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Palliative Medicine Apr 2024Seizures are an important palliative symptom, the management of which can be complicated by patients' capacity to swallow oral medications. In this setting, and the wish...
BACKGROUND
Seizures are an important palliative symptom, the management of which can be complicated by patients' capacity to swallow oral medications. In this setting, and the wish to avoid intravenous access, subcutaneous infusions may be employed. Options for antiseizure medications that can be provided subcutaneously may be limited. Subcutaneous sodium valproate may be an additional management strategy.
AIM
To evaluate the published experience of subcutaneous valproate use in palliative care, namely with respect to effectiveness and tolerability.
DESIGN
A systematic review was registered (PROSPERO CRD42023453427), conducted and reported according to PRISMA reporting guidelines.
DATA SOURCES
The databases PubMed, EMBASE and Scopus were searched for publications until August 11, 2023.
RESULTS
The searches returned 429 results, of which six fulfilled inclusion criteria. Case series were the most common study design, and most studies included <10 individuals who received subcutaneous sodium valproate. There were three studies that presented results on the utility of subcutaneous sodium valproate for seizure control, which described it to be an effective strategy. One study also described it as an effective treatment for neuropathic pain. The doses were often based on presumed 1:1 oral to subcutaneous conversion ratios. Only one study described a local site adverse reaction, which resolved with a change of administration site.
CONCLUSIONS
There are limited data on the use of subcutaneous sodium valproate in palliative care. However, palliative symptoms for which subcutaneous sodium valproate have been used successfully are seizures and neuropathic pain. The available data have described few adverse effects, supporting its use with an appropriate degree of caution.
Topics: Humans; Valproic Acid; Palliative Care; Seizures; Neuralgia
PubMed: 38444061
DOI: 10.1177/02692163241234597 -
Maturitas Jun 2024Medicinal cannabis might have a role in supporting the mental health of people with cancer. This systematic review and meta-analysis examined the efficacy and safety of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Medicinal cannabis might have a role in supporting the mental health of people with cancer. This systematic review and meta-analysis examined the efficacy and safety of medicinal cannabis, compared with any control, as an intervention for depression, anxiety, and stress symptoms in people living with cancer. A secondary aim was to examine the effect of low versus high Δ-tetrahydrocannabinol (THC) dose on these outcomes.
METHODS
Five databases were systematically searched, and complemented with a snowball search from inception to May 2023, for any type of interventional study that included humans of any age with any cancer type. Primary outcomes were incidence and severity of depression, anxiety, and stress symptoms. Secondary outcomes were mood, cognition, quality of life, appetite, nutrition status, gastrointestinal symptoms, and adverse events. Data were pooled using Review Manager. Evidence was appraised using Cochrane risk of bias tools. Confidence in the estimated effect of pooled outcomes was assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE).
RESULTS
Fifteen studies (n = 11 randomized trials, n = 4 non-randomized trials) of 18 interventions (N = 1898 total participants; 100 % ≥18 years of age) were included. Ten studies examined THC (70 % synthetic), two synthetic cannabidiol with or without THC, and six whole-plant extracts. No clinically significant effects of medicinal cannabis were found on primary outcomes. The likelihood of anxiety events increased with higher-dose synthetic THC compared with a lower dose (OR: 2.0; 95 % CI: 1.4, 2.9; p < 0.001; Confidence: very low). Medicinal cannabis (THC, cannabidiol, and whole-plant extract) increased the likelihood of improved appetite (OR: 12.3; 95 % CI: 3.5, 45.5; p < 0.001; n = 3 interventions; Confidence: moderate) and reduced severity of appetite loss (SMD: -0.4; 95 % CI: -0.8, -0.1; p = 0.009; Confidence: very low). There was very low confidence that higher doses of synthetic THC increased the likelihood of any adverse event (OR: 0.5; 95 % CI: 0.3, 0.7; p < 0.001). Medicinal cannabis had no effect on emotional functioning, mood changes, confusion, disorientation, quality of life, and gastrointestinal symptoms. Confidence in findings was limited by some studies having high or unclear risk of bias and imprecise pooled estimates.
CONCLUSIONS
There was insufficient evidence to determine the efficacy and safety of medicinal cannabis as a therapeutic intervention for depression, anxiety, or stress in people with active cancer. Further research should explore whether medicinal cannabis might improve and maintain appetite and if high-dose synthetic THC might increase the incidence of side-effects, including anxiety. To inform clinical practice, well-powered and rigorously designed trials are warranted that evaluate the effects of medicinal cannabis prescribed to target anxiety, depression, and stress.
Topics: Humans; Neoplasms; Medical Marijuana; Anxiety; Depression; Stress, Psychological; Dronabinol; Quality of Life
PubMed: 38430618
DOI: 10.1016/j.maturitas.2024.107941 -
JAMA Psychiatry May 2024Cognitive impairment contributes significantly to clinical outcome and level of function in individuals with psychotic disorders. These impairments are present already... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Cognitive impairment contributes significantly to clinical outcome and level of function in individuals with psychotic disorders. These impairments are present already at psychosis onset at a group level; however, the question of heterogeneity in cognitive function among patients has not been systematically investigated.
OBJECTIVE
To provide an updated quantification of cognitive impairment at psychosis onset before patients receive potentially confounding antipsychotic treatment, and to investigate variability in cognitive function compared with healthy controls.
DATA SOURCES
In this systematic review and meta-analysis, PubMed articles were searched up to September 15, 2022.
STUDY SELECTION
Original studies reporting data on cognitive function in antipsychotic drug-naive patients with first-episode psychosis (FEP) were included.
DATA EXTRACTION AND SYNTHESIS
Data were independently extracted by 2 researchers. Cognitive tasks were clustered according to 6 domains of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery and the domain of executive function. Random-effects model meta-analyses of mean differences and coefficient of variation ratios (CVRs) were performed, as well as meta-regressions, assessment of study quality, and publication bias.
MAIN OUTCOMES AND MEASURES
The main outcome measure was Hedges g for mean differences in cognition and CVR for within-group variability.
RESULTS
Fifty studies were included in the analysis with a total of 2625 individuals with FEP (mean [SD] age, 25.2 [3.6] years, 60% male; 40% female) and 2917 healthy controls (mean [SD] age, 26.0 [4.6]; 55% male; 45% female). In all cognitive domains, the FEP group displayed significant impairment compared with controls (speed of processing: Hedges g = -1.16; 95% CI, -1.35 to -0.98; verbal learning: Hedges g = -1.08; 95% CI, -1.28 to -0.88; visual learning: Hedges g = -1.05; 95% CI, -1.27 to -0.82; working memory: Hedges g = -1.04; 95% CI, -1.35 to -0.73; attention: Hedges g = -1.03; 95% CI, -1.24 to -0.82; reasoning/problem solving: Hedges g = -0.90; 95% CI, -1.12 to -0.68; executive function: Hedges g = -0.88; 95% CI, -1.07 to -0.69). Individuals with FEP also exhibited a larger variability across all domains (CVR range, 1.34-1.92).
CONCLUSIONS AND RELEVANCE
Results of this systematic review and meta-analysis identified cognitive impairment in FEP before the initiation of antipsychotic treatment, with large effect sizes. The high variability within the FEP group suggests the need to identify those individuals with more severe cognitive problems who risk worse outcomes and could benefit the most from cognitive remediation.
Topics: Humans; Psychotic Disorders; Cognitive Dysfunction; Executive Function; Cognition; Antipsychotic Agents; Schizophrenia
PubMed: 38416480
DOI: 10.1001/jamapsychiatry.2024.0016 -
The International Journal of... Mar 2024The efficacy of pharmacological and nutritional interventions in individuals at clinical high risk for psychosis (CHR-P) remains elusive. This study aims to investigate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy of pharmacological and nutritional interventions in individuals at clinical high risk for psychosis (CHR-P) remains elusive. This study aims to investigate the efficacy of pharmacological and nutritional interventions in CHR-P and whether these interventions can enhance the efficacy of psychological treatments.
METHODS
We systematically reviewed data from 5 databases until July 24, 2021: PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, and WanFang Data. The primary outcome was the transition to psychosis. Network meta-analyses were conducted at 3 time points (6, 12, and ≥24 months) considering both pharmacological/nutritional interventions alone and its combination with psychotherapy.
RESULTS
Out of 11 417 identified references, 21 studies were included, comprising 1983 participants. CHR-P participants receiving omega-3 polyunsaturated fatty acids treatment were associated with a lower probability of transition compared with placebo/control at 6 months (odds ratio [OR] = 0.07, 95% confidence interval [CI] = .01 to .054), 12 months (OR = 0.14, 95% CI = .03 to .66), and ≥24 months (OR = 0.16, 95% CI = .05 to .54). Moreover, risperidone plus psychotherapy was associated with a lower likelihood of transition at 6 months compared with placebo/control plus psychotherapy, but this result was not sustained over longer durations.
CONCLUSION
Omega-3 polyunsaturated fatty acids helped in preventing transitions to psychosis compared with controls.
PROSPERO REGISTRATION NUMBER
CRD42021256209.
Topics: Humans; Network Meta-Analysis; Psychotic Disorders; Fatty Acids, Omega-3; Risperidone; Odds Ratio
PubMed: 38408281
DOI: 10.1093/ijnp/pyae014 -
Addictive Behaviors Jun 2024Anxiety and depression are prevalent mental health problems in people who use illicit stimulants. Improved understanding of the temporal relationship between... (Review)
Review
OBJECTIVE
Anxiety and depression are prevalent mental health problems in people who use illicit stimulants. Improved understanding of the temporal relationship between methamphetamine, ecstasy/MDMA, or cocaine use with anxiety or depression informs public health interventions and treatment options for those experiencing this co-occurrence. This narrative systematic review sought to examine associations and temporality between the use of methamphetamine, ecstasy/MDMA, or cocaine, with anxiety or depressive symptoms. Method Systematic searches of 4 electronic databases were conducted up to August 2023. Study eligibility included the measurement of anxiety and/or depressive symptoms, and frequency of illicit stimulant use (methamphetamine, cocaine, or ecstasy/MDMA) at two separate time points, with data analysis of the association between these variables. The Joanna Briggs Critical Appraisal Checklist was utilised to assess quality. Data was extracted, and a narrative synthesis incorporating an eight-criteria framework to assess associations was conducted. Results 4432 studies were screened for eligibility; 11 studies (3 RCTs and 8 prospective cohort studies) were included. Evidence for an association between depressive symptoms and methamphetamine use was demonstrated in six studies, with temporal evidence in three studies supporting methamphetamine use preceding depressive symptoms. Three studies reported an association between cocaine use and depressive symptoms. Evidence for associations with any of the illicit stimulants and anxiety symptoms was lacking.
CONCLUSIONS
There was some evidence to support a case for temporality, particularly for methamphetamine use and depressive symptoms. Investing in longitudinal studies is pivotal to understanding the dynamic and reciprocal relationship between illicit stimulant use and anxiety or depressive symptoms. A limitation of the study was the variation in the measurement and analysis of outcomes.
Topics: Humans; N-Methyl-3,4-methylenedioxyamphetamine; Methamphetamine; Depression; Prospective Studies; Anxiety; Cocaine; Central Nervous System Stimulants; Cocaine-Related Disorders
PubMed: 38394960
DOI: 10.1016/j.addbeh.2024.107988 -
Ayahuasca and Dimethyltryptamine Adverse Events and Toxicity Analysis: A Systematic Thematic Review.International Journal of Toxicology 2024The objective of this paper is to conduct a systematic thematic review of adverse events, safety, and toxicity of traditional ayahuasca plant preparations and its main... (Review)
Review
The objective of this paper is to conduct a systematic thematic review of adverse events, safety, and toxicity of traditional ayahuasca plant preparations and its main psychoactive alkaloids (dimethyltryptamine [DMT], harmine, harmaline, and tetrahydroharmine), including discussing clinical considerations (within clinical trials or approved settings). A systematic literature search of preclinical, clinical, epidemiological, and pharmacovigilance data (as well as pertinent reviews and case studies) was conducted for articles using the electronic databases of PubMed and Web of Science (to 6 July 2023) and PsycINFO, ClinicalTrials.gov, and Embase (to 21 September 2022) and included articles in English in peer-reviewed journals. Additionally, reference lists were searched. Due to the breadth of the area covered, we presented the relevant data in a thematic format. Our searches revealed 78 relevant articles. Data showed that ayahuasca or DMT is generally safe; however, some adverse human events have been reported. Animal models using higher doses of ayahuasca have shown abortifacient and teratogenic effects. Isolated harmala alkaloid studies have also revealed evidence of potential toxicity at higher doses, which may increase with co-administration with certain medications. Harmaline revealed the most issues in preclinical models. Nevertheless, animal models involving higher-dose synthetic isolates may not necessarily be able to be extrapolated to human use of therapeutic doses of plant-based extracts. Serious adverse effects are rarely reported within healthy populations, indicating an acceptable safety profile for the traditional use of ayahuasca and DMT in controlled settings. Further randomized, controlled trials with judicious blinding, larger samples, and longer duration are needed.
Topics: Banisteriopsis; Humans; N,N-Dimethyltryptamine; Animals; Plant Extracts; Harmine; Harmaline
PubMed: 38363085
DOI: 10.1177/10915818241230916 -
BMJ (Clinical Research Ed.) Feb 2024To identify the optimal dose and modality of exercise for treating major depressive disorder, compared with psychotherapy, antidepressants, and control conditions. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To identify the optimal dose and modality of exercise for treating major depressive disorder, compared with psychotherapy, antidepressants, and control conditions.
DESIGN
Systematic review and network meta-analysis.
METHODS
Screening, data extraction, coding, and risk of bias assessment were performed independently and in duplicate. Bayesian arm based, multilevel network meta-analyses were performed for the primary analyses. Quality of the evidence for each arm was graded using the confidence in network meta-analysis (CINeMA) online tool.
DATA SOURCES
Cochrane Library, Medline, Embase, SPORTDiscus, and PsycINFO databases.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Any randomised trial with exercise arms for participants meeting clinical cut-offs for major depression.
RESULTS
218 unique studies with a total of 495 arms and 14 170 participants were included. Compared with active controls (eg, usual care, placebo tablet), moderate reductions in depression were found for walking or jogging (n=1210, κ=51, Hedges' g -0.62, 95% credible interval -0.80 to -0.45), yoga (n=1047, κ=33, g -0.55, -0.73 to -0.36), strength training (n=643, κ=22, g -0.49, -0.69 to -0.29), mixed aerobic exercises (n=1286, κ=51, g -0.43, -0.61 to -0.24), and tai chi or qigong (n=343, κ=12, g -0.42, -0.65 to -0.21). The effects of exercise were proportional to the intensity prescribed. Strength training and yoga appeared to be the most acceptable modalities. Results appeared robust to publication bias, but only one study met the Cochrane criteria for low risk of bias. As a result, confidence in accordance with CINeMA was low for walking or jogging and very low for other treatments.
CONCLUSIONS
Exercise is an effective treatment for depression, with walking or jogging, yoga, and strength training more effective than other exercises, particularly when intense. Yoga and strength training were well tolerated compared with other treatments. Exercise appeared equally effective for people with and without comorbidities and with different baseline levels of depression. To mitigate expectancy effects, future studies could aim to blind participants and staff. These forms of exercise could be considered alongside psychotherapy and antidepressants as core treatments for depression.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42018118040.
Topics: Humans; Network Meta-Analysis; Depression; Depressive Disorder, Major; Bayes Theorem; Exercise; Antidepressive Agents; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 38355154
DOI: 10.1136/bmj-2023-075847 -
The Journal of Clinical Psychiatry Feb 2024
Topics: Humans; Cannabis; Stress Disorders, Post-Traumatic; Hallucinogens
PubMed: 38353646
DOI: 10.4088/JCP.23com15279 -
BMJ Mental Health Feb 2024We examined the effect of study characteristics, risk of bias and publication bias on the efficacy of pharmacotherapy in randomised controlled trials (RCTs) for... (Meta-Analysis)
Meta-Analysis
Influence of study characteristics, methodological rigour and publication bias on efficacy of pharmacotherapy in obsessive-compulsive disorder: a systematic review and meta-analysis of randomised, placebo-controlled trials.
QUESTION
We examined the effect of study characteristics, risk of bias and publication bias on the efficacy of pharmacotherapy in randomised controlled trials (RCTs) for obsessive-compulsive disorder (OCD).
STUDY SELECTION AND ANALYSIS
We conducted a systematic search of double-blinded, placebo-controlled, short-term RCTs with selective serotonergic reuptake inhibitors (SSRIs) or clomipramine. We performed a random-effect meta-analysis using change in the Yale-Brown Obsessive-Compulsive Scale (YBOCS) as the primary outcome. We performed meta-regression for risk of bias, intervention, sponsor status, number of trial arms, use of placebo run-in, dosing, publication year, age, severity, illness duration and gender distribution. Furthermore, we analysed publication bias using a Bayesian selection model.
FINDINGS
We screened 3729 articles and included 21 studies, with 4102 participants. Meta-analysis showed an effect size of -0.59 (Hedges' G, 95% CI -0.73 to -0.46), equalling a 4.2-point reduction in the YBOCS compared with placebo. The most recent trial was performed in 2007 and most trials were at risk of bias. We found an indication for publication bias, and subsequent correction for this bias resulted in a depleted effect size. In our meta-regression, we found that high risk of bias was associated with a larger effect size. Clomipramine was more effective than SSRIs, even after correcting for risk of bias. After correction for multiple testing, other selected predictors were non-significant.
CONCLUSIONS
Our findings reveal superiority of clomipramine over SSRIs, even after adjusting for risk of bias. Effect sizes may be attenuated when considering publication bias and methodological rigour, emphasising the importance of robust studies to guide clinical utility of OCD pharmacotherapy.
PROSPERO REGISTRATION NUMBER
CRD42023394924.
Topics: Humans; Clomipramine; Selective Serotonin Reuptake Inhibitors; Publication Bias; Obsessive-Compulsive Disorder; Randomized Controlled Trials as Topic
PubMed: 38350669
DOI: 10.1136/bmjment-2023-300951 -
Journal of Psychopharmacology (Oxford,... Feb 2024Medication adherence is a prerequisite to achieving beneficial treatment outcomes. In major depressive disorder, many patients fail to complete medication regimens,... (Review)
Review
BACKGROUND
Medication adherence is a prerequisite to achieving beneficial treatment outcomes. In major depressive disorder, many patients fail to complete medication regimens, raising concern for poor treatment outcomes. It is usual to experience adverse drug reactions (ADRs) while taking antidepressants, and relative discomfort is reported by patients.
AIMS
The present review focuses on the presence of antidepressant-related side effects and the subsequent relationship with medication non-adherence.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Following the preliminary research, the research question and eligibility criteria were created based on the PICO framework. All articles retrieved from the selected databases were exported to Covidence, a Systematic Review managing software tool. Two reviewers assessed the papers to identify the risk of bias using the Joanna Briggs Institute critical appraisal tool for cross-sectional studies. Seven studies with a low-moderate risk of bias fulfilled the eligibility criteria and were conducted from 2013 to 2020 in Europe, Africa and Asia.
RESULTS
The results demonstrated high levels of suboptimal adherence ranging from 46% to 83% amongst the studied population. A variety of side effects were reported by a significant number of participants predominantly with moderate severity. A correlation between the presence of ADRs and suboptimal rates of adherence to antidepressants was found. Somnolence and headaches among other unspecified ADRs were found to increase the dropout rates for selective serotonin reuptake inhibitors.
CONCLUSIONS
The present study elucidates the need for effective interventions to facilitate antidepressant adherence and enhance doctor-patient communication, benefiting both the individuals and the healthcare system and leading to better clinical outcomes and reduction of relapse-related costs.
Topics: Adult; Humans; Depressive Disorder, Major; Cross-Sectional Studies; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Drug-Related Side Effects and Adverse Reactions; Medication Adherence
PubMed: 38344912
DOI: 10.1177/02698811231224171