BACKGROUND: Posttraumatic stress disorder (PTSD) is a prevalent and disabling disorder. Evidence that PTSD is characterised by specific psychobiological dysfunctions has contributed to a growing interest in the use of medication in its treatment.
OBJECTIVES: To assess the effects of medication for reducing PTSD symptoms in adults with PTSD.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 11, November 2020); MEDLINE (1946-), Embase (1974-), PsycINFO (1967-) and PTSDPubs (all available years) either directly or via the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR). We also searched international trial registers. The date of the latest search was 13 November 2020.
SELECTION CRITERIA: All randomised controlled trials (RCTs) of pharmacotherapy for adults with PTSD.
DATA COLLECTION AND ANALYSIS: Three review authors (TW, JI, and NP) independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. We contacted investigators to obtain missing data. We stratified summary statistics by medication class, and by medication agent for all medications. We calculated dichotomous and continuous measures using a random-effects model, and assessed heterogeneity.
MAIN RESULTS: We include 66 RCTs in the review (range: 13 days to 28 weeks; 7442 participants; age range 18 to 85 years) and 54 in the meta-analysis. For the primary outcome of treatment response, we found evidence of beneficial effect for selective serotonin reuptake inhibitors (SSRIs) compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.59 to 0.74; 8 studies, 1078 participants), which improved PTSD symptoms in 58% of SSRI participants compared with 35% of placebo participants, based on moderate-certainty evidence. For this outcome we also found evidence of beneficial effect for the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine: (RR 0.45, 95% CI 0.22 to 0.94; 1 study, 26 participants) in 65% of people on mirtazapine compared with 22% of placebo participants, and for the tricyclic antidepressant (TCA) amitriptyline (RR 0.60, 95% CI 0.38 to 0.96; 1 study, 40 participants) in 50% of amitriptyline participants compared with 17% of placebo participants, which improved PTSD symptoms. These outcomes are based on low-certainty evidence. There was however no evidence of beneficial effect for the number of participants who improved with the antipsychotics (RR 0.51, 95% CI 0.16 to 1.67; 2 studies, 43 participants) compared to placebo, based on very low-certainty evidence. For the outcome of treatment withdrawal, we found evidence of a harm for the individual SSRI agents compared with placebo (RR 1.41, 95% CI 1.07 to 1.87; 14 studies, 2399 participants). Withdrawals were also higher for the separate SSRI paroxetine group compared to the placebo group (RR 1.55, 95% CI 1.05 to 2.29; 5 studies, 1101 participants). Nonetheless, the absolute proportion of individuals dropping out from treatment due to adverse events in the SSRI groups was low (9%), based on moderate-certainty evidence. For the rest of the medications compared to placebo, we did not find evidence of harm for individuals dropping out from treatment due to adverse events.
AUTHORS' CONCLUSIONS: The findings of this review support the conclusion that SSRIs improve PTSD symptoms; they are first-line agents for the pharmacotherapy of PTSD, based on moderate-certainty evidence. The NaSSA mirtazapine and the TCA amitriptyline may also improve PTSD symptoms, but this is based on low-certainty evidence. In addition, we found no evidence of benefit for the number of participants who improved following treatment with the antipsychotic group compared to placebo, based on very low-certainty evidence. There remain important gaps in the evidence base, and a continued need for more effective agents in the management of PTSD.
BACKGROUND: The purpose of this study was to compare efficacy and acceptability among drug treatments for adults with post-traumatic stress disorder (PTSD) through a systematic review, random-effects pairwise and network meta-analyses. METHODS: Double-blind randomized controlled trials comparing pharmacological interventions for adults with PTSD were searched from database inception through Aug. 28, 2018, on Cochrane (Central), Embase, LILACS, PILOTS, PsycINFO, PubMed, and Web of Science. Clinical trial registries and the websites of pharmaceutical companies were also searched. The GRADE system was used to assess the quality of the evidence. RESULTS: The systematic review included 58 studies comprising 6766 patients randomized to 26 different interventions. Regarding efficacy, topiramate (SMD = -0.57; 95%CrI: -1.07,-0.10), risperidone (SMD = -0.53; 95%CrI: -0.93,-0.15), quetiapine (SMD = -0.59; 95%CrI: -1.06,-0.11), paroxetine (SMD = -0.35; 95%CrI: -0.48,-0.21), venlafaxine (SMD = -0.25; 95%CrI: -0.44,-0.05), fluoxetine (SMD = -0.28; 95%CrI: -0.46,-0.08), and sertraline (SMD = -0.21; 95%CrI: -0.33,-0.09) outperformed placebo. Moreover, phenelzine (RR = 3.39; 95%CrI: 1.43,11.09), lamotrigine (RR = 4.39; 95%CrI: 1.18,26.38), and fluoxetine (RR = 1.28%CrI: 1.01,1.59) outperformed placebo in terms of acceptability. CONCLUSIONS: The NMA supports topiramate, risperidone, quetiapine, paroxetine, venlafaxine, fluoxetine and sertraline as effective pharmacological choices for the treatment of PTSD. Quetiapine and topiramate have the shortcoming of relying on a few small studies, but the clinically meaningful change in symptoms is noteworthy and merits further investigation. Among the pharmacological treatments with evidence of efficacy compared to placebo, fluoxetine achieved a relatively high rank regarding acceptability. To the best of our knowledge, this is the largest contemporary NMA on the subject and the addition of new medications is an important extension of previous meta-analyses, enabling a larger number of drug comparisons. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
BACKGROUND: In the past years numerous studies have investigated the efficacy of baclofen for alcohol dependence. After publication of several reviews a number of new randomized controlled trials have been published. Two recent meta-analyses, based on largely the same studies, reported contrary results. One meta-analysis showed a positive effect on time to relapse and abstinence at endpoint. The other meta-analysis did not show an effect on the primary outcome measures.<br/> AIM: To clarify the clinical relevance of the effect of baclofen on alcohol use in patients with a disorder in the use of alcohol, in the light of the positive and the negative meta-analysis.<br/> METHOD: A systematic literature search using Medline, Embase and PsycINFO (Prisma guideline).<br/> RESULTS: We found 16 randomized controlled trials in which the effect of baclofen was studied. Seven of them showed a significant positive effect of baclofen on (one or more of the) primary outcome measures.
Background and AIMS: There are a limited number of pharmacotherapies licensed for alcohol use disorders (AUDs). Baclofen is a γ‐aminobutyric acid B (GABA‐B) agonist which is used increasingly as an off‐label treatment. A meta‐analysis of randomized controlled trials (RCTs) was conducted to determine the efficacy of baclofen in reducing drinking behaviour, craving, depression and anxiety compared with placebo. METHODS: Random‐effects meta‐analyses were computed on outcome data from 12 RCTs comparing baclofen with placebo. Included RCTs provided data on at least one of the primary outcome measures (drinking‐related: heavy drinking days, abstinent days, abstinence rates) or secondary outcome measures (craving, anxiety, depression). RESULTS: Baclofen had a significant effect on abstinence rates when using intention‐to‐treat analysis [total <i>n</i> baclofen = 307, total <i>n</i> control = 283: odds ratio (OR) = 2.67, 95% confidence interval (CI) = 1.03, 6.93; <i>Z</i> = 2.01, <i>P</i> = 0.04, <i>I²</i> = 76%, number needed to treat = 8]. No other significant effects of treatment efficacy [e.g. heavy drinking days: standardized mean differences (SMD) = −0.26, 95% CI = –0.68, 0.15; <i>Z</i> = 1.24, <i>P</i> = 0.21, <i>I</i>² = 95%] or mechanism of action (e.g. craving: SMD = −0.13, 95% CI = −0.36, 0.09; <i>Z</i> = 1.18, <i>P</i> = 0.24, <i>I²</i> = 87%) were observed. There was substantial heterogeneity in effect sizes across each analysis. CONCLUSIONS: As a treatment for alcohol use disorders, baclofen is associated with higher rates of abstinence than placebo. However, there is no superior effect of baclofen on increasing number of abstinent days, or decreasing heavy drinking, craving, anxiety or depression. These results suggest that the current increasing use of baclofen as a treatment for alcohol use disorders is premature. (PsycINFO Database Record (c) 2019 APA, all rights reserved)
A systematic review of the current literature on the efficacy of baclofen, particularly the effect of dosing, for the treatment of alcohol dependence (AD) is missing. We therefore conducted a systematic review and meta-analysis of currently available randomized placebo-controlled trials (RCTs). A systematic literature search for RCTs in AD patients comparing baclofen to placebo was performed in September 2017. The effect of baclofen treatment, and the moderating effects of baclofen dosing (low-dose (LDB) 30–60 mg versus high-dose (HDB) targeted as > 60 mg/day), and the amount of alcohol consumption before inclusion were studied. Three treatment outcomes were assessed: time to lapse (TTL), percentage days abstinent (PDA), and percentage of patients abstinent at end point (PAE). 13 RCTs from 39 records were included. Baclofen was superior to placebo with significant increases in TTL (8 RCTs, 852 patients; SMD = 0.42; 95% CI 0.19–0.64) and PAE (8 RCTs, 1244 patients; OR = 1.93; 95% CI 1.17–3.17), and a non-significant increase in PDA (7 RCTs, 457 patients; SMD = 0.21; 95% CI−0.24 to 0.66). Overall, studies with LDB showed better efficacy than studies with HDB. Furthermore, tolerability of HDB was low, but serious adverse events were rare. Meta-regression analysis showed that the effects of baclofen were stronger when daily alcohol consumption before inclusion was higher. Baclofen seems to be effective in the treatment of AD, especially among heavy drinkers. HDB is not necessarily more effective than LDB with low tolerability of HDB being an import limitation. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Background and AIMS: Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders (AUDs) is an emerging concept. Our objective was to explore the comparative effectiveness of drugs used in this indication. DESIGN: Systematic review with direct and network meta‐analysis of double‐blind randomized controlled trials (RCTs) assessing the efficacy of nalmefene, naltrexone, acamprosate, baclofen or topiramate in non‐abstinent adults diagnosed with alcohol dependence or AUDs. Two independent reviewers selected published and unpublished studies on Medline, the Cochrane Library, Embase, ClinicalTrials.gov, contacted pharmaceutical companies, the European Medicines Agency and the Food and Drug Administration, and extracted data. SETTING: Thirty‐two RCTs. Participants: A total of 6036 patients. Measurements The primary outcome was total alcohol consumption (TAC). Other consumption outcomes and health outcomes were considered as secondary outcomes. FINDINGS: No study provided direct comparisons between drugs. A risk of incomplete outcome data was identified in 26 studies (81%) and risk of selective outcome reporting in 17 (53%). Nalmefene [standardized mean difference (SMD) = −0.19, 95% confidence interval (CI) = −0.29, –0.10; <i>I</i>² = 0%], baclofen (SMD = −1.00, 95% CI = −1.80, −0.19; one study) and topiramate (SMD = −0.77, 95% CI = −1.12, –0.42; <i>I</i>² = 0%) showed superiority over placebo on TAC. No efficacy was observed for naltrexone or acamprosate. Similar results were observed for other consumption outcomes, except for baclofen (the favourable outcome on TAC was not reproduced). The number of withdrawals for safety reasons increased under nalmefene and naltrexone. No treatment demonstrated any harm reduction (no study was powered to explore health outcomes). Indirect comparisons suggested that topiramate was superior to nalmefene, naltrexone and acamprosate on consumption outcomes, but its safety profile is known to be poor. CONCLUSIONS: There is currently no high‐grade evidence for pharmacological treatment to control drinking using nalmefene, naltrexone, acamprosate, baclofen or topiramate in patients with alcohol dependence or alcohol use disorder. Some treatments show low to medium efficacy in reducing drinking across a range of studies with a high risk of bias. None demonstrates any benefit on health outcomes. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
OBJECTIVE: To evaluate the efficacy and tolerability of baclofen vs. placebo for long‐term treatment of alcohol use disorder. METHOD: Systematic review and meta‐analysis following methods of the Cochrane Collaboration Handbook (PROSPERO registration: CRD42017073663). Primary outcome was the random‐effects summary estimate of all standardized mean differences (SMDs), as calculated from the primary outcomes of each study. RESULTS: Fourteen double‐blind RCTs (1522 patients) were included. Heterogeneity was substantial for most analyses (<i>I</i>² about 75%). Baclofen showed a small, but not statistically significant superiority over placebo: SMD = 0.22 ([95% CI: −0.03; 0.47], <i>P</i> = 0.09). This result was supported by a leave‐one‐out‐analysis, and Orwin's fail‐safe N, by predefined secondary analyses (on abstinence rates and amount of drinking), and by a post hoc‐analysis of high‐dose studies (> 80 mg/day). An analysis of low risk of bias studies (SMD = 0.10 [−0.20; 0.41], <i>P</i> = 0.51, <i>I</i>² = 43.3%) found no effect. Exclusion of four studies focusing on patients with comorbidity yielded a small positive effect. Drop‐out rates were similar. CONCLUSION: Our results question baclofen's utility in the long‐term treatment of alcohol use disorder at both normal and high doses. While the confidence intervals indicate that marginally harmful or moderately beneficial effects of baclofen remain a possibility, the most likely effect size is slightly above placebo effects. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
El tratamiento del trastorno por uso de alcohol (AUD) se complica por la presencia de comorbilidad psiquiátrica incluyendo trastorno de estrés postraumático (TEPT). Esta es una revisión crítica de la literatura hasta la fecha sobre tratamientos de farmacoterapia de AUD y PTSD. Se realizó una búsqueda sistemática de la literatura utilizando los términos de PubMed MESH para los trastornos relacionados con el consumo de alcohol y sustancias, el TEPT y el tratamiento para identificar ensayos controlados aleatorios (ECA) relevantes. Los estudios fueron evaluados de forma independiente (ILP y TLS) y los que evaluaron la eficacia de una farmacoterapia para individuos diagnosticados con AUD y PTSD y fueron ECAs fueron seleccionados. Los estudios se agruparon en tres categorías: (i) los que evaluaron los tratamientos de primera línea para el TEPT, (ii) los que evaluaron los medicamentos para el AUD objetivo, y (iii) los que evaluaron los medicamentos hipotetizados para ser efectivos en el consumo de alcohol Síntomas de PTSD. Se identificaron nueve ECA; 3 se centraron en los medicamentos para tratar el TEPT, 4 se centraron en el AUD y 3 en el objetivo de ambos. Un estudio incluyó tanto un medicamento para tratar el TEPT como uno para tratar el AUD, de modo que se discutió dos veces. Todos menos uno de los estudios encontraron que los síntomas del TEPT y los resultados de beber mejoraron significativamente con el tiempo. No hay 1 agente con evidencia clara de eficacia en este grupo comórbido. Los resultados de los medicamentos para tratar el TEPT no son concluyentes debido a los resultados contradictorios. Hubo evidencia débil para apoyar el uso de medicamentos para tratar el AUD entre aquellos con comorbilidad con PTSD. Las conclusiones de los medicamentos que se plantearon para tratar ambos trastornos también fueron contradictorias. La mayoría de los estudios proporcionaron una combinación de intervenciones para tratar ambos trastornos. A pesar de los resultados contradictorios, esta revisión sugiere que las personas con AUD y TEPT comórbido puede ser prescrito con seguridad medicamentos utilizados en las poblaciones no concomitantes y los pacientes mejoran con el tratamiento.
