-
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 -
BMJ (Clinical Research Ed.) Jan 2021To investigate the efficacy and safety of antidepressants for back and osteoarthritis pain compared with placebo. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the efficacy and safety of antidepressants for back and osteoarthritis pain compared with placebo.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Medline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, International Pharmaceutical Abstracts, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from inception to 15 November and updated on 12 May 2020.
ELIGIBILITY CRITERIA FOR STUDY SELECTION
Randomised controlled trials comparing the efficacy or safety, or both of any antidepressant drug with placebo (active or inert) in participants with low back or neck pain, sciatica, or hip or knee osteoarthritis.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers extracted data. Pain and disability were primary outcomes. Pain and disability scores were converted to a scale of 0 (no pain or disability) to 100 (worst pain or disability). A random effects model was used to calculate weighted mean differences and 95% confidence intervals. Safety (any adverse event, serious adverse events, and proportion of participants who withdrew from trials owing to adverse events) was a secondary outcome. Risk of bias was assessed with the Cochrane Collaboration's tool and certainty of evidence with the grading of recommendations assessment, development and evaluation (GRADE) framework.
RESULTS
33 trials (5318 participants) were included. Moderate certainty evidence showed that serotonin-noradrenaline reuptake inhibitors (SNRIs) reduced back pain (mean difference -5.30, 95% confidence interval -7.31 to -3.30) at 3-13 weeks and low certainty evidence that SNRIs reduced osteoarthritis pain (-9.72, -12.75 to -6.69) at 3-13 weeks. Very low certainty evidence showed that SNRIs reduced sciatica at two weeks or less (-18.60, -31.87 to -5.33) but not at 3-13 weeks (-17.50, -42.90 to 7.89). Low to very low certainty evidence showed that tricyclic antidepressants (TCAs) did not reduce sciatica at two weeks or less (-7.55, -18.25 to 3.15) but did at 3-13 weeks (-15.95, -31.52 to -0.39) and 3-12 months (-27.0, -36.11 to -17.89). Moderate certainty evidence showed that SNRIs reduced disability from back pain at 3-13 weeks (-3.55, -5.22 to -1.88) and disability due to osteoarthritis at two weeks or less (-5.10, -7.31 to -2.89), with low certainty evidence at 3-13 weeks (-6.07, -8.13 to -4.02). TCAs and other antidepressants did not reduce pain or disability from back pain.
CONCLUSION
Moderate certainty evidence shows that the effect of SNRIs on pain and disability scores is small and not clinically important for back pain, but a clinically important effect cannot be excluded for osteoarthritis. TCAs and SNRIs might be effective for sciatica, but the certainty of evidence ranged from low to very low.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020158521.
Topics: Antidepressive Agents; Back Pain; Humans; Osteoarthritis; Pain Management; Sciatica; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 33472813
DOI: 10.1136/bmj.m4825 -
PloS One 2022Long acting injectable (LAI) antipsychotics are an alternative to oral antipsychotic (OAP) treatment and may be beneficial for patients in the early stages of... (Review)
Review
AIM
Long acting injectable (LAI) antipsychotics are an alternative to oral antipsychotic (OAP) treatment and may be beneficial for patients in the early stages of schizophrenia. This study aims to provide a comprehensive review on the efficacy of first-generation and second-generation LAI antipsychotics in recent-onset, first-episode, and early psychosis patients.
METHODS
MEDLINE, EMBASE, PsycINFO, and Web of Science Core databases were used to search for studies that used LAIs in early psychosis patients. Studies published up to 06 Jun 2019 were included with no language restrictions applied. Inclusion criteria were a diagnosis of schizophrenia or related disorder, where patients were in their first episode or had a duration of illness ≤5 years.
RESULTS
33 studies were included: 8 RCTs, 4 post-hoc analyses, 2 case reports, and 19 naturalistic studies. The majority of studies evaluated risperidone LAIs (N = 14) and paliperidone palmitate (N = 10), while the remainder investigated fluphenazine decanoate (N = 3), flupentixol decanoate (N = 2), and aripiprazole (N = 1). Two studies did not specify the LAI formulation used, and one cohort study compared the efficacy of multiple different LAI formulations.
CONCLUSIONS
While the majority of data is based on naturalistic studies investigating risperidone LAIs or paliperidone palmitate, LAIs may be an effective treatment for early psychosis patients in terms of adherence, relapse reduction, and symptom improvements. There is still a need to conduct more high quality RCTs that investigate the efficacy of different LAI formulations in early psychosis patients.
Topics: Antipsychotic Agents; Cohort Studies; Delayed-Action Preparations; Humans; Paliperidone Palmitate; Psychotic Disorders; Risperidone
PubMed: 35486616
DOI: 10.1371/journal.pone.0267808 -
European Archives of Psychiatry and... Oct 2018Negative symptoms are the core of schizophrenia, but whether antipsychotics are efficacious for their treatment is unclear. Moreover, there is debate whether patients in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Negative symptoms are the core of schizophrenia, but whether antipsychotics are efficacious for their treatment is unclear. Moreover, there is debate whether patients in relevant trials should have predominant negative symptoms or whether prominent negative symptoms are also acceptable.
METHODS
We systematically reviewed randomised, blinded antipsychotic drug trials in patients with schizophrenia and either predominant or prominent negative symptoms (last search Dec 12, 2017). Separate pairwise meta-analyses were conducted in these two populations. The primary outcome was negative symptoms. Depressive, symptoms, positive symptoms, and extrapyramidal side-effects were analysed as causes of secondary negative symptoms.
FINDINGS
We included 21 randomized-controlled trials with 3451 participants which revealed the following significant differences in the primary outcome: in patients with predominant negative symptoms amisulpride was superior to placebo (N = 4; n = 590, SMD 0.47, CI 0.23, 0.71), olanzapine was superior to haloperidol in a small trial (n = 35) and cariprazine outperformed risperidone (N = 1, n = 456, SMD - 0.29, CI - 0.48, - 0.11). In patients with prominent negative symptoms, olanzapine and quetiapine were superior to risperidone in single trials. Overall, studies in prominent negative symptoms were potentially more confounded by improvements of secondary negative symptoms.
INTERPRETATION
Amisulpride is the only antipsychotic that outperformed placebo in the treatment of predominant negative symptoms, but there was a parallel reduction of depression. Cariprazine was better than risperidone in a large trial that was well-controlled for secondary negative symptoms, but the trial was sponsored by its manufacturer. Future trials should apply scientifically developed definitions such as the deficit syndrome and the persistent negative symptoms concept.
Topics: Antipsychotic Agents; Humans; Schizophrenia
PubMed: 29368205
DOI: 10.1007/s00406-018-0869-3 -
Psychotherapy and Psychosomatics 2018Serotonin-noradrenaline reuptake inhibitors (SNRI) are widely used in medical practice. Their discontinuation has been associated with a wide range of symptoms. The aim... (Review)
Review
BACKGROUND
Serotonin-noradrenaline reuptake inhibitors (SNRI) are widely used in medical practice. Their discontinuation has been associated with a wide range of symptoms. The aim of this paper is to identify the occurrence, frequency, and features of withdrawal symptoms after SNRI discontinuation.
METHODS
PRISMA guidelines were followed to conduct a systematic review. Electronic databases included PubMed, the Cochrane Library, Web of Science, and MEDLINE from the inception of each database to June 2017. Titles, abstracts, and topics were searched using a combination of the following terms: "duloxetine" OR "venlafaxine" OR "desvenlafaxine" OR "milnacipran" OR "levomilnacipran" OR "SNRI" OR "second generation antidepressant" OR "serotonin norepinephrine reuptake inhibitor" AND "discontinuation" OR "withdrawal" OR "rebound." Only published trials in the English language were included.
RESULTS
Sixty-one reports met the criteria for inclusion. There were 22 double-blind randomized controlled trials, 6 studies where patients were treated in an open fashion and then randomized to a double-blind controlled phase, 8 open trials, 1 prospective naturalistic study, 1 retrospective study, and 23 case reports. Withdrawal symptoms occurred after discontinuation of any type of SNRI. The prevalence of withdrawal symptoms varied across reports and appeared to be higher with venlafaxine. Symptoms typically ensued within a few days from discontinuation and lasted a few weeks, also with gradual tapering. Late onset and/or a longer persistence of disturbances occurred as well.
CONCLUSIONS
Clinicians need to add SNRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with other types of psychotropic drugs. The results of this study challenge the use of SNRI as first-line treatment for mood and anxiety disorders.
Topics: Adrenergic Uptake Inhibitors; Desvenlafaxine Succinate; Duloxetine Hydrochloride; Humans; Mood Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Venlafaxine Hydrochloride
PubMed: 30016772
DOI: 10.1159/000491524 -
Expert Opinion on Drug Safety Jun 2022Racemic ketamine and esketamine have demonstrated rapid antidepressant effects. We aimed to review the efficacy and safety of racemic and esketamine for depression. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Racemic ketamine and esketamine have demonstrated rapid antidepressant effects. We aimed to review the efficacy and safety of racemic and esketamine for depression.
RESEARCH DESIGN AND METHODS
We conducted a PRISMA-guided review for relevant randomized controlled trials of racemic or esketamine for unipolar or bipolar major depression from database inception through 2021. We conducted random-effects meta-analyses using pooled rate ratios (RRs) and Cohen's standardized mean differences (d) with their 95% confidence intervals (CI).
RESULTS
We found 36 studies (2903 participants, 57% female, 45.1 +/- 7.0 years). Nine trials used esketamine, while the rest used racemic ketamine. The overall study quality was high. Treatment with any form of ketamine was associated with improved response (RR=2.14; 95% CI, 1.72-2.66; I2=65%), remission (RR=1.64; 95% CI, 1.33-2.02; I2=39%), and depression severity (d=-0.63; 95% CI, -0.80 to -0.45; I2=78%) against placebo. Overall, there was no association between treatment with any form of ketamine and retention in treatment (RR=1.00; 95% CI, 0.99-1.01; I2<1%), dropouts due to adverse events (RR=1.56; 95% CI, 1.00-2.45; I2<1%), or the overall number of adverse events reported per participant (OR=2.14; 95% CI, 0.82-5.60; I2=62%) against placebo.
CONCLUSIONS
Ketamine and esketamine are effective, safe, and acceptable treatments for individuals living with depression.
Topics: Antidepressive Agents; Depression; Depressive Disorder, Major; Female; Humans; Ketamine; Male
PubMed: 35231204
DOI: 10.1080/14740338.2022.2047928 -
Annals of Internal Medicine Feb 2023Primary care patients and clinicians may prefer alternative options to second-generation antidepressants for major depressive disorder (MDD). (Meta-Analysis)
Meta-Analysis Review
Nonpharmacologic and Pharmacologic Treatments of Adult Patients With Major Depressive Disorder: A Systematic Review and Network Meta-analysis for a Clinical Guideline by the American College of Physicians.
BACKGROUND
Primary care patients and clinicians may prefer alternative options to second-generation antidepressants for major depressive disorder (MDD).
PURPOSE
To compare the benefits and harms of nonpharmacologic treatments with second-generation antidepressants as first-step interventions for acute MDD, and to compare second-step treatment strategies for patients who did not achieve remission after an initial attempt with antidepressants.
DATA SOURCES
English-language studies from several electronic databases from 1 January 1990 to 8 August 2022, trial registries, gray literature databases, and reference lists to identify unpublished research.
STUDY SELECTION
2 investigators independently selected randomized trials of at least 6 weeks' duration.
DATA EXTRACTION
Reviewers abstracted data about study design and conduct, participants, interventions, and outcomes. They dually rated the risk of bias of studies and the certainty of evidence for outcomes of interest.
DATA SYNTHESIS
65 randomized trials met the inclusion criteria; eligible data from nonrandomized studies were not found. Meta-analyses and network meta-analyses indicated similar benefits of most nonpharmacologic treatments and antidepressants as first-step treatments. Antidepressants had higher risks for discontinuation because of adverse events than most other treatments. For second-step therapies, different switching and augmentation strategies provided similar symptomatic relief. The certainty of evidence for most comparisons is low; findings should be interpreted cautiously.
LIMITATIONS
Many studies had methodological limitations or dosing inequalities; publication bias might have affected some comparisons. In some cases, conclusions could not be drawn because of insufficient evidence.
CONCLUSION
Although benefits seem to be similar among first- and second-step MDD treatments, the certainty of evidence is low for most comparisons. Clinicians and patients should focus on options with the most reliable evidence and take adverse event profiles and patient preferences into consideration.
PRIMARY FUNDING SOURCE
American College of Physicians. (PROSPERO: CRD42020204703).
Topics: Humans; Adult; Depressive Disorder, Major; Network Meta-Analysis; Antidepressive Agents; Antidepressive Agents, Second-Generation; Physicians
PubMed: 36689750
DOI: 10.7326/M22-1845 -
Clinical Drug Investigation Apr 2021Second-generation antipsychotics (SGAs) for schizophrenia show different risk profiles, whose evidence has been evaluated through comparative reviews on randomized... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Second-generation antipsychotics (SGAs) for schizophrenia show different risk profiles, whose evidence has been evaluated through comparative reviews on randomized controlled trials (RCTs) and observational studies.
METHODS
We performed a systematic review and meta-analysis of weight gains, metabolic and cardiovascular side effects of SGAs, relying on both RCTs and observational studies, by comparing variations between the start of treatment and the end of follow-up. The systematic review refers to papers published from June 2009 to November 2020. PRISMA criteria were followed. No restrictions on heterogeneity level have been considered for meta-analysis. A test for the summary effect measure and heterogeneity (I metric) was used.
RESULTS
Seventy-nine papers were selected from 3076 studies (61% RCTs, 39% observational studies). Olanzapine and risperidone reported the greatest weight gain and olanzapine the largest BMI increase. Paliperidone showed the highest increase in total cholesterol, but is the only drug reporting an increase in the HDL cholesterol. Quetiapine XR showed the highest decrease in fasting glucose. Lurasidone showed the lowest increase in body weight and a reduction in BMI and was also the only treatment reporting a decrease in total cholesterol and triglycerides. The highest increase in systolic and diastolic blood pressure was reported by quetiapine XR.
CONCLUSIONS
Despite some limitations (differences in the mean dosages per patient and other side effects not included) this paper provides the first complete meta-analysis on SGAs in variations on metabolic risk profile between start of treatment and end of follow-up, with useful results for clinical practice and possibly for future economic evaluation studies.
Topics: Antipsychotic Agents; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Weight Gain
PubMed: 33686614
DOI: 10.1007/s40261-021-01000-1 -
The Cochrane Database of Systematic... Dec 2018Children's fear about dental treatment may lead to behaviour management problems for the dentist, which can be a barrier to the successful dental treatment of children.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Children's fear about dental treatment may lead to behaviour management problems for the dentist, which can be a barrier to the successful dental treatment of children. Sedation can be used to relieve anxiety and manage behaviour in children undergoing dental treatment. There is a need to determine from published research which agents, dosages and regimens are effective. This is the second update of the Cochrane Review first published in 2005 and previously updated in 2012.
OBJECTIVES
To evaluate the efficacy and relative efficacy of conscious sedation agents and dosages for behaviour management in paediatric dentistry.
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 22 February 2018); the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1) in the Cochrane Library (searched 22 February 2018); MEDLINE Ovid (1946 to 22 February 2018); and Embase Ovid (1980 to 22 February 2018). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA
Studies were selected if they met the following criteria: randomised controlled trials of conscious sedation comparing two or more drugs/techniques/placebo undertaken by the dentist or one of the dental team in children up to 16 years of age. We excluded cross-over trials.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted, in duplicate, information regarding methods, participants, interventions, outcome measures and results. Where information in trial reports was unclear or incomplete authors of trials were contacted. Trials were assessed for risk of bias. Cochrane statistical guidelines were followed.
MAIN RESULTS
We included 50 studies with a total of 3704 participants. Forty studies (81%) were at high risk of bias, nine (18%) were at unclear risk of bias, with just one assessed as at low risk of bias. There were 34 different sedatives used with or without inhalational nitrous oxide. Dosages, mode of administration and time of administration varied widely. Studies were grouped into placebo-controlled, dosage and head-to-head comparisons. Meta-analysis of the available data for the primary outcome (behaviour) was possible for studies investigating oral midazolam versus placebo only. There is moderate-certainty evidence from six small clinically heterogeneous studies at high or unclear risk of bias, that the use of oral midazolam in doses between 0.25 mg/kg to 1 mg/kg is associated with more co-operative behaviour compared to placebo; standardized mean difference (SMD) favoured midazolam (SMD 1.96, 95% confidence interval (CI) 1.59 to 2.33, P < 0.0001, I = 90%; 6 studies; 202 participants). It was not possible to draw conclusions regarding the secondary outcomes due to inconsistent or inadequate reporting or both.
AUTHORS' CONCLUSIONS
There is some moderate-certainty evidence that oral midazolam is an effective sedative agent for children undergoing dental treatment. There is a need for further well-designed and well-reported clinical trials to evaluate other potential sedation agents. Further recommendations for future research are described and it is suggested that future trials evaluate experimental regimens in comparison with oral midazolam or inhaled nitrous oxide.
Topics: Analgesics, Non-Narcotic; Anti-Anxiety Agents; Child; Chloral Hydrate; Dental Anxiety; Dental Care for Children; Humans; Hydroxyzine; Hypnotics and Sedatives; Meperidine; Midazolam; Nitrous Oxide; Preanesthetic Medication; Randomized Controlled Trials as Topic
PubMed: 30566228
DOI: 10.1002/14651858.CD003877.pub5 -
Laeknabladid Sep 2022The hallucinogen psilocybin is a potential novel treatment for treatment-resistant depression (TRD). Our goal is to review current knowledge on psilocybin and its...
The hallucinogen psilocybin is a potential novel treatment for treatment-resistant depression (TRD). Our goal is to review current knowledge on psilocybin and its efficacy in TRD. Literature searches were done on PubMed, Web of Science and Google Scholar, references reviewed in identified articles and other articles found on the website of COMPASS Pathways. Psilocybin treatment consists usually of a single oral administration of 25 mg of psilocybin along with psychological support for 5-8 hours during the ensuing hallucinogenic trip. Common side-effects include headache, nausea, fatigue and insomnia. A systematic review has demonstrated significant antidepressant efficacy in certain groups and a double-blind randomized study found antidepressant efficacy of psilocybin comparable to the SSRI escitalopram. In the phase 2 study of COMPASS Pathways, the psilocybin-COMP360 treatment led to a rapid response and remission as early as three weeks following the treatment for around one third of participants. Recent studies have shown that psilocybin significantly decreases the severity of depressive symptoms and is generally well tolerated. Further research will reveal whether it will be granted a license to treat treatment-resistant depression in the near future. There remains an urgent need for novel treatments for those who do not respond to current antidepressant therapies.
Topics: Antidepressive Agents; Depression; Depressive Disorder, Treatment-Resistant; Hallucinogens; Humans; Psilocybin; Randomized Controlled Trials as Topic
PubMed: 36040772
DOI: 10.17992/lbl.2022.09.706