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European Neuropsychopharmacology : the... Nov 2023Psilocybin is increasingly studied for its antidepressant effect, but its optimal dosage for depression remains unclear. We conducted a systematic review and a... (Meta-Analysis)
Meta-Analysis Review
Psilocybin is increasingly studied for its antidepressant effect, but its optimal dosage for depression remains unclear. We conducted a systematic review and a dose-response meta-analysis to find the optimal dosage of psilocybin to reduce depression scores. Following our protocol (CRD 42022220190) multiple electronic databases were searched from their inception until February 2023, to identify double-blind randomized placebo-controlled (RCTs) fixed-dose trials evaluating the use of psilocybin for adult patients with primary or secondary depression. A one-stage dose-response meta-analysis with restricted cubic splines was used. Cochrane risk of bias was used to assess risk of bias. Our analysis included seven studies with a total of 489 participants. Among these, four studies focused on primary depression (N = 366), including one study with patients suffering from treatment-resistant depression. The remaining three studies examined secondary depression (N = 123). The determined 95% effective doses per day (ED95) were 8.92, 24.68, and 36.08 mg/70 kg for patients with secondary depression, primary depression, and both subgroups, respectively. We observed significant dose-response associations for all curves, each plateauing at different levels, except for the bell-shaped curve observed in the case of secondary depression. Additionally, we found significant dose-response associations for various side effects, including physical discomfort, blood pressure increase, nausea/vomiting, headache/migraine, and the risk of prolonged psychosis. In conclusion, we discovered specific ED95 values for different populations, indicating higher ED95 values for treatment-resistant depression, primary depression, and secondary depression groups. Further RCTs are necessary for each population to determine the optimal dosage, allowing for maximum efficacy while minimizing side effects.
Topics: Adult; Humans; Depression; Psilocybin; Antidepressive Agents; Psychotic Disorders; Randomized Controlled Trials as Topic
PubMed: 37557019
DOI: 10.1016/j.euroneuro.2023.07.011 -
Chiropractic & Manual Therapies Feb 2021A small proportion of chiropractors, osteopaths, and other manual medicine providers use spinal manipulative therapy (SMT) to manage non-musculoskeletal disorders....
The global summit on the efficacy and effectiveness of spinal manipulative therapy for the prevention and treatment of non-musculoskeletal disorders: a systematic review of the literature.
BACKGROUND
A small proportion of chiropractors, osteopaths, and other manual medicine providers use spinal manipulative therapy (SMT) to manage non-musculoskeletal disorders. However, the efficacy and effectiveness of these interventions to prevent or treat non-musculoskeletal disorders remain controversial.
OBJECTIVES
We convened a Global Summit of international scientists to conduct a systematic review of the literature to determine the efficacy and effectiveness of SMT for the primary, secondary and tertiary prevention of non-musculoskeletal disorders.
GLOBAL SUMMIT
The Global Summit took place on September 14-15, 2019 in Toronto, Canada. It was attended by 50 researchers from 8 countries and 28 observers from 18 chiropractic organizations. At the summit, participants critically appraised the literature and synthesized the evidence.
SYSTEMATIC REVIEW OF THE LITERATURE
We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health, and the Index to Chiropractic Literature from inception to May 15, 2019 using subject headings specific to each database and free text words relevant to manipulation/manual therapy, effectiveness, prevention, treatment, and non-musculoskeletal disorders. Eligible for review were randomized controlled trials published in English. The methodological quality of eligible studies was assessed independently by reviewers using the Scottish Intercollegiate Guidelines Network (SIGN) criteria for randomized controlled trials. We synthesized the evidence from articles with high or acceptable methodological quality according to the Synthesis without Meta-Analysis (SWiM) Guideline. The final risk of bias and evidence tables were reviewed by researchers who attended the Global Summit and 75% (38/50) had to approve the content to reach consensus.
RESULTS
We retrieved 4997 citations, removed 1123 duplicates and screened 3874 citations. Of those, the eligibility of 32 articles was evaluated at the Global Summit and 16 articles were included in our systematic review. Our synthesis included six randomized controlled trials with acceptable or high methodological quality (reported in seven articles). These trials investigated the efficacy or effectiveness of SMT for the management of infantile colic, childhood asthma, hypertension, primary dysmenorrhea, and migraine. None of the trials evaluated the effectiveness of SMT in preventing the occurrence of non-musculoskeletal disorders. Consensus was reached on the content of all risk of bias and evidence tables. All randomized controlled trials with high or acceptable quality found that SMT was not superior to sham interventions for the treatment of these non-musculoskeletal disorders. Six of 50 participants (12%) in the Global Summit did not approve the final report.
CONCLUSION
Our systematic review included six randomized clinical trials (534 participants) of acceptable or high quality investigating the efficacy or effectiveness of SMT for the treatment of non-musculoskeletal disorders. We found no evidence of an effect of SMT for the management of non-musculoskeletal disorders including infantile colic, childhood asthma, hypertension, primary dysmenorrhea, and migraine. This finding challenges the validity of the theory that treating spinal dysfunctions with SMT has a physiological effect on organs and their function. Governments, payers, regulators, educators, and clinicians should consider this evidence when developing policies about the use and reimbursement of SMT for non-musculoskeletal disorders.
Topics: Asthma; Colic; Dysmenorrhea; Female; Humans; Hypertension; Manipulation, Spinal; Noncommunicable Diseases
PubMed: 33596925
DOI: 10.1186/s12998-021-00362-9 -
BMJ Open Jan 2021To determine the effects of coenzyme Q10 (CoQ10) for reduction in the severity, frequency of migraine attacks and duration of headache in adult patients with migraine. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the effects of coenzyme Q10 (CoQ10) for reduction in the severity, frequency of migraine attacks and duration of headache in adult patients with migraine.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Cochrane Central Register of Controlled Trials, CENTRAL, MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Psychological Information Database (PsycINFO) from inception till December 2019.
STUDY SELECTION
All randomised control trials comparing CoQ10 with placebo or used as an adjunct treatment included in this meta-analysis. Cross-over designs and controlled clinical trials were excluded.
DATA SYNTHESIS
Heterogeneity at face value by comparing populations, settings, interventions and outcomes were measured and statistical heterogeneity was assessed by means of the I statistic. The treatment effect for dichotomous outcomes were using risk ratios and risk difference, and for continuous outcomes, mean differences (MDs) or standardised mean difference; both with 95% CIs were used. Subgroup analyses were carried out for dosage of CoQ10 and if CoQ10 combined with another supplementation. Sensitivity analysis was used to investigate the impact risk of bias for sequence generation and allocation concealment of included studies.
RESULTS
Six studies with a total of 371 participants were included in the meta-analysis. There is no statistically significant reduction in severity of migraine headache with CoQ10 supplementation. CoQ10 supplementation reduced the duration of headache attacks compared with the control group (MD: -0.19; 95% CI: -0.27 to -0.11; random effects; I statistic=0%; p<0.00001). CoQ10 usage reduced the frequency of migraine headache compared with the control group (MD: -1.52; 95% CI: -2.40 to -0.65; random effects; I statistic=0%; p<0.001).
CONCLUSION
CoQ10 appears to have beneficial effects in reducing duration and frequency of migraine attack.
PROSPERO REGISTRATION NUMBER
CRD42019126127.
Topics: Adult; Dietary Supplements; Humans; Migraine Disorders; Ubiquinone
PubMed: 33402403
DOI: 10.1136/bmjopen-2020-039358 -
Headache Apr 2016Migraine is comorbid with obesity. Recent research suggests an association between migraine and adipocytokines, proteins that are predominantly secreted from adipose... (Review)
Review
BACKGROUND
Migraine is comorbid with obesity. Recent research suggests an association between migraine and adipocytokines, proteins that are predominantly secreted from adipose tissue and which participate in energy homeostasis and inflammatory processes.
OBJECTIVES
In this review, we first briefly discuss the association between migraine and obesity and the importance of adipose tissue as a neuroendocrine organ. We then present a systematic review of the extant literature evaluating circulating levels of adiponectin and leptin in those with migraine.
METHODS
A search of the PubMed database was conducted using the keywords "migraine," "adiponectin," and "leptin." In addition reference lists of relevant articles were reviewed for possible inclusion. English language studies published between 2005 and 2015 evaluating circulating blood concentration of adiponectin or leptin in those with migraine were included.
CONCLUSIONS
While the existing data are suggestive that adipokines may be associated with migraine, substantial study design differences and conflicting results limit definitive conclusions. Future research utilizing carefully considered designs and methodology is warranted. In particular careful and systematic characterization of pain states at the time of samples, as well as systematic consideration of demographic (e.g., age, sex) and other vital covariates (e.g., obesity status, lipids) are needed to determine if adipokines play a role in migraine pathophysiology and if any adipokine represents a viable, novel migraine biomarker, or drug target.
Topics: Adipokines; Humans; Migraine Disorders; Obesity
PubMed: 27012149
DOI: 10.1111/head.12788 -
European Stroke Journal Dec 2023Migraine is a common, disabling chronic pain condition possibly related to changes in endothelial and vascular structure and function. Several observational studies have... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Migraine is a common, disabling chronic pain condition possibly related to changes in endothelial and vascular structure and function. Several observational studies have suggested an elevated risk of cervical artery dissection (CeAD) in patients with a history of migraine. We aimed to investigate this potential association using systematic review and meta-analytic methods.
PATIENTS AND METHODS
We utilized a pre-defined search protocol to identify and screen studies related to migraine and CeAD in PubMed, Embase, and the Web of Science Core Collection. We assessed the risk of bias and performed a meta-analysis of selected studies to assess the association between migraine and CeAD. We also performed subgroup analyses by migraine subtype, biological sex, and the use of stroke versus non-stroke controls.
RESULTS
We identified 11 studies ( = 9857 patients) for inclusion in the meta-analysis. Meta-analysis showed an association between migraine and CeAD with an odds ratio of 1.74 (95%CI 1.38-2.19). There was high heterogeneity among the included studies ( = 61%). Publication bias was present but the Trim-Fill imputation suggested that the impact on results was likely minimal. Subgroup analyses revealed an association between migraine without aura and CeAD (OR 1.86, 95%CI 1.55-2.24) but not migraine with aura and CeAD (OR 1.15, 95%CI 0.71-1.88). There was no difference in the association between migraine and CeAD in men compared to women.
DISCUSSION AND CONCLUSION
A history of migraine is associated with an increased risk of CeAD. Further studies are needed to elucidate the potential pathophysiologic mechanisms underlying this association.
Topics: Male; Humans; Female; Risk Factors; Stroke; Migraine Disorders; Aortic Dissection; Arteries
PubMed: 37555306
DOI: 10.1177/23969873231191860 -
Tremor and Other Hyperkinetic Movements... 2023Episodic ataxia (EA), characterized by recurrent attacks of cerebellar dysfunction, is the manifestation of a group of rare autosomal dominant inherited disorders. EA1... (Review)
Review
BACKGROUND
Episodic ataxia (EA), characterized by recurrent attacks of cerebellar dysfunction, is the manifestation of a group of rare autosomal dominant inherited disorders. EA1 and EA2 are most frequently encountered, caused by mutations in and . EA3-8 are reported in rare families. Advances in genetic testing have broadened the and phenotypes, and detected EA as an unusual presentation of several other genetic disorders. Additionally, there are various secondary causes of EA and mimicking disorders. Together, these can pose diagnostic challenges for neurologists.
METHODS
A systematic literature review was performed in October 2022 for 'episodic ataxia' and 'paroxysmal ataxia', restricted to publications in the last 10 years to focus on recent clinical advances. Clinical, genetic, and treatment characteristics were summarized.
RESULTS
EA1 and EA2 phenotypes have further broadened. In particular, EA2 may be accompanied by other paroxysmal disorders of childhood with chronic neuropsychiatric features. New treatments for EA2 include dalfampridine and fampridine, in addition to 4-aminopyridine and acetazolamide. There are recent proposals for EA9-10. EA may also be caused by gene mutations associated with chronic ataxias (), epilepsy syndromes (), GLUT-1, mitochondrial disorders (), metabolic disorders (Maple syrup urine disease, Hartnup disease, type I citrullinemia, thiamine and biotin metabolism defects), and others. Secondary causes of EA are more commonly encountered than primary EA (vascular, inflammatory, toxic-metabolic). EA can be misdiagnosed as migraine, peripheral vestibular disorders, anxiety, and functional symptoms. Primary and secondary EA are frequently treatable which should prompt a search for the cause.
DISCUSSION
EA may be overlooked or misdiagnosed for a variety of reasons, including phenotype-genotype variability and clinical overlap between primary and secondary causes. EA is highly treatable, so it is important to consider in the differential diagnosis of paroxysmal disorders. Classical EA1 and EA2 phenotypes prompt single gene test and treatment pathways. For atypical phenotypes, next generation genetic testing can aid diagnosis and guide treatment. Updated classification systems for EA are discussed which may assist diagnosis and management.
Topics: Humans; Ataxia; Cerebellar Ataxia; Acetazolamide; Mutation
PubMed: 37008993
DOI: 10.5334/tohm.747 -
Cureus Jul 2023Drugs that act on the calcitonin gene-related peptide (CGRP) pathway herald the dawn of a new era in the management of migraine headaches. The blockade of CGRP... (Review)
Review
Drugs that act on the calcitonin gene-related peptide (CGRP) pathway herald the dawn of a new era in the management of migraine headaches. The blockade of CGRP alleviates neural inflammation and has been associated with reduced pain sensitization. Zavegepant is a third-generation drug and is the first intranasal CGRP antagonist to be developed. This systematic review aims to assess the safety, efficacy, pharmacokinetics, and tolerability of Zavegepant as an abortive treatment for migraine. Studies that assessed the safety, tolerability, and efficacy of Zavegepant for migraine were identified through a systematic literature review of PubMed, Clinicaltrials.gov, and Cochrane databases in April 2023. Our systematic review yielded a total of six studies that fit our inclusion criteria. Of these, data from only two randomized control trials (RCTs) was homogenous; hence, forest plots of results pooled from the included studies were not reported. The included studies showed that Zavegepant is an efficacious and well-tolerated abortive treatment modality for episodic migraine in adult patients. Zavegepant showed safety and efficacy in migraine treatment according to various parameters throughout the six included studies. These parameters include adverse events, pharmacokinetic properties, CGRP inhibition, effect on blood pressure/electrocardiogram, pain freedom, and freedom from most bothersome symptoms.
PubMed: 37593294
DOI: 10.7759/cureus.41991 -
The Clinical Journal of Pain Jul 2017Previous studies have demonstrated an association between migraine and major depressive disorder. However, relatively little is known about the relationship between... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Previous studies have demonstrated an association between migraine and major depressive disorder. However, relatively little is known about the relationship between suicidal ideation, with or without concurrent depression, and migraine.
OBJECTIVE
We conducted a systematic literature review to synthesize the available research focused on investigating the association of migraine with suicidal ideation.
METHODS
Relevant research papers were identified through searches of major electronic databases including PubMed, Embase (Elsevier), Web of Science (Thomson Reuters), PsycINFO (EBSCO), and Google Scholar. We performed a meta-analysis to estimate the pooled unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (95% CI) for the association between migraine and suicidal ideation extracted from each study.
RESULTS
A total of 148,977 participants in 6 studies were included in this analysis. Overall, findings from available studies documented elevated odds of suicidal ideation among individuals with migraines. In unadjusted models, the odds of suicidal ideation was 2.49-fold higher among individuals with migraine (OR, 2.49; 95% CI, 2.34-2.65) compared with those without migraine. In multivariate-adjusted models, the pooled adjusted OR of suicidal ideation was 1.31 (OR, 1.31; 95% CI, 1.10-1.55).
CONCLUSIONS
A meta-analysis of available studies suggests a modest positive association between migraine and suicidal ideation. Further studies allowing for a more comprehensive investigation of the association between migraine and the full range of suicidal behaviors are warranted. A larger and more robust evidence-base may be useful to inform the clinical screening and diagnoses of comorbid conditions in migraineurs.
Topics: Databases, Bibliographic; Humans; Migraine Disorders; Suicidal Ideation
PubMed: 27648590
DOI: 10.1097/AJP.0000000000000440 -
Neurology May 2023Cluster headache and migraine have circadian features at multiple levels (cellular, systems, and behavioral). A thorough understanding of their circadian features... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Cluster headache and migraine have circadian features at multiple levels (cellular, systems, and behavioral). A thorough understanding of their circadian features informs their pathophysiologies.
METHODS
A librarian created search criteria in MEDLINE Ovid, Embase, PsycINFO, Web of Science, and Cochrane Library. Two physicians independently performed the remainder of the systematic review/meta-analysis using Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Separate from the systematic review/meta-analysis, we performed a genetic analysis for genes with a circadian pattern of expression (clock-controlled genes or CCGs) by cross-referencing genome-wide association studies (GWASs) of headache, a nonhuman primate study of CCGs in a variety of tissues, and recent reviews of brain areas relevant in headache disorders. Altogether, this allowed us to catalog circadian features at the behavioral level (circadian timing, time of day, time of year, and chronotype), systems level (relevant brain areas where CCGs are active, melatonin and corticosteroid levels), and cellular level (core circadian genes and CCGs).
RESULTS
For the systematic review and meta-analysis, 1,513 studies were found, and 72 met the inclusion criteria; for the genetic analysis, we found 16 GWASs, 1 nonhuman primate study, and 16 imaging reviews. For cluster headache behavior, meta-analyses showed a circadian pattern of attacks in 70.5% (3,490/4,953) of participants across 16 studies, with a clear circadian peak between 21:00 and 03:00 and circannual peaks in spring and autumn. Chronotype was highly variable across studies. At the systems level, lower melatonin and higher cortisol levels were reported in cluster headache participants. At the cellular level, cluster headache was associated with core circadian genes and , and 5 of the 9 cluster headache susceptibility genes were CCGs. For migraine behavior, meta-analyses showed a circadian pattern of attacks in 50.1% (2,698/5,385) of participants across 8 studies, with a clear circadian trough between 23:00 and 07:00 and a broad circannual peak between April and October. Chronotype was highly variable across studies. At the systems level, urinary melatonin levels were lower in participants with migraine and even lower during an attack. At the cellular level, migraine was associated with core circadian genes and , and 110 of the 168 migraine susceptibility genes were CCGs.
DISCUSSION
Cluster headache and migraine are highly circadian at multiple levels, reinforcing the importance of the hypothalamus. This review provides a pathophysiologic foundation for circadian-targeted research into these disorders.
TRIAL REGISTRATION INFORMATION
The study was registered with PROSPERO (registration number CRD42021234238).
Topics: Animals; Cluster Headache; Melatonin; Genome-Wide Association Study; Migraine Disorders; Primates
PubMed: 36990725
DOI: 10.1212/WNL.0000000000207240 -
The Cochrane Database of Systematic... Nov 2015Non-prescription (over-the-counter, or OTC) analgesics (painkillers) are used frequently. They are available in various brands, package sizes, formulations, and dose.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-prescription (over-the-counter, or OTC) analgesics (painkillers) are used frequently. They are available in various brands, package sizes, formulations, and dose. They can be used for a range of different types of pain, but this overview reports on how well they work for acute pain (pain of short duration, usually with rapid onset). Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain.
OBJECTIVES
To examine published Cochrane reviews for information about the efficacy of pain medicines available without prescription using data from acute postoperative pain.
METHODS
We identified OTC analgesics available in the UK, Australia, Canada, and the USA by examining online pharmacy websites. We also included some analgesics (diclofenac potassium, dexketoprofen, dipyrone) of importance in parts of the world, but not currently available in these jurisdictions.We identified systematic reviews by searching the Cochrane Database of Systematic Reviews (CDSR) on The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. From individual reviews we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also calculated the success rate to achieve at least 50% of maximum pain relief. We also examined the number of participants experiencing any adverse event, and whether the incidence was different from placebo.
MAIN RESULTS
We found information on 21 different OTC analgesic drugs, doses, and formulations, using information from 10 Cochrane reviews, supplemented by information from one non-Cochrane review with additional information on ibuprofen formulations (high quality evidence). The lowest (best) NNT values were for combinations of ibuprofen plus paracetamol, with NNT values below 2. Analgesics with values close to 2 included fast acting formulations of ibuprofen 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg. Combinations of ibuprofen plus paracetamol had success rates of almost 70%, with dipyrone 500 mg, fast acting ibuprofen formulations 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg having success rates above 50%. Paracetamol and aspirin at various doses had NNT values of 3 or above, and success rates of 11% to 43%. We found no information on many of the commonly available low dose codeine combinations.The proportion of participants experiencing an adverse event were generally not different from placebo, except for aspirin 1000 mg and (barely) ibuprofen 200 mg plus caffeine 100 mg. For ibuprofen plus paracetamol, adverse event rates were lower than with placebo.
AUTHORS' CONCLUSIONS
There is a body of reliable evidence about the efficacy of some of the most commonly available drugs and doses widely available without prescription. The postoperative pain model is predominantly pain after third molar extraction, which is used as the industry model for everyday pain. The proportion of people with acute pain who get good pain relief with any of them ranges from around 70% at best to less than 20% at worst; low doses of some drugs in fast acting formulations were among the best. Adverse events were generally no different from placebo. Consumers can make an informed choice based on this knowledge, together with availability and price. Headache and migraine were not included in this overview.
Topics: Acute Pain; Administration, Oral; Analgesics; Humans; Nonprescription Drugs; Numbers Needed To Treat; Randomized Controlled Trials as Topic; Review Literature as Topic
PubMed: 26544675
DOI: 10.1002/14651858.CD010794.pub2