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.

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.

scholarly journals Recycling N-acetylcysteine: A review of evidence for adjunctive therapy in schizophrenia

2019 ◽  
Vol 9 (3) ◽  
pp. 116-123 ◽  
Author(s):  
Robert J. Willborn ◽  
Colleen P. Hall ◽  
Matthew A. Fuller
Keyword(s):  
Negative Symptoms ◽  
Current Evidence ◽  
Positive Symptoms ◽  
Cognitive Symptoms ◽  
Antipsychotic Therapy ◽  
Assessment Development ◽  
Cognitive Symptom ◽  
Symptom Domains ◽  
Medication Intervention

AbstractIntroductionAll symptoms in schizophrenia may impact functioning. Although Food and Drug Administration-approved medications typically benefit positive symptoms, negative symptoms are generally refractory to medication interventions. N-acetylcysteine's (NAC) influence on glutamatergic neurotransmission has been established. An emerging body of research has attempted to correlate this action with reduction in symptom severity, evaluating response in positive, negative, and cognitive symptom domains.MethodsA literature review was performed to analyze available data on NAC intervention and improvement in the positive, negative, and cognitive symptom domains in patients with schizophrenia. Quality of evidence was systematically assessed to determine level of certainty in results.ResultsThree randomized controlled trials were identified. Across studies, negative symptoms decreased more with NAC compared to placebo; ranging between 11.9% and 24.1%. The assessment determined a low level of certainty regarding benefit of NAC on negative and cognitive symptoms and moderate certainty for NAC regarding findings of side effects and lack of benefit on positive symptoms.DiscussionConsistent reporting of benefit in negative symptoms is found across studies of NAC intervention. These improvements are notable for symptoms that have generally remained refractory to medication intervention. Inconsistent benefit was reported in positive and cognitive symptoms. GRADE (grading of recommendations assessment, development and evaluation) assessment of current evidence indicates a low certainty of benefit for negative symptoms with standard use of NAC in patients with schizophrenia. However, a trial of this low-risk intervention may be warranted in patients with resistant negative symptoms and subsequent impaired functioning despite appropriate antipsychotic therapy as they may experience additional benefit in this symptom domain.

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.

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.

scholarly journals A Comparative Study between Olanzapine and Risperidone in the Management of Schizophrenia

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Saeed Shoja Shafti ◽  
Mahsa Gilanipoor
Keyword(s):  
Negative Symptoms ◽  
Primary Outcome ◽  
Positive Symptoms ◽  
Random Allocation ◽  
Severity Scale ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Superior Efficacy ◽  
Schizophrenic Patients ◽  
Risperidone Group

Introduction. Since a variety of comparisons between risperidone and olanzapine have resulted in diverse outcomes, so safety and efficacy of them were compared again in a new trial.Method. Sixty female schizophrenic patients entered into one of the assigned groups for random allocation to olanzapine or risperidone (n=30in each group) in a double-blind, 12-week clinical trial. Scale for Assessment of Positive Symptoms (SAPS) and Scale for Assessment of Negative Symptoms (SANS) were used as the primary outcome measures. Clinical Global Impressions-Severity Scale (CGI-S), Schedule for Assessment of Insight (SAI), and finally Simpson Angus Scale (SAS) as well were employed as secondary scales.Results. While both of olanzapine and risperidone were significantly effective for improvement of positive symptoms (P<0.0001), as regards negative symptoms, it was so only by means of olanzapine (P<0.0003). CGI-S and SAI, as well, were significantly improved in both of the groups. SAS increment was significant only in the risperidone group (P<0.02).Conclusion. While both of olanzapine and risperidone were equally effective for improvement of positive symptoms and insight, olanzapine showed superior efficacy with respect to negative symptoms, along with lesser extrapyramidal side effects, in comparison with risperidone.

scholarly journals Combination Therapies for the Treatment of Advanced Melanoma: A Review of Current Evidence

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Mark Voskoboynik ◽  
Hendrik-Tobias Arkenau
Keyword(s):  
Overall Survival ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoint Blockade ◽  
Advanced Melanoma ◽  
Current Evidence ◽  
Combination Therapies ◽  
Improved Outcomes ◽  
History Of ◽  
Dual Blockade

The treatment of advanced melanoma has been revolutionised in recent years with the advent of a range of new therapies. BRAF inhibitors, such as vemurafenib, have demonstrated improvements in the overall survival of patients with advanced melanoma that harbour a BRAF V600 mutation. Alongside these targeted therapies, novel immune-checkpoint inhibitors, such as ipilimumab, have also been developed and have produced similarly improved outcomes for patients. For the first time in the history of melanoma, monotherapy with each of these drugs has produced improvements in the overall survival of patients with advanced disease. Building on this initial success, there has been intense interest in developing combination therapies predominantly with either dual blockade of the MAPK oncogenic pathway or dual immune-checkpoint blockade. The current evidence for the use of these combination therapies will be presented here.

Combination Products for Glaucoma: An Overview of Treatment Principles

2007 ◽  
Vol 17 (5_suppl) ◽  
pp. 5-8
Author(s):  
C. Traverso
Keyword(s):  
Intraocular Pressure ◽  
Combination Therapy ◽  
Fixed Combination ◽  
Prescribing Patterns ◽  
Current Evidence ◽  
Evidence Based ◽  
Combination Therapies ◽  
Safety And Efficacy ◽  
Evidence Based Guidelines ◽  
Delay Progression

Glaucoma is a leading cause of blindness and visual impairment. Treatments that lower intraocular pressure (IOP) tend to delay progression of the condition. However, the target IOP cannot be achieved with monotherapy in many patients. If monotherapy adequately controls IOP and is well tolerated, it should not be changed, but if the therapy is only partially effective, a combination may be used. Combination therapy is eventually needed in many cases of glaucoma. Combinations may be given as adjunctive or preferably as fixed therapies. The mechanism of action and contraindications of the constituent agents should be taken into account when prescribing combinations, for optimal safety and efficacy. As treatment choice expands, prescribing patterns are changing worldwide. Fixed combination therapies are increasingly prescribed in Europe in particular for the treatment of glaucoma. They should be administered according to the current evidence-based guidelines.

scholarly journals Neurodevelopmental origin of cognitive impairment in schizophrenia

2014 ◽  
Vol 45 (1) ◽  
pp. 1-9 ◽  
Author(s):  
E. Bora
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Cognitive Dysfunction ◽  
Cognitive Deficits ◽  
Negative Symptoms ◽  
Clinical Symptoms ◽  
Functional Decline ◽  
Current Evidence ◽  
Neurodevelopmental Abnormalities ◽  
The Individual

Cognitive impairment is a common feature of schizophrenia; however, its origin remains controversial. Neurodevelopmental abnormalities clearly play a role in pre-morbid cognitive dysfunction in schizophrenia, yet many authors believe that schizophrenia is characterized by illness-related cognitive decline before and after onset of the psychosis that can be the result of neurodegenerative changes. The main reasons behinds such arguments include, first, the evidence showing that effect sizes of the cognitive deficits in subjects who develop adult schizophrenia gradually increase in the first two decades of life and, second, the fact that there is functional decline in many patients with schizophrenia over the years. In this Editorial, I argue that current evidence suggests that illness-related cognitive impairment is neurodevelopmental in origin and characterized by slower gain (developmental lag) but not cognitive decline continuing throughout the first two decades of life. I introduce a model suggesting that neurodevelopmental abnormality can in fact explain the course of cognitive dysfunction and variations in the trajectory of functional decline throughout the life in individuals with schizophrenia. In this model, the severity of underlying neurodevelopmental abnormality determines the age that cognitive deficits first become apparent and contributes to the cognitive reserve of the individual. Interaction of neurodevelopmental abnormality with clinical symptoms, especially negative symptoms and aging, vascular changes, psychological and iatrogenic factors contributes to the heterogeneity of the functional trajectory observed in this disorder.

scholarly journals Adjunctive pharmacotherapy for cognitive deficits in schizophrenia: meta-analytical investigation of efficacy

2013 ◽  
Vol 203 (3) ◽  
pp. 172-178 ◽  
Author(s):  
Kee-Hong Choi ◽  
Til Wykes ◽  
Matthew M. Kurtz
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Cognitive Deficits ◽  
Effect Size ◽  
Negative Symptoms ◽  
Verbal Learning ◽  
Spatial Learning And Memory ◽  
Positive Symptoms ◽  
Small Effect Size ◽  
Moderate Effect

BackgroundA growing number of studies have investigated the efficacy of novel, adjunctive pharmacotherapies for treatment of cognitive deficits in schizophrenia with conflicting results.AimsTo investigate the comparative efficacy of these agents on cognition and symptoms in schizophrenia, and to identify promising cognitive domains and candidate medications that can be incorporated in treatment trials combined with cognitive remediation to maximise treatment effects.MethodA total of 26 double-blind, placebo-controlled studies investigating medications targeted at cholinergic, glutamatergic or serotonergic receptor classes and with participants with schizophrenia or schizoaffective disorder were identified.ResultsMedications targeted at the cholinergic receptor class produced marginal improvements in verbal learning and memory (d = 0.23, P = 0.06), and donepezil, a specific type of cholinergic agonist, produced a moderate effect (d = 0.58) on spatial learning and memory. Cholinergic and glutamatergic agents produced moderate effect-size improvements on negative symptoms (d = 0.54 and d = 0.62 respectively), and small effect-size improvements on general symptoms (d = 0.46 and d = 0.41 respectively). Serotonergic agents produced small effect-size improvements in positive symptoms (d = 0.33).ConclusionsCholinergic medications produced marginal improvement in verbal learning and memory and moderate improvements on spatial learning and memory, although there was no evidence to support the use of glutamatergic or serotonergic medications as a stand-alone treatment for improving cognitive function. Cholinergic and glutamatergic agents improved negative and general symptoms, whereas serotenergic medications improved positive symptoms.

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).

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