important adverse events. RESULTS: Forty blinded RCTs with 5172 unique participants (71.5% men; mean [SD] age, 38.8 [3.7] years) were included in the analysis. Few significant differences were found in all outcomes. In the primary outcome (reported as standardized mean difference; 95% credible interval), olanzapine was more effective than quetiapine (-0.29; -0.56 to -0.02), haloperidol (-0. 29; -0.44 to -0.13), and sertindole (-0.46; -0.80 to -0.06); clozapine was more effective than haloperidol (-0.22; -0.38 to -0.07) and sertindole (-0.40; -0.74 to -0.04); and risperidone was more effective than sertindole (-0.32; -0.63 to -0.01). A pattern of superiority for olanzapine, clozapine, and risperidone was seen in other efficacy outcomes, but results were not consistent and effect sizes were usually small. In addition, relatively few RCTs were available for antipsychotics other than clozapine, haloperidol, olanzapine, and risperidone. The most surprising finding was that clozapine was not significantly better than most other drugs. CONCLUSIONS AND RELEVANCE: Insufficient evidence exists on which antipsychotic is more efficacious for patients with treatment-resistant schizophrenia, and blinded RCTs-in contrast to unblinded, randomized effectiveness studies-provide little evidence of the superiority of clozapine compared with other second-generation antipsychotics. Future clozapine studies with high doses and patients with extremely treatment-refractory schizophrenia might be most promising to change the current evidence.