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.

scholarly journals The acute efficacy of antipsychotics in schizophrenia: a review of recent meta-analyses

2018 ◽  
Vol 8 (11) ◽  
pp. 303-318 ◽  
Author(s):  
Peter M. Haddad ◽  
Christoph U. Correll
Keyword(s):  
Quality Of Life ◽  
Negative Symptoms ◽  
Mechanisms Of Action ◽  
First Episode ◽  
Positive Symptoms ◽  
Treatment Resistant ◽  
Antipsychotic Efficacy ◽  
Symptom Domains ◽  
Meta Analyses

Schizophrenia is the eighth leading cause of disability worldwide in people aged 15–44 years. Before antidopaminergic antipsychotics were introduced in the 1950s, no effective medications existed for the treatment of schizophrenia. This review summarizes key meta-analytic findings regarding antipsychotic efficacy in the acute treatment of schizophrenia, including clozapine in treatment-resistant patients. In the most comprehensive meta-analysis of randomized controlled trials conducted in multi-episode schizophrenia, antipsychotics outperformed placebo regarding total symptoms, positive symptoms, negative symptoms, depressive symptoms, quality of life and social functioning. Amongst these outcomes, the standardized mean difference for overall symptoms was largest, that is, 0.47 (95% credible interval = 0.42–0.51), approaching a medium effect size, being reduced to 0.38 when publication bias and small-trial effects were accounted for. A comparison of two meta-analyses indicated that first-episode patients, compared with multi-episode patients, were more likely to have at least minimal treatment response [⩾20% Positive and Negative Syndrome Scale (PANSS)/Brief Psychiatric Rating Scale (BPRS) score reduction: 81% versus 51%] and good response (⩾50% PANSS/BPRS score reduction: 52% versus 23%). In multi-episode schizophrenia, no response or worsening after 2 weeks of a therapeutic antipsychotic dose was highly predictive of not achieving a good response at endpoint (median treatment = 6 weeks: specificity = 86%; positive predictive value = 90%), suggesting a change in treatment should be considered in such cases. In first-episode psychosis, adequately dosed antipsychotic treatment trials for more than 2 weeks are recommended before using no response or worsening as a decision point for aborting a given antipsychotic. In clearly defined treatment-resistant schizophrenia, clozapine generally outperformed other antipsychotics, especially when dosed appropriately (target = 3–6 months’ duration; trough clozapine level ⩾350–400 μg/L) with a response rate (⩾20% PANSS/BPRS) of 33% by 3 months of treatment. High antipsychotic doses and psychotropic combinations are unlikely to be superior to standard doses of antipsychotic monotherapy. Acute antipsychotic efficacy in schizophrenia depends on the targeted symptom domain (greater efficacy: total and positive symptoms, lesser efficacy: negative symptoms, depressive symptoms, social functioning and quality of life). Greater antipsychotic efficacy is associated with higher total baseline symptom severity, treatment-naïveté/first-episode status, shorter illness duration, and trials that are nonindustry sponsored and that have a lower placebo effect. The heterogeneity of antipsychotic response across individuals and key symptom domains, the considerable degree of nonresponse/treatment resistance in multi-episode patients, and the adverse effect potential of antipsychotics are major limitations, underscoring the need to develop new medications for the treatment of schizophrenia. Drug development should include matching patient subgroups, which are identified by means of clinical and biomarker variables, to mechanisms of action of novel medications, targeting specific symptom domains, and investigating mechanisms of action other than dopaminergic blockade.

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.

scholarly journals The Use of Evidence-Based Acupuncture: Current Evidence

2022 ◽  
Author(s):  
Dedi Ardinata
Keyword(s):  
Clinical Evidence ◽  
Scientific Evidence ◽  
Current Evidence ◽  
Systematic Research ◽  
Evidence Based ◽  
Clinical Expertise ◽  
Quality Of Evidence ◽  
Assessment Development ◽  
Evidence Quality

Evidence-based medicine (EBM), which emphasizes that medical decisions must be based on the most recent best evidence, is gaining popularity. Individual clinical expertise is combined with the best available external clinical evidence derived from systematic research in the practice of EBM. The key and core of EBM is the hierarchical system for categorizing evidence. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system divides evidence quality into four categories: high, moderate, low, and very low. GRADE is based on the lowest quality of evidence for any of the outcomes that are critical to making a decision, reducing the risk of mislabeling the overall evidence quality, when evidence for a critical outcome is lacking. This principle is also used in acupuncture as a complementary and integrative treatment modality, but incorporating scientific evidence is more difficult due to a number of factors. The goal of this chapter is to discuss how to establish a clinical evidence system for acupuncture, with a focus on the current quality of evidence for a variety of conditions or diseases.

Schizophrenia, Mental State, and Mother—Infant Interaction: Examining the Relationship

1999 ◽  
Vol 33 (6) ◽  
pp. 902-911 ◽  
Author(s):  
Martien Snellen ◽  
Kerry Mack ◽  
Tom Trauer
Keyword(s):  
Mental State ◽  
Therapeutic Intervention ◽  
Negative Symptoms ◽  
Positive Symptoms ◽  
Treatment Resistant ◽  
Optimal Care ◽  
The Relationship

Objective: The aim of this study is to examine the role that disturbance of mental state of hospitalised mothers with a postpartum schizophrenic illness plays in determining the quality of mother-infant interactions. Method: We examined the relationship between the nature and severity of symptomatology in mothers with schizophrenia and the quality of her interactions with her infant in a sample of 15 mother-infant dyads admitted to a psychiatric Mother-Baby Unit. Data were obtained at admission and discharge. Results: Mothers with florid positive symptoms and prominent negative symptoms of schizophrenia and their infants were identified as being at particular risk of displaying disturbed interactions. The adverse contribution of negative symptoms was often not evident until after the positive symptoms had resolved. Conclusions: Given that negative symptoms are often treatment resistant, optimal care of mothers with schizophrenia and their infants needs to involve ongoing therapeutic intervention which specifically addresses disturbances of mother-infant interaction. Further research is required to identify which interventions are likely to be of greatest benefit.

scholarly journals Efficacy of Memantine in Schizophrenic Patients: A Systematic Review

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Giuseppe Di Iorio ◽  
Gaia Baroni ◽  
Marco Lorusso ◽  
Chiara Montemitro ◽  
Maria Chiara Spano ◽  
...  
Keyword(s):  
Systematic Review ◽  
Negative Symptoms ◽  
Positive Symptoms ◽  
Cognitive Symptoms ◽  
Review Of The Literature ◽  
Excitatory Neurotransmitter ◽  
Aspartate Receptor ◽  
Schizophrenic Patients ◽  
Promising Treatment

Several evidences support the hypothesis that glutamatergic dysfunction may be implicated in the pathogenesis of schizophrenia and in the last few years great interest has been focused on the role of the N-methyl-D-aspartate receptor (NMDAR). Glutamate is the main excitatory neurotransmitter in human CNS and it plays a prominent role in synaptic plasticity, learning, and memory and other cognitive functions. Increasing interest in memantine add-on therapy in schizophrenic patients with negative and cognitive symptoms may suggest that memantine could be a new promising treatment in schizophrenia. The aim of this update was to evaluate clinical data about the memantine effectiveness in schizophrenic patients. Our systematic review of the literature highlights that memantine therapy in schizophrenic patients seems to improve mainly negative symptoms while positive symptoms and cognitive symptoms did not improve significantly.

scholarly journals The Use of Stimulant Augmentation of Second Generation Antipsychotics in the Management of Negative Symptoms of Schizophrenia: A Case Report

2018 ◽  
Vol 3 (08) ◽  
Author(s):  
Heela Azizi ◽  
Yu Hao Zeng ◽  
Jisha Kallikkadan ◽  
Alexa Kahn ◽  
Olaniyi Olayinka ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Positive Symptoms ◽  
Antipsychotic Therapy ◽  
Case Presentation ◽  
Point Reduction ◽  
Second Generation Antipsychotics ◽  
Potential Benefits ◽  
Stimulant Medications ◽  
Negative Syndrome ◽  
Mesocortical Pathway

Background: Negative symptoms of schizophrenia have been demonstrated to be due to decreased dopamine in the mesocortical pathways. Stimulant medications are a class of medications that can increase dopamine activity in the mesocortical pathway. Case Presentation: We present the case of a patient whose negative symptoms improved from a Positive and Negative Syndrome (PANSS) score of 39 to 11 on the negative symptoms subscale during a three-week trial of dopamine agonist augmentation of antipsychotic therapy. The score on the positive symptoms subscale on PANSS remained low with a two-point reduction at the end of the three-week period. Conclusion: The potential benefits of using stimulant medications in treating negative symptoms of schizophrenia are discussed.

scholarly journals Cognitive Dysfunction in Schizophrenia

2020 ◽  
Vol 9 (2) ◽  
pp. 52
Author(s):  
Susana Anggar Kusuma ◽  
Yunias Setiawati
Keyword(s):  
Problem Solving ◽  
Mental Disorder ◽  
Negative Symptoms ◽  
Memory Function ◽  
Cognitive Disorder ◽  
Positive Symptoms ◽  
Cognitive Symptoms ◽  
Affective Symptoms ◽  
Attention Function ◽  
Severe Disorder

Schizophrenia is a mental disorder which includes: positive symptoms, negative symptoms, cognitive symptoms, affective symptoms and aggressive symptoms. Cognitive disorder is the most severe disorder compared to other symptoms of schizophrenia because it can interfere with daily functions, including memory function, attention function, problem solving function, speech function and social skills.

Doing no harm: Addressing the quality of evidence in translating research to practice in preliminary research fields

2017 ◽  
Vol 5 (4) ◽  
pp. 490
Author(s):  
Mei'En Lim ◽  
Corrine Reid
Keyword(s):  
Research Evaluation ◽  
Evidence Base ◽  
Current Evidence ◽  
Rating Systems ◽  
Quality Of Evidence ◽  
Assessment Development ◽  
Research Fields ◽  
Evidence Quality ◽  
Evidence Rating

Background: Current evidence appraisal rating systems, such as the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, are oriented toward and anchored by randomized controlled trials (RCTs) as the gold standard methodology. In many fields, this standard of evidence is rarely, if ever, met. Often, research at the clinical application end of the translational process is embedded in real world practice that does not lend itself to RCTs and is characterised by more pragmatic research using mixed methodologies. Arguably, accountability through research evaluation is even more important in such cases where research design is preliminary and clinical impact is, often, already a reality. Further, practice translation must be privileged as the central goal of the research synthesis under such circumstances in that the destination of all clinical science is the person of the patient.. Methods: In response to these demand characteristics, a practitioner-informed research framework was used to drive and pilot development of an evidence quality grading system that could accommodate a disparate and oblique evidence base. Reid’s person-centered framework was used to establish whether clinician-derived criteria for quality research practice had been met. Results: This brief report presents the Quality of Evidence Rating System (QERS) in the hope of facilitating discussion about accountability pathways for translational scientist-practitioners.Conclusion: The QERS provides a scaffold to help when looking for evidence that researchers have consciously addressed the issues of evidence quality when reporting their research in the published literature.

scholarly journals Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities

CNS Spectrums ◽  
2019 ◽  
Vol 24 (S1) ◽  
pp. 38-69 ◽  
Author(s):  
Amanda Krogmann ◽  
Luisa Peters ◽  
Laura von Hardenberg ◽  
Katja Bödeker ◽  
Viktor B. Nöhles ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Negative Symptoms ◽  
Partial Agonist ◽  
Treatment Resistance ◽  
Positive Symptoms ◽  
Acid Oxidase ◽  
Cognitive Symptoms ◽  
Amino Acid Oxidase ◽  
Negative Results ◽  
Long Acting

Schizophrenia remains one of the most severe medical diseases. Current dopamine modulating first-generation and second-generation antipsychotics target mainly positive symptoms, but not/inadequately negative and cognitive symptoms. Additional challenges include non-adherence and adverse effects, especially cardiometabolic dysregulation. This review evaluates new/emerging pharmacological treatments for schizophrenia. Therapies targeting total symptoms include cannabidiol, D3 antagonist/5-HT1A partial agonist F17464, lumateperone (ITI-007), phosphodiesterase 10A (PDE10A) inhibitors MK-8189 and TAK-063, sodium nitroprusside, and trace amine-associated receptor-1 (TAAR1) agonist RO5263397 and SEP-363856. Treatments targeting negative symptoms include the PDE10A inhibitor LuAF-11167, 5-HT2A inverse agonist pimavanserin, sigma-2/5-HT2A antagonist roluperidone (MIN-101), and d-amino acid oxidase (DAAO) inhibitor TAK-831. Agents targeting primarily cognitive dysfunction are the glycine transporter-1 inhibitor BI-425809 and cannabidiol. Therapies targeting residual positive symptoms/treatment-resistant schizophrenia include pimavanserin, dopamine D1/D2 antagonist LuAF-35700, and DAAO inhibitor sodium benzoate. Two new long-acting injectable antipsychotic formulations, Aripiprazole Lauroxil NanoCrystal® and the first subcutaneous injectable LAI Perseris (RBP-7000), were recently approved by U.S. Food and Drug Administration, and positive results were announced for Risperidone ISM®, each achieving therapeutic levels within 24 hours, without need for initial oral cotreatment/loading injection-strategies. Paliperidone palmitate 6-monthly intramuscularly injectable and Risperidone subcutaneously injectable TV46000 are currently under investigation. Finally, the samidorphan+olanzapine combination targets reduced weight gain liability, while maintaining olanzapine’s efficacy. Most of these trial programs are still ongoing or have yielded mixed or even negative results. Thus, additional mechanisms of action and agents require study to improve schizophrenia outcomes for total/positive symptoms with reduced adverse effects, but also cognitive symptoms, negative symptoms, and treatment resistance, the areas of greatest need in schizophrenia currently.

Predictors of persistence of ultrahigh risk symptoms and predictors of transition into psychosis

2011 ◽  
Vol 26 (S2) ◽  
pp. 2086-2086
Author(s):  
M. van der Gaag ◽  
J. Rietdijk ◽  
H. Ising ◽  
S. Dragt ◽  
R. Klaassen ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Genetic Risk ◽  
Help Seeking ◽  
Negative Symptoms ◽  
Predictor Variables ◽  
Positive Symptoms ◽  
Personal Beliefs ◽  
Inclusion Period

AimsTo determine predictors of transition from ultrahigh risk into psychosis.MethodThe Dutch EDIE trial has included 201 people with an ultrahigh risk for psychosis. These were included with both a referral based strategy and a screening all help-seeking people strategy. The study had a 24 month inclusion period and an 18 mont follow-up period with each patient. The preliminary results are presented.ResultsA loogistic regression was performed over 164 cases. 29 patients developed a psychosis.Predictor variables were depression, social intercation anxiety, positive symptoms on the CAARMS, negative symptoms on the CAARMS, quality of life, social functioning, genetic risk, and the personal beliefs about illness.The backward logistice regression (likelyhood ratio) discarded four variables. Predictors of psychosis were depression, positive symptoms, genetic liability and beliefs about illness at basline.ConclusionsPeople with hihd scores on depression and positive symptoms are likely to develop a psychosis. Also those who have a psychotic parent and positive symptoms a more lekly to make a transition. Interestingly people that consider their condition as hopeless, feel entrapped by their condition, excluded by other pople and not in control of symptoms also have a heightened chance for developing psychosis in this sample.

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