Effective Treatment For Negative Symptoms Research Articles

Cariprazine as a treatment for negative psychotic symptoms in first-episode psychosis: case series.

Negative psychotic symptoms are among the most disabling features of schizophrenia, and are strongly associated with relatively poor clinical and functional outcomes. However, there are no effective treatments for negative symptoms, and this represents a major unmet clinical need. Recent research has shown that negative symptoms are already present in many patients at illness onset. There is evidence that cariprazine may improve negative symptoms in patients with chronic schizophrenia. However, its utility in treating negative symptoms in the early stage of the disorder is unclear. Here, we report six cases of patients with first-episode psychosis who were treated with cariprazine.

High frequency repetitive transcranial magnetic stimulation of dorsomedial prefrontal cortex for negative symptoms in patients with schizophrenia: A double-blind, randomized controlled trial

Negative symptoms are the major challenge in clinical management of schizophrenia. Dorsomedial prefrontal cortex (DMPFC) has been suggested to be highly involved in the mechanisms of negative symptoms of schizophrenia. However, the effect of repetitive Transcranial Magnetic Stimulation (rTMS) over DMPFC has not yet been well studied. In this double-blind, randomized controlled rTMS clinical trial, thirty-three participants (17 in active group and 16 in sham group) were enrolled. This study includes the rTMS treatment phase (lasts for 4 weeks) and a subsequently naturalistic follow-up phase (lasts for another 4 weeks). Schizophrenia patients with prominently negative symptoms were randomly assigned to receive 10 Hz or sham rTMS intervention. The score change in Scale of Negative Symptoms (SANS) was defined as the primary outcome measure. There was a significant decrease in negative symptoms, especially affective flattening and anhedonia in schizophrenia patients after DMPFC-rTMS intervention. Moreover, the negative symptoms improvement could maintain at least another 4 weeks. In addition, no memory impairment or serious adverse reaction of rTMS emerged. Our results suggest that high frequency rTMS over DMPF may represent a safe and effective treatment for negative symptoms in patients with schizophrenia.

Main methods of psychotherapy for negative schizophrenia symptoms

The review covers publications on the main methods of psychotherapy that can reduce negative symptoms of schizophrenia. Negative symptoms are difficult to treat, and generally persist despite standard antipsychotic treatment. Combined methods including medical and non-medical treatments can be more effective and fully meet the therapeutic needs of a patient. We examined the effects of cognitive-behavioral therapy, social skills training, and family interventions on negative symptoms. The negative symptoms of schizophrenia underlie poor functioning, impaired professional performance and patient disability, thereby being a key factor in the enormous financial cost to the healthcare. Effective treatment of negative symptoms will lead to clinical and functional recovery in patients with schizophrenic spectrum disorders.

Effectiveness of Integrated Neurocognitive Therapy on Cognitive Impairment and Functional Outcome for Schizophrenia Outpatients.

Cognitive impairment is highly prevalent in patients with schizophrenia and schizoaffective disorder. Many interventions have been developed to treat cognitive deficit, since it has a strong impact on functional outcome; however, there are no integrated interventions targeting multiple neuro- and social-cognitive domains with a particular focus on the generalization of the effects of therapy on the functional outcome. Recently, a group of experts has developed a cognitive remediation group therapy approach called Integrated Neurocognitive Therapy (INT), which includes exercises to improve the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) neuro- and social-cognitive domains. This systematic review and meta-analysis aimed to assess the efficacy of this approach. We conducted a search of PubMed, Scopus, Web of Science, and PsycINFO to select primary studies evaluating INT in schizophrenic and schizoaffective patients. The primary outcomes of the meta-analysis included negative and positive symptoms and global functioning. Two randomized controlled trials met inclusion criteria. A total of 217 participants were included. Based on the results from the Positive and Negative Syndrome Scale (PANSS), a significant pooled effect size was observed for negative symptoms, which demonstrated not only an improvement in the patients treated immediately after therapy but also a permanence of positive results at a 9–12-month follow-up. On the other hand, no significant effect size was observed for positive symptoms. In addition, a significant pooled effect size was found for Global Assessment of Functioning (GAF), which shows how INT's integrated approach has lasting positive implications on patients' functional outcome. We concluded that INT might be an effective treatment for negative symptoms and global functioning in patients with schizophrenia, compared to treatment as usual (TAU).

F225. LEVODOPA AUGMENTATION OF ANTIPSYCHOTICS FOR THE TREATMENT OF NEGATIVE SYMPTOMS IN SCHIZOPHRENIA

BackgroundNegative symptoms (i.e., motivation deficits and diminished emotional expression) are prevalent in schizophrenia and consistently linked with functional impairment for affected individuals. Despite advances in psychopharmacology for schizophrenia, there remain no effective treatments for these negative symptoms. Older literature, however, suggests that levodopa in conjunction with antipsychotic treatment can have beneficial effects for patients with schizophrenia. While supporting the safety and potential efficacy of dopamine augmentation, these studies did not evaluate effects within specific symptom domains, particularly negative symptoms. This open-label pilot study was conducted to evaluate the preliminary efficacy and safety of levodopa augmentation of antipsychotics for the treatment of negative symptoms.MethodsTen stable outpatients with schizophrenia between the ages of 18 and 60 were enrolled. All were treated with stable atypical antipsychotic monotherapy for at least eight weeks, and had a minimum total score of 30 on the Scale for the Assessment of Negative Symptoms (SANS). Participants were treated with adjunctive open-label levodopa/carbidopa, with dose titration to levodopa 300mg TID over 38 days as tolerated, and dose maintenance for the remainder of the eight-week trial. Baseline assessments consisted of the SANS, Scale for the Assessment of Positive Symptoms (SAPS), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), Calgary Depression Scale for Schizophrenia (CDSS), MATRICS Consensus Cognitive Battery (MCCB), and Quality of Life Scale (QLS) for community functioning. Treatment side effects were evaluated with the Simpson Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), Abnormal Involuntary Movement Scale (AIMS), UKU side effect rating scale (UKU), Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS), Yale-Brown Obsessive Compulsive Scale (YBOCS), and Barratt Impulsiveness Scale (BIS). Participants were reassessed on measures of psychosis and side effects weekly for the first four weeks, and every two weeks thereafter. The SANS and CGI were repeated at weeks 4 and 8, with the MCCB and QLS re-administered at week 8. Statistical analyses included the intent-to-treat sample (i.e., participants who received at least one dose of study medication) and consisted of linear mixed models for change in SANS total score (our primary outcome), and change in other clinical and side effects measures as a result of treatment.ResultsEnrolled participants (eight male and two female) had a mean age of 37.2 years. Seven participants completed the study, with three participants dropping out. The mean final dose of levodopa for study completers was 835.7 mg (SD 170.1). Levodopa augmentation resulted in a significant improvement in negative symptoms, with a mean SANS reduction for study completers of 15.3 (SD 5.7). This equated to a mean SANS improvement of 25.5% (range 17% to 57%), with 43% of study completers experiencing > 20% improvement in SANS score. Notably, significant improvement in negative symptoms emerged after the first four weeks of treatment. There was no significant change in positive symptoms, nor other clinical outcomes or side effect measures.DiscussionOur findings suggest that levodopa augmentation of antipsychotics may be an effective and well-tolerated treatment for negative symptoms in schizophrenia. These findings, however, need replication in larger randomized controlled trials. With the dearth of available treatments for negative symptoms, levodopa augmentation may represent a novel pharmacologic strategy to address this critical unmet therapeutic need for schizophrenia.

F58. COMMUNITY-BASED MULTI-SITE RANDOMIZED CONTROLLED TRIAL OF BEHAVIORAL ACTIVATION FOR NEGATIVE SYMPTOMS OF INDIVIDUALS WITH CHRONIC SCHIZOPHRENIA

BackgroundAs existing treatments for negative symptoms in schizophrenia have limited empirical support, development of effective treatments for negative symptoms in schizophrenia is in urgent need. Behavioral activation (BA), which is an evidence-based treatment for depression, is a promising candidate treatment for negative symptoms as it proved its feasibility and preliminary efficacy in non-randomized controlled trial for community dwelling individuals with chronic schizophrenia (Choi et al., 2015; Mairs et al., 2011). The primary purpose of the current study was to investigate whether BA would improve negative symptoms as compared with treatment as usual (TAU) for community dwelling individuals with chronic schizophrenia in a multi-site randomized controlled trial. In addition, we explored whether BA would improve other psychiatric symptoms, quality of life and neuro-cognitive functioning.MethodsFor multi-site trials, mental health professionals were trained with BA manual (Choi et al., 2015) and their fidelity was checked by the authors. BA was delivered in a group format once a week for 10 weeks. Participants aged 18 years or older were recruited from community mental health centers and day hospitals in Seoul and Gyeonggi-do area. A total of seventy-two patients with negative symptoms of schizophrenia were randomly assigned into either BA+TAU or TAU. As a primary outcome, negative symptoms were measured using clinical interviews (e.g., BNSS, CAINS, PANSS negative symptoms factor) and self-report questionnaires (i.e., MAP-SR) before and after the 10-week treatments. The secondary outcome measures included other psychiatric symptoms, quality of life, and neuro-cognitive assessment.ResultsBA was well accepted by community dwelling individuals with chronic schizophrenia (drop-out rates of BA+TAU and TAU, 10% and 14%, respectively). Intention-to-treat analyses indicated that compared to TAU condition, BA+TAU group showed greater improvement in negative symptoms, as measured by CAINS, BNSS, and PANSS negative symptom factor (Time*Group interaction effects, F=7.476, p<.01 for CAINS total; F=5.663, p<.05 for BNSS total; F=6.092, p<.05 for PANSS negative symptoms factor). In addition, the results indicated group differences in favor of BA+TAU on the PANSS general psychopathology factor and the Quality of Life, but not neurocognitive functioning (Time*Group interaction effects, F=5.660, p<.05 for PANSS general psychopathology factor; F=7.541, p<.01 for QOL total).DiscussionThe results of the current study demonstrate the feasibility and the efficacy of BA+TAU for negative symptoms of community dwelling individuals with chronic schizophrenia as compared to TAU when delivered by BA trained mental health professionals. Thus, it is speculated that BA is an effective adjunct psychosocial approach to usual comprehensive psychiatric rehabilitation for negative symptoms. Since the current study is ongoing and follow-up data will be available by the time of presentation at SIRS 2018, it will be examined whether benefits of BA would be maintained 3 months after the termination of 10-week BA treatment.

Negative symptoms of psychosis: A life course approach and implications for prevention and treatment.

Negative symptoms are a cause of enduring disability in serious mental illness. In spite of this, the development of effective treatments for negative symptoms has remained slow. The challenge of improving negative symptom outcomes is compounded by our limited understanding of their aetiology and longitudinal development. A literature search was conducted for life course approach of negative symptoms using PubMed. Further articles were included following manual checking of reference lists and other search strategies. The paper contains a theoretical synthesis of the literature, summarized using conceptual models. Negative symptom definitions are compared and considered within a context of the life course. Previous studies suggest that several illness phases may contribute to negative symptoms, highlighting our uncertainty in relation to the origin of negative symptoms. Similar to other aspects of schizophrenia, negative symptoms likely involve a complex interplay of several risk and protective factors at different life phases. Concepts suggested in this article, such as "negative symptom reserve" theory, require further research, which may inform future prevention and treatment strategies.

Psychological and psychosocial interventions for negative symptoms in psychosis: Systematic review and meta-analysis

BackgroundNegative symptoms observed in patients with psychotic disorders undermine quality of life and functioning. Antipsychotic medications have a limited impact. Psychological and psychosocial interventions, with medication, are recommended. However, evidence for the effectiveness of specific non-biological interventions warrants detailed examination.AimsTo conduct a meta-analytic and systematic review of the literature on the effectiveness of non-biological treatments for negative symptoms in psychotic disorders.MethodWe searched for randomised controlled studies of psychological and psychosocial interventions in psychotic disorders that reported outcome on negative symptoms. Standardised mean differences (SMDs) in values of negative symptoms at the end of treatment were calculated across study domains as the main outcome measure.ResultsA total of 95 studies met our criteria and 72 had complete quantitative data. Compared with treatment as usual cognitive-behavioural therapy (pooled SMD -0.34, 95% CI -0.55 to -0.12), skills-based training (pooled SMD -0.44, 95% CI -0.77 to -0.10), exercise (pooled SMD -0.36, 95% CI -0.71 to -0.01), and music treatments (pooled SMD -0.58, 95% CI -0.82 to -0.33) provide significant benefit. Integrated treatment models are effective for early psychosis (SMD -0.38, 95% CI -0.53 to -0.22) as long as the patients remain in treatment. Overall quality of evidence was moderate with a high level of heterogeneity.ConclusionsSpecific psychological and psychosocial interventions have utility in ameliorating negative symptoms in psychosis and should be included in the treatment of negative symptoms. However, more effective treatments for negative symptoms need to be developed.

The impact of gender on treatment effectiveness of body psychotherapy for negative symptoms of schizophrenia: A secondary analysis of the NESS trial data

Despite promising findings from small-scale studies suggesting that body psychotherapy may be an effective treatment for negative symptoms, these results were not replicated in a recent multisite trial. In this trial a far smaller proportion of women were recruited relative to earlier studies, which may be an issue given the gender mix of the sample evaluated has been found to affect trial outcomes in schizophrenia. Using data from our multisite trial, the interaction between gender and treatment allocation as a predictor of outcomes was examined in 275 participants (72 women and 203 men) randomised to either a body psychotherapy or Pilates group. Negative symptoms were found to significantly reduce in women randomised to the body psychotherapy condition in comparison to Pilates, while no such effect was detected in men. Consistent with the smaller trials, this improvement was found to relate predominantly to expressive deficits. These findings suggest that body psychotherapy may be an effective treatment for negative symptoms in women. These findings emphasise the importance of sample characteristics in determining trial outcome in psychological treatment studies.

Clinical effectiveness and cost-effectiveness of body psychotherapy in the treatment of negative symptoms of schizophrenia: a multicentre randomised controlled trial.

The negative symptoms of schizophrenia significantly impact on quality of life and social functioning, and current treatment options are limited. In this study the clinical effectiveness and cost-effectiveness of group body psychotherapy as a treatment for negative symptoms were compared with an active control. A parallel-arm, multisite randomised controlled trial. Randomisation was conducted independently of the research team, using a 1 : 1 computer-generated sequence. Assessors and statisticians were blinded to treatment allocation. Analysis was conducted following the intention-to-treat principle. In the cost-effectiveness analysis, a health and social care perspective was adopted. age 18-65 years; diagnosis of schizophrenia with symptoms present at > 6 months; score of ≥ 18 on Positive and Negative Syndrome Scale (PANSS) negative symptoms subscale; no change in medication type in past 6 weeks; willingness to participate; ability to give informed consent; and community outpatient. inability to participate in the groups and insufficient command of English. Participants were recruited from NHS mental health community services in five different Trusts. All groups took place in local community spaces. Control intervention: a 10-week, 90-minute, 20-session group beginners' Pilates class, run by a qualified Pilates instructor. Treatment intervention: a 10-week, 90-minute, 20-session manualised group body psychotherapy group, run by a qualified dance movement psychotherapist. The primary outcome was the PANSS negative symptoms subscale score at end of treatment. Secondary outcomes included measures of psychopathology, functional, social, service use and treatment satisfaction outcomes, both at treatment end and at 6-month follow-up. A total of 275 participants were randomised (140 body psychotherapy group, 135 Pilates group). At the end of treatment, 264 participants were assessed (137 body psychotherapy group, 127 Pilates group). The adjusted difference in means of the PANSS negative subscale at the end of treatment was 0.03 [95% confidence interval (CI) -1.11 to 1.17], showing no advantage of the intervention. In the secondary outcomes, the mean difference in the Clinical Assessment Interview for negative symptoms expression subscale at the end of treatment was 0.62 (95% CI -1.23 to 0.00), and in extrapyramidal movement disorder symptoms -0.65 (95% CI -1.13 to -0.16) at the end of treatment and -0.58 (95% CI -1.07 to -0.09) at 6 months' follow-up, showing a small significant advantage of body psychotherapy. No serious adverse events related to the interventions were reported. The total costs of the intervention were comparable with the control, with no clear evidence of cost-effectiveness for either condition. Owing to the absence of a treatment-as-usual arm, it is difficult to determine whether or not both arms are an improvement over routine care. In comparison with an active control, group body psychotherapy does not have a clinically relevant beneficial effect in the treatment of patients with negative symptoms of schizophrenia. These findings conflict with the review that led to the current National Institute for Health and Care Excellence guidelines suggesting that arts therapies may be an effective treatment for negative symptoms. Determining whether or not this lack of effectiveness extends to all types of art therapies would be informative. Current Controlled Trials ISRCTN842165587. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 11. See the NIHR Journals Library website for further project information.

Symptômes négatifs de la schizophrénie : de l’électrophysiologie à l’électrothérapie

The aim of this review of the literature is to summarize the state of the knowledge concerning the relationship between negative symptoms in schizophrenia, electrophysiology and electrotherapy. The scientific literature search of international articles was performed during August and September 2015 using the PubMed electronic database. We used the following MeSH terms: “Negative symptoms”, “Schizophrenia”, “Electrophysiology”, “Neurophysiology”, “EEG power”, “Alpha rhythm”, “Transcranial magnetic stimulation”, “Transcranial direct current stimulation”, “Electroconvulsive therapy”, “Neurofeedback”, “Vagus Nerve Stimulation”, “Deep Brain Stimulation”, and “State dependent”. Negative symptoms in schizophrenia are associated with altered activity in prefrontal cortex in functional neuroimaging studies. This is in line with electrophysiological measurements that found a change in EEG spectral power in the alpha frequency band over prefrontal brain regions. The notion of functional hypofrontality has led to hypotheses that electrotherapy applied to the prefrontal cortex may be an effective treatment of negative symptoms in schizophrenia. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) were used to increase cortical activity in schizophrenia and achieve a clinical effect on negative symptoms. Three meta-analyses confirmed, with a moderate effect size, that rTMS is an effective treatment option for negative symptoms in schizophrenia. The two subsequently published prospective multicenter studies, however, found opposite results from each other. Two randomized controlled studies suggested that tDCS is an effective treatment option for negative symptoms. There is no study on the efficacy of neurofeedback, vagal nerve stimulation or deep brain stimulation on negative symptoms in schizophrenia. Additional studies are needed to confirm the efficacy of rTMS and tDCS on negative symptoms in schizophrenia. Influencing factors, related to clinical and stimulation parameters, of rTMS and tDCS on negative symptoms should be better investigated. Effects related to electrophysiological brain activity of the patient, especially in the alpha band, during the stimulation should also be better investigated. The action of electrotherapy may be state dependent, and a better understanding of electrophysiological effects of electrotherapy techniques could enable their optimization.

C.05.02 Assessment of functioning and quality of life in schizophrenia and the relevance for clinical practice

Many patients with schizophrenia suffer from poor social functioning, with high levels of unemployment being one particular consequence. Negative symptoms tend to persist during periods of clinical stability and may have a detrimental effect on function. This paper aims to investigate the relationship between negative symptoms and ability to function.The EGOFORS study measured negative symptoms in 295 schizophrenia patients in 11 European sites using the PANSS Negative Subscale and assessment scales for psychosocial function: Global Assessment of Functioning (GAF), Personal and Social Performance (PSP), Quality of Life Scale (QLS), Functional Remission of General Schizophrenia (FROGS), Psychosocial Remission in Schizophrenia (PSRS) and Subjective Wellbeing under Neuroleptics (SWN). The relationships between the PANSS Negative Subscale and the functional scales were investigated, adjusting for differences between study sites. Being in work, duration of illness, age of onset and number of years of education were also investigated for a relationship with function.There were strong, statistically significant correlations between PANSS Negative Subscale and all of the function scales (95% confidence intervals for the correlation coefficients: PSRS 0.77–0.91; FROGS 0.74–0.89; QLS 0.74–0.92; GAF 0.64–0.78; PSP 0.63–0.80) except the SWN. All of the functional scales except SWN were at least moderately related to one another. All of the items in each of the PANSS Negative Subscale and the function scales contributed to the relationships between them. Better functioning correlated strongly with participants being in work.This study shows a strong and significant relationship between negative symptoms and psychosocial functioning. Given the impact of negative symptoms on psychosocial function, much more emphasis should be placed on developing effective treatments for negative symptoms, given that most patients with schizophrenia now live in community settings and require to function adequately to support their quality of life.

Pharmacological treatment of negative symptoms in schizophrenia.

Effective treatment of negative symptoms is one of the most important unmet needs in schizophrenic disorders. Because the evidence on current psychopharmacological treatments is unclear, the authors reviewed the findings published to date by searching PubMed with the keywords negative symptoms, antipsychotics, antidepressants, glutamatergic compounds, monotherapy and add-on therapy and identifying additional articles in the reference lists of the resulting publications. The findings presented here predominantly focus on results of meta-analyses. Evidence for efficacy of current psychopharmacological medications is difficult to assess because of methodological problems and inconsistent results. In general, the second-generation antipsychotics (SGAs) do not appear to have good efficacy in negative symptoms, although some show better efficacy than first-generation antipsychotics, some of which also demonstrated efficacy in negative symptoms. Specific trials on predominant persistent negative symptoms are rare and have been performed with only a few SGAs. More often, trials on somewhat persistent negative symptoms evaluate add-on strategies to ongoing antipsychotic treatment. Such trials, mostly on modern antidepressants, have demonstrated some efficacy. Several trials with small samples have evaluated add-on treatment with glutamatergic compounds, such as the naturally occurring amino acids glycine and D-serine and new pharmacological compounds. The results are highly inconsistent, although overall efficacy results appear to be positive. The unsatisfactory and inconsistent results can be partially explained by methodological problems. These problems need to be solved in the future, and the authors propose some possible solutions. Further research is required to identify effective treatment for the negative symptoms of schizophrenia.

Evaluating negative-symptom-like behavioural changes in developmental models of schizophrenia

Many lines of evidence suggest that schizophrenia has a major developmental component and that environmental factors that disrupt key stages of development, such as maternal stress during pregnancy as a result of infection or malnutrition, can increase the risk of developing schizophrenia in later life. This review examines how non-clinical neurodevelopmental models pertinent to schizophrenia have been evaluated for their ability to reproduce behavioural deficits related to the negative symptoms of schizophrenia. The more frequently used are the prenatal application of the mitotoxic agent methylazoxymethanol, prenatal immune challenge and the neonatal ventral hippocampus lesion model. In general they have been extensively evaluated in models considered relevant to positive symptoms of schizophrenia. In contrast, very few studies have examined tests related to negative symptoms and, when they have, it has almost exclusively been a social interaction model. Other aspects related to negative symptoms such as anhedonia, affective flattening and avolition have almost never been studied. Further studies examining other components of negative symptomatology are needed to more clearly associate these deficits with a schizophrenia-like profile as social withdrawal is a hallmark of many disorders. Although there are no truly effective treatments for negative symptoms, better characterisation with a broader range of drugs used in schizophrenia will be necessary to better evaluate the utility of these models. In summary, developmental models of schizophrenia have been extensively studied as models of positive symptoms but, given the unmet need in the clinic, the same effort now needs to be made with regard to negative symptoms.

Tools to Assess Negative Symptoms in Schizophrenia

Although effective treatments for negative symptoms are currently limited, clinicians still need to assess and monitor them because of their impact on patient functioning. Further, documenting patients' negative symptoms provides a complete clinical record that the clinician can use to make systematic and careful treatment decisions. Several tools for assessing negative symptoms in schizophrenia are available, including the Clinical Global Impression scale (CGI), the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), the 16-item Negative Symptoms Assessment (NSA-16), and the Schedule for Deficit Syndrome (SDS). Additionally, newer instruments are in development-the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Brief Negative Symptoms Scale (BNSS)-and are yielding promising results. This overview outlines these assessment tools so that clinicians can measure negative symptom severity and track treatment response for their patients with schizophrenia.

Friends and symptom dimensions in patients with psychosis: a pooled analysis.

BackgroundHaving friends is associated with more favourable clinical outcomes and a higher quality of life in mental disorders. Patients with schizophrenia have fewer friends than other mentally ill patients. No large scale studies have evaluated so far what symptom dimensions of schizophrenia are associated with the lack of friendships.MethodsData from four multi-centre studies on outpatients with schizophrenia and related disorders (ICD F20-29) were included in a pooled analysis (N = 1396). We established whether patients had close friends and contact with friends by using the equivalent items on friendships of the Manchester Short Assessment of Quality of Life or of the Lancashire Quality of Life Profile. Symptoms were measured by the Brief Psychiatric Rating Scale or by the identical items included in the Positive and Negative Syndrome Scale.ResultsSeven hundred and sixty-nine patients (55.1%) had seen a friend in the previous week and 917 (65.7%) had someone they regarded as a close friend. Low levels of negative symptoms and hostility were significantly associated with having a close friend and contact with a friend. Overall, almost twice as many patients with absent or mild negative symptoms had met a friend in the last week, compared with those with moderate negative symptoms.ConclusionsHigher levels of negative symptoms and hostility are specifically associated with the lack of friendships in patients with psychotic disorders. These findings suggest the importance of developing effective treatments for negative symptoms and hostility in order to improve the probability of patients with schizophrenia to have friends.

Negative symptoms and psychosocial functioning in schizophrenia: Neglected but important targets for treatment

BackgroundMany patients with schizophrenia suffer from poor social functioning, with high levels of unemployment being one particular consequence. Negative symptoms tend to persist during periods of clinical stability and may have a detrimental effect on function. This paper aims to investigate the relationship between negative symptoms and ability to function. MethodsThe EGOFORS study measured negative symptoms in 295 schizophrenia patients in 11 European sites using the PANSS Negative Subscale and assessment scales for psychosocial function: Global Assessment of Functioning (GAF), Personal and Social Performance (PSP), Quality of Life Scale (QLS), Functional Remission of General Schizophrenia (FROGS), Psychosocial Remission in Schizophrenia (PSRS) and Subjective Wellbeing under Neuroleptics (SWN). The relationships between the PANSS Negative Subscale and the functional scales were investigated, adjusting for differences between study sites. Being in work, duration of illness, age of onset and number of years of education were also investigated for a relationship with function. ResultsThere were strong, statistically significant correlations between PANSS Negative Subscale and all of the function scales (95% confidence intervals for the correlation coefficients: PSRS 0.77–0.91; FROGS 0.74–0.89; QLS 0.74–0.92; GAF 0.64–0.78; PSP 0.63–0.80) except the SWN. All of the functional scales except SWN were at least moderately related to one another. All of the items in each of the PANSS Negative Subscale and the function scales contributed to the relationships between them. Better functioning correlated strongly with participants being in work. ConclusionThis study shows a strong and significant relationship between negative symptoms and psychosocial functioning. Given the impact of negative symptoms on psychosocial function, much more emphasis should be placed on developing effective treatments for negative symptoms, given that most patients with schizophrenia now live in community settings and require to function adequately to support their quality of life.

Clinical evaluation of negative symptoms in schizophrenia

The florid positive symptoms of schizophrenia (hallucinations, delusions, grossly disordered thinking) are often obvious. By comparison, negative symptoms (flattened affect, impoverished speech, apathy, avolition, anhedonia) are subtler and more difficult to recognize and diagnose. However, there is increasing recognition of the importance of negative symptoms in patients with schizophrenia. Secondary negative symptoms attributable to such factors as unrelieved positive symptoms, the adverse effects of antipsychotic pharmacotherapy, or social isolation may subside with resolution of such factors. In contrast, primary negative symptoms are an intrinsic aspect of schizophrenia; they are persistent and have been associated with poorer clinical outcomes. Although the lack of a reliably effective treatment for negative symptoms is a serious unmet need in this patient population, accurate diagnosis is still important. Assessment of suspected negative symptoms, using validated rating scales, can help to rule out comorbid affective or cognitive disorders that may mimic negative symptoms and to distinguish primary negative symptoms from potentially reversible secondary negative symptoms. This article reviews the definitions and classification of negative symptoms, compares the tools available for their assessment, and offers practical clinical algorithms for sorting through the differential diagnosis.

Effect of body-oriented psychological therapy on negative symptoms in schizophrenia: a randomized controlled trial

In order to improve the treatment of medication-resistant negative symptoms in schizophrenia, new interventions are needed. Neuropsychological considerations and older reports in the literature point towards a potential benefit of body-oriented psychological therapy (BPT). This is the first randomized controlled trial specifically designed to test the effectiveness of manualized BPT on negative symptoms in chronic schizophrenia. Out-patients with DSM-IV continuous schizophrenia were randomly allocated to either BPT (n=24) or supportive counseling (SC, n=21). Both therapies were administered in small groups in addition to treatment as usual (20 sessions over 10 weeks). Changes in negative symptom scores on the Positive and Negative Symptom Scale (PANSS) between baseline, post-treatment and 4-month follow-up were taken as primary outcome criteria in an intention-to-treat analysis. Patients receiving BPT attended more sessions and had significantly lower negative symptom scores after treatment (PANSS negative, blunted affect, motor retardation). The differences held true at 4-month follow-up. Other aspects of psychopathology and subjective quality of life did not change significantly in either group. Treatment satisfaction and ratings of the therapeutic relationship were similar in both groups. BPT may be an effective treatment for negative symptoms in patients with chronic schizophrenia. The findings should merit further trials with larger sample sizes and detailed studies to explore the therapeutic mechanisms involved.

Clozapine, Olanzapine, Risperidone, and Haloperidol in the Treatment of Patients With Chronic Schizophrenia and Schizoaffective Disorder

Objective: The authors compared the efficacy and safety of three atypical antipsychotics (clozapine, olanzapine, and risperidone) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder. Method: In a double-blind trial, 157 inpatients with a history of suboptimal treatment response were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol for 14 weeks (an 8-week escalation and fixeddose period followed by a 6-week variable-dose period). Results: Clozapine, risperidone, and olanzapine (but not haloperidol) resulted in statistically significant improvements in total score on the Positive and Negative Syndrome Scale. Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol. The atypical drugs, particularly olanzapine and clozapine, were associated with weight gain. Conclusions: The effects of atypical antipsychotics in this population were statistically significant but clinically modest. The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective. Clozapine was the most effective treatment for negative symptoms. However, the differences among treatments were small.