-
Brain & Spine 2024TBIs contribute in over one-third of injury-related deaths with mortality rates as high as 50% in trauma centers serving the most severe TBI. The effect of TBI on... (Review)
Review
INTRODUCTION
TBIs contribute in over one-third of injury-related deaths with mortality rates as high as 50% in trauma centers serving the most severe TBI. The effect of TBI on mortality is about 10% across all ages. Amantadine hydrochloride is one of the most commonly prescribed medications for patients undergoing inpatient neurorehabilitation who have disorders of consciousness. It is a dopamine (DA) receptor agonist and a N-Methyl-D-aspartate (NMDA) receptor antagonist via dopamine release and dopamine reuptake inhibition. The current study will synthesize the current available evidence and show the effect of Amantadine in functional improvement after TBI.
RESEARCH QUESTION
Does Amantadine have an effect on functional improvement of TBI patients?
MATERIAL AND METHODS
This systematic review included all randomized placebo-controlled trials that compare the use of Amantadine versus placebo for functional improvement of patients after TBI. Outcome measures included DRS, GCS and/or GOS scores.
RESULTS
Three studies with a total of 281 patients were included in the quantitative analyses. GRADE assessments show that there was a high certainty of evidence for functional improvement in terms of DRS scores.
DISCUSSION AND CONCLUSION
Evidence of this review show that the use of Amantadine may have a beneficial effect on functional outcome in moderate to severe traumatic brain injuries among adult patients. Given the still-limited body of knowledge, more relevant studies must be made exploring the impact of Amantadine therapies on promoting functional recovery within the brain injury rehabilitation care continuum, with the goals of achieving larger sample sizes and establishing the early- or later-treatment beneficial effects.
PubMed: 38465280
DOI: 10.1016/j.bas.2024.102773 -
European Journal of Pain (London,... Aug 2019N-methyl-D-aspartate (NMDA) receptors are involved in pain signalling and neuroplasticity. Memantine has been shown to have analgesic properties in pre-clinical and... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
N-methyl-D-aspartate (NMDA) receptors are involved in pain signalling and neuroplasticity. Memantine has been shown to have analgesic properties in pre-clinical and small clinical studies. We conducted a systematic review and meta-analysis to assess the efficacy of memantine to prevent or reduce chronic pain.
DATABASES AND DATA TREATMENT
MEDLINE, EMBASE and CENTRAL databases were searched for comparative trials using memantine, either against placebo or active medications, for chronic pain in adults. Pain relief was considered our primary outcome. Meta-analyses were conducted if outcomes were reported in two or more studies. Outcomes were reported as mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI). Quality was assessed using the GRADE approach.
RESULTS
Among 454 citations, 15 studies were included with populations predominantly consisting of neuropathic conditions and fibromyalgia. Overall, we observed unclear reporting of randomization and allocation methods, apart from potential for publication bias. Among the 11 studies looking at chronic pain treatment, the difference in end pain score with memantine was not significant: MD = -0.58 units (95% CI -1.31, 0.14); I = 82% (low quality). In two surgical studies using memantine for pain prevention, memantine decreased pain intensity: MD = -1.02 units (95% CI -1.38, -0.66); I = 0%. Dizziness was significantly more common with memantine: RR = 4.90 (95% CI 1.26, 18.99); I = 52% (moderate quality).
CONCLUSION
The current evidence regarding the use of memantine for chronic pain is limited and uncertain. Despite its potential, pain relief achieved in clinical studies is small and is associated with an increase in dizziness.
SIGNIFICANCE
Despite a sound rationale, the benefit of using memantine for chronic pain is unclear. Our systematic review and meta-analysis show that memantine may have the potential to decrease pain. However, it can also increase common adverse effects. Considering the small number of studies with potential for bias and inconclusive evidence, there was low to very low certainty. Hence, no clear recommendations can be made about its routine clinical use until larger and more definitive studies are conducted.
Topics: Adult; Analgesics; Chronic Pain; Fibromyalgia; Humans; Memantine; Receptors, N-Methyl-D-Aspartate
PubMed: 30848504
DOI: 10.1002/ejp.1393 -
The Cochrane Database of Systematic... Sep 2020Antisocial personality disorder (AsPD) is associated with rule-breaking, criminality, substance use, unemployment, relationship difficulties, and premature death.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antisocial personality disorder (AsPD) is associated with rule-breaking, criminality, substance use, unemployment, relationship difficulties, and premature death. Certain types of medication (drugs) may help people with AsPD. This review updates a previous Cochrane review, published in 2010.
OBJECTIVES
To assess the benefits and adverse effects of pharmacological interventions for adults with AsPD.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, 13 other databases and two trials registers up to 5 September 2019. We also checked reference lists and contacted study authors to identify studies.
SELECTION CRITERIA
Randomised controlled trials in which adults (age 18 years and over) with a diagnosis of AsPD or dissocial personality disorder were allocated to a pharmacological intervention or placebo control condition.
DATA COLLECTION AND ANALYSIS
Four authors independently selected studies and extracted data. We assessed risk of bias and created 'Summary of findings tables' and assessed the certainty of the evidence using the GRADE framework. The primary outcomes were: aggression; reconviction; global state/global functioning; social functioning; and adverse events.
MAIN RESULTS
We included 11 studies (three new to this update), involving 416 participants with AsPD. Most studies (10/11) were conducted in North America. Seven studies were conducted exclusively in an outpatient setting, one in an inpatient setting, and one in prison; two studies used multiple settings. The average age of participants ranged from 28.6 years to 45.1 years (overall mean age 39.6 years). Participants were predominantly (90%) male. Study duration ranged from 6 to 24 weeks, with no follow-up period. Data were available from only four studies involving 274 participants with AsPD. All the available data came from unreplicated, single reports, and did not allow independent statistical analysis to be conducted. Many review findings were limited to descriptive summaries based on analyses carried out and reported by the trial investigators. No study set out to recruit participants on the basis of having AsPD; many participants presented primarily with substance abuse problems. The studies reported on four primary outcomes and six secondary outcomes. Primary outcomes were aggression (six studies) global/state functioning (three studies), social functioning (one study), and adverse events (seven studies). Secondary outcomes were leaving the study early (eight studies), substance misuse (five studies), employment status (one study), impulsivity (one study), anger (three studies), and mental state (three studies). No study reported data on the primary outcome of reconviction or the secondary outcomes of quality of life, engagement with services, satisfaction with treatment, housing/accommodation status, economic outcomes or prison/service outcomes. Eleven different drugs were compared with placebo, but data for AsPD participants were only available for five comparisons. Three classes of drug were represented: antiepileptic; antidepressant; and dopamine agonist (anti-Parkinsonian) drugs. We considered selection bias to be unclear in 8/11 studies, attrition bias to be high in 7/11 studies, and performance bias to be low in 7/11 studies. Using GRADE, we rated the certainty of evidence for each outcome in this review as very low, meaning that we have very little confidence in the effect estimates reported. Phenytoin (antiepileptic) versus placebo One study (60 participants) reported very low-certainty evidence that phenytoin (300 mg/day), compared to placebo, may reduce the mean frequency of aggressive acts per week (phenytoin mean = 0.33, no standard deviation (SD) reported; placebo mean = 0.51, no SD reported) in male prisoners with aggression (skewed data) at endpoint (six weeks). The same study (60 participants) reported no evidence of difference between phenytoin and placebo in the number of participants reporting the adverse event of nausea during week one (odds ratio (OR) 1.00, 95% confidence interval (CI) 0.06 to 16.76; very low-certainty evidence). The study authors also reported that no important side effects were detectable via blood cell counts or liver enzyme tests (very low-certainty evidence). The study did not measure reconviction, global/state functioning or social functioning. Desipramine (antidepressant) versus placebo One study (29 participants) reported no evidence of a difference between desipramine (250 to 300 mg/day) and placebo on mean social functioning scores (desipramine = 0.19; placebo = 0.21), assessed with the family-social domain of the Addiction Severity Index (scores range from zero to one, with higher values indicating worse social functioning), at endpoint (12 weeks) (very low-certainty evidence). Neither of the studies included in this comparison measured the other primary outcomes: aggression; reconviction; global/state functioning; or adverse events. Nortriptyline (antidepressant) versus placebo One study (20 participants) reported no evidence of a difference between nortriptyline (25 to 75 mg/day) and placebo on mean global state/functioning scores (nortriptyline = 0.3; placebo = 0.7), assessed with the Symptom Check List-90 (SCL-90) Global Severity Index (GSI; mean of subscale scores, ranging from zero to four, with higher scores indicating greater severity of symptoms), at endpoint (six months) in men with alcohol dependency (very low-certainty evidence). The study measured side effects but did not report data on adverse events for the AsPD subgroup. The study did not measure aggression, reconviction or social functioning. Bromocriptine (dopamine agonist) versus placebo One study (18 participants) reported no evidence of difference between bromocriptine (15 mg/day) and placebo on mean global state/functioning scores (bromocriptine = 0.4; placebo = 0.7), measured with the GSI of the SCL-90 at endpoint (six months) (very low-certainty evidence). The study did not provide data on adverse effects, but reported that 12 patients randomised to the bromocriptine group experienced severe side effects, five of whom dropped out of the study in the first two days due to nausea and severe flu-like symptoms (very low-certainty evidence). The study did not measure aggression, reconviction and social functioning. Amantadine (dopamine agonist) versus placebo The study in this comparison did not measure any of the primary outcomes.
AUTHORS' CONCLUSIONS
The evidence summarised in this review is insufficient to draw any conclusion about the use of pharmacological interventions in the treatment of antisocial personality disorder. The evidence comes from single, unreplicated studies of mostly older medications. The studies also have methodological issues that severely limit the confidence we can draw from their results. Future studies should recruit participants on the basis of having AsPD, and use relevant outcome measures, including reconviction.
Topics: Adult; Aggression; Alcohol-Related Disorders; Amantadine; Antisocial Personality Disorder; Anxiety; Bromocriptine; Desipramine; Female; Humans; Male; Middle Aged; Nortriptyline; Phenytoin; Placebos; Psychotropic Drugs; Randomized Controlled Trials as Topic
PubMed: 32880105
DOI: 10.1002/14651858.CD007667.pub3 -
Neurodegenerative Disease Management Dec 2020Fatigue is a debilitating symptom of multiple sclerosis (MS) affecting at least 75% of patients. Amantadine has been tested for MS-related fatigue treatment but... (Meta-Analysis)
Meta-Analysis
Fatigue is a debilitating symptom of multiple sclerosis (MS) affecting at least 75% of patients. Amantadine has been tested for MS-related fatigue treatment but efficacy and safety remain unclear. We performed a systematic review and meta-analysis of qualified literatures searched until 30 April 2020. A total of 11 clinical trials were included. The meta-analysis revealed improvement of MS-related fatigue with amantadine treatment using the patients' subjective responses and validated fatigue scales. Amantadine is the most studied drug that has shown improvement of MS-related fatigue, with mild side effects and good tolerability. Larger studies using a standard measurement for MS-related fatigue are recommended to improve the quality of evidence. Safety and efficacy on long-term use needs further investigation.
Topics: Amantadine; Fatigue; Female; Humans; Male; Multiple Sclerosis
PubMed: 33012266
DOI: 10.2217/nmt-2020-0030 -
Journal of Parkinson's Disease 2021Many studies on Parkinson's disease (PD) patients affected by Coronavirus-disease-2019 (COVID-19) were recently published. However, the small sample size of infected...
BACKGROUND
Many studies on Parkinson's disease (PD) patients affected by Coronavirus-disease-2019 (COVID-19) were recently published. However, the small sample size of infected patients enrolled in most studies did not allow to draw robust conclusions on the COVID-19 impact in PD.
OBJECTIVE
We aimed to assess whether the prevalence and outcome of COVID-19 in PD patients are different from those observed in the general population.
METHODS
We conducted a systematic review of studies reporting data on PD patients with a diagnosis of COVID-19 (PD-COVID+). We extracted prevalence, clinical-demographic data, outcome, and mortality. We also analyzed risk or protective factors based on comparisons between PD-COVID+ and control populations with PD without COVID-19 or without PD with COVID-19.
RESULTS
We included 16 studies reporting on a total of 11,325 PD patients, 1,061 with a confirmed diagnosis of COVID-19. The median infection prevalence ranged from 0.6% to 8.5%. PD-COVID+ patients had a median age of 74 and a disease duration of 9.4 years. Pooling all PD-COVID+ patients from included studies, 28.6% required hospitalization, 37.1% required levodopa dose increasing, and 18.9% died. The case fatality was higher in PD-COVID+ patients than the general population, with longer PD duration as a possible risk factor for worse outcome. Amantadine and vitamin D were proposed as potential protective factors.
CONCLUSION
Available studies indicate a higher case fatality in PD patients affected by COVID-19 than the general population. Conversely, current literature does not definitively clarify whether PD patients are more susceptible to get infected. The potential protective role of vitamin D and amantadine is intriguing but deserves further investigation.
Topics: Antiparkinson Agents; COVID-19; Case-Control Studies; Humans; Levodopa; Parkinson Disease; Vitamin D; COVID-19 Drug Treatment
PubMed: 33749619
DOI: 10.3233/JPD-202463 -
Journal of Alzheimer's Disease : JAD 2023Alzheimer's disease (AD) is the most common type of dementia, causing progressive decline of memory, thinking, and behavior, impairing daily functioning. Early AD (eAD)...
BACKGROUND
Alzheimer's disease (AD) is the most common type of dementia, causing progressive decline of memory, thinking, and behavior, impairing daily functioning. Early AD (eAD) includes mild cognitive impairment (MCI) due to AD and mild AD dementia.
OBJECTIVE
The aim of this study was to investigate symptomatic treatment prevalence and treatment patterns in eAD.
METHODS
Embase, MEDLINE, and EBM Reviews were searched in November 2021 for observational studies reporting symptomatic treatment patterns in eAD. The range of patients receiving treatment was collated. Risk of bias was assessed using the Joanna Briggs Institute (JBI) prevalence tool. Two independent reviewers screened the records, one performed data extraction and quality assessment while a second checked.
RESULTS
Twenty-one studies (prospective and retrospective cohorts, cross-sectional studies, and a survey) were included. Population size ranged from 23 to 2,028. Worldwide, 18 to 35% of patients diagnosed with MCI due to AD received any AChE inhibitor (three studies; n = 631), 7 to 8% memantine (two studies; n = 229), and 9% combination therapy (one study; n = 402). Patients receiving no treatment ranged from 41 to 54% (two studies; n = 733). Worldwide, in mild AD dementia patients, 13 to 89% received any AChE inhibitor (six studies; n = 3,715), 1 to 21% memantine (five studies, n = 3,527), and 0.4 to 39% combination therapy (four studies, n = 3,018). Patients receiving no treatment ranged from 9 to 26% (five studies, n = 4,073).
CONCLUSION
Limitations in reporting led to unclear risk of bias. The results reveal a pattern of use of symptomatic treatment in eAD beyond approved labels and highlights the opportunity for new consensus guidelines to inform clinical practice.
Topics: Humans; Alzheimer Disease; Memantine; Prospective Studies; Cross-Sectional Studies; Retrospective Studies; Dementia; Cognitive Dysfunction; Disease Progression
PubMed: 36404542
DOI: 10.3233/JAD-220471 -
Headache Sep 2021The purpose of this systematic review is to assess the efficacy and safety of memantine for the prophylactic treatment of episodic migraine.
OBJECTIVE
The purpose of this systematic review is to assess the efficacy and safety of memantine for the prophylactic treatment of episodic migraine.
BACKGROUND
Migraine is a prevalent chronic disease with significant costs to the health care system. Although various prophylactic treatment options are available, these medications have limitations based on efficacy, potential side effects, and patient preference. Memantine is an N-methyl-d-aspartate receptor antagonist used in dementia treatment that may have potential benefit for migraine prophylaxis.
METHODS
A systematic search of PubMed, Embase, and CENTRAL databases was conducted to identify relevant published studies through December 2020 using the search terms: migraine disorders, migraine, headache disorders, or headache and memantine. Studies selected for the systematic review included prospective, interventional designs and evaluated memantine for prophylaxis of migraine. Animal studies, case reports, abstracts, review articles, protocols without results, and studies not written in English were excluded. Data were extracted using a standardized systematic process and included author, publication date, study design, sample size, patient characteristics, treatment regimen, clinical efficacy outcomes, and adverse drug effects.
RESULTS
Four articles were identified for inclusion representing two prospective open-label studies and two randomized, double-blind trials, evaluating 183 patients on memantine overall. A reduction in number of migraine days and headache severity were shown in all four studies in the participants treated with memantine. The most common adverse effects included somnolence, sedation, and nausea, none of which were severe.
CONCLUSION
The studies in this review establish that memantine has the potential for use as a treatment option for episodic migraine. Additional long-term studies using an active comparator would be useful to further elucidate its role.
Topics: Excitatory Amino Acid Antagonists; Humans; Memantine; Migraine Disorders; Outcome Assessment, Health Care; Receptors, N-Methyl-D-Aspartate
PubMed: 34352118
DOI: 10.1111/head.14186 -
Frontiers in Pharmacology 2023Opioid-induced hyperalgesia (OIH) is an adverse event of prolonged opioid use that increases pain intensity. The optimal drug to prevent these adverse effects is still...
Opioid-induced hyperalgesia (OIH) is an adverse event of prolonged opioid use that increases pain intensity. The optimal drug to prevent these adverse effects is still unknown. We aimed to conduct a network meta-analysis to compare different pharmacological interventions for preventing the increase in postoperative pain intensity caused by OIH. Several databases were searched independently for randomized controlled trials (RCTs) comparing various pharmacological interventions to prevent OIH. The primary outcomes were postoperative pain intensity at rest after 24 h and the incidence of postoperative nausea and vomiting (PONV). Secondary outcomes included pain threshold at 24 h after surgery, total morphine consumption over 24 h, time to first postoperative analgesic requirement, and shivering incidence. In total, 33 RCTs with 1711 patients were identified. In terms of postoperative pain intensity, amantadine, magnesium sulphate, pregabalin, dexmedetomidine, ibuprofen, flurbiprofen plus dexmedetomidine, parecoxib, parecoxib plus dexmedetomidine, and S (+)-ketamine plus methadone were all associated with milder pain intensity than placebo, with amantadine being the most effective (SUCRA values = 96.2). Regarding PONV incidence, intervention with dexmedetomidine or flurbiprofen plus dexmedetomidine resulted in a lower incidence than placebo, with dexmedetomidine showing the best result (SUCRA values = 90.3). Amantadine was identified as the best in controlling postoperative pain intensity and non-inferior to placebo in the incidence of PONV. Dexmedetomidine was the only intervention that outperformed placebo in all indicators. https://www.crd.york.ac. uk/prospero/display_record.php?, CRD42021225361.
PubMed: 37426819
DOI: 10.3389/fphar.2023.1199794 -
The Cochrane Database of Systematic... Oct 2019Lidocaine, mexiletine, tocainide, and flecainide are local anesthetics which give an analgesic effect when administered orally or parenterally. Early reports described... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lidocaine, mexiletine, tocainide, and flecainide are local anesthetics which give an analgesic effect when administered orally or parenterally. Early reports described the use of intravenous lidocaine or procaine to relieve cancer and postoperative pain. Interest reappeared decades later when patient series and clinical trials reported that parenteral lidocaine and its oral analogs tocainide, mexiletine, and flecainide relieved neuropathic pain in some patients. With the recent publication of clinical trials with high quality standards, we have reviewed the use of systemic lidocaine and its oral analogs in neuropathic pain to update our knowledge, to measure their benefit and harm, and to better define their role in therapy.
OBJECTIVES
To evaluate pain relief and adverse effect rates between systemic local anesthetic-type drugs and other control interventions.
SEARCH METHODS
We searched MEDLINE (1966 through 15 May 2004), EMBASE (January 1980 to December 2002), Cancer Lit (through 15 December 2002), Cochrane Central Register of Controlled Trials (2nd Quarter, 2004), System for Information on Grey Literature in Europe (SIGLE), and LILACS, from January 1966 through March 2001. We also hand searched conference proceedings, textbooks, original articles and reviews.
SELECTION CRITERIA
We included trials with random allocation, that were double blinded, with a parallel or crossover design. The control intervention was a placebo or an analgesic drug for neuropathic pain from any cause.
DATA COLLECTION AND ANALYSIS
We collected efficacy and safety data from all published and unpublished trials. We calculated combined effect sizes using continuous and binary data for pain relief and adverse effects as primary and secondary outcome measurements, respectively.
MAIN RESULTS
Thirty-two controlled clinical trials met the selection criteria; two were duplicate articles. The treatment drugs were intravenous lidocaine (16 trials), mexiletine (12 trials), lidocaine plus mexiletine sequentially (one trial), and tocainide (one trial). Twenty-one trials were crossover studies, and nine were parallel. Lidocaine and mexiletine were superior to placebo [weighted mean difference (WMD) = -11; 95% CI: -15 to -7; P < 0.00001], and limited data showed no difference in efficacy (WMD = -0.6; 95% CI: -7 to 6), or adverse effects versus carbamazepine, amantadine, gabapentin or morphine. In these trials, systemic local anesthetics were safe, with no deaths or life-threatening toxicities. Sensitivity analysis identified data distribution in three trials as a probable source of heterogeneity. There was no publication bias.
AUTHORS' CONCLUSIONS
Lidocaine and oral analogs were safe drugs in controlled clinical trials for neuropathic pain, were better than placebo, and were as effective as other analgesics. Future trials should enroll specific diseases and test novel lidocaine analogs with better toxicity profiles. More emphasis is necessary on outcomes measuring patient satisfaction to assess if statistically significant pain relief is clinically meaningful.
Topics: Administration, Cutaneous; Anesthesia, Local; Anesthetics, Local; Humans; Neuralgia; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31684682
DOI: 10.1002/14651858.CD003345.pub2 -
The Journal of Clinical Psychiatry May 2020To examine the efficacy of pharmacologic treatments for tardive dyskinesia (TD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To examine the efficacy of pharmacologic treatments for tardive dyskinesia (TD).
DATA SOURCES
PubMed was searched on December 12, 2017, for randomized, placebo-controlled trials examining the treatment of TD using the search terms (drug-induced dyskinesia OR tardive dyskinesia) AND (psychotic disorders OR schizophrenia).
STUDY SELECTION
Studies were included if they examined tardive dyskinesia treatment as the primary outcome and were randomized and placebo-controlled trials.
DATA EXTRACTION
The effect size (standard mean difference) of improvement (compared to placebo) stratified by medication class is reported for each of the trials included in this systematic review. A meta-analysis was conducted utilizing a fixed-effects model.
RESULTS
Vitamin E was associated with significantly greater reduction in TD symptoms compared to placebo (standardized mean difference [SMD] = 0.31 ± 0.08; 95% CI, 0.16 to 0.46; z = 4.1; P < .001). There was significant evidence of publication bias in vitamin E studies (Egger test: P = .02). Shorter duration of treatment and lower dose of vitamin E were significantly associated with greater measured treatment benefit. Vitamin B₆ was associated with significantly greater reduction in TD symptoms compared to placebo (SMD = 1.41 ± 0.22; 95% CI, 0.98 to 1.85; z = 6.4; P < .001) in 2 trials conducted by the same research group. Vesicular monoamine transporter 2 (VMAT2) inhibitors demonstrated significant benefit on tardive dyskinesia symptoms compared to placebo (SMD = 0.63 ± 0.11; 95% CI, 0.41 to 0.85; z = 5.58; P < .005). Amantadine was associated with significantly greater score reduction compared to placebo (SMD = 0.46 ± 0.21; 95% CI, 0.05 to 0.87; z = 2.20; P < .05). Calcium channel blockers were not associated with significantly greater score reduction compared to placebo (SMD = 0.31 ± 0.33; 95% CI, -0.34 to 0.96; z = 0.93; P = .35).
CONCLUSIONS
Data from multiple trials suggests that VMAT2 inhibitors, vitamin E, vitamin B₆, and amantadine may be effective for the treatment of TD. Evidence of publication bias and a significant negative association of dose and duration of treatment with measured efficacy suggest that the benefits of vitamin E in TD may be overstated. Head-to-head trials are needed to compare the efficacy and cost-effectiveness of pharmacologic agents for TD.
Topics: Humans; Psychotropic Drugs; Tardive Dyskinesia
PubMed: 32459404
DOI: 10.4088/JCP.19r12798