Chittaranjan Andrade

Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms.

BACKGROUND It is generally believed that selective serotonin reuptake inhibitor (SSRI) drugs increase the risk of abnormal bleeding and decrease the risk of ischemic heart disease events by blocking the uptake of serotonin into platelets, leading to an impairment in the platelet hemostatic response. OBJECTIVE To perform a detailed qualitative review of existing literature on the association of abnormal bleeding with the use of SSRIs. DATA SOURCES We conducted a PubMed search during June 2009 using the search terms antidepressants and SSRIs (including the names of individual SSRIs: fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, and escitalopram) in association with bleeding, platelets, hemostasis, nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, antiplatelet drugs, proton pump inhibitors, peptic ulcer, premenstrual dysphoric disorder, menstruation, pregnancy, postpartum hemorrhage, surgery, tooth extraction, dental bleeding, stroke, ischemic heart disease, and other terms related to the field. We then searched the reference lists of identified studies. STUDY SELECTION We provide a qualitative discussion of all studies that would inform clinicians about the mechanisms of bleeding and bleeding risks associated with these drugs in different clinical contexts. RESULTS Epidemiologic studies show that SSRI use is associated with roughly doubled odds of upper gastrointestinal (GI) bleeding; bleeding at other sites has been less commonly described, as has a possibly increased risk of bleeding associated with surgical procedures. The risk of SSRI-associated GI bleeding is increased with the concurrent use of NSAIDs, anticoagulants, and antiplatelet agents and is decreased by concurrent proton pump inhibitors. The risk of bleeding is increased in patients with cirrhosis of the liver or liver failure. There is, curiously, little literature on use of SSRIs and menstrual or postpartum blood loss. Selective serotonin reuptake inhibitors appear protective against ischemic heart disease events. The data are too limited to allow interpretations about influences on ischemic and hemorrhagic stroke. CONCLUSIONS On the basis of the findings of our literature search, we suggest that SSRI-induced increase in gastric acid secretion may explain the GI bleeding risk and that SSRI-related effects on platelet reactivity, endothelial reactivity, and inflammatory markers may explain the ischemic heart disease protective effect. Because the absolute risk of GI bleeds with SSRIs is low, precautions are probably necessary only in high-risk patients, such as those with acid-peptic disease and those with a history of bleeds. We discuss management issues and areas for future research.

Continuation and maintenance ECT: a review of recent research.

Continuation and maintenance electroconvulsive therapy (ECT) is used to reduce the risk for relapse and recurrence of illness in patients who fare poorly with continuation and maintenance medication regimens. Despite the potential value of these ECT schedules, both are relatively neglected in clinical practice. This article therefore reviews the last decade of research on the subject. Although the research comprises mostly single and multiple case reports and small open studies, continuation and maintenance ECT does emerge as a safe and effective treatment for relapse- and recurrence-prone patients who have responded to a course of ECT.

A survey of the practice of electroconvulsive therapy in Asia.

Objective: To describe a comprehensive survey of the practice of electroconvulsive therapy (ECT) in Asia. Method: Between 2001 and 2003, a 29-item questionnaire was sent to 977 psychiatric facilities in 45 Asian countries. Results: Completed questionnaires were returned by 334 (34.2%) institutions in 29 (64.4%) countries. Electroconvulsive therapy was available in 257 institutions in 23 countries. During the year before the survey, 39,875 patients (62% men) received a mean of 7.1 ECT treatments. Most patients (73.1%) were 18 to 44 years old; few were younger than 18 years (6.0%) or older than 64 years (4.4%). Indications for ECT were schizophrenia (41.8%), major depression (32.4%), mania (14.0%), catatonia (6.9%), drug abuse (1.8%), dysthymia (1.6%), and others. Brief-pulse ECT devices were used in only 115 (58.4%) of 197 institutions. Routine electroencephalographic monitoring was conducted in only 59 (23.0%) institutions. Bilateral electrode placement was invariable in 202 (78.6%) institutions. Unmodified ECT was administered to 22,194 (55.7%) patients at 141 (54.9%) institutions in 14 countries. Continuation ECT was available in only 115 (44.7%) institutions in 17 countries. No institution had a formal ECT training program. Conclusions: The practice of ECT in Asia may seem suboptimal: schizophrenia, not depression, is the most common indication; most institutions offer sine-wave ECT; unmodified ECT is commonly administered; bilateral electrode placement is invariable in most institutions; electroencephalographic monitoring is uncommon; continuation ECT is infrequent; and no formal training in ECT is available. We speculate that the suboptimal practices reflect felt needs and ground realities in standards of medical care in developing countries rather than a misuse of ECT.

Suicide: An Indian perspective

Suicide is the third leading cause of death among young adults worldwide. There is a growing recognition that prevention strategies need to be tailored to the region-specific demographics of a country and to be implemented in a culturally-sensitive manner. This review explores the historical, epidemiological and demographic factors of suicide in India and examines the strategies aimed at the prevention of suicide. There has been an increase in the rates of suicide in India over the years, although trends of both increases and decline in suicide rates have been present. Distinct from global demographic risk factors, In India, marital status is not necessarily protective and the female: male ratio in the rate of suicide is higher. The motives and modes of suicide are also distinct from western countries. Preventive strategies implemented at a community level and identifying vulnerable individuals maybe more effective than global strategies.

Once- to twice-daily, 3-year domiciliary maintenance transcranial direct current stimulation for severe, disabling, clozapine-refractory continuous auditory hallucinations in schizophrenia.

Background Some patients with schizophrenia suffer from continuous auditory hallucinations that are refractory to antipsychotic medications. Methods Transcranial direct current stimulation (tDCS) was used to treat a 24-year-old female schizophrenia patient who had severe, clozapine-refractory, continuous, psychosocially and cognitively disabling auditory hallucinations. The tDCS cathode was placed midway between T3 and P3, and the anode over F3, in the 10-20 electroencephalogram electrode positioning system. Results Once daily, 20-minute tDCS sessions at 1-mA intensity produced noticeable improvement within a week: cognitive and psychosocial functioning improved, followed by attenuation in the experience of hallucinations. There was greater than 90% self-reported improvement within 2 months. Benefits accelerated when the current was raised to 3 mA; treatment duration was increased to 30-minute sessions, and session frequency was increased to twice daily. The patient improved from a psychosocially vegetative state to near-normal functioning. Once- to twice-daily domiciliary tDCS was continued across nearly 3 years and is still ongoing. Benefits attenuated or were even lost when alternate day session spacing was attempted, or when electrode positioning was changed; benefits were regained when the original stimulation protocol was reintroduced. There was confirmation of benefit in 2 separate on-off-on situations, which occurred inadvertently and under blinded conditions. There were no adverse events attributable to tDCS. Conclusions This is the first report in literature of the safe and effective use of daily to twice-daily, domiciliary, 30-min, 1- to 3-mA tDCS sessions across nearly 3 years for the treatment of continuous, disabling, clozapine-refractory auditory hallucinations in schizophrenia. Key learning points emerging from this case are presented and discussed.

The prevention and treatment of cognitive decline and dementia: An overview of recent research on experimental treatments

The prevention and treatment of cognitive impairment in the elderly has assumed increasing importance in an aging population. This article presents a qualitative review of recent research on experimental interventions for the prevention and treatment of mild cognitive impairment and Alzheimers disease in elderly subjects. Interventions addressed range from lifestyle measures to pharmacological treatments. Epidemiological studies suggest that dietary measures, physical exercise, and mental activity may reduce the risk of cognitive impairment and Alzheimers disease in elderly subjects. Statins may protect against incident dementia, and lithium may convey similar benefits to bipolar patients. Ginkgo appears ineffective as a primary preventive measure. Donepezil but not Vitamin E may benefit persons with mild cognitive impairment. Experimental treatments potentially useful for Alzheimers disease include dimebon, PBT2 and etanercept; the safety and efficacy of the Alzheimers vaccine remains to be proven, and growth hormone secretagogue and tarenflurbil are likely ineffective. Herbal treatments merit study in elderly subjects with cognitive syndromes.

Feasibility, Safety, and Efficacy of the Combination of D -Serine and Computerized Cognitive Retraining in Schizophrenia: An International Collaborative Pilot Study

The combination of pharmacotherapy and cognitive retraining (CRT) for the cognitive deficits of schizophrenia may be more efficacious than either approach alone, but this has not yet been tested. This study evaluated the feasibility, safety, tolerability, and efficacy of 12 weeks of D-serine, combined with CRT in the treatment of cognitive deficits in schizophrenia at two academic sites in parallel, in India and the United States. In a randomized, partial double-blind, placebo-controlled, parallel-group design, 104 schizophrenia subjects (US site=22, Indian site=82) were randomized to: (1) D-serine (30 mg/kg)+CRT (5 h/week), (2) D-serine+control CRT, (3) CRT+placebo D-serine, and (4) placebo+control CRT. Completion rates were 84 and 100% in the Indian and US samples, respectively. On various outcome measures of safety and tolerability, the interventions were well tolerated. D-Serine and CRT did not show any significant effect on the Global Cognitive Index, although both interventions showed differential site effects on individual test performance. CRT resulted in a significant improvement in Verbal Working Memory, and a trend toward improvement in Attention/Vigilance. This is the first study to demonstrating the feasibility, safety, and tolerability of combination pharmacotherapy and CRT in a multicenter international clinical trial. These preliminary findings provide support for future studies using higher doses of D-serine that have been shown to be efficacious or other pharmacotherapies, along with the newer cognitive remediation strategies that are individualized and that target basic information processing.

Memory protective effect of indomethacin against electroconvulsive shock-induced retrograde amnesia in rats

BACKGROUND Nonsteroidal antiinflammatory drugs (NSAIDs) have been suggested to retard cognitive decrements in patients with Alzheimers disease. We postulated that NSAIDs also may protect acute disruption of memory. METHODS We studied the effect of indomethacin (4 mg/kg/day) administered daily for 19 days on retrograde amnesia induced by two once-daily electroconvulsive shocks in rats. RESULTS Indomethacin produced statistically significant prolongation of recall latency in a passive avoidance task using a step-down apparatus. CONCLUSIONS Our study suggests that NSAIDs may prevent memory disruption through other mechanisms apart from attenuating chronic inflammation. In patients receiving electroconvulsive therapy, as in those diagnosed with Alzheimers disease, antiinflammatory drugs may hold promise in the attenuation of cognitive impairments.

ECT for treatment-resistant schizophrenia: a response from the far East to the UK. NICE report.

Background: There is controversy about the proper place of electroconvulsive therapy (ECT) in the management of the schizophrenic patient, and the important issues related to theory and practice remain to be resolved, especially in the context of medication-resistant schizophrenia. Method: We briefly summarize existing research in the field. We next use a narrative method to describe in a single article the large body of research from Thailand that, during the past decade, has systematically studied issues related to the use of ECT in medication-resistant schizophrenia. We integrate the findings of the Thai efforts with the results of other research and consider the theoretical and practical importance of the reviewed work. Results: The ECT treatment data validate a BRPS cutoff of 25 as a definition of recovery in patients with treatment-refractory schizophrenia, and a cutoff of 37 as a definition of subsequent relapse or suitability for entry into a treatment protocol. A 3-week post-ECT stabilization period identifies patients who maintain improvement and who can be legitimately considered to have sustained response to ECT. Clinical characteristics of such responders and symptoms responsive to ECT are described. Higher stimulus dose hastens response to ECT but does not improve responsiveness. Continuation ECT (C-ECT) combined with maintenance-neuroleptic medication is associated with better treatment outcome than either treatment alone. The combined treatment also improves quality of life and functioning in the long-term. Conclusions: These findings convey several useful thoughts for research into and the practice of ECT for schizophrenia.

Pharmacological Attenuation of Electroconvulsive Therapy-Induced Cognitive Deficits : Theoretical Background and Clinical Findings

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.