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Prospective Randomized Trial Evaluating Ketamine for Adult Bronchoscopy.
Fruchter, O, Manevich, Y, Carmi, U, Rozengarten, D, Kramer, MR
Journal of bronchology & interventional pulmonology. 2017;(4):279-284
Abstract
BACKGROUND AND OBJECTIVES Ketamine has been used in pediatric flexible fiberoptic bronchoscopy (FFB). Its efficacy and safety for sedation of adults undergoing FFB has not been thoroughly investigated, and, consequently, it is not used by most interventional bronchoscopists. We aimed to evaluate the safety and efficacy of sedation for FFB under ketamine-propofol-midazolam (KPM) compared with the fentanyl-propofol-midazolam (FPM) regimen. MATERIALS AND METHODS This was a prospective randomized trial of adult patients (n=80) undergoing FFB, randomized to receive sedation with either KPM (n=39) or FPM (n=41). Vital signs including transcutaneous carbon dioxide tension (TcPCO2) were continuously monitored. Sedation-related complications and interventions to maintain respiratory and hemodynamic stability were compared. Both operator and patient were blinded to the sedation regimen used. The operator's and patient's satisfaction from sedation were assessed following recovery. RESULTS Maximal intraprocedural TcPCO2 values and minimal oxygen saturation did not differ significantly between the KPM and FPM groups (63.2±11.4 mm Hg vs. 61.1±7.2 mm Hg) and (77.1%±12.5% vs. 81.8%±12.0%), respectively. No significant differences were noted between the KPM and FPM groups with respect to sedation-related respiratory or hemodynamic complications. The operator's and patient's satisfaction from sedation was similar between the groups. CONCLUSIONS Ketamine is as safe and effective as fentanyl for adult analgesia and sedation during FFB. In light of this observation and the fact that ketamine does not cause hemodynamic suppression, like most sedative agents, and is a potent bronchodilator, should encourage its more widespread use for adult sedation during FFB.
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Mood and neuropsychological effects of different doses of ketamine in electroconvulsive therapy for treatment-resistant depression.
Zhong, X, He, H, Zhang, C, Wang, Z, Jiang, M, Li, Q, Zhang, M, Huang, X
Journal of affective disorders. 2016;:124-30
Abstract
BACKGROUND Treatment-resistant depression (TRD) is a growing clinical challenge. Electroconvulsive therapy (ECT) is an effective tool for TRD treatment. However, there remains a subset of patients who do not respond to this treatment with common anesthetic agent. Ketamine, a noteworthy anesthetic agent, has emerged as an augmentation to enhance the antidepressant efficacy of ECT. Trials of i.v. ketamine in TRD indicated dose-related mood enhancing efficacy. We aimed to explore anesthetic and subanesthetic concentrations of ketamine in ECT for TRD with respect to their impact on mood and neuropsychological effects. METHODS Ninety TRD patients (36 males, 54 females; average age, 30.6 years old) were randomly assigned to receive either ketamine (0.8mg/kg) (n=30), subanesthetic ketamine (0.5mg/kg) plus propofol (0.5mg/kg) (n=30) or propofol (0.8mg/kg) (n=30) as an anesthetic and underwent 8 ECT sessions. The primary outcome measures were the 17-item Hamilton Depression Rating Scale (HDRS-17), cognitive assessments and seizure parameters. RESULTS The ketamine group had an earlier improvement in HDRS-17, longer seizure duration, lower electric quantity, a higher remission rate, and a lower degree of executive cognitive impairment compared to the ketamine+propofol and propofol groups. The ketamine+propofol group showed earlier improvement in the HDRS-17, a longer seizure duration and a different seizure energy index when compared to the propofol group. LIMITATIONS The postoperative dissociative side effect was not assessed. CONCLUSIONS Both anesthetic and subanesthetic concentrations of ketamine have rapid mood enhancing actions in ECT for TRD, while anesthetic concentrations results in larger magnitudes of antidepression and cognitive protection. ECT with ketamine anesthesia might be an optimized therapy for patients with TRD.
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Rapid antidepressant effects of repeated doses of ketamine compared with electroconvulsive therapy in hospitalized patients with major depressive disorder.
Ghasemi, M, Kazemi, MH, Yoosefi, A, Ghasemi, A, Paragomi, P, Amini, H, Afzali, MH
Psychiatry research. 2014;(2):355-61
Abstract
Accumulating evidence suggests that N-methyl-d-aspartate receptor (NMDAR) antagonists (e.g. ketamine) may exert rapid antidepressant effects in MDD patients. In the present study, we evaluated the rapid antidepressant effects of ketamine compared with the electroconvulsive therapy (ECT) in hospitalized patients with MDD. In this blind, randomized study, 18 patients with DSM-IV MDD were divided into two groups which received either three intravenous infusions of ketamine hydrochloride (0.5 mg/kg over 45 min) or ECT on 3 test days (every 48 h). The primary outcome measure was the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS), which was used to rate overall depressive symptoms at baseline, 24 h after each treatment, 72 h and one week after the last (third) ketamine or ECT. Within 24 h, depressive symptoms significantly improved in subjects receiving the first dose of ketamine compared with ECT group. Compared to baseline level, this improvement remained significant throughout the study. Depressive symptoms after the second dose ketamine was also lower than the second ECT. This study showed that ketamine is as effective as ECT in improving depressive symptoms in MDD patients and have more rapid antidepressant effects compared with the ECT.
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The efficacy of gabapentin versus stabilization splint in management of sleep bruxism.
Madani, AS, Abdollahian, E, Khiavi, HA, Radvar, M, Foroughipour, M, Asadpour, H, Hasanzadeh, N
Journal of prosthodontics : official journal of the American College of Prosthodontists. 2013;(2):126-31
Abstract
PURPOSE This study aimed to determine if the use of gabapentin is more efficacious than a stabilization splint with regard to the intensity of masseter muscle contractions and/or sleep quality for patients experiencing sleep bruxism (SB). MATERIALS AND METHODS Twenty patients with SB participated in this clinical study. They were randomly divided into two treatment groups: stabilization splint group (n = 10) and gabapentin group (n = 10). The first polysomnographic examination was performed before the beginning of the experiment for all the participants. At the end of a 2-month period of stabilization splint therapy or gabapentin usage, a second polysomnographic recording was made. RESULTS Statistically significant reductions in the number of SB episodes per hour and per night, bruxism time index, total duration of SB episodes per night and number of SB episodes in stages NR I and NR II (p < 0.05) were observed in both groups after treatment. Both treatments significantly reduced the mean intensity of masseter muscle contractions during SB episodes. Moreover, the participants treated with gabapentin showed a significant improvement in total sleep time, slow wave sleep (stage III), and sleep efficiency (p < 0.05). CONCLUSIONS Gabapentin could be an effective treatment modality in SBs, especially in those with poor sleep quality.
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Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial.
Brown, PD, Pugh, S, Laack, NN, Wefel, JS, Khuntia, D, Meyers, C, Choucair, A, Fox, S, Suh, JH, Roberge, D, et al
Neuro-oncology. 2013;(10):1429-37
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Abstract
BACKGROUND To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT). METHODS Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine (20 mg/d), within 3 days of initiating radiotherapy for 24 weeks. Serial standardized tests of cognitive function were performed. RESULTS Of 554 patients who were accrued, 508 were eligible. Grade 3 or 4 toxicities and study compliance were similar in the 2 arms. There was less decline in delayed recall in the memantine arm at 24 weeks (P = .059), but the difference was not statistically significant, possibly because there were only 149 analyzable patients at 24 weeks, resulting in only 35% statistical power. The memantine arm had significantly longer time to cognitive decline (hazard ratio 0.78, 95% confidence interval 0.62-0.99, P = .01); the probability of cognitive function failure at 24 weeks was 53.8% in the memantine arm and 64.9% in the placebo arm. Superior results were seen in the memantine arm for executive function at 8 (P = .008) and 16 weeks (P = .0041) and for processing speed (P = .0137) and delayed recognition (P = .0149) at 24 weeks. CONCLUSIONS Memantine was well tolerated and had a toxicity profile very similar to placebo. Although there was less decline in the primary endpoint of delayed recall at 24 weeks, this lacked statistical significance possibly due to significant patient loss. Overall, patients treated with memantine had better cognitive function over time; specifically, memantine delayed time to cognitive decline and reduced the rate of decline in memory, executive function, and processing speed in patients receiving WBRT. RTOG 0614, ClinicalTrials.gov number CT00566852.
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The NMDA antagonist ketamine and the 5-HT agonist psilocybin produce dissociable effects on structural encoding of emotional face expressions.
Schmidt, A, Kometer, M, Bachmann, R, Seifritz, E, Vollenweider, F
Psychopharmacology. 2013;(1):227-39
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RATIONALE Both glutamate and serotonin (5-HT) play a key role in the pathophysiology of emotional biases. Recent studies indicate that the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine and the 5-HT receptor agonist psilocybin are implicated in emotion processing. However, as yet, no study has systematically compared their contribution to emotional biases. OBJECTIVES This study used event-related potentials (ERPs) and signal detection theory to compare the effects of the NMDA (via S-ketamine) and 5-HT (via psilocybin) receptor system on non-conscious or conscious emotional face processing biases. METHODS S-ketamine or psilocybin was administrated to two groups of healthy subjects in a double-blind within-subject placebo-controlled design. We behaviorally assessed objective thresholds for non-conscious discrimination in all drug conditions. Electrophysiological responses to fearful, happy, and neutral faces were subsequently recorded with the face-specific P100 and N170 ERP. RESULTS Both S-ketamine and psilocybin impaired the encoding of fearful faces as expressed by a reduced N170 over parieto-occipital brain regions. In contrast, while S-ketamine also impaired the encoding of happy facial expressions, psilocybin had no effect on the N170 in response to happy faces. CONCLUSION This study demonstrates that the NMDA and 5-HT receptor systems differentially contribute to the structural encoding of emotional face expressions as expressed by the N170. These findings suggest that the assessment of early visual evoked responses might allow detecting pharmacologically induced changes in emotional processing biases and thus provides a framework to study the pathophysiology of dysfunctional emotional biases.
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Validity, significance, strengths, limitations, and evidentiary value of real-world clinical data for combination therapy in Alzheimer's disease: comparison of efficacy and effectiveness studies.
Atri, A, Rountree, SD, Lopez, OL, Doody, RS
Neuro-degenerative diseases. 2012;(1-4):170-4
Abstract
BACKGROUND Randomized controlled efficacy trials (RCTs), the scientific gold standard, are required for regulatory approval of Alzheimer's disease (AD) interventions, yet provide limited information regarding real-world therapeutic effectiveness. OBJECTIVE To compare the nature of evidence regarding the combination of approved AD treatments from RCTs versus long-term observational controlled studies (LTOCs). METHODS Comparisons of strengths, limitations, and evidence level for monotherapy [cholinesterase inhibitor (ChEI) or memantine] and combination therapy (ChEI + memantine) in RCTs versus LTOCs. RESULTS RCTs examined highly selected populations over months. LTOCs collected data across multiple AD stages in large populations over many years. RCTs and LTOCs show similar patterns favoring combination over monotherapy over placebo/no treatment. Long-term combination therapy compared to monotherapy reduced cognitive and functional decline and delayed time to nursing home admission. Persistent treatment was associated with slower decline. While LTOCs used control groups, adjusted for multiple covariates, had higher external validity, and favorable ethical, practical and cost considerations, their limitations included potential selection bias due to lack of placebo comparisons and randomization. CONCLUSIONS Naturalistic LTOCs provide complementary long-term level II evidence to complement level I evidence from short-term RCTs regarding therapeutic effectiveness in AD that may otherwise be unobtainable. A coordinated strategy/consortium to pool LTOC data from multiple centers to estimate long-term comparative effectiveness, risks/benefits, and costs of AD treatments is needed.
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A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression.
Diazgranados, N, Ibrahim, L, Brutsche, NE, Newberg, A, Kronstein, P, Khalife, S, Kammerer, WA, Quezado, Z, Luckenbaugh, DA, Salvadore, G, et al
Archives of general psychiatry. 2010;(8):793-802
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CONTEXT Existing therapies for bipolar depression have a considerable lag of onset of action. Pharmacological strategies that produce rapid antidepressant effects-for instance, within a few hours or days-would have an enormous impact on patient care and public health. OBJECTIVE To determine whether an N-methyl-D-aspartate-receptor antagonist produces rapid antidepressant effects in subjects with bipolar depression. DESIGN A randomized, placebo-controlled, double-blind, crossover, add-on study conducted from October 2006 to June 2009. SETTING Mood Disorders Research Unit at the National Institute of Mental Health, Bethesda, Maryland. Patients Eighteen subjects with DSM-IV bipolar depression (treatment-resistant). INTERVENTIONS Subjects maintained at therapeutic levels of lithium or valproate received an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days 2 weeks apart. The Montgomery-Asberg Depression Rating Scale was used to rate subjects at baseline and at 40, 80, 110, and 230 minutes and on days 1, 2, 3, 7, 10, and 14 postinfusion. MAIN OUTCOME MEASURES Change in Montgomery-Asberg Depression Rating Scale primary efficacy measure scores. RESULTS Within 40 minutes, depressive symptoms significantly improved in subjects receiving ketamine compared with placebo (d = 0.52, 95% confidence interval [CI], 0.28-0.76); this improvement remained significant through day 3. The drug difference effect size was largest at day 2 (d = 0.80, 95% CI, 0.55-1.04). Seventy-one percent of subjects responded to ketamine and 6% responded to placebo at some point during the trial. One subject receiving ketamine and 1 receiving placebo developed manic symptoms. Ketamine was generally well tolerated; the most common adverse effect was dissociative symptoms, only at the 40-minute point. CONCLUSION In patients with treatment-resistant bipolar depression, robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist.
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Crossover trial of gabapentin and memantine as treatment for acquired nystagmus.
Thurtell, MJ, Joshi, AC, Leone, AC, Tomsak, RL, Kosmorsky, GS, Stahl, JS, Leigh, RJ
Annals of neurology. 2010;(5):676-80
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We conducted a masked, crossover, therapeutic trial of gabapentin (1,200mg/day) versus memantine (40 mg/day) for acquired nystagmus in 10 patients (aged 28-61 years; 7 female; 3 multiple sclerosis [MS]; 6 post-stroke; 1 post-traumatic). Nystagmus was pendular in 6 patients (4 oculopalatal tremor; 2 MS) and jerk upbeat, hemi-seesaw, torsional, or upbeat-diagonal in each of the others. For the group, both drugs reduced median eye speed (p < 0.001), gabapentin by 32.8% and memantine by 27.8%, and improved visual acuity (p < 0.05). Each patient improved with 1 or both drugs. Side effects included unsteadiness with gabapentin and lethargy with memantine. Both drugs should be considered as treatment for acquired forms of nystagmus.
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Improvement of negative and positive symptoms in treatment-refractory schizophrenia: a double-blind, randomized, placebo-controlled trial with memantine as add-on therapy to clozapine.
de Lucena, D, Fernandes, BS, Berk, M, Dodd, S, Medeiros, DW, Pedrini, M, Kunz, M, Gomes, FA, Giglio, LF, Lobato, MI, et al
The Journal of clinical psychiatry. 2009;(10):1416-23
Abstract
BACKGROUND Glutamate deregulation may be involved in the neuropathology of schizophrenia, mainly through N-methyl-d-aspartate (NMDA) receptor dysfunction. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease, acts as a weak nonselective NMDA receptor antagonist. The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to clozapine in patients with refractory schizophrenia. METHOD In this double-blind, placebo-controlled study, outpatients with refractory schizophrenia according to DSM-IV clinical criteria were randomly assigned, from March 2005 to February 2008, to receive either 20 mg/d memantine (n = 10) or placebo (n = 11), in addition to clozapine, for 12 weeks. The primary outcome measure was the total score on the 18-item Brief Psychiatry Rating Scale (BPRS) and BPRS subscales of positive and negative symptoms. Secondary outcomes were global severity of disease as measured by the Clinical Global Impressions scale (CGI), cognition as assessed by the Mini-Mental State Examination (MMSE), and extrapyramidal symptoms as assessed by the Simpson-Angus Scale (SAS). RESULTS Twenty-one participants completed the study and were used in the analysis. Significant improvement (P < .01) on the total BPRS score, its subscales of positive (effect size [ES] = -1.38) and negative (ES = -3.33) symptoms, the CGI score (ES = 1.56), and the MMSE score was observed with memantine as compared with placebo. No significant changes in extrapyramidal symptoms were observed. CONCLUSIONS Memantine add-on to clozapine therapy was associated with improvement in negative and positive symptoms in refractory schizophrenia patients. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00757978.