Andrade C

References (11)

Title : How to Use Percentiles to Better Understand Standardized Mean Difference (SMD) as a Measure of Effect Size - Andrade_2023_J.Clin.Psychiatry_84_23f15028
Author(s) : Andrade C
Ref : J Clin Psychiatry , 84 : , 2023
Abstract : The standardized mean difference (SMD) is the difference between the means of a variable, expressed not in its original unit but in the unit of standard deviation (SD). SMDs of 0.2, 0.5, and 0.8 are conventionally considered to be small, medium, and large, respectively. The reader, however, obtains no real world understanding of an SMD from these adjectives. This article suggests a solution: SMDs and their 95% confidence intervals can be better understood if they are converted into percentile scores. The procedure is explained, step by step, with reference to a meta-analysis that found that cholinesterase inhibitors (ChEIs) significantly attenuated delusions and hallucinations in Alzheimer disease and Parkinson disease with SMDs that ranged from -0.08 to -0.14. After conversion of these SMDs to percentile scores, the reader is shown that the average patient in the ChEI treatment arms would have improved by just 3 to 7 percentile places relative to the average patient in the placebo arms. So, whereas the findings were statistically significant, they would perhaps be so small as to be clinically unobservable in the average patient. All that the reader needs to do to convert an SMD into a percentile score is to locate a table that presents area under the normal curve, understand how the table presents what it does, look up the SMD value in the table, and obtain the percentile score from the value in the table. The entire procedure is very easily understood and takes less than a minute, starting from locating the table through an online search to obtaining the percentile score for the SMD.
ESTHER : Andrade_2023_J.Clin.Psychiatry_84_23f15028
PubMedSearch : Andrade_2023_J.Clin.Psychiatry_84_23f15028
PubMedID: 37555679

Title : Cholinesterase Inhibitors for Delusions and Hallucinations in Alzheimer Disease and Parkinson Disease: Questionably Significant Benefits - Andrade_2023_J.Clin.Psychiatry_84_23f15009
Author(s) : Andrade C
Ref : J Clin Psychiatry , 84 : , 2023
Abstract : Delusions and hallucinations are common in Alzheimer disease (AD) and Parkinson disease (PD), especially in the later stages of illness. Antipsychotic drugs are effective in treating these psychotic symptoms but are associated with an increased risk of serious adverse events, including mortality. There is therefore a need to explore other treatment approaches. In this context, a recent individual patient data meta-analysis of 17 randomized controlled trials (RCTs) conducted in AD (12 RCTs) and PD (5 RCTs) found that the cholinesterase inhibitor (ChEI) drugs donepezil, rivastigmine, and galantamine attenuated the severity of both delusions and hallucinations in both AD and PD. Most of these trials were 24 weeks in duration. The effect sizes, expressed as standardized mean differences (SMDs), were, however, small, lying in the -0.08 to -0.14 range. These values are so small as to be perhaps clinically insignificant. When analyses were restricted to data from patients who actually had delusions and hallucinations at baseline, all effect sizes became larger, lying in the -0.13 to -0.39 range; however, after correcting for multiple hypothesis testing, only the finding for delusions in PD remained statistically significant. The meta-analysis did not provide information on what the best doses were, how long it took for improvement to become evident, and what proportion of patients showed remission from psychotic symptoms. Whereas the signal identified in this meta-analysis merits examination in appropriately designed RCTs, the findings of the meta-analysis may not much change current treatment strategies because patients with dementia would probably anyway receive a ChEI. Therefore, if psychotic symptoms persist for 24 weeks despite optimally dosed ChEI treatment, and if behavioral and psychosocial interventions do not help, clinicians may need to consider the potential benefits vs risks of other drugs, such as atypical antipsychotics and pimavanserin, in a shared decision-making process.
ESTHER : Andrade_2023_J.Clin.Psychiatry_84_23f15009
PubMedSearch : Andrade_2023_J.Clin.Psychiatry_84_23f15009
PubMedID: 37530610

Title : Reconsideration of the Benefits of Pharmacological Interventions for the Attenuation of the Cognitive Adverse Effects of Electroconvulsive Therapy - Andrade_2022_J.Clin.Psychiatry_83_22f14668
Author(s) : Andrade C
Ref : J Clin Psychiatry , 83 : , 2022
Abstract : The cognitive adverse effects (AEs) of electroconvulsive therapy (ECT) limit the wider use of the treatment. These AEs can be attenuated by changing the way ECT is administered; however, such changes may reduce the response rate, the speed of response, or both. A recent systematic review and meta-analysis identified more than a dozen pharmacologic interventions in 26 randomized controlled trials (RCTs) that sought to reduce ECT-induced cognitive AEs. Because of large differences across RCTs, only a few outcomes for a few interventions could be pooled in meta-analysis, and most pooled analyses included only 2-3 RCTs. Important findings were that acetylcholinesterase inhibitors, ketamine, memantine, and liothyronine were associated with improved global cognitive functioning at 1-14 days post-ECT. Anti-inflammatory treatments and opioid receptor antagonists were not associated with improvement in general cognitive outcome at 1-14 days post-ECT. Meta-analysis was not possible for the remaining interventions, including piracetam, melatonin, pemoline, nortriptyline, herbal agents, drugs acting on the cortisol pathway, opioid receptor antagonists, l-tryptophan, vasopressin analogs, calcium channel blockers, and others; in individual RCTs, some of these interventions attenuated some cognitive measures as some time points after ECT. Regrettably, none of the RCTs examined clinically meaningful outcomes such as subjective cognitive impairment, impairments in daily life, and persistent autobiographical memory deficits. Future research should study such clinically meaningful outcomes (rather than laboratory tests), using pharmacologic interventions, perhaps in combination, for ECT procedures that are associated with higher cognitive AE burden. A risk is that whatever attenuates ECT-induced cognitive AEs may also attenuate ECT-related therapeutic benefits.
ESTHER : Andrade_2022_J.Clin.Psychiatry_83_22f14668
PubMedSearch : Andrade_2022_J.Clin.Psychiatry_83_22f14668
PubMedID: 36198062

Title : Methylphenidate and Other Pharmacologic Treatments for Apathy in Alzheimer's Disease - Andrade_2022_J.Clin.Psychiatry_83_22f14398
Author(s) : Andrade C
Ref : J Clin Psychiatry , 83 :22f14398 , 2022
Abstract : Apathy is a common and important yet often ignored neuropsychiatric symptom of Alzheimer's disease (AD). Cholinesterase inhibitors and memantine, used to treat AD, appear ineffective against apathy. A meta-analysis of 4 randomized, placebo-controlled trials (RCTs) found that psychostimulants significantly attenuated apathy ratings in AD. However, the pooled sample size in this meta-analysis was just 156, and one of the trials was a 2-week crossover study with a large effect. A large RCT (n = 200) has now been published. This study found that methylphenidate (MPH; 20 mg/d) was superior to placebo in the attenuation of apathy scores in patients with possible or probable, mild to moderate AD; the advantage was evident by the end of the second month of treatment and remained evident to the end of 6 months. The effect size at 6 months was small (Cohen d = 0.37). In this RCT, disappointingly, MPH was not superior to placebo on secondary outcomes, including informant-rated apathy, dependence, activities of daily living, quality of life, and neurocognitive performance; caregiver burden was not formally studied. Speculatively, the psychosocial intervention provided to all participants in this RCT may have boosted response in the placebo group, thereby attenuating differences in outcomes between the MPH and placebo groups. A reasonable conclusion is that whereas MPH may attenuate the severity of apathy in patients with AD across as long as 6 months, the absence of improvements in measures of dependence, activities of daily living, and quality of life suggest that this effect of MPH on apathy may not be clinically significant. An unanswered question is whether the benefits of MPH may be clinically significant in real world practice settings in which the delivery of behavioral interventions is not feasible.
ESTHER : Andrade_2022_J.Clin.Psychiatry_83_22f14398
PubMedSearch : Andrade_2022_J.Clin.Psychiatry_83_22f14398
PubMedID: 35120284

Title : Efficacy of donepezil for the attenuation of memory deficits associated with electroconvulsive therapy - Dutta_2020_Psychiatry.Res_293_113397
Author(s) : Dutta LCB , Sarkar CP , Andrade C
Ref : Psychiatry Res , 293 :113397 , 2020
Abstract : We sought to confirm and extend the findings of studies that reported that acetylcholinesterase inhibitor drugs protect against electroconvulsive therapy (ECT)-induced cognitive impairment. We randomized 30 patients with depression (n=24) or schizophrenia (n=6) to receive either donepezil (10 mg/day; n=15) or placebo (n=15) during a fixed course of 6 thrice-weekly, modified, bifrontotemporal sine wave ECT, and for 30 days subsequently. We assessed memory using the Postgraduate Institute Memory Scale (PGI-MS) at baseline, and again at days 2, 7, and 30 after the ECT course. At baseline, memory functioning was comparable in the 2 groups. At 2 days post-ECT, memory functioning was impaired on almost all 10 subtests and on the total scale. At 30 days post-ECT, memory functioning improved to (numerically) above baseline levels on almost all subtests and on the total scale, with the bulk of the improvement evident by day 7, itself. There was no significant difference between groups in the primary outcome, improvement in PGI-MS scores between Days 2 and 30 post-ECT. On almost all subtests, also, there was no significant difference between groups. In summary, we found that donepezil (10 mg/day) did not improve memory outcomes after ECT.
ESTHER : Dutta_2020_Psychiatry.Res_293_113397
PubMedSearch : Dutta_2020_Psychiatry.Res_293_113397
PubMedID: 32835925

Title : Toxicity and Antitumor Activity of a Thiophene-Acridine Hybrid - Lisboa_2019_Molecules_25_
Author(s) : Lisboa T , Silva D , Duarte S , Ferreira R , Andrade C , Lopes AL , Ribeiro J , Farias D , Moura R , Reis M , Medeiros K , Magalhaes H , Sobral M
Ref : Molecules , 25 : , 2019
Abstract : The antitumor effects of thiophene and acridine compounds have been described; however, the clinical usefulness of these compounds is limited due to the risk of high toxicity and drug resistance. The strategy of molecular hybridization presents the opportunity to develop new drugs which may display better target affinity and less serious side effects. Herein, 2-((6-Chloro-2-methoxy-acridin-9-yl)amino)-5,6,7,8-tetrahydro-4H-cyclohepta[b]-th iophene-3-carbonitrile (ACS03), a hybrid thiophene-acridine compound with antileishmanial activity, was tested for toxicity and antitumor activity. The toxicity was evaluated in vitro (on HaCat and peripheral blood mononuclear cells) and in vivo (zebrafish embryos and acute toxicity in mice). Antitumor activity was also assessed in vitro in HCT-116 (human colon carcinoma cell line), K562 (chronic myeloid leukemic cell line), HL-60 (human promyelocytic leukemia cell line), HeLa (human cervical cancer cell line), and MCF-7 (breast cancer cell line) and in vivo (Ehrlich ascites carcinoma model). ACS03 exhibited selectivity toward HCT-116 cells (Half maximal inhibitory concentration, IC50 = 23.11 +/- 1.03 microM). In zebrafish embryos, ACS03 induced an increase in lactate dehydrogenase, glutathione S-transferase, and acetylcholinesterase activities. The LD50 (lethal dose 50%) value in mice was estimated to be higher than 5000 mg/kg (intraperitoneally). In vivo, ACS03 (12.5 mg/kg) induced a significant reduction in tumor volume and cell viability. In vivo antitumor activity was associated with the nitric oxide cytotoxic effect. In conclusion, significant antitumor activity and weak toxicity were recorded for this hybrid compound, characterizing it as a potential anticancer compound.
ESTHER : Lisboa_2019_Molecules_25_
PubMedSearch : Lisboa_2019_Molecules_25_
PubMedID: 31878135

Title : Cognitive effects with rivastigmine augmentation of risperidone: A 12-month, randomized, double-blind, placebo-controlled study in schizophrenia - Kumar_2017_Indian.J.Psychiatry_59_219
Author(s) : Kumar PNS , Mohemmedali SP , Anish PK , Andrade C
Ref : Indian J Psychiatry , 59 :219 , 2017
Abstract : OBJECTIVE: An important challenge in schizophrenia therapeutics is to develop an efficacious treatment for cognitive impairment. Acetylcholinesterase inhibitors, such as rivastigmine, have been studied for improving cognitive performance in these patients. MATERIALS AND
METHODS: Rivastigmine (uptitrated to 6 mg/day) was given as an add-on therapy to risperidone-treated stable schizophrenia patients in a randomized, double-blind, placebo-controlled design. Of 67 patients who met eligibility criteria, 55 were recruited into the study. Twenty-eight were assigned to rivastigmine and 27 to placebo. These patients completed tests of attention, executive functioning, verbal skills, verbal and visuospatial working memory, and psychomotor speed on five occasions: at baseline, and at the end of the 1st, 3rd, 6th, and 12th months.
RESULTS: The groups were similar in terms of sociodemographic profile and baseline clinical characteristics (Positive and Negative Syndrome Scale and Clinical Global Impression-Severity). Contrary to expectations, rivastigmine patients showed poorer outcomes on several cognitive measures. Rivastigmine patients experienced also more psychological as well as neurological side effects. Core psychopathology ratings, however, did not differ between rivastigmine and placebo groups.
CONCLUSIONS: Our study does not support the long-term use of rivastigmine as an augmentation agent in schizophrenia. Rivastigmine may be associated with higher incidence of psychological and neurological side effects in patients with schizophrenia.
ESTHER : Kumar_2017_Indian.J.Psychiatry_59_219
PubMedSearch : Kumar_2017_Indian.J.Psychiatry_59_219
PubMedID: 28827871

Title : Cholinesterase inhibitor treatment may double the risk of hospitalisation for bradycardia -
Author(s) : Andrade C
Ref : Evid Based Ment Health , 13 :91 , 2010
PubMedID: 20682831

Title : Pharmacological attenuation of electroconvulsive therapy--induced cognitive deficits: theoretical background and clinical findings - Pigot_2008_J.ECT_24_57
Author(s) : Pigot M , Andrade C , Loo C
Ref : J Ect , 24 :57 , 2008
Abstract : Electroconvulsive therapy (ECT) is an effective treatment for depression and other psychiatric disorders. However, the practice of ECT is limited by memory and nonmemory cognitive adverse effects. Technical strategies such as a preference for unilateralover bilateral ECT and low-dose over high-dose stimulation reduce these cognitive adverse effects but may also be associated with lesser treatment efficacy or slower treatment response. This article therefore reviews the use of psychopharmacological agents in the attenuation of ECT-induced cognitive deficits with 2 objectives: the identification of implicated mechanisms and the identification of putative efficacy in both animal and human studies. Drugs examined include N-methyl-d-aspartate receptor antagonists, cyclooxygenase inhibitors, calcium channel blockers, cholinesterase inhibitors, glucocorticoid receptor antagonists, thyroid hormones, opioid antagonists, NO donors, nootropic agents, and other medications. Although the clinical data at present are sparse and inconsistent, many recently opened lines of research improve our understanding of the mechanisms involved as well as suggest possible avenues for the testing of new treatments with the potential to attenuate the cognitive adverse effects of ECT.
ESTHER : Pigot_2008_J.ECT_24_57
PubMedSearch : Pigot_2008_J.ECT_24_57
PubMedID: 18379337

Title : Correlation of time course of blood cholinesterase activity and toxic manifestations of acute methylparathion in antidote treated rats - Venkataraman_1994_Ind.J.Physiol.Pharmacol_38_214
Author(s) : Venkataraman BV , Rani MA , Andrade C , Joseph T
Ref : Indian Journal of Physiology & Pharmacology , 38 :214 , 1994
Abstract : Study was conducted to find out the correlation between red blood cholinesterase (RBC ChE) and plasma butyryl cholinesterase (BCHE) activities and toxic signs of oral methylparathion (MPT) and their recovery pattern with or without atropine treatment in female rats. Enzyme activity was estimated before and after an oral dose of MPT (7.5 mg/kg-1) at various time intervals upto 120 hr. Antidote groups received atropine (10 mg/kg-1, i.p.), either alone or with diazepam (2.5 mg/kg-1, i.p.), at the onset of toxic signs. Inhibition of enzyme activity served as definite index of acute toxicity of MPT. RBC ChE activity correlated with the intensity of toxic signs in no-antidote rats, while in atropine treated groups, there was no correlation. BCHE levels did not correlate with toxic signs in any of the groups except in the fatal group. The resynthesis of both the enzymes was complete in 120 hr study and did not synchronize with the recovery pattern of animals from toxic signs. Compared to BCHE, RBC ChE activity was found to be a more sensitive indicator for the diagnosis of severity of MPT toxicity.
ESTHER : Venkataraman_1994_Ind.J.Physiol.Pharmacol_38_214
PubMedSearch : Venkataraman_1994_Ind.J.Physiol.Pharmacol_38_214
PubMedID: 7814086

Title : Improved colorimetric method for cholinesterase activity - Venkataraman_1993_Ind.J.Physiol.Pharmacol_37_82
Author(s) : Venkataraman BV , Rani MA , Andrade C , Joseph T
Ref : Indian Journal of Physiology & Pharmacology , 37 :82 , 1993
Abstract : A modified colorimetric method for the estimation of cholinesterase activity has been worked out using two different substrates, acetylthiocholine iodide for total cholinesterase and a specific substrate, butyrylthiocholine iodide for pseudocholinesterase in the same sample. This is a modification of the method described by Voss and Sachsse (1970) wherein acetylthiocholine iodide was used for both total and pseudo cholinesterase activities. The pseudocholinesterase obtained with acetylthiocholine iodide was significantly higher (P < 0.0001) than that with butyrylthiocholine iodide either in whole blood or serum samples. Acetylthiocholine iodide while reacting with pseudocholinesterase in serum or plasma samples might also be interacting with the small quantities of acetylcholinesterase present. It is therefore suggested that butyrylthiocholine iodide and acetylthiocholine iodide may be used to determine pseudocholinesterase and total cholinesterase activities respectively. The use of two substrates with a few more alterations in the experimental conditions increased the validity of this simple and rapid colorimetric method.
ESTHER : Venkataraman_1993_Ind.J.Physiol.Pharmacol_37_82
PubMedSearch : Venkataraman_1993_Ind.J.Physiol.Pharmacol_37_82
PubMedID: 8449554