Behavioural pharmacology of the new generation of antipsychotic agents

1999 ◽  
Vol 174 (S38) ◽  
pp. 5-11 ◽  
Author(s):  
N. A. Moore
Keyword(s):  
Side Effects ◽  
Cognitive Deficits ◽  
Therapeutic Efficacy ◽  
Negative Symptoms ◽  
Social Withdrawal ◽  
Antipsychotic Agents ◽  
Positive Symptoms ◽  
Extrapyramidal Side Effects ◽  
New Generation ◽  
Motor Disturbances

Antipsychotic agents have been the mainstay in the management of schizophrenia for a number of years. Their therapeutic efficacy is primarily attributed to dopamine receptor antagonism (Creese et al, 1976), leading to a reduction in the positive symptoms of schizophrenia such as paranoia and hallucinations. Unfortunately, they have little effect on the negative symptoms (such as flattened affect, poverty of speech, anhedonia and social withdrawal) or cognitive deficits. The blockade of central dopamine receptors by classical antipsychotic agents also leads to the development of both acute and chronic motor disturbances (extrapyramidal side-effects) (EPS) (Meltzer, 1992).

Symptômes Positifs Et Négatifs De La Schizophrénie: Une Mise à jour

1994 ◽  
Vol 39 (7) ◽  
pp. 407-414 ◽  
Author(s):  
Marc-André Roy ◽  
Xavier Devriendt
Keyword(s):  
Cognitive Deficits ◽  
Negative Symptoms ◽  
Three Dimensions ◽  
Positive Symptoms ◽  
Research Questions

The purpose of this article is to summarize the results of studies examining the validity of the positive and negative sub-types of schizophrenia as proposed by Crow. The authors summarized Crow's model's predictions in the form of 12 research questions and examined whether its predictions were confirmed. The following predictions are generally confirmed by the data collected: (i) it is possible to measure negative symptoms with accuracy; (ii) the negative symptoms predict a deterioration; (Hi) the negative symptoms are generally correlated with overall cognitive deficits; (iv) each dimension appears to have distinct neurobiological substrata. However, several elements of the Crow model are not supported by the data collected. Among the necessary modifications, the most important are as follows: (i) it appears more productive to conceive of the negative symptoms as distinct dimensions, rather than distinct diseases; (ii) at least three dimensions exist for describing the symptoms of schizophrenia; (Hi) the negative symptoms are not necessarily intrinsic to the schizophrenic process, and they may be due to other causes; (iv) the negative symptoms are not necessarily irreversible, and can be improved under ataractics; (v) the positive symptoms, in particular those relating to disorganization, can also be correlated with cognitive deficits.

Combination Treatments for Schizophrenia

CNS Spectrums ◽  
2004 ◽  
Vol 9 (S9) ◽  
pp. 19-23 ◽  
Author(s):  
Alexander L. Miller
Keyword(s):  
Electroconvulsive Therapy ◽  
Cognitive Deficits ◽  
Negative Symptoms ◽  
Current Evidence ◽  
Positive Symptoms ◽  
Combination Therapies ◽  
Safety And Efficacy ◽  
Combination Treatments ◽  
Improved Outcomes ◽  
Expert Recommendations

ABSTRACTCombination treatments, especially combinations of antipsychotics, are used frequently for schizophrenia, despite a paucity of evidence regarding their safety and efficacy. Because the literature basis is weak and expert recommendations are largely lacking, providers should be vigilant in documenting improved outcomes for patients thought to benefit from combination treatments. Target symptoms that have been studied include psychosis, cognitive deficits, and negative symptoms. The strongest evidence is for augmentation of clozapine with another antipsychotic or with electroconvulsive therapy for persistent positive symptoms. Combination treatments for cognitive deficits and negative symptoms are being actively investigated, but current evidence is insufficient to recommend available agents for these components of schizophrenia. It is important that appropriate monotherapies be given adequate trials before resorting to combination therapies.

Psychopharmacology of olanzapine

1999 ◽  
Vol 174 (S38) ◽  
pp. 52-58 ◽  
Author(s):  
C. M. E. Stephenson ◽  
L. S. Pilowsky
Keyword(s):  
Side Effects ◽  
Atypical Antipsychotic ◽  
Antipsychotic Drug ◽  
Therapeutic Efficacy ◽  
Atypical Antipsychotics ◽  
Extrapyramidal Side Effects ◽  
Atypical Antipsychotic Drug ◽  
Blood Monitoring

The development of atypical antipsychotics has revolutionised the treatment of schizophrenia, as well as providing new insights into its cause. The archetypal atypical antipsychotic is clozapine, which has therapeutic advantages over traditional antipsychotics, as well as a low potential for producing extrapyramidal side-effects (EPS) (Kane et al, 1988). However, clozapine causes agranulocytosis in 1% of patients, and there has consequently been a search for novel atypical antipsychotics, as efficacious as clozapine, but without the need for intensive blood monitoring. There has been much discussion of the definition and characteristics of an atypical antipsychotic drug, and an operational understanding seems to have been agreed upon, that atypical drugs have therapeutic efficacy in treating schizophrenia, without producing EPS (Deutch et al, 1991; Kerwin, 1994).

New dopaminergic and non-dopaminergic theories in schizophrenia and their therapeutic impact

1997 ◽  
Vol 9 (2) ◽  
pp. 64-67
Author(s):  
R.S. Kahn
Keyword(s):  
Cognitive Deficits ◽  
Negative Symptoms ◽  
Dopamine Neurons ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
The Core ◽  
Schizophrenic Patients ◽  
Core Symptoms ◽  
Influential Theory

The dopamine (DA) hypothesis of schizophrenia, postulating that schizophrenia is characterized by increased dopamine function, has been the most influential theory on the pathogenesis of schizophrenia. It has recently been revised based on the appreciation that the core symptoms of schizophrenia may not be the positive (psychotic) symptoms, but rather the negative symptoms and the cognitive deficits found in schizophrenic patients. This revision has prompted the hypothesis that schizophrenia is characterized by both decreased prefrontal dopamine activity (causing deficit symptoms) and increased dopamine activity in mesolimbic dopamine neurons (causing positive symptoms).Notwithstanding this revision of a role for dopamine in schizophrenia, it has become increasingly evident that dysfunction of other monoaminergic systems may be as important in contributing to the pathophysiology of schizophrenia. Specifically, the putative role of serotonin (5-hydroxytryptamine, 5-HT) in schizophrenia is gaining considerable attention. Several observations, such as the ability of the 5-HT antagonist, ritanserin, to alleviate schizophrenic symptoms and, when added to haloperidol (Haldol®), to decrease its extrapyramidal side-effects (EPS), have stimulated studies into a role of 5-HT in schizophrenia. The finding that clozapine (Leponex®), clinically superior to conventional neuroleptics, is a weak DA2 antagonist but a potent 5-HT1c and 5-HT2 antagonist has further stimulated 5-HT-related research in schizophrenia.

Risperidone in the treatment of psychoses in the elderly: a case report series

2002 ◽  
Vol 17 (2) ◽  
pp. 96-103 ◽  
Author(s):  
R. Bullock ◽  
S. Libretto
Keyword(s):  
Side Effects ◽  
Elderly Patients ◽  
Negative Symptoms ◽  
Case Reports ◽  
Antipsychotic Agents ◽  
The Elderly ◽  
The Body ◽  
Continuous Treatment ◽  
Atypical Antipsychotic Agents

SummaryRisperidone is one of the newer atypical antipsychotic agents, which combines potent serotonin and dopamine receptor antagonism. It shows efficacy against the positive and negative symptoms of schizophrenic psychoses and other psychotic conditions, and has a low propensity to cause extrapyramidal side effects. The aim of these case reports in elderly patients is to provide the benefit of personal experience with risperidone to the body of published literature and to demonstrate the types of patients that may benefit from treatment. These cases were compiled retrospectively from data collected on referral and during routine hospital appointments. This series covers four main areas of concern when treating the elderly: low-maintenance dosing minimising the likelihood of adverse events; successful treatment of patients previously uncontrolled and experiencing side effects with other antipsychotics; the possibility of intermittent rather than continuous treatment; and the benefits to patients, carers and the health services. At low doses, risperidone is an effective and well-tolerated treatment for psychoses in elderly patients that improves the quality of life for both patients and their caregivers.

Current use of atypical antipsychotics

2002 ◽  
Vol 17 (S4) ◽  
pp. 377s-384s ◽  
Author(s):  
F. Müller-Spahn
Keyword(s):  
Side Effects ◽  
Negative Symptoms ◽  
Atypical Antipsychotics ◽  
Term Treatment ◽  
Dopamine Neurons ◽  
Positive Symptoms ◽  
Onset Of Action ◽  
Conventional Antipsychotics ◽  
Long Term Treatment ◽  
Insufficient Response

SummaryIn terms of the phenomenology of schizophrenia, there are four targets for drug treatments: positive symptoms, negative symptoms, affective dysfunction, and cognitive dysfunction. Because of the side-effects of both conventional antipsychotics and the new atypicals, there still is a need to search for better-tolerated antipsychotics. Conventional antipsychotics have two principal limitations: 30–40% of patients have an insufficient response to them, and they have a large variety of adverse effects. Side-effects will reduce patients’ compliance with treatment, as well as their immediate quality of life, and may therefore unfavorably affect rehabilitation. Four principal features differentiate atypical from conventional antipsychotics, yet have not been established for all atypicals: fewer extrapyramidal side-effects, greater efficacy in the treatment of negative symptoms, specific pharmacological receptor binding profiles, and greater selective effect on the mesolimbic dopamine neurons than on nigrostriatal neurons. The pharmacological profile of amisulpride is completely different to that of other atypical antipsychotics. It has a high selectivity for D2 and D3 dopamine receptors, and thus would be expected to be devoid of unwanted side-effects associated with action on other neurotransmitter systems. It acts preferentially on the mesocortical and mesolimbic systems. It has an earlier onset of action than haloperidol. Amisulpride is a compound with a dual mode of action. At low doses it blocks presynaptic dopamine autoreceptors, inducing an increased dopaminergic neurotransmission, and at high doses it blocks postsynaptic dopaminergic activity. It is at least as effective as haloperidol, flupenthixol, and risperidone in controlling positive symptoms, as well as having efficacy for negative symptoms. It has less propensity to induce weight gain than do other atypical antipsychotics. For the 60–80% of patients with schizophrenia who require long-term treatment, drug tolerability is crucially important, as it will improve compliance, and therefore reduce relapse rate.

Receptor mechanisms of antipsychotic drug atypicality

1998 ◽  
Vol 13 (S1) ◽  
pp. 5s-8s
Author(s):  
GP Reynolds
Keyword(s):  
Side Effects ◽  
Animal Models ◽  
Negative Symptoms ◽  
Atypical Antipsychotics ◽  
Mechanisms Of Action ◽  
Antipsychotic Treatment ◽  
Extrapyramidal Side Effects ◽  
Treatment Resistant ◽  
Pharmacological Profile ◽  
New Compounds

SummaryRecent advances in antipsychotic treatment of schizophrenia have offered several new compounds which avoid many of the limitations of the classical antipsychotics. These so-called ‘atypical’ antipsychotics have fewer extrapyramidal side effects, greater efficacy against negative symptoms and greater efficacy in otherwise treatment-resistant patients. However, the mechanism of action of these atypical antipsychotics is still unclear. The several receptors currently implicated in the pharmacological profile of these atypical antipsychotics include subtypes of those for dopamine, serotonin, noradrenaline, and acetylcholine among others. The current hypotheses for possible mechanisms of action of atypical antipsychotics are discussed along with the experimental correlates of antipsychotic efficacy in animal models.

Cognitive Enhancement in Schizophrenia

2017 ◽  
Author(s):  
James Gilleen
Keyword(s):  
Drug Development ◽  
Cognitive Training ◽  
Cognitive Deficits ◽  
Negative Symptoms ◽  
Cognitive Enhancement ◽  
Cognitive Impairments ◽  
Cognitive Remediation ◽  
Current Status ◽  
Positive Symptoms ◽  
Social Deficits

Schizophrenia is characterized by a constellation of heterogeneous symptoms including hallucinations and delusions, motivational and social deficits, and cognitive impairments. Although positive symptoms have historically been the target for drug development, in recent years, attention has turned to cognitive and negative symptoms. Cognitive deficits in schizophrenia are associated with significant impairments in functional, social, and employment outcomes, and although they are widely researched and relatively well understood, there are no currently approved compounds to treat them. This chapter provides a selective review of the current status of approaches developed to improve cognition in schizophrenia. It covers pharmacological approaches as well as cognitive training and cognitive remediation techniques. It also explores the various study design issues and challenges that contribute to the difficulties in discovering reliable ways to improve the cognitive deficits present in schizophrenia.

Sulpiride: an advance in neuroleptics?

1984 ◽  
Vol 22 (8) ◽  
pp. 31-32
Keyword(s):  
Side Effects ◽  
Social Withdrawal ◽  
Extrapyramidal Side Effects ◽  
Schizophrenic Patients ◽  
Substituted Benzamide ◽  
The Uk

Sulpiride (Dolmatil - Squibb) is a substituted benzamide related to metoclopramide. It has only recently been marketed in the UK, but has been used in Europe for many years. The manufacturer claims that the drug has both antidepressive and neuroleptic properties, and that it is of particular benefit for schizophrenic patients who develop social withdrawal. Extrapyramidal side effects are claimed to be less than with conventional neuroleptics.

Psychotic-like experiences and depressive symptoms in a community sample of adolescents

2011 ◽  
Vol 26 (6) ◽  
pp. 396-401 ◽  
Author(s):  
M. Barragan ◽  
K.R. Laurens ◽  
J.B. Navarro ◽  
J.E. Obiols
Keyword(s):  
Depressive Symptoms ◽  
Negative Symptoms ◽  
Psychotic Disorders ◽  
Social Withdrawal ◽  
Community Sample ◽  
Principal Component ◽  
Positive Symptoms ◽  
Principal Component Factor Analysis ◽  
Positive Experiences ◽  
Affective Flattening

AbstractPurposeStudies of psychotic-like experiences (PLEs) within community samples of adolescents have explored predominantly positive experiences. There is a paucity of research examining the prevalence and correlates of negative PLEs, and whether particular subtypes of negative PLEs can be identified among the general population of adolescents. This study examined the association of both positive and negative PLEs with depressive symptoms, including detailed analysis of subtypes of positive and negative psychosis dimensions.MethodA community sample of 777 adolescents (50.9% girls: mean age 14.4 years) completed a questionnaire assessing positive and negative PLEs and depressive symptoms.ResultsPrincipal component factor analysis identified four factors of positive symptoms (persecutory ideation, grandiose thinking, first-rank/hallucinatory experiences and self-referential thinking), and three factors of negative symptoms (social withdrawal, affective flattening, and avolition). Depressive symptoms were associated positively with persecutory ideation, first-rank/hallucinatory experiences, social withdrawal, and avolition, whereas grandiose thinking related negatively with depressive symptoms. Neither self-referential thinking nor affective flattening related to self-reported depression.ConclusionsThese findings support the view that not all types of positive and negative PLEs in adolescence are associated with depression and, therefore, they may not confer the same vulnerability for psychotic disorders.

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