dextromethorphan and Psychomotor-Agitation

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

Agitation is common and distressing in patients with Alzheimer-type dementia, but safe, effective treatments remain elusive. Psychological treatments are first-line options, but they have limited efficacy. Off-label psychotropic medications are frequently used, but they also have limited effectiveness, and their use may have harmful side effects, including death. Areas covered: This review discusses the history leading to the conception of AVP-786 (deuterated (d6)-dextromethorphan/quinidine), its pharmacokinetic and pharmacodynamic profiles and safety issues, together with an overview of recent clinical trials. Data were found in the medical literature, in US and EU clinical trial registries and in information provided by the manufacturer. Expert opinion: AVP-786 is one of six investigational compounds in recent phase III clinical development for agitation in Alzheimer disease (AD). Quinidine and deuteration appear to prolong dextromethorphan's plasma half-life and facilitate brain penetration. The FDA granted fast-track designation to AVP-786 and allowed use of data generated on dextromethorphan-quinidine (AVP-923, Nuedexta®) for regulatory filings. AVP-923 reduced agitation in AD and was well tolerated in a phase II RCT that included more than 200 patients. A phase III clinical development program of AVP-786 for AD agitation was recently initiated. This program is expected to start generating results in July 2018.

Topics: Alzheimer Disease; Animals; Brain; Deuterium; Dextromethorphan; Drug Combinations; Humans; Psychomotor Agitation; Quinidine; Randomized Controlled Trials as Topic; Tissue Distribution; Treatment Outcome

Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are associated with significant negative outcomes for patients and their caregivers. Agitation, one of the most distressing NPS, lacks well-established long-term interventions that are both effective and safe. While non-pharmacological interventions are the suggested first-line treatment, it isn't effective in managing symptoms for every patient. In such cases, clinicians turn to the use of pharmacological interventions. Traditionally, these interventions consist of off-label use of antipsychotics, sedative/hypnotics, anxiolytics, acetylcholinesterase inhibitors, memantine and antidepressants, where the efficacy doesn't necessarily outweigh the associated risks.. Gains made in understanding the neurobiological mechanisms underlying agitation have fueled several recent clinical trials. A comprehensive literature search for published articles evaluating pharmacologic interventions for agitation in AD was done. A review of some of these clinical trials was completed: dextromethorphan/quinidine, scyllo-inositol, brexpiprazole, prazosin, cannabinoids, dronabinol and citalopram show promise in treating agitation.. Neurobiological findings and enhanced trial designs have re-ignited the area of pharmacological treatment of NPS. Although further research is needed to fully determine the safety, tolerability and efficacy of these treatments, the mission to finding effective treatments for NPS such as agitation in patients with dementia is well underway.

Topics: Alzheimer Disease; Cannabinoid Receptor Agonists; Cannabinoids; Citalopram; Clinical Trials, Phase III as Topic; Dextromethorphan; Drug Combinations; Humans; Psychomotor Agitation; Quinidine; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Topics: Antitussive Agents; Dextromethorphan; Humans; Psychomotor Agitation

Topics: Aged; Aggression; Cannabinoid Receptor Agonists; Cytochrome P-450 CYP2D6 Inhibitors; Dextromethorphan; Dronabinol; Drug Therapy, Combination; Excitatory Amino Acid Antagonists; Humans; Lewy Body Disease; Male; Paroxetine; Psychomotor Agitation

Topics: Alzheimer Disease; Dextromethorphan; Female; Humans; Male; Psychomotor Agitation; Quinidine

Topics: Alzheimer Disease; Dextromethorphan; Female; Humans; Male; Psychomotor Agitation; Quinidine

Topics: Alzheimer Disease; Dextromethorphan; Female; Humans; Male; Psychomotor Agitation; Quinidine

Topics: Alzheimer Disease; Dextromethorphan; Female; Humans; Male; Psychomotor Agitation; Quinidine

A patient presented with agitation, paranoia, and psychosis following ingestion of dextromethorphan, propoxyphene, and hydrocodone, a previously unreported combination. Symptoms resolved with antipsychotics and cessation of offending drugs. The pharmacodynamics of dextromethorphan and the opioids, including drug interactions are discussed, and several potential mechanisms for the production of the patient's symptoms are proposed.

Topics: Analgesics, Opioid; Dextromethorphan; Drug Interactions; Female; Humans; Middle Aged; Psychomotor Agitation; Psychotic Disorders