Second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and related disorders, also other mental disorders. However, the efficacy and safety of SGAs for treating other mental disorders is unclear. A systematic literature search for randomized, placebo-controlled trials of 11 SGAs for treating 18 mental disorders apart from schizophrenia were carried out from database inception to April 3, 2022. The primary outcome was the mean change in the total score for different mental disorders. The secondary outcome was the odds ratio (OR) of response, remission rates and risk ratio (RR) of adverse events (AEs). A total of 181 studies (N = 65,480) were included. All SGAs showed significant effects in treating other mental disorders compared with placebo, except autistic disorder and dementia. Aripiprazole is the most effective treatment for bipolar mania [effect size = -0.90, 95% CI: -1.59, -0.21] and Tourette's disorder [effect size = -0.80, 95% CI: -1.14, -0.45], olanzapine for bipolar depression [effect size = -0.86, 95% CI: -1.32, -0.39] and post-traumatic stress disorder [effect size = -0.98, 95% CI: -1.55, -0.41], lurasidone for depression [effect size = -0.66, 95% CI: -0.82, -0.50], quetiapine for anxiety [effect size = -1.20, 95% CI: -1.96, -0.43], sleep disorders [effect size = -1.2, 95% CI: -1.97, -0.58], and delirium [effect size = -0.36, 95% CI: -0.70, -0.03], and risperidone for obsessive-compulsive disorder [effect size = -2.37, 95% CI: -3.25, -1.49], respectively. For safety, AE items for each SGAs was different. Interestingly, we found that some AEs of OLZ, QTP, RIS and PALI have significant palliative effects on some symptoms. Significant differences in the efficacy and safety of different SGAs for treatment of other mental disorders should be considered for choosing the drug and for the balance between efficacy and tolerability for the specific patient. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
BACKGROUND: Post-traumatic stress disorder (PTSD) is a mental disorder that can emerge after an individual experiences a traumatic event such as physical abuse, sexual/relationship violence, combat exposure, witnessing death, or serious injury. This study aimed to identify the most suitable drugs for the management of PTSD based on a network meta-analysis (NMA).
METHODS: Six databases (Ovid Medline, EMBase, CENTRAL, PsycINFO, Ovid Health and Psychosocial Instruments, and Web of Science) were searched from inception to September 6, 2022.
RESULTS: Thirty articles with a total of 5170 participants were included. Compared with placebo, active drugs including olanzapine (SMD = -0.66, 95% CI: -1.19 to -0.13), risperidone (SMD = -0.23, 95% CI: -0.42 to -0.03), quetiapine (SMD = -0.49, 95% CI: -0.93 to -0.04), venlafaxine (SMD = -0.29, 95% CI: -0.42 to -0.16), sertraline (SMD = -0.23, 95% CI: -0.34 to -0.11), paroxetine (SMD = -0.48, 95% CI: -0.60 to -0.36) and fluoxetine (SMD = -0.27, 95% CI: -0.42 to -0.12), significantly reduced the total clinician-administered PTSD scale score.
CONCLUSION: The results of this study support the use of paroxetine, venlafaxine, and quetiapine as first-line treatment for PTSD. In addition, quetiapine is recommended for patients with PTSD affected by symptoms of hyperarousal and re-experience disorder. Clinicians should prescribe medications based on the severity of PTSD symptoms and other conditions to develop the best treatment strategy for this patient population.
QUESTION: Randomised controlled trials assessing treatments for anxiety, obsessive-compulsive and stress-related disorders often present high placebo response rates in placebo groups. Understanding the placebo response is essential in accurately estimating the benefits of pharmacological agents; nevertheless, no studies have evaluated the placebo response across these disorders using a lifespan approach.
STUDY SELECTION AND ANALYSIS: We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies and international registers from inception to 9 September 2022. The primary outcome was the aggregate measure of internalising symptoms of participants in the placebo arms of randomised controlled trials designed to assess the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) in individuals diagnosed with anxiety, obsessive-compulsive or stress-related disorders. The secondary outcomes were placebo response and remission rates. Data were analysed through a three-level meta-analysis.
FINDINGS: We analysed 366 outcome measures from 135 studies (n=12 583). We found a large overall placebo response (standardised mean difference (SMD)=-1.11, 95% CI -1.22 to -1.00). The average response and remission rates in placebo groups were 37% and 24%, respectively. Larger placebo response was associated with a diagnosis of generalised anxiety disorder and post-traumatic stress disorder, when compared with panic, social anxiety and obsessive-compulsive disorder (SMD range, 0.40-0.49), and with absence of a placebo lead-in period (SMD=0.44, 95% CI 0.10 to 0.78). No significant differences were found in placebo response across age groups. We found substantial heterogeneity and moderate risk of bias.
CONCLUSIONS: Placebo response is substantial in SSRI and SNRI trials for anxiety, obsessive-compulsive and stress-related disorders. Clinicians and researchers should accurately interpret the benefits of pharmacological agents in contrast to placebo response.
PROSPERO REGISTRATION NUMBER: CRD42017069090.
ObjectivesWhile extant research indicates an inverse association between self-compassion and mindfulness with non-suicidal self-injury (NSSI) and suicidal thoughts and behaviors (STBs), estimates of magnitude remain unknown. The present systematic review and meta-analysis aim to quantify the relationship between self-compassion and mindfulness with engagement in NSSI and STBs.MethodsLiterature searches in four electronic databases (PsycINFO, MEDLINE, Scopus, ProQuest Dissertations, and Theses Global) were conducted. Effect sizes were estimated using pooled correlation coefficients and a random effects model. Meta-regressions with mixed-effect models were used to determine the moderators of the associations.ResultsSixty-eight independent samples from 62 different articles (N = 53,797) met inclusion criteria. Analyses yielded a medium negative correlation between self-compassion and mindfulness with both NSSI and STBs. Among mindfulness facets, the nonjudging, acting with awareness, and describing facets demonstrated the largest significant correlations with both STBs and NSSI. The self-coldness dimension (vs self-warmth dimension) of self-compassion demonstrated the largest correlation to STBs. There was a stronger negative correlation between self-compassion and mindfulness with engagement in NSSI and STBs in adolescent samples (than in clinical and college student samples) and with STBs’ recency (reported within the past 12 months vs lifetime). Associations between NSSI and STBs with self-compassion and mindfulness were greater in lower-quality studies and studies with younger or male samples, although effect sizes remained modest.ConclusionsFindings suggest that self-compassion and mindfulness may buffer against NSSI and STBs. Future study regarding the efficacy and effectiveness of self-compassion and mindfulness-based interventions among NSSI and STB populations is warranted.Meta-analysis registrationPROSPERO CRD42020167823. (PsycInfo Database Record (c) 2022 APA, all rights reserved)
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: Yoga is increasingly used as a therapeutic treatment and seems to improve psychiatric conditions such as anxiety disorders and depression. The aim of this systematic review was to assess the evidence of yoga for reducing symptoms of posttraumatic stress disorder (PTSD). METHODS: The Cochrane Library, Medline/PubMed, PsycINFO, Scopus, and IndMED were searched through July 2017 for randomized controlled trials (RCTs) assessing the effects of yoga on symptoms of PTSD. Mean differences (MD) and standardized mean differences (SMD) with 95% confidence intervals (CI) were computed. The quality of evidence and the strength of recommendation were graded according to the GRADE recommendations. RESULTS: Seven RCT<sub>s</sub> (<i>N</i> = 284) were included. Meta-analysis revealed low quality evidence for clinically relevant effects of yoga on PTSD symptoms compared to no treatment (SMD = − 1.10, 95% CI [− 1.72, − 0.47], <i>p</i> < .001, I² = 72%; MD = − 13.11, 95% CI [− 17.95, − 8.27]); and very low evidence for comparable effects of yoga and attention control interventions (SMD = − 0.31, 95%CI = [− 0.84, 0.22], <i>p</i> = .25; I² = 43%). Very low evidence was found for comparable retention of patients in the trial for yoga and no treatment (OR = 0.68, 95%CI [0.06, 7.72]) or attention control interventions (OR = 0.66, 95%CI [0.10, 4.46]). No serious adverse events were reported. Limitations: Few RCTs with only limited sample size were available. CONCLUSIONS: Only a weak recommendation for yoga as an adjunctive intervention for PTSD can be made. More high quality research is needed to confirm or disconfirm these findings. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
OBJECTIVE: To systematically review outcomes from randomized controlled trials (RCTs) of mind–body treatments for PTSD. METHODS: Inclusion criteria based on guidelines for assessing risk of bias were used to evaluate articles identified through electronic literature searches. RESULTS: Twenty‐two RCTs met inclusion standards. In most of the nine mindfulness and six yoga studies, significant between‐group effects were found indicating moderate to large effect size advantages for these treatments. In all seven relaxation RCT's, relaxation was used as a control condition and five studies reported significant between‐group differences on relevant PTSD outcomes in favor of the target treatments. However, there were large within‐group symptom improvements in the relaxation condition for the majority of studies. CONCLUSIONS: Although many studies are limited by methodologic weaknesses, recent studies have increased rigor and, in aggregate, the results for mindfulness, yoga, and relaxation are promising. Recommendations for design of future mind–body trials are offered. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
OBJECTIVE: About a third of service members returning from post-9/11 deployment in Afghanistan and Iraq report combat-related mental health conditions, but many do not seek conventional treatment. Mind-body therapies have been offered as alternative approaches to decreasing post-traumatic stress disorder (PTSD), but no review of studies with veterans of post-9/11 operations was found. The objective of this study was to fill that gap.
DESIGN: A systematic literature review was conducted following the preferred items for systematic reviews and meta-analyses (PRISMA) guidelines. PubMed MeSH terms were used to capture articles reporting on the military population (veteran and veterans) with PTSD who received a portable mind-body intervention (e.g., mindfulness, mind-body therapy, and yoga). PubMed/MEDLINE and PsycINFO were searched. Studies were included if participants were a mixed group of war veterans, as long as some post-9/11 veterans were included. In addition, participants must have had a diagnosis of PTSD or subthreshold PTSD, and the PTSD must have been attributable to combat, rather than another event, such as sexual trauma or natural disaster.
RESULTS: Of 175 records identified, 15 met inclusion criteria. Studies reported on seated or gentle yoga that included breath work, meditation, mantra repetition, or breathing exercises. For 14 of the 15 studies, study retention was 70% or higher. Overall, studies reported significant improvements in PTSD symptoms in participants in these interventions. Although each study included post-9/11 veterans, about 85% of participants were from other conflicts, predominantly Vietnam.
CONCLUSION: Although findings were positive, future studies are needed to evaluate the short- and long-term impact of mind-body therapies on larger samples of post-9/11 veterans and to address research questions related to broadening service member and veteran participation in these therapies.
Second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and related disorders, also other mental disorders. However, the efficacy and safety of SGAs for treating other mental disorders is unclear. A systematic literature search for randomized, placebo-controlled trials of 11 SGAs for treating 18 mental disorders apart from schizophrenia were carried out from database inception to April 3, 2022. The primary outcome was the mean change in the total score for different mental disorders. The secondary outcome was the odds ratio (OR) of response, remission rates and risk ratio (RR) of adverse events (AEs). A total of 181 studies (N = 65,480) were included. All SGAs showed significant effects in treating other mental disorders compared with placebo, except autistic disorder and dementia. Aripiprazole is the most effective treatment for bipolar mania [effect size = -0.90, 95% CI.: -1.59, -0.21] and Tourette's disorder [effect size = -0.80, 95% CI.: -1.14, -0.45], olanzapine for bipolar depression [effect size = -0.86, 95% CI.: -1.32, -0.39] and post-traumatic stress disorder [effect size = -0.98, 95% CI.: -1.55, -0.41], lurasidone for depression [effect size = -0.66, 95% CI.: -0.82, -0.50], quetiapine for anxiety [effect size = -1.20, 95% CI.: -1.96, -0.43], sleep disorders [effect size = -1.2, 95% CI.: -1.97, -0.58], and delirium [effect size = -0.36, 95% CI.: -0.70, -0.03], and risperidone for obsessive-compulsive disorder [effect size = -2.37, 95% CI.: -3.25, -1.49], respectively. For safety, AE items for each SGAs was different. Interestingly, we found that some AEs of OLZ, QTP, RIS and PALI have significant palliative effects on some symptoms. Significant differences in the efficacy and safety of different SGAs for treatment of other mental disorders should be considered for choosing the drug and for the balance between efficacy and tolerability for the specific patient. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
