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The Cochrane Database of Systematic... Oct 2016This is an updated version of the original Cochrane review published in Issue 12, 2011. Phantom limb pain (PLP) is pain that arises in the missing limb after amputation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane review published in Issue 12, 2011. Phantom limb pain (PLP) is pain that arises in the missing limb after amputation and can be severe, intractable, and disabling. Various medications have been studied in the treatment of phantom pain. There is currently uncertainty in the optimal pharmacologic management of PLP.
OBJECTIVES
This review aimed to summarise the evidence of effectiveness of pharmacologic interventions in treating PLP.
SEARCH METHODS
For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), MEDLINE, and Embase for relevant studies. We ran the searches for the original review in September 2011 and subsequent searches for this update up to April 2016. We sought additional studies from clinical trials databases and reference lists of retrieved papers.
SELECTION CRITERIA
We included randomised and quasi-randomised trials studying the effectiveness of pharmacologic interventions compared with placebo, another active treatment, or no treatment, in established PLP. We considered the following outcomes: change in pain intensity, function, sleep, depression or mood, quality of life, adverse events, treatment satisfaction, and withdrawals from the study.
DATA COLLECTION AND ANALYSIS
We independently assessed issues of study quality and extracted efficacy and adverse event data. Due to the wide variability in the studies, we did not perform a meta-analysis for all the interventions and outcomes, but attempted to pool the results of some studies where possible. We prepared a qualitative description and narrative summary of results. We assessed clinical heterogeneity by making qualitative comparisons of the populations, interventions, outcomes/outcome measures, and methods.
MAIN RESULTS
We added only one new study with 14 participants to this updated review. We included a 14 studies (10 with low risk of bias and 4 with unclear risk of bias overall) with a total of 269 participants. We added another drug class, botulinum neurotoxins (BoNTs), in particular botulinum toxin A (BoNT/A), to the group of medications reviewed previously. Our primary outcome was change in pain intensity. Most studies did not report our secondary outcomes of sleep, depression or mood, quality of life, treatment satisfaction, or withdrawals from the study.BoNT/A did not improve phantom limb pain intensity during the six months of follow-up compared with lidocaine/methylprednisolone.Compared with placebo, morphine (oral and intravenous) was effective in decreasing pain intensity in the short term with reported adverse events being constipation, sedation, tiredness, dizziness, sweating, voiding difficulty, vertigo, itching, and respiratory problems.The N-methyl D-aspartate (NMDA) receptor antagonists ketamine (versus placebo; versus calcitonin) and dextromethorphan (versus placebo), but not memantine, had analgesic effects. The adverse events of ketamine were more serious than placebo and calcitonin and included loss of consciousness, sedation, hallucinations, hearing and position impairment, and insobriety.The results for gabapentin in terms of pain relief were conflicting, but combining the results favoured treatment group (gabapentin) over control group (placebo) (mean difference -1.16, 95% confidence interval -1.94 to -0.38; 2 studies). However, gabapentin did not improve function, depression score, or sleep quality. Adverse events experienced were somnolence, dizziness, headache, and nausea.Compared with an active control benztropine mesylate, amitriptyline was not effective in PLP, with dry mouth and dizziness as the most frequent adverse events based on one study.The findings for calcitonin (versus placebo; versus ketamine) and local anaesthetics (versus placebo) were variable. Adverse events of calcitonin were headache, vertigo, drowsiness, nausea, vomiting, and hot and cold flushes. Most of the studies were limited by their small sample sizes.
AUTHORS' CONCLUSIONS
Since the last version of this review, we identified another study that added another form of medical therapy, BoNTs, specifically BoNT/A, to the list of pharmacologic interventions being reviewed for clinical efficacy in phantom limb pain. However, the results of this study did not substantially change the main conclusions. The short- and long-term effectiveness of BoNT/A, opioids, NMDA receptor antagonists, anticonvulsants, antidepressants, calcitonins, and local anaesthetics for clinically relevant outcomes including pain, function, mood, sleep, quality of life, treatment satisfaction, and adverse events remain unclear. Based on a small study, BoNT/A (versus lidocaine/methylprednisolone) does not decrease phantom limb pain. Morphine, gabapentin, and ketamine demonstrate favourable short-term analgesic efficacy compared with placebo. Memantine and amitriptyline may not be effective for PLP. However, results must be interpreted with caution, as they were based mostly on a small number of studies with limited sample sizes that varied considerably and also lacked long-term efficacy and safety outcomes. The direction of efficacy of calcitonin, local anaesthetics, and dextromethorphan needs further clarification. Overall, the efficacy evidence for the reviewed medications is thus far inconclusive. Larger and more rigorous randomised controlled trials are needed for us to reach more definitive conclusions about which medications would be useful for clinical practice.
Topics: Analgesics, Opioid; Anesthetics; Anticonvulsants; Antidepressive Agents; Botulinum Toxins, Type A; Calcitonin; Humans; Neurotoxins; Phantom Limb; Randomized Controlled Trials as Topic; Receptors, N-Methyl-D-Aspartate
PubMed: 27737513
DOI: 10.1002/14651858.CD006380.pub3 -
Neurology and Therapy Dec 2018Drug-induced parkinsonism (DIP) and tardive dyskinesia (TD) are stigmatizing movement disorders associated with exposure to dopamine receptor blocking agents such as... (Review)
Review
INTRODUCTION
Drug-induced parkinsonism (DIP) and tardive dyskinesia (TD) are stigmatizing movement disorders associated with exposure to dopamine receptor blocking agents such as antipsychotics, but they differ in their pathophysiology and clinical management. Treatment for one may worsen the other, and there are important diagnostic clues that assist in making an accurate assessment and instituting a rational treatment plan.
METHODS
A literature review was executed to identify articles relating to the presentation, pathophysiology, epidemiology, and management of DIP and TD.
RESULTS
DIP and TD prevalence estimates range from approximately 20 to 35% among antipsychotic users, but may be higher in select populations. DIP often presents as bradykinesia and rigidity, as well as rhythmic tremor, and the majority of cases appear within hours to weeks of initiation of therapy with an antipsychotic, or if dosage of the antipsychotic is increased. TD onset is delayed, typically appearing after at least 3 months or longer of treatment, and patients will commonly present with involuntary, abnormal facial movements such as lip smacking, puckering, chewing, or tongue protrusion. DIP often resolves with discontinuation of the causative agent, but TD may be permanent. Broadly, proposed mechanisms underlying these adverse events include decreased dopamine concentrations in the nigrostriatal pathway of the striatum and dopamine hypersensitivity, for DIP and TD, respectively. Pharmacologic treatment approaches for DIP have commonly included anticholinergic agents such as benztropine; however, anticholinergic medications can make TD worse. Switching the antipsychotic medication to one with lower propensity for DIP is an option for some patients. Amantadine, a non-anticholinergic agent used for the treatment of DIP, may be preferred in patients with comorbid DIP and TD. In TD, treatment options include the new reversible vesicular monoamine 2 transporter inhibitors, valbenazine and deutetrabenazine.
CONCLUSIONS
It is important for clinicians to be able to recognize DIP and TD in patients using antipsychotics so that they can minimize the impact of these adverse events on their patients' quality of life. Accurate diagnosis will drive the selection of the correct treatment. Plain language summary available for this article.
PubMed: 30027457
DOI: 10.1007/s40120-018-0105-0 -
Biomedicines Feb 2022(1) Background: Over the last decade, misuse and diversion of medications has appeared to be increasingly concerning phenomena, including a range of different molecules.... (Review)
Review
(1) Background: Over the last decade, misuse and diversion of medications has appeared to be increasingly concerning phenomena, including a range of different molecules. As current knowledge on the abuse of centrally acting anticholinergics is limited, the aim of the present study is to review the relevant published data, focusing on the following molecules: benztropine, biperiden, scopolamine, orphenadrine, and benzhexol/trihexyphenidyl (THP). (2) Methods: A systematic literature review was carried out using Pubmed, Scopus, and Web of Science databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Research methods were registered on PROSPERO (CRD42021257293). (3) Results: A total of 48 articles, including case reports, surveys, and retrospective case series analyses, were included. Most articles focused on benzhexol/THP ( = 25), and benztropine ( = 4). The routes of administration were mostly oral, and macrodoses together concomitant illicit drugs, e.g., cocaine, have been recorded. Toxidromes included both physical (e.g., tachycardia, tachypnoea, dilatated pupils, dry skin, urinary retention, ataxia, etc.) and psychiatric symptoms (e.g., anxiety, agitation, delirium, etc.). Fatal outcomes were very rare but reported. (4) Conclusion: Results from the present study show that anticholinergic misusing issues are both widespread worldwide and popular. Considering the potential adverse effects associated, healthcare professionals should be vigilant and monitor eventual misusing issues.
PubMed: 35203563
DOI: 10.3390/biomedicines10020355 -
Biomedicines Mar 2023Gastric cancer (GC) ranked as the fifth most incident cancer in 2020 and the third leading cause of cancer mortality. Surgical prevention and radio/chemotherapy are the...
Gastric cancer (GC) ranked as the fifth most incident cancer in 2020 and the third leading cause of cancer mortality. Surgical prevention and radio/chemotherapy are the main approaches used in GC treatment, and there is an urgent need to explore and discover innovative and effective drugs to better treat this disease. A new strategy arises with the use of repurposed drugs. Drug repurposing coupled with drug combination schemes has been gaining interest in the scientific community. The main objective of this project was to evaluate the therapeutic effects of alternative drugs in GC. For that, three GC cell lines (AGS, MKN28, and MKN45) were used and characterized. Cell viability assays were performed with the reference drug 5-fluororacil (5-FU) and three repurposed drugs: natamycin, nitazoxanide, and benztropine. Nitazoxanide displayed the best results, being active in all GC cells. Further, 5-FU and nitazoxanide in combination were tested in MKN28 GC cells, and the results obtained showed that nitazoxanide alone was the most promising drug for GC therapy. This work demonstrated that the repurposing of drugs as single agents has the ability to decrease GC cell viability in a concentration-dependent manner.
PubMed: 36979779
DOI: 10.3390/biomedicines11030799 -
Pain Physician Jan 2021Diabetic peripheral neuropathy (DPN) is a most common devitalizing complication of diabetes mellitus, which is primarily characterized by sensory loss, paresthesia,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic peripheral neuropathy (DPN) is a most common devitalizing complication of diabetes mellitus, which is primarily characterized by sensory loss, paresthesia, prickling, pain, or allodynia.
OBJECTIVES
To evaluate the relative efficacy and safety of the interventions used in the DPN pain management and rank their order.
STUDY DESIGN
A systematic review and Bayesian network meta-analysis (NMA).
METHODS
Randomized, controlled trials were identified through a comprehensive, systematic literature exploration, primarily utilizing the PubMed, EMBASE, Ovid, and Cochrane Library databases. The efficacy and safety outcomes consist of the proportion of patients reporting either 30% or 50% pain reduction and overall withdrawal or withdrawal due to adverse drug events, respectively. Effect estimates from Bayesian NMA were presented as odds ratio (OR) with 95% credible intervals (CrI). Heterogeneity and convergence were assessed by using I2 and deviation information criteria. The risk of bias was evaluated by using Pedro Scale.
RESULTS
A total of 3,246 potentially relevant trials were identified and screened, finally 43 trials consisting of 7,877 randomized patients met the inclusion criteria. Statistically significant treatment difference for 50% pain reduction was reported for duloxetine vs. placebo (OR: 2.50; CrI: 1.62-3.91), mirogabalin vs. placebo (OR: 3.25; CrI: 1.16-9.35), pregabalin vs. placebo (OR: 2.33; CrI: 1.69-3.27), duloxetine vs. carbamazepine (OR: 3.37; CrI: 1.07-10.90), mirogabalin vs. carbamazepine (OR: 4.39; CrI: 1.01-19.63), mirogabalin vs. lamotrigine (OR: 4.05: CrI: 1.07-15.77), pregabalin vs. lamotrigine (OR: 2.90, CrI: 1.19-7.22) and pregabalin vs. nortriptyline (OR: 4.10, CrI: 1.13-5.28). Nortriptyline reported the highest possibility of achieving 30% and 50% pain reduction. Sodium valproate and benztropine reported the highest probability of total withdrawals and withdrawals due to adverse drug events, respectively.
LIMITATION
The different follow-up time of the included studies can result in the variation of intended results.
CONCLUSION
Nortriptyline reported the advantage relative to other drugs in achieving 30% and 50% pain reduction from the baseline. Gabapentin reported a significance of 50% pain reduction relative to placebo.
Topics: Bayes Theorem; Diabetic Neuropathies; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 33400429
DOI: No ID Found -
British Journal of Clinical Pharmacology Feb 2023Olanzapine pamoate is an intramuscular depot injection for the treatment of schizophrenia. Approximately 1.4% of patients develop a serious adverse event called...
Olanzapine pamoate is an intramuscular depot injection for the treatment of schizophrenia. Approximately 1.4% of patients develop a serious adverse event called post-injection delirium/sedation syndrome (PDSS), characterised by drowsiness, anticholinergic and extrapyramidal symptoms. The objective is to investigate olanzapine PDSS presentations including clinical features and treatment approach. This is a retrospective review of olanzapine PDSS patients from three toxicology units and the NSW Poisons Information Centre between 2017 and 2022. Adult patients were included if they had intramuscular olanzapine then developed PDSS criteria. Clinical symptoms, treatment, timing and length of symptoms were extracted into a preformatted Excel database. There were 18 patients included in the series, with a median age of 49 years (interquartile range [IQR]: 38-58) and male predominance (89%). Median onset time post injection was 30 min (IQR: 11-38). PDSS symptoms predominate with drowsiness, confusion and dysarthria. Median length of symptoms was 24 h (IQR: 20-54). Most common treatment included supportive care without any pharmacological intervention (n = 10), benzodiazepine (n = 4) and benztropine (n = 3). In one case, bromocriptine and physostigmine followed by oral rivastigmine were given to manage antidopaminergic and anticholinergic symptoms respectively. This proposed treatment combination could potentially alleviate some of the symptoms but needs further studies to validate the findings. In conclusion, this case series supports the characterisation of PDSS symptomology predominantly being anticholinergic with similar onset (<1 h) and duration (<72 h). Bromocriptine is proposed to manage PDSS if patients develop severe dopamine blockade and physostigmine followed by rivastigmine for anticholinergic delirium.
Topics: Adult; Humans; Male; Middle Aged; Female; Olanzapine; Antipsychotic Agents; Bromocriptine; Physostigmine; Rivastigmine; Benzodiazepines; Delirium
PubMed: 36349832
DOI: 10.1111/bcp.15588