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Frontiers in Neuroscience 2020Gamma-aminobutyric acid (GABA) is a non-proteinogenic amino acid and is the main inhibitory neurotransmitter in the mammalian brain. GABA's stress-reducing, and sleep...
Gamma-aminobutyric acid (GABA) is a non-proteinogenic amino acid and is the main inhibitory neurotransmitter in the mammalian brain. GABA's stress-reducing, and sleep enhancing effects have been established. However, although several human clinical trials have been conducted, results regarding the role of natural and/or biosynthetic oral GABA intake on stress and sleep are mixed. We performed a systematic review to examine whether natural and/or biosynthetic oral GABA intake has an effect on stress and sleep. We systematically searched on PubMed database for studies published up to February 2020 following PRISMA guidelines. Only placebo-controlled human trials that assessed stress, sleep, and related psychophysiological outcomes as a response to natural GABA (i.e., GABA that is present naturally in foods) or biosynthetic GABA (i.e., GABA that is produced via fermentation) intake were included. Fourteen studies met the criteria and were included in the systematic review. Although more studies are needed before any inferences can be made about the efficacy of oral GABA consumption on stress and sleep, results show that there is limited evidence for stress and very limited evidence for sleep benefits of oral GABA intake.
PubMed: 33041752
DOI: 10.3389/fnins.2020.00923 -
Journal of Psychiatric Research Dec 2021Following recovery from COVID-19, an increasing proportion of individuals have reported the persistence and/or new onset of symptoms which collectively have been... (Review)
Review
Following recovery from COVID-19, an increasing proportion of individuals have reported the persistence and/or new onset of symptoms which collectively have been identified as post-COVID-19 syndrome by the National Institute for Health and Care Excellence. Although depressive symptoms in the acute phase of COVID-19 have been well characterized, the frequency of depression following recovery of the acute phase remains unknown. Herein, we sought to determine the frequency of depressive symptoms and clinically-significant depression more than 12 weeks following SARS-CoV-2 infection. A systematic search of PubMed, Ovid Medline and Google Scholar for studies published between January 1, 2020 and June 5, 2021 was conducted. Frequency and factors associated with depression in post-COVID-19 syndrome were recorded and qualitatively assessed through narrative synthesis. Methodological quality and risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale (NOS) for prospective cohort studies. Of 316 articles identified through our systematic search, eight studies were included. The frequency of depressive symptoms +12 weeks following SARS-CoV-2 infection ranged from 11 to 28%. The frequency of clinically-significant depression and/or severe depressive symptoms ranged from 3 to 12%. The severity of acute COVID-19 was not associated with the frequency of depressive symptoms. However, the component studies were highly heterogeneous with respect to mode of ascertainment, time of assessment, and location and age of patients. The majority of studies did not include an unexposed control group. Future research should endeavour to produce a standardized classification of post-COVID-19 syndrome, and as well as include unexposed control groups.
Topics: COVID-19; Depression; Humans; Prospective Studies; SARS-CoV-2; Post-Acute COVID-19 Syndrome
PubMed: 34619491
DOI: 10.1016/j.jpsychires.2021.09.054 -
Scientific Reports Aug 2018We carried out systematic review and meta-analysis to evaluate whether peripheral levels of pro-inflammatory markers including Interleukin-1 beta (IL-1β), Interleukin-6... (Meta-Analysis)
Meta-Analysis Review
We carried out systematic review and meta-analysis to evaluate whether peripheral levels of pro-inflammatory markers including Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF- α) and C-Reactive Protein (CRP) are significantly higher in elderly with depression and Alzheimer's disease. We searched Pubmed, PsycINFO and Embase, and thirty-four relevant studies (2609 with Depression, 1645 with Alzheimer's disease and 14363 Controls) were included. Compared with controls, IL-1β (pooled standardized mean difference [SMD]: 0.642; 95% confidence interval [CI]: 0.078-1.206; significant heterogeneity: I = 86.28%) and IL-6 (pooled SMD: 0.377; 95% CI: 0.156-0.598; significant heterogeneity: I = 88.75%) were significantly elevated in depression. There was no difference in TNF-α (p = 0.351) and CRP (p = 0.05) between those with depression and controls. Compared with controls, IL-1β (pooled SMD: 1.37, 95% CI: 0.06-2.68, significant heterogeneity: I = 96.01%) was significantly elevated in Alzheimer's disease. There were no differences in IL-6 (p = 0.138), TNF-α (p = 0.451) and CRP (p = 0.07) between elderly with Alzheimer's disease and controls. After Bonferroni adjustment, only IL-6 remained significantly higher in depression. Elderly with depression have higher IL-6 than controls, while those with Alzheimer's disease did not have higher peripheral inflammatory markers.
Topics: Adaptor Proteins, Signal Transducing; Aged; Alzheimer Disease; C-Reactive Protein; Depression; Depressive Disorder; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Middle Aged; Proteins
PubMed: 30104698
DOI: 10.1038/s41598-018-30487-6 -
CNS Drugs Mar 2017Many children and adolescents with attention deficit/hyperactivity disorder (ADHD) are treated with stimulant and non-stimulant medication. ADHD medication may be... (Meta-Analysis)
Meta-Analysis Review
Cardiovascular Effects of Stimulant and Non-Stimulant Medication for Children and Adolescents with ADHD: A Systematic Review and Meta-Analysis of Trials of Methylphenidate, Amphetamines and Atomoxetine.
BACKGROUND
Many children and adolescents with attention deficit/hyperactivity disorder (ADHD) are treated with stimulant and non-stimulant medication. ADHD medication may be associated with cardiovascular effects. It is important to identify whether mean group effects translate into clinically relevant increases for some individual patients, and/or increase the risk for serious cardiovascular adverse events such as stroke or sudden death.
OBJECTIVES
To evaluate potential cardiovascular effects of these treatments, we conducted a systematic review and meta-analysis of the effects of methylphenidate (MPH), amphetamines (AMP), and atomoxetine (ATX) on diastolic and systolic blood pressure (DBP, SBP) and heart rate (HR) in children and adolescents with ADHD.
METHODS
We conducted systematic searches in electronic databases (PsychINFO, EMBASE and Medline) to identify published trials which involved individuals who were (i) diagnosed with ADHD and were aged between 0-18 years; (ii) treated with MPH, AMP or ATX and (iii) had their DBP and SBP and/or HR measured at baseline (pre) and the endpoint (post) of the study treatment. Studies with an open-label design or a double-blind randomised control design of any duration were included. Statistical analysis involved calculating differences between pre- and post-treatment measurements for the various cardiovascular parameters divided by the pooled standard deviation. Further, we assessed the percentage of clinically relevant increased BP or HR, or documented arrhythmias.
RESULTS
Eighteen clinical trials met the inclusion criteria (10 for MPH, 5 for AMP, and 7 for ATX) with data from 5837 participants (80.7% boys) and average duration of 28.7 weeks (range 4-96 weeks). All three medications were associated with a small, but statistically significant pre-post increase of SBP (MPH: standard mean difference [SMD] 0.25, 95% confidence interval [CI] 0.08-0.42, p < 0.01; AMP: SMD 0.09, 95% CI 0.03-0.15, p < 0.01; ATX: SMD 0.16, 95% CI 0.04-0.27, p = 0.01). MPH did not have a pre-post effect on DBP and HR. AMP treatment was associated with a small but statistically significant pre-post increase of DBP (SMD 0.16, CI 0.03-0.29, p = 0.02), as was ATX treatment (SMD 0.22, CI 0.10-0.34, p < 0.01). AMP and ATX were associated with a small to medium statistically significant pre-post increase of HR (AMP: SMD 0.37, CI 0.13-0.60, p < 0.01; ATX: SMD 0.43, CI 0.26-0.60, p < 0.01). The head-to-head comparison of the three medications did not reveal significant differences. Sensitivity analyses revealed that AMP studies of <18 weeks reported higher effect sizes on DBP compared with longer duration studies (F(1) = 19.55, p = 0.05). Further, MPH studies published before 2007 reported higher effect sizes on SBP than studies after 2007 (F(1) = 5.346, p = 0.05). There was no effect of the following moderators: type of medication, doses, sample size, age, gender, type of ADHD, comorbidity or dropout rate. Participants on medication reported 737 (12.6%) other cardiovascular effects. Notably, 2% of patients discontinued their medication treatment due to any cardiovascular effect. However, in the majority of patients, the cardiovascular effects resolved spontaneously, medication doses were changed or the effects were not considered clinically relevant. There were no statistically significant differences between the medication treatments in terms of the severity of cardiovascular effects.
CONCLUSIONS
Statistically significant pre-post increases of SBP, DBP and HR were associated with AMP and ATX treatment in children and adolescents with ADHD, while MPH treatment had a statistically significant effect only on SBP in these patients. These increases may be clinically significant for a significant minority of individuals that experience larger increases. Since increased BP and HR in general are considered risk factors for cardiovascular morbidity and mortality during adult life, paediatric patients using ADHD medication should be monitored closely and regularly for HR and BP.
Topics: Adolescent; Amphetamines; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Central Nervous System Stimulants; Child; Child, Preschool; Clinical Trials as Topic; Heart Rate; Humans; Infant; Methylphenidate; Psychotropic Drugs
PubMed: 28236285
DOI: 10.1007/s40263-017-0410-7 -
JAMA Psychiatry Jun 2023The relative efficacy of ketamine and electroconvulsive therapy (ECT) in adults with major depressive episode (MDE) needs clarification. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The relative efficacy of ketamine and electroconvulsive therapy (ECT) in adults with major depressive episode (MDE) needs clarification.
OBJECTIVE
To compare depression rating outcomes with ketamine vs ECT in adults with MDE and to compare response and remission rates, number of sessions to response and remission, and adverse effects.
DATA SOURCES
Two investigators independently systematically searched MEDLINE, ScienceDirect, and Google Scholar databases using a combination of relevant Medical Subject Headings terms and free-text keywords from database inception through May 15, 2022, to identify relevant English-language trials.
STUDY SELECTION
Parallel-group randomized clinical trials (RCTs).
DATA EXTRACTION AND SYNTHESIS
Two investigators independently extracted data and assessed risk of bias. One-week posttreatment outcomes were pooled as standardized mean difference (SMD; Hedges g) for continuous outcomes and risk ratio (RR) for categorical outcomes in random-effects meta-analyses.
MAIN OUTCOMES AND MEASURES
Efficacy outcomes were 1-week (or nearest) posttreatment depression ratings, 1-week (or nearest) study-defined response and remission rates, and number of sessions to treatment response and remission. Safety outcomes were reported adverse effects.
RESULTS
Five trials (ketamine group: n = 141; ECT group: n = 137) were meta-analyzed. The overall pooled SMD for posttreatment depression ratings was -0.39 (95% CI, -0.81 to 0.02; I2 = 45%; 5 RCTs). For this efficacy outcome, in a sensitivity analysis of methodologically stronger trials, ECT was superior to ketamine (SMD, -0.45; 95% CI, -0.75 to -0.14; I2 = 6%; 2 RCTs). ECT was also superior to ketamine for study-defined response (RR, 1.27; 95% CI, 1.06-1.53; I2 = 0%; 3 RCTs) and remission (RR, 1.43; 95% CI, 1.12-1.82; I2 = 0%; 2 RCTs) rates. No significant differences were noted between groups for number of sessions to response and remission and for cognitive outcomes. Key limitations were small number of studies, limited sample size, and high risk of bias in all trials.
CONCLUSION AND RELEVANCE
The findings of this systematic review and meta-analysis suggest an efficacy advantage for ECT over ketamine in adults with MDE. These conclusions are tempered by the small number and size of existing trials.
Topics: Adult; Humans; Ketamine; Electroconvulsive Therapy; Depressive Disorder, Major
PubMed: 37043224
DOI: 10.1001/jamapsychiatry.2023.0562 -
Brain and Behavior Jun 2019Transcranial magnetic stimulation (TMS) has been evaluated as an effective treatment option for patients with major depressive disorder. However, there are limited... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Transcranial magnetic stimulation (TMS) has been evaluated as an effective treatment option for patients with major depressive disorder. However, there are limited studies that have evaluated the efficacy of TMS for other neuropsychiatric disorders such as anxiety and trauma-related disorders. We reviewed the literature that has evaluated TMS as a treatment for anxiety and trauma-related disorders.
METHODS
We searched for articles published up to December 2017 in Embase, Medline, and ISI Web of Science databases, following the Preferred Items for Reporting of Systematic Reviews and Meta-Analyses (PRISMA) statement. Articles (n = 520) evaluating TMS in anxiety and trauma-related disorders were screened and a small subset of these that met the eligibility criteria (n = 17) were included in the systematic review, of which nine evaluated TMS in posttraumatic stress disorder (PTSD), four in generalized anxiety disorder (GAD), two in specific phobia (SP), and two in panic disorder (PD). The meta-analysis was performed with PTSD and GAD since PD and SP had an insufficient number of studies and sample sizes.
RESULTS
Among anxiety and trauma-related disorders, TMS has been most widely studied as a treatment for PTSD. TMS demonstrated large overall treatment effect for both PTSD (ES = -0.88, 95% CI: -1.42, -0.34) and GAD (ES = -2.06, 95% CI: -2.64, -1.48), including applying high frequency over the right dorsolateral prefrontal cortex. Since few studies have evaluated TMS for SP and PD, few conclusions can be drawn.
CONCLUSIONS
Our meta-analysis suggests that TMS may be an effective treatment for GAD and PTSD.
Topics: Anxiety Disorders; Humans; Stress Disorders, Post-Traumatic; Transcranial Magnetic Stimulation; Treatment Outcome
PubMed: 31066227
DOI: 10.1002/brb3.1284 -
Frontiers in Psychiatry 2021Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce...
Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce cognitive, antidepressant, anxiolytic, and antiaddictive effects suggested to arise from biological changes similar to conventional antidepressants or the rapid-acting substance ketamine. The proposed route is by inducing brain neuroplasticity. This review attempts to summarize the evidence that psychedelics induce neuroplasticity by focusing on psychedelics' cellular and molecular neuroplasticity effects after single and repeated administration. When behavioral parameters are encountered in the selected studies, the biological pathways will be linked to the behavioral effects. Additionally, knowledge gaps in the underlying biology of clinical outcomes of psychedelics are highlighted. The literature searched yielded 344 results. Title and abstract screening reduced the sample to 35; eight were included from other sources, and full-text screening resulted in the final selection of 16 preclinical and four clinical studies. Studies ( = 20) show that a single administration of a psychedelic produces rapid changes in plasticity mechanisms on a molecular, neuronal, synaptic, and dendritic level. The expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), is changed after a single administration of psychedelics, resulting in changed neuroplasticity. The latter included more dendritic complexity, which outlasted the acute effects of the psychedelic. Repeated administration of a psychedelic directly stimulated neurogenesis and increased BDNF mRNA levels up to a month after treatment. Findings from the current review demonstrate that psychedelics induce molecular and cellular adaptations related to neuroplasticity and suggest those run parallel to the clinical effects of psychedelics, potentially underlying them. Future (pre)clinical research might focus on deciphering the specific cellular mechanism activated by different psychedelics and related to long-term clinical and biological effects to increase our understanding of the therapeutic potential of these compounds.
PubMed: 34566723
DOI: 10.3389/fpsyt.2021.724606 -
JAMA Network Open Nov 2022Use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades, but there are concerns regarding their... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades, but there are concerns regarding their cardiovascular safety.
OBJECTIVE
To provide an updated synthesis of evidence on whether ADHD medications are associated with the risk of a broad range of cardiovascular diseases (CVDs).
DATA SOURCES
PubMed, Embase, PsycINFO, and Web of Science up to May 1, 2022.
STUDY SELECTION
Observational studies investigating the association between ADHD medications (including stimulants and nonstimulants) and risk of CVD.
DATA EXTRACTION AND SYNTHESIS
Independent reviewers extracted data and assessed study quality using the Good Research for Comparative Effectiveness (GRACE) checklist. Data were pooled using random-effects models. This study is reported according to the Meta-analyses of Observational Studies in Epidemiology guideline.
MAIN OUTCOMES AND MEASURES
The outcome was any type of cardiovascular event, including hypertension, ischemic heart disease, cerebrovascular disease, heart failure, venous thromboembolism, tachyarrhythmias, and cardiac arrest.
RESULTS
Nineteen studies (with 3 931 532 participants including children, adolescents, and adults; 60.9% male), of which 14 were cohort studies, from 6 countries or regions were included in the meta-analysis. Median follow-up time ranged from 0.25 to 9.5 years (median, 1.5 years). Pooled adjusted relative risk (RR) did not show a statistically significant association between ADHD medication use and any CVD among children and adolescents (RR, 1.18; 95% CI, 0.91-1.53), young or middle-aged adults (RR, 1.04; 95% CI, 0.43-2.48), or older adults (RR, 1.59; 95% CI, 0.62-4.05). No significant associations for stimulants (RR, 1.24; 95% CI, 0.84-1.83) or nonstimulants (RR, 1.22; 95% CI, 0.25-5.97) were observed. For specific cardiovascular outcomes, no statistically significant association was found in relation to cardiac arrest or arrhythmias (RR, 1.60; 95% CI, 0.94-2.72), cerebrovascular diseases (RR, 0.91; 95% CI, 0.72-1.15), or myocardial infarction (RR, 1.06; 95% CI, 0.68-1.65). There was no associations with any CVD in female patients (RR, 1.88; 95% CI, 0.43-8.24) and in those with preexisting CVD (RR, 1.31; 95% CI, 0.80-2.16). Heterogeneity between studies was high and significant except for the analysis on cerebrovascular diseases.
CONCLUSIONS AND RELEVANCE
This meta-analysis suggests no statistically significant association between ADHD medications and the risk of CVD across age groups, although a modest risk increase could not be ruled out, especially for the risk of cardiac arrest or tachyarrhythmias. Further investigation is warranted for the cardiovascular risk in female patients and patients with preexisting CVD as well as long-term risks associated with ADHD medication use.
Topics: Adolescent; Child; Middle Aged; Humans; Female; Male; Aged; Cardiovascular Diseases; Attention Deficit Disorder with Hyperactivity; Heart Disease Risk Factors; Central Nervous System Stimulants; Heart Arrest; Observational Studies as Topic
PubMed: 36416824
DOI: 10.1001/jamanetworkopen.2022.43597 -
The Cochrane Database of Systematic... Nov 2023A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines.
OBJECTIVES
To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Specialised Register, CENTRAL, CDSR, MEDLINE, Ovid Embase and PsycINFO to 26 May 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of people aged 18 years or older of either sex and any ethnicity with clinically diagnosed panic disorder, with or without agoraphobia. We included trials that compared the effectiveness of antidepressants and benzodiazepines with each other or with a placebo.
DATA COLLECTION AND ANALYSIS
Two authors independently screened titles/abstracts and full texts, extracted data and assessed risk of bias. We analysed dichotomous data and continuous data as risk ratios (RRs), mean differences (MD) or standardised mean differences (SMD): response to treatment (i.e. substantial improvement from baseline as defined by the original investigators: dichotomous outcome), total number of dropouts due to any reason (as a proxy measure of treatment acceptability: dichotomous outcome), remission (i.e. satisfactory end state as defined by global judgement of the original investigators: dichotomous outcome), panic symptom scales and global judgement (continuous outcome), frequency of panic attacks (as recorded, for example, by a panic diary; continuous outcome), agoraphobia (dichotomous outcome). We assessed the certainty of evidence using threshold analyses.
MAIN RESULTS
Overall, we included 70 trials in this review. Sample sizes ranged between 5 and 445 participants in each arm, and the total sample size per study ranged from 10 to 1168. Thirty-five studies included sample sizes of over 100 participants. There is evidence from 48 RCTs (N = 10,118) that most medications are more effective in the response outcome than placebo. In particular, diazepam, alprazolam, clonazepam, paroxetine, venlafaxine, clomipramine, fluoxetine and adinazolam showed the strongest effect, with diazepam, alprazolam and clonazepam ranking as the most effective. We found heterogeneity in most of the comparisons, but our threshold analyses suggest that this is unlikely to impact the findings of the network meta-analysis. Results from 64 RCTs (N = 12,310) suggest that most medications are associated with either a reduced or similar risk of dropouts to placebo. Alprazolam and diazepam were associated with a lower dropout rate compared to placebo and were ranked as the most tolerated of all the medications examined. Thirty-two RCTs (N = 8569) were included in the remission outcome. Most medications were more effective than placebo, namely desipramine, fluoxetine, clonazepam, diazepam, fluvoxamine, imipramine, venlafaxine and paroxetine, and their effects were clinically meaningful. Amongst these medications, desipramine and alprazolam were ranked highest. Thirty-five RCTs (N = 8826) are included in the continuous outcome reduction in panic scale scores. Brofaromine, clonazepam and reboxetine had the strongest reductions in panic symptoms compared to placebo, but results were based on either one trial or very small trials. Forty-one RCTs (N = 7853) are included in the frequency of panic attack outcome. Only clonazepam and alprazolam showed a strong reduction in the frequency of panic attacks compared to placebo, and were ranked highest. Twenty-six RCTs (N = 7044) provided data for agoraphobia. The strongest reductions in agoraphobia symptoms were found for citalopram, reboxetine, escitalopram, clomipramine and diazepam, compared to placebo. For the pooled intervention classes, we examined the two primary outcomes (response and dropout). The classes of medication were: SSRIs, SNRIs, TCAs, MAOIs and BDZs. For the response outcome, all classes of medications examined were more effective than placebo. TCAs as a class ranked as the most effective, followed by BDZs and MAOIs. SSRIs as a class ranked fifth on average, while SNRIs were ranked lowest. When we compared classes of medication with each other for the response outcome, we found no difference between classes. Comparisons between MAOIs and TCAs and between BDZs and TCAs also suggested no differences between these medications, but the results were imprecise. For the dropout outcome, BDZs were the only class associated with a lower dropout compared to placebo and were ranked first in terms of tolerability. The other classes did not show any difference in dropouts compared to placebo. In terms of ranking, TCAs are on average second to BDZs, followed by SNRIs, then by SSRIs and lastly by MAOIs. BDZs were associated with lower dropout rates compared to SSRIs, SNRIs and TCAs. The quality of the studies comparing antidepressants with placebo was moderate, while the quality of the studies comparing BDZs with placebo and antidepressants was low.
AUTHORS' CONCLUSIONS
In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes.
Topics: Adult; Humans; Panic Disorder; Selective Serotonin Reuptake Inhibitors; Paroxetine; Fluoxetine; Venlafaxine Hydrochloride; Serotonin and Noradrenaline Reuptake Inhibitors; Alprazolam; Clomipramine; Reboxetine; Clonazepam; Desipramine; Network Meta-Analysis; Antidepressive Agents; Antidepressive Agents, Tricyclic; Benzodiazepines; Diazepam
PubMed: 38014714
DOI: 10.1002/14651858.CD012729.pub3 -
Pharmacology, Biochemistry, and Behavior Sep 2023Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications.... (Review)
Review
Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications. These phyto-cannabinoids have multiple biological targets, including the body's endocannabinoid system. There is growing scientific interest in the use of CBD, a non-intoxicating compound, to ameliorate symptoms associated with neurodevelopmental disorders. However, its suitability as a pharmaceutical intervention has not been reliably established in these clinical populations. This systematic review examines the nine published randomised controlled trials (RCTs) that have probed the safety and efficacy of CBD in individuals diagnosed with attention deficit hyperactivity disorder, autism spectrum disorder, intellectual disability, Tourette Syndrome, and complex motor disorders. Studies were identified systematically through searching four databases: Medline, CINAHL complete, PsycINFO, and EMBASE. Inclusion criteria were randomised controlled trials involving CBD and participants with neurodevelopmental disorders. No publication year or language restrictions were applied. Relevant data were extracted from the identified list of eligible articles. After extraction, data were cross-checked between the authors to ensure consistency. Several trials indicate potential efficacy, although this possibility is currently too inconsistent across RCTs to confidently guide clinical usage. Study characteristics, treatment properties, and outcomes varied greatly across the included trials. The material lack of comparable RCTs leaves CBD's suitability as a pharmacological treatment for neurodevelopmental disorders largely undetermined. A stronger evidence base is urgently required to establish safety and efficacy profiles and guide the ever-expanding clinical uptake of cannabis-derived compounds in neurodevelopmental disorders. Prospero registration number: CRD42021267839.
Topics: Humans; Cannabidiol; Cannabinoids; Cannabis; Hallucinogens; Attention Deficit Disorder with Hyperactivity; Dronabinol; Randomized Controlled Trials as Topic
PubMed: 37543051
DOI: 10.1016/j.pbb.2023.173607