dextromethorphan and Dementia

To determine the most efficacious and acceptable treatments of agitation in dementia.. MEDLINE, EMBASE, PsycINFO, CENTRAL and clinicaltrials.gov were searched up to 7 February 2017. Two independent reviewers selected randomized controlled trials (RCTs) of treatments to alleviate agitation in people with all-types dementia. Data were extracted using standardized forms and study quality was assessed using the revised Cochrane Risk of Bias Tool for RCTs. Data were pooled using meta-analysis. The primary outcome, efficacy, was 8-week response rates defined as a 50% reduction in baseline agitation score. The secondary outcome was treatment acceptability defined as treatment continuation for 8 weeks.. Thirty-six RCTs comprising 5585 participants (30.9% male; mean ± standard deviation age, 81.8 ± 4.9 years) were included. Dextromethorphan/quinidine [odds ratio (OR) 3.04; 95% confidence interval (CI), 1.63-5.66], risperidone (OR 1.96; 95% CI, 1.49-2.59) and selective serotonin reuptake inhibitors as a class (OR 1.61; 95% CI, 1.02-2.53) were found to be significantly more efficacious than placebo. Haloperidol appeared less efficacious than nearly all comparators. Most treatments had noninferior treatment continuation compared to placebo, except oxcarbazepine, which was inferior. Findings were supported by subgroup and sensitivity analyses.. Risperidone, serotonin reuptake inhibitors as a class and dextromethorphan/quinidine demonstrated evidence of efficacy for agitation in dementia, although findings for dextromethorphan/quinidine were based on a single RCT. Our findings do not support prescribing haloperidol due to lack of efficacy, or oxcarbazepine due to lack of acceptability. The decision to prescribe should be based on comprehensive consideration of the benefits and risks, including those not evaluated in this meta-analysis.

Topics: Antipsychotic Agents; Dementia; Dextromethorphan; Drug Combinations; Humans; Network Meta-Analysis; Psychometrics; Psychomotor Agitation; Quinidine; Randomized Controlled Trials as Topic; Risperidone; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Treatment Outcome

Phase 3 trials supporting dextromethorphan/quinidine (DM/Q) use as a treatment for pseudobulbar affect (PBA) were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). The PRISM II study provides additional DM/Q experience with PBA secondary to dementia, stroke, or traumatic brain injury (TBI).. Participants in this open-label, multicenter, 90-day trial received DM/Q 20/10 mg twice daily. The primary outcome was the Center for Neurologic Study-Lability Scale (CNS-LS), assessing change in PBA episode frequency and severity. The CNS-LS final visit score was compared to baseline (primary analysis) and to the response in a previously conducted placebo-controlled trial with DM/Q in patients with ALS or MS. Secondary outcomes included change in PBA episode count and Clinical Global Impression of Change with respect to PBA as rated by a clinician (CGI-C) and by the patient or caregiver (PGI-C).. The study enrolled 367 participants with PBA secondary to dementia, stroke, or TBI. Mean (standard deviation [SD]) CNS-LS score improved significantly from 20.4 (4.4) at baseline to 12.8 (5.0) at Day 90/Final Visit (change, -7.7 [6.1]; P < .001, 95 % CI: -8.4, -7.0). This magnitude of improvement was consistent with DM/Q improvement in the earlier phase-3, placebo-controlled trial (mean [95 % CI] change from baseline, -8.2 [-9.4, -7.0]) and numerically exceeds the improvement seen with placebo in that study (-5.7 [-6.8, -4.7]). Reduction in PBA episode count was 72.3 % at Day 90/Final Visit compared with baseline (P < .001). Scores on CGI-C and PGI-C showed that 76.6 and 72.4 % of participants, respectively, were "much" or "very much" improved with respect to PBA. The most frequently occurring adverse events (AEs) were diarrhea (5.4 %), headache (4.1 %), urinary tract infection (2.7 %), and dizziness (2.5 %); 9.8 % had AEs that led to discontinuation. Serious AEs were reported in 6.3 %; however, none were considered treatment related.. DM/Q was shown to be an effective and well-tolerated treatment for PBA secondary to dementia, stroke, or TBI. The magnitude of PBA improvement was similar to that reported in patients with PBA secondary to ALS or MS, and the adverse event profile was consistent with the known safety profile of DM/Q.. Clinicaltrials.gov, NCT01799941, registered on 25 February 2013.

Topics: Aged; Brain Injuries, Traumatic; Dementia; Dextromethorphan; Drug Administration Schedule; Drug Combinations; Excitatory Amino Acid Antagonists; Female; Humans; Male; Middle Aged; Pseudobulbar Palsy; Quinidine; Severity of Illness Index; Stroke; Treatment Outcome

The present work aimed to investigate the induction of circadian rhythm dysfunction and dementia upon chronic exposure to light-light and its reversal by melatonin in Wistar rats. Animals underwent different light-dark conditions, viz., light/dark (LD), light/light (LL), and dark/dark (DD) in respective groups for 4 months. Melatonin 0.5 mg/kg s.c., dextromethorphan 50 μg/100 g s.c., and mifepristone 25 μg/100 g s.c. were given once a day. Chronic LL and DD conditions significantly increased brain glutamate and cortisol levels. The LL period caused a deficit in spatial memory, working memory, decision making, and exploration of novel objects, compared to LD animals. A significant (

Topics: Animals; Biomarkers; Circadian Rhythm; Dementia; Dextromethorphan; Glutamic Acid; Hydrocortisone; Light; Melatonin; Mifepristone; N-Methylaspartate; Oxidative Stress; Rats; Rats, Wistar

In 2010, the US Food and Drug Administration (FDA) approved a combination of dextromethorphan hydrobromide and quinidine sulfate for the treatment of pseudobulbar affect after studies in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This medication, however, may be commonly prescribed in patients with dementia and/or Parkinson disease (PD).. To investigate the prescribing patterns of dextromethorphan-quinidine, including trends in associated costs.. This population-based cohort study of patients prescribed dextromethorphan-quinidine used data from 2 commercial insurance databases, Optum Clinformatics Data Mart and Truven Health MarketScan. The Medicare Part D Prescription Drug Program data set was used to evaluate numbers of prescriptions and total reported spending by the Centers for Medicare & Medicaid Services. Patients were included if they were prescribed dextromethorphan-quinidine from October 29, 2010, when the drug was approved, through March 1, 2017, for Optum and December 31, 2015, for Truven. Data were analyzed from December 1, 2017, through August 1, 2018.. The proportion of patients prescribed dextromethorphan-quinidine with a diagnosis of MS, ALS, or dementia and/or PD, as well as the number of patients with a history of heart failure (a contraindication for the drug).. In the commercial health care databases, 12 858 patients filled a prescription for dextromethorphan-quinidine during the study period. Mean (SD) age was 66.0 (18.5) years, 66.7% were women, and 13.3% had a history of heart failure. Combining results from both databases, few patients had a diagnosis of MS (8.4%) or ALS (6.8%); most (57.0%) had a diagnosis of dementia and/or PD. In the Medicare Part D database, the number of patients prescribed dextromethorphan-quinidine increased 15.3-fold, from 3296 in 2011 to 50 402 in 2016. Reported spending by Centers for Medicare & Medicaid Services on this medication increased from $3.9 million in 2011 to $200.4 million in 2016.. Despite approval by the FDA for pseudobulbar affect based on studies of patients with ALS or MS, dextromethorphan-quinidine appears to be primarily prescribed for patients with dementia and/or PD.

Topics: Aged; Amyotrophic Lateral Sclerosis; Dementia; Dextromethorphan; Drug Combinations; Excitatory Amino Acid Antagonists; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Parkinson Disease; Pseudobulbar Palsy; Quinidine; United States; United States Food and Drug Administration

Dextromethorphan (DM)/quinidine (Q) is an approved treatment for pseudobulbar affect (PBA) based on trials in amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness and tolerability for PBA secondary to dementia, stroke, or traumatic brain injury; dementia cohort results are reported.. This was an open-label, multicenter, 90 day trial; patients received DM/Q 20/10 mg twice daily. Primary outcome was change in Center for Neurologic Study-Lability Scale (CNS-LS) score. Secondary outcomes included PBA episode count and Clinical and Patient/Caregiver Global Impression of Change scores with respect to PBA (CGI-C/PGI-C).. 134 patients were treated. CNS-LS improved by a mean (SD) of 7.2 (6.0) points at Day 90/Endpoint (P<.001) vs. baseline. PBA episodes were reduced 67.7% (P<.001) vs. baseline; global measures showed 77.5% CGI-C and 76.5% PGI-C "much"/"very much" improved. Adverse events included headache (7.5%), urinary tract infection (4.5%), and diarrhea (3.7%); few patients dropped out for adverse events (10.4%).. DM/Q significantly reduced PBA symptoms in patients with dementia; reported adverse events were consistent with the known safety profile of DM/Q. Trial Registration clinicaltrials.gov identifier: NCT01799941.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Dementia; Dementia, Vascular; Dextromethorphan; Diarrhea; Drug Combinations; Excitatory Amino Acid Antagonists; Female; Frontotemporal Dementia; Headache; Humans; Lewy Body Disease; Male; Middle Aged; Pseudobulbar Palsy; Quinidine; Urinary Tract Infections

The concomitant use of herb and prescription medications is increasing globally. Herb-drug interactions are therefore a clinically important problem. Yokukansan (YKS), a Japanese traditional herbal medicine, is one of the most frequently used herbal medicines. It is effective for treating the behavioral and psychological symptoms of dementia. We investigated the potential effects of YKS on drug-metabolizing enzyme activities in humans. An open-label repeat-dose study was conducted in 26 healthy Japanese male volunteers (age: 22.7±2.3 years) with no history of smoking. An 8-h urine sample was collected after a 150-mg dose of caffeine and a 30-mg dose of dextromethorphan before and after the administration of YKS (2.5 g, twice a day for 1 week). The activities of cytochrome P450 (CYP) 1A2, CYP2D6, CYP3A, xanthine oxidase (XO) and N-acetyltransferase 2 (NAT2) were assessed based on the urinary metabolic indices of caffeine and dextromethorphan, and the urinary excretion ratio of 6β-hydroxycortisol to cortisol. There were no statistically significant differences in the activities of the examined enzymes before or after the 7-d administration of YKS. Although further studies assessing the influence of YKS on the pharmacokinetics and pharmacodynamics of the substrates of the drug-metabolizing enzymes are needed to verify the present results, YKS is unlikely that a pharmacokinetic interaction will occur with concomitantly administered medications that are predominantly metabolized by the CYP1A2, CYP2D6, CYP3A, XO and NAT2.

Topics: Adult; Arylamine N-Acetyltransferase; Behavior; Caffeine; Cytochrome P-450 Enzyme System; Dementia; Dextromethorphan; Drug Interactions; Drugs, Chinese Herbal; Healthy Volunteers; Humans; Hydrocortisone; Male; Middle Aged; Xanthine Oxidase