The acute efficacy of antipsychotics in schizophrenia: a review of recent 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.

Download Full-text

Dimensions of Outcome with Clozapine

The British Journal of Psychiatry ◽

10.1192/s000712500029692x ◽

1992 ◽

Vol 160 (S17) ◽

pp. 46-53 ◽

Cited By ~ 146

Author(s):

Herbert Y. Meltzer

Keyword(s):

Quality Of Life ◽

Negative Symptoms ◽

Treatment Compliance ◽

Family Burden ◽

Positive Symptoms ◽

Treatment Resistant ◽

Cost Of Treatment ◽

Schizophrenic Patients ◽

The Cost

Various outcome measures following clozapine administration to neuroleptic-resistant schizophrenic patients are considered. The importance of a multidimensional perspective is emphasised. There was significant improvement in positive symptoms, some negative symptoms, quality of life, some types of cognitive function (e.g. semantic memory), extrapyramidal function, and tardive dyskinesia. Readmission to hospital, and family burden were markedly reduced, which achieved significant savings in the cost of treatment. Compliance with clozapine and weekly blood testing can be achieved in the majority of treatment-resistant cases. These benefits may occur independently of each other.

Download Full-text

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

Mental Health Clinician ◽

10.9740/mhc.2019.05.116 ◽

2019 ◽

Vol 9 (3) ◽

pp. 116-123 ◽

Cited By ~ 1

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.

Download Full-text

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

Australian & New Zealand Journal of Psychiatry ◽

10.1046/j.1440-1614.1999.00641.x ◽

1999 ◽

Vol 33 (6) ◽

pp. 902-911 ◽

Cited By ~ 46

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.

Download Full-text

Effect of substance misuse in early psychosis

The British Journal of Psychiatry ◽

10.1192/s0007125000297791 ◽

1998 ◽

Vol 172 (S33) ◽

pp. 134-136 ◽

Cited By ~ 72

Author(s):

Jean Addington ◽

Donald Addington

Keyword(s):

Quality Of Life ◽

Substance Use ◽

Negative Symptoms ◽

Substance Misuse ◽

Age Of Onset ◽

Past History ◽

Psychotic Symptoms ◽

First Episode ◽

History Of

Background Studies examining the temporal relationship between substance use and the onset of psychotic symptoms in schizophrenia are inconclusive.Method Three groups of out-patients with schizophrenia were compared on onset of illness, symptoms and quality of life. Fifty-one subjects had no past or present history of substance misuse, 29 subjects had a history of past substance misuse occurring around the onset of their illness, and 33 subjects were currently misusing substances.Results Current substance misusers had poorer quality of life scores and less negative symptoms than the non-users. Those who had a past history of substance misuse had a significantly earlier age of onset than those with no substance use.Conclusions Attention should be paid to substance misuse present at the first episode. Treatment for schizophrenia should begin even though a diagnosis of drug-induced psychosis cannot be ruled out.

Download Full-text

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

European Psychiatry ◽

10.1016/s0924-9338(11)73789-0 ◽

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.

Download Full-text

Effect of positive and negative symptoms on schizophrenia related quality of life of hospitalized schizophrenic patients at Sargodha and Lahore: Moderating role of neuropsychiatric symptoms

Journal of the Pakistan Medical Association ◽

10.47391/jpma.1105 ◽

2020 ◽

pp. 1-11

Author(s):

Tehmina kousar ◽

Muhammad Naveed Riaz

Keyword(s):

Quality Of Life ◽

Negative Correlation ◽

Negative Symptoms ◽

Significant Positive Correlation ◽

Neuropsychiatric Symptoms ◽

Significant Negative Correlation ◽

Positive Symptoms ◽

Related Quality ◽

Schizophrenic Patients

Abstract Objective: The purpose of study was to find out the moderating effect of neuropsychiatric symptoms in the relationship between positive-negative symptoms of schizophrenia with quality of life of schizophrenic patients. Subject and Methods: This cross-sectional study was conducted at Lahore and Sargodha, Pakistan. Data was collected by administering the Positive and Negative of Schizophrenia Questionnaire, Quality of Life of Schizophrenia Scale and Neuropsychiatry Inventory. SPSS-23 has been used for data analysis. The study has been completed in one year. The data was collected from September 4, 2017 to November 1, 2018 after 10am in the morning. Results: The findings indicate that positive symptoms have significant positive correlation with negative symptoms (p < .001) and neuropsychiatric symptoms (p < .001) whereas significant negative correlation with schizophrenia quality of life (p < .001). Negative symptoms have significant positive correlation with neuropsychiatric symptoms (p < .001) whereas significant negative correlation with schizophrenia related quality of life (p < .001). Neuropsychiatric symptoms have significant negative correlation with schizophrenia quality of life (p < .001) in the study. Moreover, neuropsychiatric symptoms moderated between negative symptoms and schizophrenia related quality of life. Conclusion: In this study, findings suggested that negative symptoms and neuropsychiatric symptoms have positive association with quality of life of schizophrenic patients whereas positive symptoms have inverse relationship. The study also revealed that neuropsychiatric symptoms enhanced the effect of negative symptoms on quality of life of schizophrenic patients. Keywords: Schizophrenia, Positive Symptoms, Negative Symptoms, Quality of Life, Neuropsychiatric Symptoms Continuous...

Download Full-text

The centrality of motivation in psychosocial functioning: Network and bifactor analysis of the Quality of Life Scale in first episode psychosis

10.31234/osf.io/hdzye ◽

2021 ◽

Author(s):

Samuel Abplanalp ◽

Kim T. Mueser ◽

Daniel Fulford

Keyword(s):

Quality Of Life ◽

Psychosocial Functioning ◽

Negative Symptoms ◽

First Episode Psychosis ◽

First Episode ◽

Episode Psychosis ◽

Quality Of Life Scale ◽

Life Scale ◽

Bifactor Modeling

Psychosocial functioning impairment is prevalent in first episode psychosis and chronic schizophrenia. The Quality of Life Scale (QLS) is a widely-used tool to measure psychosocial functioning; however, given the overlap between negative symptoms and functioning, along with the QLS being conceptualized initially as a measure of the deficit syndrome, it is unclear whether summing QLS items into a total score is an appropriate measure of overall psychosocial functioning. This study aimed to examine the centrality of QLS items and the appropriateness of using a QLS total score. Participants with first episode psychosis (n = 404) completed the QLS. Item centrality was assessed using a network analysis approach, while reliability and dimensionality of the QLS total score and subscales were measured using bifactor modeling and related psychometric indices. Network analysis results showed that an item relating to motivation was the most central item within the scale. Moreover, bifactor modeling results found that motivation and other items relating to negative symptoms may reflect the QLS total score more strongly than other functioning (i.e., Interpersonal, Instrumental) domains. Based on these findings, we urge researchers to use caution when using a QLS total score, as it may unequally confound functional domains and motivation. Moreover, our results continue to underscore the importance of negative symptoms, particularly motivational impairment, in psychosocial functioning. Future studies should aim to examine the centrality of other functioning measures in psychosis and schizophrenia, as our results suggest that psychosocial functioning may be greatly influenced by motivation.

Download Full-text

The subjective quality of life in deficit and nondeficit schizophrenic patients

European Psychiatry ◽

10.1016/j.eurpsy.2005.04.010 ◽

2005 ◽

Vol 20 (4) ◽

pp. 346-348 ◽

Cited By ~ 7

Author(s):

Pascal Delamillieure ◽

Dominique Ochoa-Torres ◽

Thierry Vasse ◽

Perrine Brazo ◽

Raphaël Gourevitch ◽

...

Keyword(s):

Quality Of Life ◽

Negative Symptoms ◽

Subjective Quality ◽

Positive Symptoms ◽

Subjective Quality Of Life ◽

General Psychopathology ◽

Schizophrenic Patients

AbstractWe assessed the subjective quality of life (QOL) of 30 deficit schizophrenic patients compared to 112 nondeficit schizophrenic patients. The deficit patients did not differ in term of QOL, total score of positive symptoms, general psychopathology from the nondeficit patients. This result suggested an absence of impact of primary negative symptoms on the subjective QOL in schizophrenic patients.

Download Full-text

S236. QUALITY OF LIFE AND ASSOCIATION WITH SYMPTOMS IN PATIENTS WITH SCHIZOPHRENIA SIX YEARS AFTER FIRST EPISODE PSYCHOSES

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa031.302 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S128-S129

Author(s):

Gitte Andersen ◽

Helle Schaebel ◽

Johannes Gehr ◽

Birte Glenthoj ◽

Mette Ødegaard Nielsen

Keyword(s):

Quality Of Life ◽

Life Satisfaction ◽

Social Relations ◽

Negative Symptoms ◽

First Episode ◽

Antipsychotic Treatment ◽

Housing Situation ◽

Symptomatic Remission

Abstract Background Quality of Life in patients with schizophrenia is an important part of successful treatment outcome. Our previous results showed, that despite symptomatic improvement after six weeks of antipsychotic treatment, the overall Quality of Life was not improved. The aim of the present study is to explore Quality of Life after six years, and the association with symptomatic remission or symptoms in general. The following hypothesizes were tested: Quality of life will be improved after six years, and patients in remission will report a better Quality of Life compared to patients not in remission. Further, low Quality of Life will be associated with high level of negative symptoms. Methods In this study 69 antipsychotic drug-naïve, first episode patients with schizophrenia (ICD-10) were included between 2009–2013, and 31 patients where re-examined after 6.7 years (range 4.2–8.3). Quality of Life was reported by answering a validated questionnaire counting 18 questions, divided into three domains: Housing Situation, Social Relations and Life Satisfaction. Higher scores indicate higher satisfaction within the domain. Symptoms were assessed using Positive and Negative Syndrome Scale (PANSS) at baseline and follow up. Additionally, at follow up negative symptoms were assessed with Brief Negative Symptoms Scale (BNSS), focusing on three domains: Anhedonia, Asociality, and Avolition. For statistical analysis, Spearman Rank, paired T-test and Mann-Whitney U-test were used. Results The overall Quality of Life was improved (p=0.013) after six years. The improvement was found in Housing Situation (p<0.001) and Social Relation (p<0.001) but not in Life Satisfaction (p=0.9) Symptomatic remission was observed in 15 (48%) patients. Quality of Life in patients in remission did not differ from patients without remission (p=0.16) Patients improved in PANSS total, positive, negative and general score (all p<0.001). A negative correlation was observed between Quality of Life (Social Relations) and PANSS-negative (r=-0.40, p<0.05), and PANSS-total score (r=-0.43 p<0.05), and between Quality of Life (Life Satisfaction) and PANSS-general (r=-0.53, p<0.01) and PANSS-total score(r=-0.44, p=0.05). There was no correlation between Quality of Life and positive symptoms. All three Quality of Life subdomains correlated with BNSS total (p<0.05, r<-0.42). This was driven by a high correlation with Anhedonia (all r<-0.55, all p<0.005) and Asociality (all r<-0.51, all p<0.005) but no correlation with Avolition. Discussion Patients in this study improved their subjective Quality of Life over a six-year period. This improvement was found within their Social Relations and an improved Housing Situation. In contrast, there was no improvement in patients’ Life Satisfaction. Remission was found in half of the patients. Although Quality of life was associated with total symptom severity, it seemed to be independent of symptomatic remission. Quality of life was most associated with the level of negative symptoms, especially with Anhedonia and Asociality. This is in line with previous findings of associations between negative symptoms and the ability to maintain social relations and to function in everyday life. The results underline the importance of increased focus on negative symptoms.

Download Full-text