piperidines and Mental-Disorders

Since 1998, when the laboratory of Medicinal Pharmacology was established in the Graduate School of Pharmaceutical Sciences, Osaka University, I have been interested in psychopharmacological research topics. During this period, we identified a number of novel regulatory mechanisms that control the prefrontal dopamine system through functional interaction between serotonin1A and dopamine D2 receptors or between serotonin1A and σ1 receptors. Our findings suggest that strategies that enhance the prefrontal dopamine system may have therapeutic potential in the treatment of psychiatric disorders. We also found that environmental factors during development strongly impact the psychological state in adulthood. Furthermore, we clarified the pharmacological profiles of the acetylcholinesterase inhibitors donepezil, galantamine, and rivastigmine, providing novel insights into their mechanisms of action. Finally, we developed the female encounter test, a novel method for evaluating motivation in mice. This simple method should help advance future psychopharmacological research. In this review, we summarize the major findings obtained from our recent studies in mice.

Topics: Alzheimer Disease; Animals; Cholinesterase Inhibitors; Disease Models, Animal; Donepezil; Dopamine; Drug Discovery; Environment; Female; Galantamine; Indans; Male; Mental Disorders; Mice; Molecular Targeted Therapy; Motivation; Piperidines; Psychopharmacology; Rats; Receptor, Serotonin, 5-HT1A; Receptor, Serotonin, 5-HT1D; Receptors, Dopamine D2; Research; Rivastigmine

Endoplasmic reticulum (ER) protein sigma-1 receptor represents unique chaperone activity in the central nervous system, and it exerts a potent influence on a number of neurotransmitter systems. Several lines of evidence suggest that activation of sigma-1 receptor plays a role in the pathophysiology of neuropsychiatric diseases, as well as in the mechanisms of some therapeutic drugs and neurosteroids. Preclinical studies showed that some selective serotonin reuptake inhibitors (SSRIs; fluvoxamine, fluoxetine, excitalopram), donepezil, and ifenprodil act as sigma-1 receptor agonists. Furthermore, sigma-1 receptor agonists could improve the N-methyl-D-aspartate (NMDA) antagonist phencyclidine (PCP)-induced cognitive deficits in mice. A study using positron emission tomography have demonstrated that an oral administration of fluvoxamine or donepezil could bind to sigma-1 receptor in the healthy human brain, suggesting that sigma-1 receptor might be involved in the therapeutic mechanisms of these drugs. Moreover, case reports suggest that sigma-1 receptor agonists, including fluvoxamine, and ifenprodil, may be effective in the treatment of cognitive impairment in schizophrenia, delirium in elderly people, and flashbacks in post-traumatic stress disorder. In this review article, the author would like to discuss the clinical implication of sigma-1 receptor agonists, including endogenous neurosteroids, in the neuropsychiatric diseases.

Topics: Animals; Donepezil; Humans; Indans; Mental Disorders; Models, Neurological; Neurotransmitter Agents; Piperidines; Receptors, sigma; Selective Serotonin Reuptake Inhibitors; Sigma-1 Receptor

Neuropsychiatric symptoms are common in Alzheimer's disease (AD) and other neurodegenerative disorders. Recent progress has been made with clinical trials, advancing new therapies for psychosis in Parkinson's disease (PD), agitation in AD, and apathy in AD. Definitions have emerged for agitation and apathy in patients with cognitive impairment, facilitating recruitment of clinical trial populations. Progress in clinical trial design and the agents being assessed promise to advance therapies for disabling symptoms and improve quality of life for patients and caregivers.

Topics: Alzheimer Disease; Apathy; Citalopram; Clinical Trials as Topic; Cognition Disorders; Humans; Mental Disorders; Piperidines; Research Design; Therapies, Investigational; Treatment Outcome; Urea

Topics: Animals; Brain; Camphanes; Carbazoles; Carrier Proteins; Central Nervous System Diseases; Drug Discovery; GABA Plasma Membrane Transport Proteins; GABA Uptake Inhibitors; Humans; Isoxazoles; Mental Disorders; Molecular Targeted Therapy; Nipecotic Acids; Piperidines; Tiagabine

To review the main advances related to the potential therapeutic use of cannabinoid compounds in psychiatry.. A search was performed in the online databases PubMed, ScieELO, and Lilacs for studies and literature reviews concerning therapeutic applications of cannabinoids in psychiatry, especially cannabidiol, rimonabant, Delta(9)-tetrahydrocannabinol, and their analogues.. Cannabidiol was found to have therapeutic potential with antipsychotic, anxiolytic, and antidepressant properties, in addition to being effective in other conditions. Delta(9)-tetrahydrocannabinol and its analogues were shown to have anxiolytic effects in the treatment of cannabis dependence and to function as an adjuvant in the treatment of schizophrenia, although additional studies are necessary to support this finding. Rimonabant was effective in the treatment of the subjective and physiological symptoms of cannabis intoxication and functioned as an adjuvant in the treatment of tobacco addiction. The potential to induce adverse reactions such as depression and anxiety restrained the clinical use of this CB(1) antagonist.. Cannabinoids may be of great therapeutic interest to psychiatry; however, further controlled trials are necessary to confirm the existing findings and to establish the safety of such compounds.

Topics: Animals; Cannabidiol; Dronabinol; Humans; Mental Disorders; Piperidines; Psychotropic Drugs; Pyrazoles; Rimonabant

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are the two most common types of dementing neurodegenerative disease after Alzheimer's disease (AD). Both of these conditions are often diagnosed late or not at all.. Selective literature review.. The severe cholinergic and dopaminergic deficits that are present in both DLB and PDD produce not only motor manifestations, but also cognitive deficits, mainly in the executive and visual-constructive areas, as well as psychotic manifestations such as visual hallucinations, delusions, and agitation. The intensity of these manifestations can fluctuate markedly over the course of the day, particularly in DLB. Useful tests for differential diagnosis include magnetic resonance imaging and electroencephalography; in case of clinical uncertainty, nuclear medical procedures and cerebrospinal fluid analysis can be helpful as well. Neuropathological studies have revealed progressive alpha-synuclein aggregation in affected areas of the brain. In DLB, beta-amyloid abnormalities are often seen as well.. DLB should be included in the differential diagnosis of early dementia. If motor manifestations arise within one year (DLB), dopaminergic treatment should be initiated. On the other hand, patients with Parkinson's disease should undergo early screening for signs of dementia so that further diagnostic and therapeutic steps can be taken in timely fashion, as indicated. Cholinesterase inhibitors are useful for the treatment of cognitive deficits and experiential/behavioral disturbances in both DLB (off-label indication) and PDD (approved indication).

Topics: Aged; Brain; Cholinesterase Inhibitors; Cross-Sectional Studies; Dementia; Diagnosis, Differential; Diagnostic Imaging; Donepezil; Early Diagnosis; Humans; Indans; Lewy Body Disease; Mental Disorders; Neuropsychological Tests; Parkinson Disease; Phenylcarbamates; Piperidines; Randomized Controlled Trials as Topic; Rivastigmine

The study aim was to conduct a systematic review of the evidence from randomized, placebo controlled trials related to the efficacy of donepezil, rivastigmine and galantamine in the treatment of behavioral and psychological symptoms of Alzheimer's disease.. Electronic database searches of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were carried out using multiple search terms. Articles included were original publications of randomized, placebo-controlled trials of monotherapy of donepezil, rivastigmine or galantamine that reported a behavioral outcome measure.. 14 studies were identified that matched inclusion criteria. Nine were of donepezil, three of galantamine and two of rivastigmine. Median study treatment length was 24 weeks (range 12-170). Most studies used the Neuropsychiatric Inventory as a behavioral outcome measure although three used specific scales for either agitation or apathy. Four studies were specifically designed to assess behavioral outcomes whilst in the majority of studies behavioral outcomes were only secondary measures. Three studies found statistically significant, albeit modest, differences in the change of NPI total score between drug and placebo. The interpretation of the results of many studies is limited by methodological considerations, including generally low NPI scores at baseline and the investigation of behavioral and psychological symptoms of dementia (BPSD) as secondary outcomes.. The evidence base regarding the efficacy of cholinesterase inhibitors in BPSD is limited, in part due to methodological considerations. In the absence of alternative safe and effective management options, the use of cholinesterase inhibitors is an appropriate pharmacological strategy for the management of BPSD in Alzheimer's disease.

Topics: Aged; Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Evidence-Based Medicine; Galantamine; Humans; Indans; Mental Disorders; Nootropic Agents; Phenylcarbamates; Piperidines; Randomized Controlled Trials as Topic; Rivastigmine; Treatment Outcome

Several cardiometabolic factors present in obese and insulin-resistant individuals represent a continuum of increasing risk for the development of type 2 diabetes and cardiovascular disease. The importance of abdominal obesity as an independent risk factor is underscored by its association with adverse endocrine function. Recent evidence from animal and human studies has shown a role for the endocannabinoid system in maintaining energy balance and glucose and lipoprotein metabolism, with overactivity linked to aberrant glycemic and lipoprotein control, and a link to adiposity. Modulation of this system through endocannabinoid-receptor blockade has resulted in an improvement in a number of important risk factors in clinical trials, including visceral and subcutaneous abdominal adipose tissue, glucose tolerance, dyslipidemia and measures of inflammation. These findings may have significant implications for the management of patients at risk of developing cardiovascular and metabolic disease; however, the occurrence of psychiatric adverse events with rimonabant may preclude further development of centrally active endocannabinoid receptor antagonists for the treatment of cardiometabolic disorders. Future research is needed to explore the role of selective peripheral CB(1) receptor antagonists in the treatment of patients at high cardiometabolic risk.

Topics: Animals; Cannabinoid Receptor Modulators; Cardiovascular Diseases; Clinical Trials as Topic; Endocannabinoids; Humans; Mental Disorders; Obesity, Abdominal; Piperidines; Pyrazoles; Receptor, Cannabinoid, CB1; Rimonabant; Risk Factors

The cannabinoid-1 receptor blockers have been proposed in the management of obesity and obesity-related liver diseases (fatty liver as NAFLD or NASH). Due to increasing number of patients to be potentially treated and the need to assess the advantage of this treatment in terms of risk/benefit, we analyze the side events reported during the treatment with rimonabant by a systematic review and meta-analysis of all randomized controlled studies.. All published randomized controlled trials using rimonabant versus placebo in adult subjects were retrieved. Relative risks (RR) with 95% confidence interval for relevant adverse events and number needed to harm was calculated.. Nine trials (n = 9635) were considered. Rimonabant 20 mg was associated with an increased risk of adverse event (RR 1.35; 95%CI 1.17-1.56), increased discontinuation rate (RR 1.79; 95%CI 1.35-2.38), psychiatric (RR 2.35; 95%CI 1.66-3.34), and nervous system adverse events (RR 2.35; 95%CI 1.49-3.70). The number needed to harm for psychiatric adverse events is 30.. Rimonabant is associated with an increased risk of adverse events. Despite of an increasing interest for its use on fatty liver, the security profile and efficacy it is needs to be carefully assessed before its recommendation. At present the use of rimonabant on fatty liver cannot be recommended.

Topics: Cannabinoid Receptor Antagonists; Fatty Liver; Humans; Mental Disorders; Nervous System Diseases; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Rimonabant; Treatment Outcome

Tachykinins (TKs) are small peptides widely distributed in the central and peripheral nervous systems where they act as neurotransmitters. Potent and selective TKs antagonists have been developed in the last 20 years and many efforts have been made to prove their efficacy in the treatment of various diseases. Herein the most prominent results in the clinical development are reported and discussed. For aprepitant, the only compound of this class to have been launched to date, results of clinical studies and postmarketing cost-effectiveness data for the treatment of chemotherapy-induced emesis are discussed. The field is still well active, as currently proof-of-concept studies for indications initially missed (i.e., depression) are ongoing and new targets are under investigation.

Topics: Antiemetics; Aprepitant; Asthma; Clinical Trials as Topic; Gastrointestinal Diseases; Humans; Mental Disorders; Morpholines; Neurokinin-1 Receptor Antagonists; Piperazines; Piperidines; Receptors, Neurokinin-2; Receptors, Neurokinin-3; Sleep Initiation and Maintenance Disorders

The impact of behavioral symptoms associated with Alzheimer's disease is substantial. These symptoms contribute to diminished quality of life for patients and caregivers and increase the cost of care in nursing homes. Early recognition of behavioral symptoms and appropriate treatment are important for successful management. Nonpharmacologic strategies remain the cornerstone of the management of Alzheimer's disease-related behavioral symptoms. However, nonpharmacologic strategies may not be effective for problem behaviors, and pharmacologic intervention may be necessary. Relevant articles were identified through various MEDLINE searches with no date restrictions, with an emphasis on recent studies that used cholinesterase inhibitors and memantine. Additional reports of interest were identified from the reference lists of these articles. To facilitate cross-study analyses in the review of cholinesterase inhibitors and memantine, the database search was limited to randomized, placebo-controlled trials that used the Neuropsychiatric Inventory to assess behavioral symptoms of Alzheimer's disease. Overall, evidence from trials of cholinesterase inhibitors and memantine suggests that when these agents are optimized for the various stages of Alzheimer's disease, they can also prevent the emergence of neuropsychiatric symptoms. Although results from the literature are not uniformly positive, cholinesterase inhibitors have been shown to produce significant improvements in behavioral symptoms in patients with both mild- to-moderate and moderate-to-severe Alzheimer's disease. Evidence also indicates that memantine might be of benefit as an adjunct to long-term cholinesterase inhibitor treatment in patients with moderate-to-severe Alzheimer's disease and that memantine monotherapy may have some beneficial effects on behavior in patients with mild-to-moderate disease. Of importance, although no direct comparisons have been performed, these agents seem to have an improved safety and tolerability profile compared with the frequently used antipsychotic drugs. When nonpharmacologic strategies are deemed insufficient to ease problem behaviors in patients with Alzheimer's disease, treatment with cholinesterase inhibitors, alone or in combination with memantine as appropriate for the stage of disease, may be considered as a first-line option in the early pharmacologic management of Alzheimer's disease-related behavioral symptoms.

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Galantamine; Humans; Indans; Memantine; Mental Disorders; Piperidines; Time Factors

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Evidence-Based Medicine; Geriatric Assessment; Humans; Indans; Mental Disorders; Nootropic Agents; Phenylcarbamates; Piperidines; Positron-Emission Tomography; Rivastigmine; Tacrine

Management of Alzheimer disease is based on drug and nondrug treatments. Specific drug treatment includes acetylcholinesterase inhibitors and memantine. They show moderate efficacy superior to that of placebo for global condition, cognitive disorders, need for care, and behavioral problems, but do not prevent further decline. These treatments remain underused. The efficacy of psychotropic drugs (antidepressants, neuroleptics, and antipsychotic agents) in treating behavioral problems is not well documented. Nondrug activities and interventions have not been sufficiently evaluated scientifically. These involve interventions against the consequences of the disease (loss of autonomy, malnutrition) and helping patients' family caregivers. Among these activities, the best evaluated and most interesting are: educational programs for caregivers, occupational therapy at home, and interventions at home by nurses specially trained as case managers.

Topics: Aged; Alzheimer Disease; Animals; Antipsychotic Agents; Caregivers; Case Management; Cholinesterase Inhibitors; Disease Models, Animal; Donepezil; Dopamine Agents; Excitatory Amino Acid Antagonists; Follow-Up Studies; Forecasting; Health Education; Humans; Indans; Memantine; Mental Disorders; Meta-Analysis as Topic; Nootropic Agents; Occupational Therapy; Piperidines; Practice Guidelines as Topic; Psychotropic Drugs; Randomized Controlled Trials as Topic; Time Factors

Ampakines are a structurally diverse family of small molecules that positively modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors, and thereby enhance fast, excitatory transmission throughout the brain. Surprisingly, ampakines have discrete effects on brain activity and behavior. Because their excitatory synaptic targets mediate communication between cortical regions, serve as sites of memory encoding, and regulate the production of growth factors, ampakines have a broad range of potential therapeutic applications. Several of these possibilities have been tested with positive results in preclinical models; preliminary clinical work has also been encouraging.

Topics: Animals; Brain; Cognition Disorders; Dioxoles; Drug Evaluation, Preclinical; Excitatory Amino Acid Agonists; Humans; Memory; Mental Disorders; Nerve Growth Factors; Oxazines; Piperidines; Protein Conformation; Receptors, AMPA

Topics: Aged; Aged, 80 and over; Antidepressive Agents; Donepezil; Female; Humans; Indans; Male; Mental Disorders; Piperidines; Spinocerebellar Degenerations; Thyrotropin-Releasing Hormone; Trinucleotide Repeat Expansion

CX-516 is one of a series of AMPA modulators under development by Cortex, in collaboration with Shire and Servier, for the potential treatment of Alzheimer's disease (AD), schizophrenia and mild cognitive impairment (MCI) [234221]. By June 2001, CX-516 was in phase II trials for both schizophrenia and attention deficit hyperactivity disorder (ADHD) [412513]. A phase II trial in fragile X syndrome and autism was expected to start in May 2002 [449861]. In October 2001, Cortex was awarded a Phase II SBIR grant of $769,818 from the National Institutes of Mental Health to investigate the therapeutic potential of AMPAkines in schizophrenia. This award was to support a phase IIb study of CX-516 as a combination therapy in schizophrenia patients concomitantly treated with olanzapine. The trial was to enroll 80 patients and employ a randomized, double-blind, placebo-controlled design in which the placebo group was to receive olanzapine plus placebo and the active group was to receive olanzapine plus CX-516 [425982]. In April 2000, Shire and Cortex signed an option agreement in which Shire was to evaluate CX-516for the treatment of ADHD. Under the terms of the agreement, Shire would undertake a double-blind, placebo-controlled evaluation of CX-516 involving ADHD patients. If the study proved effective, Shire would have the right to convert its option into an exclusive worldwide license for the AMPAkines for ADHD under a development and licensing agreement. Should Shire elect to execute this agreement, Shire would bear all future developmental costs [363618]. By February 2002, Cortex and Servier had revealed their intention to begin enrolment for an international study of an AMPAkine compound as a potential treatment for MCI in the near future. Assuming enrollment proceeded as anticipated, results were expected during the second quarter of 2003 [439301]. By May 2002, phase II trials were underway [450134]. In March 2002, Cortex was awarded extended funding under the University of California BioSTAR projectfor the research project: 'Ampakine modulation of brain neurotrophin expression: a novel therapeutic strategy'. This funding was expected to amount to $193,000 over a two-year period [444872].

Topics: Animals; Clinical Trials as Topic; Dioxoles; Drug Industry; Humans; Mental Disorders; Piperidines

To review the effect of cholinesterase inhibitors on the behavioural and neuropsychiatric symptoms of dementia and discuss the current clinical guidelines for the prescription of cholinesterase inhibitors in Australia.. This paper reports the case of a patient with clinical diagnosis of dementia with lewy bodies (DLB) who was referred to an old age psychiatry service for the treatment of severe visual hallucinations and behavioural problems.. Pharmacological treatment with olanzapine produced marked parkinsonism, agitation and confusion. A cholinesterase inhibitor, donepezil, was introduced. The introduction of donepezil was associated with cognitive improvement (mini-mental state examination [MMSE] increased from 23 to 27) and complete remission of behavioural symptoms.. That cholinesterase inhibitors may have a role in the management of behavioural symptoms of dementia and the current Australian PBS guidelines for prescribing cholinesterase inhibitors are clinically restrictive. This has clinical and ethical implications that need to be addressed by consumers, the medical community and regulating authorities.

Topics: Aged; Aged, 80 and over; Australia; Cholinesterase Inhibitors; Donepezil; Ethics; Hallucinations; Humans; Indans; Lewy Body Disease; Male; Mental Disorders; Piperidines

Recently, a series of 5-HT7 receptor antagonists have been developed (24,29,36,68). Among them SB-258741, R-(+)-1-(toluene-3-sulfonyl)-2-[2-(4-methylpiperidin-1-yl)ethyl]-pyrrolidine, (compound "13" in 36,37) was one of the most potent and specific compounds. Due to a lack of specific ligands the pharmacology of 5-HT7 receptor antagonists is still relatively unexplored. It has been suggested, however, that 5-HT7 receptor ligands could be useful in the therapy of various disorders such as sleep disorders, schizophrenia, depression, migraine, epilepsy, pain, or memory impairment. Many of these conceivable indications are not supported by pharmacological data. It is, therefore, of particular interest to review the data generated from studies of one of these most potent and specific 5-HT7 receptor antagonists, SB-258741, with a goal of testing the validity of the proposed clinical indications. In this review, the author describes pharmacology of this compound in order to define its potential clinical use. The available safety pharmacology data are discussed in an attempt to predict potential side effects of specific 5-HT7 receptor antagonists.

Topics: Animals; Brain; Mental Disorders; Models, Animal; Nervous System Diseases; Piperidines; Pyrrolidines; Receptors, Serotonin; Serotonin Antagonists; Tosyl Compounds

Acetylcholinesterase inhibitors (ChEIs) enhance neuronal transmission by increasing the availability of acetylcholine in muscarinic and nicotinic receptors. This effect is believed to be responsible for the beneficial and protective effects of ChEIs on cognition in patients with Alzheimer's disease (AD). Effects of ChEIs on mood and behavior have also been reported. Earlier observations were limited by the exclusive availability of intravenous forms of administration, the short half-life of the formulations, and the high frequency of peripheral side effects. The introduction, in recent years, of better tolerated and less invasive compounds has rekindled the interest in cholinergic central nervous system mechanisms and has given rise to studies in areas other than cognition. The ChEI donepezil has been involved in the largest number of studies and positive reports. Preliminary observations suggest the possible value of ChEIs in the management of behavioral dysregulation, apathy, irritability, psychosis, depression, mania, tics, and delirium and in the diagnosis of depression, panic, and personality disorders.

Topics: Affect; Aged; Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Humans; Indans; Mental Disorders; Piperidines

Topics: Humans; Mental Disorders; Piperidines; Ritanserin; Serotonin Antagonists

Topics: Adult; Delayed-Action Preparations; Female; Humans; Male; Mental Disorders; Middle Aged; Penfluridol; Piperidines

Topics: Amitriptyline; Analgesics; Antidepressive Agents; Chlorpromazine; Diazepam; Diphenhydramine; Eye Diseases; Glaucoma; Histamine H1 Antagonists; Humans; Imipramine; Intraocular Pressure; Lithium; Mental Disorders; Mephenesin; Meprobamate; Piperidines; Psychotropic Drugs; Secologanin Tryptamine Alkaloids; Tranquilizing Agents; Trihexyphenidyl

Topics: Adolescent; Adult; Aged; Alcoholism; Antisocial Personality Disorder; Child; Dementia; Epilepsy; Female; Humans; Intellectual Disability; Male; Mental Disorders; Middle Aged; Neurotic Disorders; Nitriles; Paranoid Disorders; Personality Disorders; Phenothiazines; Piperidines; Psychotic Disorders; Schizophrenia; Tranquilizing Agents

Electroconvulsive therapy (ECT) is among the most effective treatments of several life-threatening psychiatric disorder. Despite effective therapy, ECT-induced seizure could cause several adverse effects including cognitive disorders and memory impairment. Drugs such as thiopental, which have been prescribed for anesthesia required for ECT, are known as drugs with cognitive effects. This pilot randomized clinical trial tried to assess the feasibility of using a lower dose of thiopental in combination with remifentanil instead of a higher challenging dose of a single drug with cognitive side effects such as thiopental. We evaluated post-ECT cognitive impairment in patients who received remifentanil-thiopental compared with thiopental-placebo group.. One hundred twenty patients with psychiatric disorders between the ages of 18 and 60 years were enrolled. The patients were randomized into 2 groups who received either thiopental sodium (4 mg/kg) and remifentanil (1 μg/kg) or thiopental sodium (3 mg/kg, placebo). The psychiatric patients were examined using mini-mental state examination in terms of the cognitive deficits before ECT as well as 5 and 24 hours after ECT. Statistical analyses were done using Statistical Package for the Social Sciences version 16. Unpaired t test, χ2 test, and analysis of variance were used to determine the association of variables.. All the patients completed the trial. There were no reports of adverse effects. In terms of depth of anesthesia measured by bispectral index, no significant difference was observed. Regarding mini-mental state examination scores, the difference was not statistically significant.. Depth of anesthesia was similar between the groups.

Topics: Adolescent; Adult; Anesthesia; Anesthetics, Intravenous; Cognition Disorders; Consciousness Monitors; Double-Blind Method; Electroconvulsive Therapy; Female; Hemodynamics; Humans; Male; Mental Disorders; Middle Aged; Neuropsychological Tests; Pilot Projects; Piperidines; Remifentanil; Thiopental; Young Adult

Behavioral and psychological symptoms of dementia (BPSD) occur in up to 80% of Alzheimer's disease (AD) patients and represent one of the most common reasons for early institutionalization and increase in management costs.. This study evaluated the effects of four drugs (memantine, donepezil, rivastigmine, galantamine) in BPSD in AD patients.. This was a prospective, longitudinal, randomized, open-label, 4-arm, parallel-group, 12-month clinical trial carried out in 177 AD patients. The severity of BPSD was evaluated at baseline and after treatment with memantine (n = 48), donepezil (n = 42), rivastigmine (n = 46), and galantamine (n = 41), by using the Neuropsychiatric Inventory (NPI) and the Behavioural Pathology in Alzheimer's Disease (BEHAVE-AD) scales.. The NPI and BEHAVE-AD total scores improved from baseline to month 12 in all groups. The improvements in both scales were statistically significant in the memantine, donepezil, and rivastigmine groups, but not in the galantamine group. Responder analyses showed that treatment with memantine and rivastigmine resulted in more patients improving on NPI and BEHAVE-AD score, respectively. Agitation/aggression was the NPI item with the highest improvements (significantly versus baseline in the memantine and in the rivastigmine groups), while aggression and anxiety/phobias were the mostly improved BEHAVE-AD items (significantly in the rivastigmine group for both and in the rivastigmine group only for anxiety/phobias). All treatments were well tolerated: most of adverse events reported were transient and of mild-to-moderate intensity.. This study suggests that specific drugs for AD, especially memantine and rivastigmine, may be effective in the improvement of BPSD in patients with mild to moderate AD, without major side effects.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Behavioral Symptoms; Cholinesterase Inhibitors; Dementia; Donepezil; Excitatory Amino Acid Antagonists; Female; Galantamine; Humans; Indans; Longitudinal Studies; Male; Memantine; Mental Disorders; Phenylcarbamates; Piperidines; Psychiatric Status Rating Scales; Rivastigmine

Blockade of the endocannabinoid receptor reduces obesity and improves metabolic abnormalities such as triglycerides, HDL cholesterol, and fasting blood glucose. We assessed whether rimonabant would improve major vascular event-free survival.. This double-blind, placebo-controlled trial was undertaken in 974 hospitals in 42 countries. 18,695 patients with previously manifest or increased risk of vascular disease were randomly assigned to receive either rimonabant 20 mg (n=9381) or matching placebo (n=9314). Randomisation was stratified by centre, implemented with an independent interactive voice response system, and all study personnel and participants were masked to group assignment. The primary endpoint was the composite of cardiovascular death, myocardial infarction, or stroke, as determined via central adjudication. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00263042.. At a mean follow-up of 13.8 months (95% CI 13.6-14.0), the trial was prematurely discontinued because of concerns by health regulatory authorities in three countries about suicide in individuals receiving rimonabant. All randomised participants were analysed. At the close of the trial (Nov 6, 2008), the composite primary endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 364 (3.9%) patients assigned to rimonabant and 375 (4.0%) assigned to placebo (hazard ratio 0.97, 95% CI 0.84-1.12, p=0.68). With rimonabant, gastrointestinal (3038 [33%] vs 2084 [22%]), neuropsychiatric (3028 [32%] vs 1989 [21%]), and serious psychiatric side-effects (232 [2.5%] vs 120 [1.3%]) were significantly increased compared with placebo. Four patients in the rimonabant group and one in the placebo group committed suicide.. The premature termination of this trial has important lessons for drug development. A drug that was being marketed for weight loss, but being tested for improving cardiovascular outcomes, induced a level of serious neuropsychiatric effects that was deemed unacceptable by regulatory authorities, and both the drug and the trial were abruptly terminated.. Sanofi-Aventis.

Topics: Aged; Aged, 80 and over; Cannabinoid Receptor Antagonists; Cardiovascular Diseases; Double-Blind Method; Drug Approval; Female; Gastrointestinal Diseases; Humans; Male; Mental Disorders; Obesity; Piperidines; Pyrazoles; Rimonabant; Suicide

The aim of the present study was to determine the efficacy, side-effects and tolerability of blonanserin for treating refractory behavioural psychological symptoms of dementia (BPSD). The present study was a 12-week, prospective, structured clinical trial of blonanserin for the treatment of BPSD. The degree of cognitive function, activities of daily living score, and the degree of BPSD were determined using the Mini-Mental State Examination (MMSE), Disability Assessment for Dementia (DAD), Neuropsychiatric Inventory (NPI) and the Rating Scale for Aggressive Behaviour in the Elderly (RAGE). The severity of extrapyramidal symptoms was assessed using the Drug-Induced Extrapyramidal Symptoms scale (DIEEPS). Five patients were enrolled. These patients met the NINCDS-ADRDA criteria. The patients were prescribed more than two kinds of existing antipsychotic drugs and were considered refractory cases; the drugs were discontinued because they were ineffectual and side-effects appeared. Each drug was prescribed independently for at least 2 weeks. The mean changes (at baseline and at the last week, respectively) in the MMSE (12.25, 9.25), in the DAD (6.5, 6.75), in the RAGE (5.5, 5.3) and in the DIEEPS (0.5, 1.5) were minimal. The mean changes in the NPI were two or fewer points. Some side-effects (one gait abnormality and one pneumonia) were observed. The results of this preliminary study show that blonanserin does not have adequate efficacy for the treatment of refractory BPSD.

Topics: Aged; Aged, 80 and over; Aggression; Alzheimer Disease; Basal Ganglia Diseases; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Female; Humans; Japan; Male; Mental Disorders; Mental Status Schedule; Neuropsychological Tests; Piperazines; Piperidines; Prospective Studies; Psychometrics; Receptor, Serotonin, 5-HT2A; Treatment Outcome

The objective of this study was to conduct exploratory analyses of data pertaining to the efficacy of donepezil treatment of patients with severe behavioral disturbances. Preliminary studies suggest that cholinesterase inhibitors, including donepezil, may reduce behavioral disturbances in patients with Alzheimer disease (AD). Most patients included in clinical trials have had low levels of psychopathology at baseline, and the effect of cholinesterase inhibitors on patients with more severe behavioral disturbances is unknown. The authors report the effects of donepezil on behavioral disturbances in patients with relatively severe psychopathology at baseline.. This is a hypothesis-driven secondary analysis of a three-phase study involving donepezil and sertraline. In phase 1, psychotropic agents were withdrawn; in phase 2, patients were treated in an open-label fashion with donepezil for 8 weeks; and in phase 3, patients on donepezil were randomized to receive placebo or sertraline for an additional 12 weeks. The data set analyzed is comprised of the patient population treated with donepezil (without sertraline) for 20 weeks. One hundred twenty patients were included in the analyses. Mean age was 76 years, average Mini-Mental State Examination Score was 18, and mean Neuropsychiatric Inventory (NPI) total score was 30. Primary efficacy assessments were the NPI, the Clinical Global Impression-Improvement, and the Clinical Global Impression-Severity scales. Secondary measures included the Behavioral Pathology in Alzheimer's Disease Rating Scale, The Hamilton Depression Rating Scale, and the Alzheimer's Disease Functional Assessment and Change Scale.. Excellent concurrent validity was noted between the NPI and the Behavioral Pathology in Alzheimer's Disease Rating Scale. The total score of the NPI was significantly reduced over the 20 weeks of therapy with donepezil. Sixty-two percent of patients had at least a 30% reduction in the total NPI score (significantly greater than the number with no meaningful response). Likewise, more patients had total or partial resolution of depression and delusions than those who had no meaningful change. Factor analysis of baseline NPI data revealed five factors, including a psychosis factor, an agitation factor, mood factor, frontal lobe function factor, and appetite and eating disorders factor. Clinically meaningful treatment effect sizes were notable for the delusion factor (0.340) and the mood factor (0.39). There were significant correlations between the Clinical Global Impression-Improvement and reductions in mood and agitation scores.. The results of these analyses suggest that donepezil reduces behavioral symptoms, particularly mood disturbances and delusions, in patients with AD with relatively severe psychopathology.

Topics: Aged; Cholinesterase Inhibitors; Dementia; Demography; Donepezil; Double-Blind Method; Factor Analysis, Statistical; Female; Humans; Indans; Male; Mental Disorders; Middle Aged; Piperidines; Prevalence; Sertraline; Severity of Illness Index; Treatment Outcome

To determine preliminarily whether donepezil will improve memory, behavior, and global function after chronic traumatic brain injury (TBI).. Sixteen-week open-label study.. Outpatient TBI rehabilitation program.. Four patients with chronic, severe TBI.. Donepezil 5mg daily for 8 weeks followed by 10mg daily for 4 weeks.. Memory measures included the Rey Auditory Verbal Learning Test (RAVLT), the Complex Figure Test (CFT), items from the Rivermead Behavioural Memory Test (RBMT), and a semantic fluency task. The Neuropsychiatric Inventory (NPI) evaluated behavior and affect. Function was assessed by using the FIM instrument and a clinical global impression of change.. On the RAVLT, the mean scores for learning and short- and long-term recall improved by 0.4, 1.04, and.83 standard deviations (SDs) above baseline, respectively. On the CFT, the mean scores for short-term recall and long-term recall improved by 1.56 and 1.38 SDs above baseline, respectively. A positive trend was observed on the RBMT and on the NPI subscales.. Donepezil may improve some aspects of memory and behavior in persons with chronic TBI. Randomized clinical trials are required to support these preliminary findings.

Topics: Adult; Brain Injuries; Chronic Disease; Donepezil; Humans; Indans; Male; Memory Disorders; Mental Disorders; Neuropsychological Tests; Nootropic Agents; Piperidines; Treatment Outcome

A double-blind placebo-controlled cross-over trial was carried out to evaluate the efficacy and safety of the combined serotonin-dopamine antagonist risperidone in mentally retarded patients with persistent behavioural disturbances. After an observation period of 1 week, risperidone 4-12 mg or placebo was administered during 3 weeks as add-on treatment to the existing medication, followed by a 1-week single-blind placebo wash-out, and another 3 weeks of double-blind treatment with the cross-over medication. Thirty-seven patients participated in the trials; 30 completed the study. Risperidone was significantly superior to placebo in its effect on the Aberrant Behaviour Checklist and the Clinical Global Impression. The Extrapyramidal Symptom Rating Scale did not show any differences between risperidone and placebo. Two patients experienced hypotension at the start of the risperidone administration. Sedation and drowsiness were the most frequently reported treatment-emergent adverse events. The results of this trial warrant further investigation into the therapeutic assets of risperidone in this indication, as add-on therapy and as monotherapy.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Intellectual Disability; Isoxazoles; Male; Mental Disorders; Middle Aged; Piperidines; Placebos; Risperidone

In order to evaluate serotonin (5-HT) function in panic disorder, a double blind placebo controlled study was conducted with ritanserin, a specific 5-HT2 receptor antagonist, and fluvoxamine, a selective 5-HT reuptake inhibitor, in 60 patients with panic disorder. Patients were treated for 8 weeks with 150 mg fluvoxamine, 20 mg ritanserin or placebo; these dose levels were reached after 1 week. In addition, as an index of 5-HT function in panic disorder, plasma concentration of beta-endorphin, cortisol and 5-hydroxyindolacetic-acid (5-HIAA) were measured. Furthermore, 5-HT uptake in blood platelets was assessed. Noradrenergic function was assessed by measuring plasma MHPG concentration. In addition, plasma melatonin concentration was measured. Treatment with fluvoxamine resulted in a profound reduction in the number of panic attacks, followed by a decrease in avoidance behavior. Treatment with ritanserin appeared to be ineffective. During treatment no significant changes were observed in plasma concentrations of beta-endorphin, cortisol, 5-HIAA and MHPG. With respect to 5-HT kinetics in blood platelets, a substantial increase in Km was observed after treatment with fluvoxamine, whereas Vmax decreased. After treatment with fluvoxamine, plasma concentration of melatonin was significantly increased, which suggests that melatonin synthesis is in part under serotonergic control. The findings of the present study do not support the hypothesis that 5-HT2 receptors are supersensitive in patients suffering from panic disorder, but allow no conclusions about the involvement of other 5-HT receptor subtypes.

Topics: Adult; beta-Endorphin; Blood Platelets; Double-Blind Method; Fear; Female; Fluvoxamine; Humans; Hydrocortisone; Hydroxyindoleacetic Acid; Male; Melatonin; Mental Disorders; Methoxyhydroxyphenylglycol; Norepinephrine; Oximes; Panic; Piperidines; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Ritanserin; Serotonin

The involvement of central serotonergic mechanisms in the organisation of human sleep has been confirmed in several single and multiple-dose clinico-pharmacological studies with the specific serotonin-S2-antagonist ritanserin. The pronounced thymosthenic effect observed with this compound in patients suffering from dysthymia, generalized anxiety disorder and negative symptoms of schizophrenia can possibly be attributed to a restoration of the energetic function during the night as a consequence of a dramatic increase in slow wave sleep during treatment with ritanserin.

Topics: Clinical Trials as Topic; Humans; Mental Disorders; Piperidines; Ritanserin; Serotonin Antagonists; Sleep

The results of evaluating the therapeutic efficacy of the new psychotropic drugs adepren, didepil, anq tempalgin made by the "Farmakhim" plant (the People's Republic of Bulgaria) are presented. Clinical trials revealed new facts that allowed to expand the scope of the indications for use formulated in the "Farmakhim" recommendations. It was found that Adepren could be used with success (in addition to the indications suggested by "Farmakhim") in the treatment of patients with depressive-paranoid paroxysms of periodic schizophrenia taking its course in the presence of general depression, as well as patients with somatogenic lingering astheno-depressive states. The therapeutic efficacy of didepil (an antiepileptic) was found to be in a direct relationship with the disease duration, character of the attacks, presence or absence of epileptic chandes of personality. The effect was the best in cases of a short duration of the disease and absence of gross epileptic personality changes, when the paroxysmal disorders were confined mostly to grand mals. A new scheme for arresting the epileptic status with didepil solution is offered. For the first time the efficacy of tempalgin in the treatment of patients suffering from alcoholic abstinence syndrome was substantiated. Optimal doses of the drugs have been determined with regard to the disease nosology and the leading syndrome. Contraindications to the use of the drugs have also been formulated.

Topics: Adolescent; Adult; Aminopyrine; Aminoquinolines; Child; Clinical Trials as Topic; Depression; Dipyrone; Drug Combinations; Epilepsy; Female; Humans; Male; Mental Disorders; Middle Aged; Phenobarbital; Piperidines; Piperidones; Procyclidine; Psychotropic Drugs; Pyrrolidines; Substance Withdrawal Syndrome; Syndrome

Topics: Adult; Antipsychotic Agents; Chronic Disease; Clinical Trials as Topic; Female; Hospitalization; Hospitals, Psychiatric; Humans; Male; Mental Disorders; Phenothiazines; Piperidines; Schizophrenia

Topics: Acute Disease; Adolescent; Adult; Aggression; Chlorpromazine; Clinical Trials as Topic; Emotions; Evaluation Studies as Topic; Female; Humans; Injections, Intramuscular; Male; Mental Disorders; Middle Aged; Neurotic Disorders; Nitriles; Phenothiazines; Piperidines; Psychotic Disorders; Tranquilizing Agents

Topics: Adolescent; Aggression; Child; Child Behavior Disorders; Chlorpromazine; Clinical Trials as Topic; Diazepam; Evaluation Studies as Topic; Female; Humans; Male; Mental Disorders; Motor Activity; Nitriles; Phenothiazines; Piperidines; Placebos; Tranquilizing Agents

Topics: Attitude of Health Personnel; Benzimidazoles; Clinical Trials as Topic; Delayed-Action Preparations; Drug Therapy; Electroencephalography; Health Facilities; Humans; Mental Disorders; Methods; Neurologic Examination; Piperidines; Psychiatric Status Rating Scales; Time Factors; Tranquilizing Agents

Topics: Aged; Analysis of Variance; Dementia; Female; Humans; Male; Mental Disorders; Minerals; Piperidines; Placebos; Psychological Tests; Vitamins

High impulsivity will increase the risk of criminal behavior, drug abuse, and suicide. We chose two drugs by following a strategy recently we proposed for identifying potential anti-impulsivity drugs, and examined the effects on impulsive action in rats by using a 3-choice serial reaction time task. We showed that the administration of blonanserin, an atypical antipsychotic, reduced impulsive actions in a U-shaped manner. 1-(2-Pyriidinyl)-piperazine, an active metabolite of buspirone or tandospirone, also slightly reduced impulsive actions, though it impaired motor functions. These results affirm the validity of our strategy, but require its refinement for developing anti-impulsivity drugs.

Topics: Animals; Antipsychotic Agents; Behavior, Animal; Impulsive Behavior; Male; Mental Disorders; Piperazines; Piperidines; Rats; Rats, Wistar; Reaction Time

The acetylcholinesterase inhibitor (AChEI) donepezil (DON) is recommended as a potential treatment for cognition after clinical traumatic brain injury (TBI) and therefore may be prescribed as an adjunct therapy during rehabilitation. However, a dose-response study evaluating DON after a controlled cortical impact (CCI) injury in rats did not reveal cognitive benefits.. The aim of this study was to determine the effect of DON on behavioral and histological outcome when combined with environmental enrichment (EE), a preclinical model of neurorehabilitation. It was hypothesized that the combined treatments would produce a synergistic effect yielding improved recovery over neurorehabilitation alone.. Isoflurane-anesthetized adult male rats received a CCI or sham injury and then were randomly assigned to EE or standard (STD) housing plus systemic injections of DON (0.25 mg/kg) or vehicle (VEH; 1.0 mL/kg saline) once daily for 19 days beginning 24 hr after injury. Function was assessed by established motor and cognitive tests on post-injury days 1-5 and 14-19, respectively. Cortical lesion volume was quantified on day 19.. DON was ineffective when administered alone. In contrast, EE conferred significant motor and cognitive benefits, and reduced cortical lesion volume vs. STD (p < 0.05). Combining the therapies weakened the efficacy of rehabilitation as revealed by diminished motor and cognitive recovery in the TBI+EE+DON group vs. the TBI+EE+VEH group (p < 0.05).. These data replicate previous findings showing that EE is beneficial and DON is ineffective after CCI and add to the literature a novel and unpredicted finding that supports neither the hypothesis nor the use of DON for TBI. Investigation of other AChEIs after CCI injury is necessary to gain further insight into the value of this therapeutic strategy.

Topics: Analysis of Variance; Animals; Brain Injuries, Traumatic; Cerebral Cortex; Cognition Disorders; Disease Models, Animal; Donepezil; Environment; Indans; Male; Maze Learning; Mental Disorders; Motor Activity; Neurologic Examination; Nootropic Agents; Piperidines; Psychomotor Performance; Rats; Rats, Sprague-Dawley; Rotarod Performance Test; Time Factors

The nomenclature of drugs is a critical aspect of science, since it can direct research and optimize treatment choices. Traditionally drugs acting on CNS receptors have been classified as either agonists or antagonists. Recently a new class of ligand, the inverse agonist, has been identified in some receptor systems. Inverse agonists have opposite actions to those of agonists but the effects of both of these can be blocked by antagonists. Pimavanserin is a new 5-HT2A receptor acting drug that has been given market authorization for psychosis in Parkinson׳s disease. The FDA have termed it an inverse agonist, but this conclusion is based on in-vitro data. In this paper we discuss the evidence for such a claim being made for pimavanserin in the human brain and conclude that this is not currently sufficient. It is therefore premature to conclude that the actions of pimavanserin in humans are due to inverse agonism, and we are of the opinion that it should be called a 5-HT2A antagonist until better evidence emerges.

Topics: Animals; Humans; Mental Disorders; Piperidines; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT1 Receptor Antagonists; Urea

Topics: Aged; Bipolar Disorder; Cholinesterase Inhibitors; Donepezil; Female; Humans; Indans; Male; Mental Disorders; Middle Aged; Piperidines

Early treatment discontinuation will have a negative effect on a drug's benefit-risk profile if discontinuation occurs earlier in time than the positive effects of treatment. This non-persistence of therapy has been associated with an increased risk of adverse health outcomes.. The aim of this study was to explore relationships between patient characteristics and reasons for and time to discontinuation of rimonabant therapy, focusing on psychiatric events, because these were the main safety concerns for rimonabant.. A modified prescription-event monitoring (M-PEM) study was conducted for rimonabant. Descriptive statistics were used to describe the patient population. Rate ratios with 95% confidence intervals (CIs) were calculated to explore associations between patient characteristics and selected categories of reasons for stopping (RfS). Median times to discontinuation were compared using the Mann-Whitney U test.. The cohort comprised 10,011 users of rimonabant, three of which were excluded from this analysis because of missing age or sex. A total of 7204 patients (72.0%) stopped using rimonabant (median observation time 323 days, interquartile range: 279-371 days). In addition, patients with a history of psychiatric illness were more likely to discontinue rimonabant therapy early for all reasons, but most pronounced due to psychiatric events (rate ratio 1.79; 95% CI 1.54, 2.09) than those without a history of psychiatric illness. In contrast, the rates of discontinuation due to lack of effectiveness, any clinical events and psychiatric events in patients with cardiovascular disease, type 2 diabetes mellitus, dyslipidaemia or hypertension tended to be lower (not all being significant) than those without. For patients who discontinued treatment due to lack of effectiveness, the median time to discontinuation was significantly shorter for patients with a history of psychiatric illness, compared with patients without a history of psychiatric illness (86 vs 97 days, p = 0.03). For patients discontinuing treatment due to psychiatric events, the difference in median time to discontinuation was also 11 days (64 vs 75 days, p = 0.38), although not statistically significant. For patients stopping due to any clinical event, median time to discontinuation was comparable for patients with and without a history of psychiatric illness (61 vs 63 days, p = 0.90).. In this study, reasons for and time to discontinuation were associated with patient characteristics such as medical history. Patients discontinued treatment because of psychiatric events early after starting. In general, identification and characterization of early discontinuers, and increasing the understanding of reasons for stopping, may help healthcare professionals to develop targeted interventions to further improve treatment compliance, thereby optimizing treatment benefits and drug safety.

Topics: Adult; Body Mass Index; Cannabinoid Receptor Antagonists; Cohort Studies; Drug Monitoring; Drug Prescriptions; Female; Humans; Male; Mental Disorders; Middle Aged; Obesity; Patient Compliance; Piperidines; Pyrazoles; Rimonabant; Risk Factors; Substance Withdrawal Syndrome; Time Factors

Topics: Aged; Brain; Cholinesterase Inhibitors; Cross-Sectional Studies; Dementia; Diagnosis, Differential; Diagnostic Imaging; Donepezil; Early Diagnosis; Evidence-Based Medicine; Humans; Indans; Lewy Body Disease; Mental Disorders; Neuropsychological Tests; Parkinson Disease; Phenylcarbamates; Piperidines; Randomized Controlled Trials as Topic; Rivastigmine

We have found that galantamine, but not donepezil, reversed isolation rearing-induced deficits of prepulse inhibition (PPI) via an activation of muscarinic M1 receptors. To explain this difference, the present study examined the effects of these acetylcholinesterase inhibitors on muscarinic receptor-mediated responses in in vitro and in vivo systems. Ca(2+) -imaging study showed that donepezil, but not galantamine, blocked a muscarinic agonist carbachol-induced increase in intracellular Ca(2+) levels in SH-SY5Y cells. Moreover, a microdialysis study showed that intraperitoneal administration of donepezil, but not galantamine, attenuated a preferential M1 receptor agonist Ndesmethylclozapine-induced increase in dopamine release in mouse cerebral cortex. These results suggest that donepezil, but not galantamine, has an ability to block muscarinic receptor function and imply that the differential effects may be responsible for the difference in the effects on isolation rearing-induced deficits of PPI between these drugs. Synapse, 2011. © 2011 Wiley-Liss, Inc.

Topics: Animals; Animals, Outbred Strains; Cell Line, Tumor; Cerebral Cortex; Cholinesterase Inhibitors; Disease Models, Animal; Donepezil; Galantamine; Humans; Indans; Male; Mental Disorders; Mice; Muscarinic Antagonists; Piperidines; Receptors, Muscarinic

Although often providing more reliable and informative findings relative to other study designs, longitudinal investigations of prevalence and predictors of suicidal behaviour remain uncommon. This paper compares 12-month prevalence rates for suicidal ideation and suicide attempt at baseline and follow-up; identifies new cases and remissions; and assesses the capacity of baseline data to predict serious suicidality at follow-up, focusing on age and gender differences.. 6,666 participants aged 20-29, 40-49 and 60-69 years were drawn from the first (1999-2001) and second (2003-2006) waves of a general population survey. Analyses involved multivariate logistic regression.. At follow-up, prevalence of suicidal ideation and suicide attempt had decreased (8.2%-6.1%, and 0.8%-0.5%, respectively). However, over one quarter of those reporting serious suicidality at baseline still experienced it four years later. Females aged 20-29 never married or diagnosed with a physical illness at follow-up were at greater risk of serious suicidality (OR = 4.17, 95% CI = 3.11-5.23; OR = 3.18, 95% CI = 2.09-4.26, respectively). Males aged 40-49 not in the labour force had increased odds of serious suicidality (OR = 4.08, 95% CI = 1.6-6.48) compared to their equivalently-aged and employed counterparts. Depressed/anxious females aged 60-69 were nearly 30% more likely to be seriously suicidal.. There are age and gender differentials in the risk factors for suicidality. Life-circumstances contribute substantially to the onset of serious suicidality, in addition to symptoms of depression and anxiety. These findings are particularly pertinent to the development of effective population-based suicide prevention strategies.

Topics: Adult; Age Distribution; Age Factors; Aged; Azepines; Cause of Death; Data Collection; Depressive Disorder; Female; Follow-Up Studies; Health Status; Humans; Longitudinal Studies; Male; Mental Disorders; Middle Aged; Piperidines; Prevalence; Risk Factors; Sex Factors; Suicide; Suicide, Attempted

AD is characterized by a widespread cognitive impairment and deficit in functional competency to perform activities of daily living (ADL). The longitudinal reliability of cognitive and functional performance indices and the strength of relationship between patients cognitive impairment and their functional competence are still open issues. The aim of this study has been to evaluate, in a selected sample of patients with AD treated with AChEl, the slopes of cognitive impairment and disability. Among 249 AD patients, according to DSM-IV criteria, with presence/absence of associated vascular lesions (AD+VD), eligible for AChEl treatment, we selected subjects with mild to moderate cognitive impairment, without high comorbidity and severe psychiatric disease, with caregiver who resided with, or had frequent contact with the patient. Patients that changed treatment shifting from one AChEl to another, that didn't tolerate inhibitors (drop-out), and that presented behavioral and psychological symptoms of dementia (BPSD) requiring neuroleptic treatment during the study period were excluded from the final analysis. A sample of 99 subjects (30 males, 69 females; mean age of 79.4+/-5.0 years), completing a 15 months follow-up was considered. Cognitive performance remained stable after 15 months of treatment, but disability increased. No difference was found due to the AChEl compound used. The same hold true for the subgroups with presence/absence of a vascular components, whereas subgroup with mild cognitive performance showed a cognitive decline, parallel to the functional one. Our data underline the efficacy of AChEl in the treatment of AD with presence/absence of vascular component. Nevertheless, the judgement on the level of efficacy of AChEl could be biased by the level of reliability of the indices considered.

Topics: Activities of Daily Living; Aged; Alzheimer Disease; Cholinesterase Inhibitors; Cognition Disorders; Diagnostic and Statistical Manual of Mental Disorders; Disability Evaluation; Donepezil; Female; Follow-Up Studies; Galantamine; Humans; Indans; Male; Mental Disorders; Neuropsychological Tests; Phenylcarbamates; Piperidines; Rivastigmine; Severity of Illness Index

Dementia with Lewy Bodies (DLB) is the second most common form of dementia in the elderly. Core features of the DLB are fluctuating cognitive symptoms, visual hallucinations and spontaneous parkinsonism. The clinical diagnostic criteria are very useful in the differentiation between DLB and Alzheimer's disease. The deficits in cholinergic neurotransmission are pronounced and associated with cognitive and psychotic symptoms. An 83 years old patient with DLB showed well formed recurrent visual hallucinations and fluctuating cognition and attention. There was no response to treatment with atypical neuroleptics. The patient responded within few days to treatment with Donepezil. Both cognitive and behavioural symptoms were improved significantly.

Topics: Aged; Cholinesterase Inhibitors; Donepezil; Hallucinations; Humans; Indans; Lewy Body Disease; Male; Mental Disorders; Piperidines; Treatment Outcome

Topics: Anti-Obesity Agents; Cannabinoid Receptor Antagonists; Cannabinoids; Central Nervous System; Central Nervous System Diseases; Drug Approval; Germany; Humans; Mental Disorders; Metabolic Syndrome; Piperidines; Pyrazoles; Rimonabant; United States; United States Food and Drug Administration; Weight Loss

A hyperdopaminergic state in humans has been hypothesized to contribute to the pathology of a number of psychiatric illnesses, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Mice that display elevated synaptic levels of dopamine due to a genetically engineered deletion of the dopamine transporter (DAT) model behavioral deficits that simulate the above conditions. As novel treatment strategies for these disorders have focused on the serotonin (5-HT) 2A receptor, we determined the capacity of the highly selective 5-HT(2A) receptor antagonist M100907 to reverse behavioral deficits in DAT knockout (KO) mice. Prior to drug treatment, DAT KO mice exhibited increased levels of locomotor activity and highly linearized movement in a novel environment, as well as reduced prepulse inhibition (PPI) of acoustic startle, compared to wild-type littermates. Treatment with M100907 (0.3-1.0 mg/kg, but not 0.1 mg/kg) reversed locomotor deficits in DAT KO mice. Similarly, treatment with 1.0 mg/kg M100907 reversed the PPI deficits in DAT KO mice. These data indicate that selective 5-HT(2A) receptor antagonists, such as M100907, may represent a class of drugs that can be used to treat conditions in which a chronic, elevated dopaminergic tone is present and contributes to abnormal behavior and sensorimotor gating deficits.

Topics: Acoustic Stimulation; Analysis of Variance; Animals; Dopamine Plasma Membrane Transport Proteins; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Fluorobenzenes; Gait Disorders, Neurologic; Inhibition, Psychological; Locomotion; Membrane Glycoproteins; Membrane Transport Proteins; Mental Disorders; Mice; Mice, Knockout; Nerve Tissue Proteins; Piperidines; Reflex, Acoustic; Reversal Learning; Serotonin 5-HT2 Receptor Antagonists; Spatial Behavior

We report the first case of repaglinide-induced factitious hypoglycemia in a young male. This case posed a challenging diagnostic dilemma because commercial assays for repaglinide are not available. Furthermore, the patient had a series of positive diagnostic tests such as high proinsulin and localizing intra-arterial calcium stimulation suggestive of insulinoma. This case, again, demonstrates the importance of pure clinical judgment in the face of often-conflicting laboratory data in making a correct diagnosis and the requirement of definitive data for an appropriate therapeutic resolution.

Topics: Adolescent; Blood Glucose; Carbamates; Diagnosis, Differential; Fasting; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Secretion; Male; Mental Disorders; Piperidines; Poisoning

Topics: Acetates; Aged; Aged, 80 and over; Alzheimer Disease; Amines; Anticonvulsants; Cholinesterase Inhibitors; Cyclohexanecarboxylic Acids; Donepezil; Drug Therapy, Combination; Gabapentin; gamma-Aminobutyric Acid; Humans; Indans; Male; Mental Disorders; Piperidines; Psychiatric Status Rating Scales; Treatment Outcome

The authors tested the hypothesis that behavioral disturbances are reported at significantly lower rates by caregivers of Alzheimer's disease (AD) patients receiving the antidementia drug donepezil, compared with a group of patients receiving no antidementia drug treatment. Patients administered donepezilfor 6 months (n=84) were compared with patients not on donepezil (n=248). Patients taking donepezil had significantly lower levels of behavioral disturbances than patients not receiving this agent (P< or =0.011). Specifically, donepezil patients were described as significantly (P< or =0.05) less likely to be threatening, destroy property, and talk loudly. Also, significantly fewer patients receiving donepezil were treated with sedatives (P< or =0.005). These findings support the growing body of evidence that cholinesterase inhibitors have psychotropic properties and reduce behavioral disturbances in patients with AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Caregivers; Cost of Illness; Donepezil; Humans; Indans; Mental Disorders; Neuropsychological Tests; Nootropic Agents; Personality Assessment; Piperidines

Behavioral abnormalities are common in Alzheimer disease (AD); cholinergic treatment reduces the behavioral disturbances of some patients with AD. Characterizing the pretreatment profile of patients who are likely to respond to cholinergic therapy will aid the efficient use of clinical resources.. To determine the baseline behavioral profile for 86 patients with AD treated with the cholinesterase inhibitor donepezil hydrochloride.. Open-label retrospective study of treatment-related behavioral assessments. Based on previous double-blind placebo-controlled experience using the Neuropsychiatric Inventory (NPI), patients were divided into responder (> or =4-point total NPI score decrease, indicating improvement), unchanged (+/-3-point total NPI score change), or nonresponder (> or =4-point total NPI score increase, indicating worsening) groups. The Mini-Mental State Examination assessed cognitive response.. Behavioral improvement was seen in 35 patients (41%), worsening in 24 (28%), and no change in 27 (31%). Comparison of profiles in behavioral responders vs nonresponders revealed significantly worse delusions (P = .04), agitation (P = .04), depression (P = .006), anxiety (P = .02), apathy (P = .003), disinhibition (P = .02), and irritability (P<.001) at baseline in responders. Five behaviors changed significantly from baseline, improving for the responders and worsening for the nonresponders: delusions (P = .003 for nonresponders, P = .004 for responders), agitation (P = .01), anxiety (P = .006 for nonresponders, P = .004 for responders), disinhibition (P = .02 for nonresponders, P = .05 for responders), and irritability (P = .003 for nonresponders, P = .001 for responders). The behavioral changes were dose dependent. Cognition did not change significantly with donepezil treatment within any group.. Donepezil has psychotropic properties, and pretreatment behaviors help predict patients' responses to treatment.

Topics: Aged; Alzheimer Disease; Cholinesterase Inhibitors; Cognition Disorders; Donepezil; Female; Humans; Indans; Male; Mental Disorders; Neuropsychological Tests; Piperidines; Prognosis; Retrospective Studies; Severity of Illness Index; Treatment Outcome

Topics: Aged; Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Humans; Indans; Mental Disorders; Piperidines

Treatments in Alzheimer's disease include treatment of cognitive impairment and behavioral manifestations (agitation, depression, anxiety, delusions). It should be noted that many non cognitive behaviors may have some relations to underlying cognitive impairment. In the not too distant future, physicians can expect to see a variety of medications and controversies over the benefits of slowing symptoms with cholinergic therapeutics approved for clinical use and (or) preventing progression of Alzheimer's disease assessed in clinical trials will emerge.

Topics: Aggression; Alzheimer Disease; Anti-Anxiety Agents; Antidepressive Agents; Antipsychotic Agents; Carbamates; Cholinesterase Inhibitors; Clinical Trials as Topic; Cognition Disorders; Depression; Donepezil; Humans; Indans; Mental Disorders; Neuroprotective Agents; Nootropic Agents; Phenylcarbamates; Piperidines; Rivastigmine; Sleep Wake Disorders; Tacrine

Topics: Adolescent; Adult; Antipsychotic Agents; Community Mental Health Services; Humans; Isoxazoles; Mental Disorders; Piperidines; Risperidone

Topics: Adult; Aged; Aged, 80 and over; Blood Platelets; Female; Humans; Imipramine; Male; Mental Disorders; Middle Aged; Paroxetine; Piperidines; Psychotropic Drugs; Radioligand Assay; Serotonin Antagonists

In our open study, ritanserin was shown to be an antidepressant low in side effects with a rapid onset of action. In contrast to the results reported by Ceulemanns, patients suffering from melancholia could also be treated with ritanserin. Similar to amitriptyline, ritanserin is able to provoke psychotic symptoms in schizophrenic patients despite the absence of an anticholinergic action. Ritanserin appears to improve mood and subjective well-being of depressive schizophrenic patients as supplementary therapy to a highly potent neuroleptic. This is consistent with the experience of Gelders. The relevance of the results described is restricted by the fact that the patients received an above-average intensive medical care besides the pharmacotherapy. In addition, the expectations of the patients with regard to ritanserin were extremely high and they expected an above-average effect of the ritanserin treatment.

Topics: Adult; Depressive Disorder; Female; Humans; Male; Mental Disorders; Middle Aged; Piperidines; Psychiatric Status Rating Scales; Ritanserin; Serotonin Antagonists

Topics: Aged; Aggression; Animals; Antidepressive Agents; Chemical Phenomena; Chemistry; Depression; Drug Therapy, Combination; Female; Haplorhini; Humans; Male; Mental Disorders; Middle Aged; Obsessive-Compulsive Disorder; Phobic Disorders; Piperidines; Rabbits; Rats; Satiation; Serotonin Antagonists; Sexual Behavior

The difficulties of regular drug intake in long term treatments for psychotic patients gave rise to the need of using medicines at the longest possible intervals, facilitating thus adequate control and regularity. Penfluridol is a neuroleptic meeting that requirement: it is necessary only one dose per week. This paper reviews the results of Penfluridol in 26 patients (20 inpatients and 6 outpatients), ages between 17 and 54 with a mean of 36.8, sex feminine, and the following diagnoses: schizophrenia, paranoid: 14, simple: 8, hebephrenic: 3, catatonic: 1. The patients, divided in two groups of 13 each, had one oral dose a week, of between 10 and 100 mg, during 90 days. The first group took only Penfluridol, suppressing any other medicaments. The other group added Penfluridol to the prescriptions already in use. The results, as described in tables I and II, were evaluated according to 36 items. The general evaluation was positive with no negative biases. The side effects were scarce and temporary: insomnia in 7 cases during the first week, and extra-pyramidal symptoms in another 7 cases, that were controlled with antiparkinsonians. The conclusion is that Penfluridol is a valuable contribution to longterm treatments in psychoses.

Topics: Administration, Oral; Adolescent; Adult; Drug Evaluation; Female; Humans; Mental Disorders; Middle Aged; Penfluridol; Piperidines

Topics: Antipsychotic Agents; Brain Diseases; Brain Injuries; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Hyperkinesis; Intellectual Disability; Male; Mental Disorders; Phenothiazines; Piperidines; Schizophrenia, Childhood

Topics: Adult; Butyrophenones; Female; Humans; Male; Mental Disorders; Piperidines; Schizophrenia; Tranquilizing Agents

Topics: Adolescent; Adult; Antidepressive Agents; Child; Child, Preschool; Delayed-Action Preparations; Dibenzazepines; Fluphenazine; Humans; Lithium; Mental Disorders; Piperidines; Sulfonamides; Tranquilizing Agents

Topics: Adult; Aged; Autistic Disorder; Delusions; Depressive Disorder, Major; Female; Humans; Male; Mental Disorders; Paranoid Disorders; Piperidines; Schizophrenia; Spiro Compounds; Time Factors; Tranquilizing Agents

Topics: Adolescent; Adult; Aged; Delusions; Female; Humans; Injections, Intramuscular; Male; Mental Disorders; Middle Aged; Neurotic Disorders; Piperidines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenia, Disorganized; Schizophrenia, Paranoid; Spiro Compounds; Tranquilizing Agents

Topics: Adult; Delayed-Action Preparations; Female; Humans; Mental Disorders; Middle Aged; Piperidines; Spiro Compounds

Topics: Anxiety; Benzimidazoles; Chronic Disease; Hallucinations; Humans; Ketones; Mental Disorders; Piperidines; Psychotic Disorders; Schizophrenia; Schizophrenia, Disorganized; Tranquilizing Agents

Topics: 1-Propanol; Adjustment Disorders; Adult; Aged; Antidepressive Agents; Antiparkinson Agents; Anxiety Disorders; Basal Ganglia Diseases; Biperiden; Bipolar Disorder; Delayed-Action Preparations; Depression; Depressive Disorder, Major; Female; Humans; Mental Disorders; Middle Aged; Paranoid Disorders; Piperidines; Schizophrenia, Disorganized; Tranquilizing Agents; Tremor

Topics: Adolescent; Brazil; Child; Child, Preschool; Epilepsy; Evaluation Studies as Topic; Female; Humans; Male; Mental Disorders; Nitriles; Phenothiazines; Piperidines; Tranquilizing Agents

Topics: Adolescent; Adult; Aged; Drug Synergism; Female; Humans; Male; Mental Disorders; Middle Aged; Phenothiazines; Piperidines; Sulfones; Thioridazine

Topics: Animals; Drug Combinations; Drug Tolerance; Humans; Mental Disorders; Piperidines; Psychotic Disorders; Rats; Schizophrenia; Tranquilizing Agents

Topics: Benzimidazoles; Evaluation Studies as Topic; Humans; Mental Disorders; Piperidines; Tranquilizing Agents

Topics: Benzimidazoles; Chronic Disease; Delayed-Action Preparations; Humans; Ketones; Mental Disorders; Piperidines; Schizophrenia; Tranquilizing Agents

Topics: Adolescent; Aggression; Anxiety; Child; Child Behavior Disorders; Child, Preschool; Humans; Mental Disorders; Nitriles; Phenothiazines; Piperidines; Social Behavior Disorders; Tranquilizing Agents

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Autistic Disorder; Autonomic Nervous System; Catatonia; Female; Hallucinations; Humans; Hypnotics and Sedatives; Liver Function Tests; Male; Mental Disorders; Nausea; Neurotic Disorders; Paranoid Disorders; Personality Disorders; Phenothiazines; Piperidines; Schizophrenia; Sleep Wake Disorders; Stimulation, Chemical; Sweating; Tremor; Vascular Diseases; Vomiting

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Butyrophenones; Fluorine; Haloperidol; Humans; Mental Disorders; Middle Aged; Piperidines; Trifluperidol

Topics: Aggression; Carbamazepine; Dibenzazepines; Humans; Mental Disorders; Nitriles; Phenothiazines; Piperidines; Thioridazine; Tranquilizing Agents

Topics: Adult; Aged; Hallucinations; Humans; Male; Mental Disorders; Middle Aged; Paranoid Disorders; Piperidines; Psychotic Disorders; Schizophrenia

Topics: Antidepressive Agents; Butyrophenones; Fluorine; Humans; Mental Disorders; Piperidines; Schizophrenia; Tranquilizing Agents; Trifluperidol

Topics: Adult; Anesthesia, Local; Anesthetics, Local; Anilides; Anus Diseases; Humans; Mental Disorders; Middle Aged; Piperidines; Xylenes

Topics: Adolescent; Adult; Aged; Amygdala; Astrocytoma; Brain Neoplasms; Central Nervous System Diseases; Cerebral Cortex; Chronic Disease; Electroencephalography; Electrophysiology; Epilepsy, Temporal Lobe; Female; Humans; Male; Mental Disorders; Middle Aged; Parasympatholytics; Piperidines; Temporal Lobe

Topics: Amobarbital; Diethylpropion; Environment; Humans; Mental Disorders; Piperidines; Psychopharmacology

Topics: Blood Glucose; Carbohydrate Metabolism; Diabetes Mellitus; Glucose Tolerance Test; Hallucinations; Hospitals, Psychiatric; Inpatients; Mental Disorders; Piperidines; Placebos; Schizophrenia; Toxicology

Topics: Antisocial Personality Disorder; Bipolar Disorder; Depression; Drug Combinations; Glycolates; Hallucinogens; Mental Disorders; Piperidines; Psychotic Disorders; Pyrrolidines; Schizophrenia; Toxicology

Topics: Adolescent; Bender-Gestalt Test; Central Nervous System Stimulants; Drug Combinations; Glycolates; Hallucinogens; Humans; Lysergic Acid Diethylamide; Mental Disorders; Piperidines; Projective Techniques; Psychological Tests; Psychopharmacology; Pyrrolidines; Succinates; Toxicology

Topics: Antisocial Personality Disorder; Anxiety; Anxiety Disorders; Atropine; Bipolar Disorder; Depression; Drug Combinations; Drug Therapy; Electroencephalography; Glycolates; Hallucinogens; Mental Disorders; Piperidines; Psychoses, Alcoholic; Psychotic Disorders; Pyrrolidines; Schizophrenia; Toxicology

Topics: Bipolar Disorder; Butyrophenones; Hallucinations; Humans; Hypnotics and Sedatives; Intellectual Disability; Mental Disorders; Paranoid Disorders; Paresis; Parkinsonian Disorders; Piperidines; Psychomotor Agitation; Psychotic Disorders; Schizophrenia

Topics: Bipolar Disorder; Butyrophenones; Chorea; Drug Therapy; Electromyography; Haloperidol; Humans; Huntington Disease; Mental Disorders; Movement Disorders; Piperidines; Psychotic Disorders; Temperament

Topics: Mental Disorders; Phenothiazines; Piperidines; Psychotic Disorders; Tranquilizing Agents

Topics: Anesthetics; Humans; Mental Disorders; Perception; Piperidines; Sensation Disorders

Topics: Counseling; Electroconvulsive Therapy; Humans; Mental Disorders; Piperidines; Psychotherapy; Tranquilizing Agents

Topics: Drug Combinations; Glycolates; Hallucinations; Humans; Mental Disorders; Mentally Ill Persons; Piperidines; Pyrrolidines

Topics: Chlorpromazine; Dementia; Humans; Mental Disorders; Opium; Piperidines; Psychopharmacology; Psychotic Disorders; Reserpine

Topics: Electroconvulsive Therapy; Humans; Mental Disorders; Piperidines; Psychosurgery; Psychotherapy

Topics: Chronic Disease; Hallucinations; Humans; Mental Disorders; Piperidines; Psychopharmacology; Syndrome

Topics: Anesthetics; Hallucinogens; Humans; Mental Disorders; Phencyclidine; Piperidines

Topics: Electroconvulsive Therapy; Mental Disorders; Piperidines; Psychosurgery; Psychotherapy

Topics: Mental Disorders; Phenothiazines; Piperidines; Promazine; Psychotic Disorders

Topics: Disease; Mental Disorders; Piperidines; Psychosurgery; Psychotic Disorders; Veterans

Topics: Dementia; Double-Blind Method; Humans; Mental Disorders; Piperidines; Psychotic Disorders

Topics: Chlorpromazine; Lysergic Acid Diethylamide; Mental Disorders; Piperidines; Psychotic Disorders

Topics: Electroencephalography; Mental Disorders; Piperidines

Topics: Central Nervous System; Central Nervous System Stimulants; Humans; Mental Disorders; Nervous System; Piperidines; Psychotic Disorders

Topics: Chlorpromazine; Lysergic Acid; Lysergic Acid Diethylamide; Mental Disorders; Piperidines; Psychotherapy; Psychotropic Drugs; Reserpine

Topics: Electroconvulsive Therapy; Mental Disorders; Piperidines; Psychotic Disorders

Topics: Electroconvulsive Therapy; Mental Disorders; Piperidines; Psychotherapy

Topics: Mental Disorders; Piperidines; Psychosurgery; Psychotic Disorders

Topics: Barbiturates; Electroconvulsive Therapy; Humans; Hypnotics and Sedatives; Mental Disorders; Piperidines; Psychotherapy; Tranquilizing Agents

Topics: Electroconvulsive Therapy; Hypnotics and Sedatives; Mental Disorders; Nervous System Diseases; Piperidines; Psychosurgery; Psychotherapy

Topics: Hospitals, State; Humans; Mental Disorders; Methylphenidate; Piperidines; Psychosurgery; Psychotherapy; Tranquilizing Agents

Topics: Aged; Antihypertensive Agents; Central Nervous System Stimulants; Disease; Mental Disorders; Methylphenidate; Piperidines; Reserpine; Secologanin Tryptamine Alkaloids

Topics: Chlorpromazine; Electroconvulsive Therapy; Mental Disorders; Piperidines; Psychotic Disorders; Reserpine; Secologanin Tryptamine Alkaloids

Topics: Chlorpromazine; Electroconvulsive Therapy; Mental Disorders; Piperidines; Psychopharmacology; Psychosurgery; Psychotherapy; Secologanin Tryptamine Alkaloids

Topics: Central Nervous System Stimulants; Humans; Mental Disorders; Piperidines

Topics: Electroconvulsive Therapy; Mental Disorders; Mentally Ill Persons; Piperidines; Psychosurgery; Psychotherapy; Reserpine; Secologanin Tryptamine Alkaloids

Topics: Chlorpromazine; Hospitalization; Humans; Mental Disorders; Piperidines; Psychosurgery; Psychotic Disorders; Reserpine; Secologanin Tryptamine Alkaloids

Topics: Anticonvulsants; Central Nervous System Stimulants; Chlorpromazine; Mental Disorders; Muscle Relaxants, Central; Piperidines; Psychiatry; Psychotherapy; Secologanin Tryptamine Alkaloids

Topics: Bridged-Ring Compounds; Hallucinations; Humans; Mental Disorders; Piperidines; Psychotic Disorders; Syndrome; Urea

Topics: Anticonvulsants; Electroconvulsive Therapy; Humans; Hypnotics and Sedatives; Mental Disorders; Piperidines; Psychiatry

Topics: Mental Disorders; Piperidines; Psychosurgery; Psychotherapy; Reserpine

Topics: Mental Disorders; Piperidines

Topics: Autonomic Agents; Hypnotics and Sedatives; Mental Disorders; Nervous System Diseases; Piperidines; Psychotherapy

Topics: Electroconvulsive Therapy; Electroencephalography; Humans; Hypnotics and Sedatives; Mental Disorders; Piperidines; Sleep

Topics: Humans; Mental Disorders; Piperidines

Topics: Humans; Mental Disorders; Piperidines; Schizophrenia

Topics: Hypnotics and Sedatives; Mental Disorders; Piperidines; Psychiatry; Psychotherapy

Topics: Electroconvulsive Therapy; Mental Disorders; Piperidines; Psychotherapy; Psychotic Disorders

Topics: Mental Disorders; Piperidines; Psychotic Disorders; Schizophrenia

Topics: Central Nervous System Stimulants; Depression; Depressive Disorder; Mental Disorders; Methylphenidate; Piperidines; Psychotherapy; Reserpine; Secologanin Tryptamine Alkaloids