Significant Reduction In Negative Symptoms Research Articles

Exercise4Psychosis: A randomised control trial assessing the effect of moderate-to-vigorous exercise on inflammatory biomarkers and negative symptom profiles in men with first-episode psychosis

IntroductionFirst-Episode Psychosis (FEP) is a devastating mental health condition that commonly emerges during early adulthood, and is characterised by a disconnect in perceptions of reality. Current evidence suggests that inflammation and perturbed immune responses are involved in the pathology of FEP and may be associated specifically with negative symptoms. Exercise training is a potent anti-inflammatory stimulus that can reduce persistent inflammation, and can improve mood profiles in general populations. Therefore, exercise may represent a novel adjunct therapy for FEP. The aim of this study was to assess the effect of exercise on biomarkers of inflammation, negative symptoms of psychosis, and physiological health markers in FEP. MethodsSeventeen young males (26.67 ± 6.64 years) were recruited from Birmingham Early Intervention in Psychosis Services and randomised to a 6-week exercise programme consisting of two-to-three sessions per week that targeted 60–70 % heart-rate max (HRMax), or a treatment as usual (TAU) condition. Immune T-helper (Th-) cell phenotypes and cytokines, symptom severity, functional wellbeing, and cognition were assessed before and after 6-weeks of regular exercise. ResultsParticipants in the exercise group (n = 10) achieved 81.11 % attendance to the intervention, with an average exercise intensity of 67.54 % ± 7.75 % HRMax. This led to favourable changes in immune cell phenotypes, and a significant reduction in the Th1:Th2 ratio (−3.86 %) compared to the TAU group (p = 0.014). After the exercise intervention, there was also a significant reduction in plasma IL-6 concentration (–22.17 %) when compared to the TAU group (p = 0.006). IL-8, and IL-10 did not show statistically significant differences between the groups after exercise. Symptomatically, there was a significant reduction in negative symptoms after exercise (−13.54 %, Positive and Negative Syndrome Scale, (PANSS) Negative) when compared to the TAU group (p = 0.008). There were no significant change in positive or general symptoms, functional outcomes, or cognition (all p > 0.05). DiscussionRegular moderate-to-vigorous physical activity is feasible and attainable in clinical populations. Exercise represents a physiological tool that is capable of causing significant inflammatory biomarker change and concomitant symptom improvements in FEP cohorts, and may be useful for treatment of symptom profiles that are not targeted by currently prescribed antipsychotic medication.

Longitudinal Investigation of Auditory Dynamic Range Deficits in Early Psychosis and its Relationship to Negative Symptoms.

Despite accounting for significant disease morbidity in schizophrenia, the neuropathological basis of negative symptoms remains poorly understood and options for treatment limited. Our recent study identified robust associations between diminished auditory cortex (AC) dynamic range and social functioning impairments and negative symptoms in first episode psychosis (FESz). The current investigation examined the progression of these relationships 4-8 months from baseline testing. Twenty-six FESz and 38 healthy controls (HC) were tested at baseline and follow-up. Magnetoencephalography (MEG) was recorded during binaural presentation of tones (75, 80, and 85 dB). Assessments included the MATRICS cognitive consensus battery (MCCB) and Global Functioning: Role and Social scales (GFR/GFS) and the Positive and Negative Syndrome Scale. Overall, FESz exhibited a blunted response to increasing tone intensity relative to HC. While this deficit did not change over time at the group level, recovery of right hemisphere AC dynamic range (85-75 dB response) among FESz individuals was associated with reductions in negative symptoms (ρ = -0.50). Diminished dynamic range was also associated with impaired GFS (ρ = 0.65), GFR (ρ = 0.51), and MCCB (ρ = 0.49) at baseline and increased negative symptoms at baseline (ρ = -0.53) and follow-up (ρ = -0.51). Despite persistent dynamic range impairment in FESz as a group, individual recovery of this AC response property was associated with significant reduction in negative symptoms. Identification of a functional neural deficit that tracts progression of negative symptoms during a critical period for disease modification is essential to the management of these devastating and historically treatment refractory symptoms.

Effect of dexamethasone on reducing pain and gastrointestinal symptoms associated with cesarean section: a systematic review and meta-analysis

Background: Dexamethasone has analgesic and antiemetic actions that have been documented in the literature. Therefore, we performed a systematic review and meta-analysis to investigate its overall effectiveness in reducing a variety of negative outcomes after cesarean section. Objectives: To investigate the efficacy and safety of dexamethasone for reducing pain associated with cesarean section, nausea, vomiting, pruritus, postoperative need for analgesia, postoperative antiemetic requests and headache. Methods: We searched PubMed, Cochrane CENTRAL, SCOPUS, and Web of Science for relevant clinical trials. We then performed a systematic review and meta-analysis, including only randomized, placebo-controlled clinical trials. Our main population target was women undergoing elective cesarean delivery. The intervention under consideration was dexamethasone administered both by intravenous (IV) or subcutaneous (SC) over a variety of doses. The comparator was a placebo. Our main outcomes included: (1) perceptions as indicated by pain scores, (2) occurrence of nausea and (3) occurrence of vomiting. Secondary outcomes included: (4) occurrence of pruritus, (5) need for postoperative analgesia, (6) need for postoperative antiemetic drugs and (7) occurrence of headache. We assessed the quality of included studies using the risk of bias tool described in Cochrane's handbook for systematic reviews of interventions. Results: We found that dexamethasone seemed to significantly reduce scores for pain at rest (p<0.001), as well as occurrence of nausea (p<0.001) and vomiting (p<0.001). The drug also showed significant reduction of negative symptoms in other secondary outcomes, including need for postoperative analgesia (p<0.001) and postoperative antiemetic drugs (p<0.001). However, the drug showed no significant effect in reducing headache and pruritus or in improving pain at movement scores. Conclusion: Dexamethasone appears to decrease perception of pain at rest and protects against nausea and vomiting. However, it does not seem effective against headaches or pruritus.

Do adjunctive art therapies reduce symptomatology in schizophrenia? A meta-analysis.

Art therapies are advocated by national bodies, such as the United Kingdom's National Institute for Health and Care Excellence, to alleviate the negative symptoms associated with schizophrenia. The last decade has however, seen several new larger well-controlled trials published suggesting an update is timely. To asses randomised controlled trials (RCT) of art therapies for reducing the symptoms of schizophrenia - particularly negative symptoms. Searches of PubMed and Scopus were conducted until May 2019 for RCTs examining the impact of art therapies on psychosis (positive, negative and total) symptoms in people diagnosed with schizophrenia. Study quality was assessed using the Cochrane risk of bias tool. Random effects meta-analyses were used to derive overall effect sizes. Moderator analyses were conducted using both meta-regression and categorical comparisons. We identified 133 articles, of which 9 RCTs involving 948 participants (475 assigned to art therapies and 473 controls) met our inclusion criteria. Using random effects models, we calculated pooled effect sizes (Hedges g) for end-of-trial symptomatic outcomes. Effect sizes both for total symptoms [g = -0.27, 95% confidence interval (CI) -0.60 to 0.05, k = 6] and for positive symptoms (g = -0.10, 95%CI -0.35 to 0.15, k = 6) were non-significant; however, we did find significant reduction of negative symptoms (g = -0.42, 95%CI -0.70 to -0.14, k = 9). Meta-regression revealed that negative symptom reduction was larger in trials with a greater proportion of women and in trials with younger patients. Crucially, the negative symptom reduction following art therapies was limited to lower quality trials and did not emerge in trials that used blind assessment of outcomes. This review presents a comprehensive meta-analysis of art therapies in schizophrenia in terms of both studies included and participant numbers. We found that art therapies did not significantly reduce total or positive symptoms. A "small" therapeutic effect was found for negative symptoms, but we show that the effect is not present in blind trials and may be subject to publication bias.

Negative Symptom Interventions in Youth at Risk of Psychosis: A Systematic Review and Network Meta-analysis.

Youth at clinical high risk (CHR) for psychosis often demonstrate significant negative symptoms, which have been reported to be predictive of conversion to psychosis and a reduced quality of life but treatment options for negative symptoms remain inadequate. Therefore, we conducted a systematic review and network meta-analysis of all intervention studies examining negative symptom outcomes in youth at CHR for psychosis. The authors searched PsycINFO, Medline, Embase, CINAHL, and EBM from inception to December 2016. Studies were selected if they included any intervention that reported follow-up negative symptoms in youth at CHR for psychosis. Treatment comparisons were evaluated using both pairwise and network meta-analyses. Due to the differences in negative symptom scales the effect sizes were reported as the standardized mean difference (SMD). Of 3027 citations, 32 studies met our inclusion criteria, including a total of 2463 CHR participants. The null hypothesis was not rejected for any of the 11 treatments. N-methyl-D-aspartate-receptor (NMDAR) modulators trended toward a significant reduction in negative symptoms compared to placebo (SMD = -0.54; 95% CI = -1.09 to 0.02; I2 = 0%, P = .06). In respective order of descending effectiveness as per the treatment hierarchy, NMDAR modulators were more effective than family therapy, need-based interventions, risperidone, amisulpride, cognitive behavioral therapy, omega-3, olanzapine, supportive therapy, and integrated psychological interventions. Efficacy and effectiveness were not confirmed for any negative symptom treatment. Many studies had small samples and the majority were not designed to target negative symptoms.

A Review of Clinical and Economic Evaluations Applied to Psychotropic Therapies Used in the Treatment of Schizophrenia in Argentina.

Schizophrenia is considered a serious mental disorder that affects over 21 million people worldwide, and is associated with disability that frequently affects the patient’s educational and working performance. In Argentina, two of the most widely used antipsychotics in the treatment of this disorder are haloperidol and risperidone. Both are provided free to patients without health coverage in public healthcare facilities. In this paper we seek to review the clinical and economic benefits of prescribing psychotropic therapies based on haloperidol (a first-generation antipsychotic that is part of the butyrophenone group of drugs) versus risperidone [an atypical or second-generation antipsychotic (neuroleptic) drug] in adult patients who have been diagnosed with schizophrenia. To achieve this objective, an exhaustive search of relevant articles published between 2006 and April 2017 was conducted. This literature search showed that intermittent treatment usually fails to prevent relapses due to irregular protection, therefore continuous treatment is more effective. Although the injectable formats of both drugs [haloperidol depot and long-acting injectable risperidone (LAIR)] have not proven to have significant differences with regard to clinical effectiveness vis-à-vis the tablet formats, they showed a lower cost-effectiveness ratio by reducing patients’ relapses. Moreover, LAIR exhibits superior cost effectiveness compared with haloperidol depot. Haloperidol is less expensive than risperidone but is less cost effective; in comparison with haloperidol, treatment with risperidone produces (1) an improvement in quality-adjusted life-years, and (2) a significant reduction in negative symptoms. In most cases, antipsychotic treatments are effective in controlling the positive and negative symptoms associated with schizophrenia, allowing patients to live in their communities without any impairments. However, it is extremely important to combine pharmacological treatment with other measures that constitute psychosocial therapy.

Expectancies of success as a predictor of negative symptoms reduction over 18 months in individuals with schizophrenia

Negative symptoms are often enduring and lead to poor functional outcomes in individuals with schizophrenia. The cognitive model of negative symptoms proposes that low expectancies of success contribute to the development and maintenance of negative symptoms; however, longitudinal investigations assessing these beliefs and negative symptoms are needed. The current study examined whether an individual’s baseline expectancies of success – one’s beliefs about future success and goal attainment – predicted negative symptoms reduction over 18 months in individuals with schizophrenia-spectrum disorders (n=118). Data were collected at baseline, 9 months, and 18 months as part of a randomized controlled trial of Illness Management and Recovery. A mixed effects regression analysis revealed a significant reduction in negative symptoms over time, with a significant interaction effect between time and baseline expectancies of success. After controlling for baseline negative symptoms, demographic variables, and treatment conditions, those with high and moderate baseline expectancies of success evidenced a significant reduction in negative symptoms at 18 months, while those with low baseline expectancies of success did not evidence reduced negative symptoms. Findings support the cognitive model of negative symptoms and suggest that expectancies of success may be a useful treatment target for interventions aimed at reducing negative symptoms.

P03-203 - Observation of the effectiveness of a comprehensive and systematic treatment and rehabilitation in the social house. A case report

IntroductionThe authors present a comprehensive-efficacy of pharmacotherapy and rehabilitation in the social house for people with mental health disorders carried out systematically for many years in the 40 year old patient.ObjectivesPatient 40 years old, male, secondary education, imposed a total inability to work. The first episode of the disease was in his 25 years, a syndrome of depression in a moderate degree, the next episode of schizophrenia-catatonic. In the therapy was used first generation antipsychotics, despite regular medication had not obtained complete remission and frequent exacerbations were the cause of several subsequent hospitalizations. During the last hospitalization in 1997, recognizing the diagnosis was verified with paranoid schizophrenia. After discharge, the patient in accordance with the recommendation began rehabilitation in the social house for people with mental health disorders, which still continue. Because of side effects after the previously used antipsychotic drugs second-generation - ziprasidone was incorporated in 2005. The use of this drug caused a significant decrease in body weight, increased social activity (a return to artistic activities - painting), improving the quality of life. Due to persistent chronic anxiety has been further adjustment of treatment in 2008 included amisulpride and valproate.ConclusionsThe treatment used a comprehensive, full remission of symptoms generation, and a significant reduction in negative symptoms. Currently, the patient actively participates in all activities organized in the environmental treatment of self-help home, living independently in daily activities, carry out the artistic passion of winning prizes at exhibitions and presentations of work.

S16-01 - Primary and enduring negative symptoms in first episode and chronic patients with schizophrenia

Negative symptoms of schizophrenia have often been associated with poor functional outcome and poor response to antipsychotic treatment. Studies reporting drug induced significant reduction of negative symptoms after treatment actually refer to negative symptoms secondary to positive, depressive and/or extrapyramidal symptoms. Negative symptoms that do not improve following antipsychotic treatment represent a real challenge for future development of effective treatments. Two approaches have been so far proposed to improve research on these negative symptoms. The first one is based on the identification of primary and enduring negative symptoms, that characterize a schizophrenia subtype known as deficit schizophrenia (DS). The prevalence of DS is 15%–20% in population based samples, but tends to be much lower in first-episode patients. Individuals with DS have worse long-term outcome and poorer response to antipsychotics than those with other forms of schizophrenia. The second approach is based on the identification of persistent negative symptoms, which are likely to be primary, but may be secondary. Few data are available on the prevalence of persistent negative symptoms in patients with schizophrenia. In first episode subjects from the EUFEST study 11% of the study sample showed persistent negative symptoms (PNS). They had poorer functional outcome and lower remission rates than those without PNS after 1 year of treatment. Research on clinical and biological correlated of primary and/or persistent negative symptoms might help in reducing schizophrenia heterogeneity and developing new treatments.

P03-158 - The efficacy of cognitive- behavior group therapy and social skill trainings on reduction of negative symptoms of schizophrenic patients

IntroductionSchizophrenia is a destructive disease that can break the personality structure down in severe conditions and causes disturbance of thoughts, feelings and actions, and thus affects the personal, family and social performance and relationships, and disturbs them.AimsThe aim of this study is the investigation of the efficacy of cognitive -behavior therapy and social skill trainings on reduction of negative symptoms of schizophrenic patients.MethodsThe present study is experimental design based on pre-test, post-test with control group and to select randomly, the available sampling method was used. (15persons)were selected for each group and they were randomly assigned to two groups: experimental group (combination of cognitive-behavior group therapy and social skill training) and control group (cognitive- behavior group therapy).ResultsAfter three months the administration of combination program of cognitive-behavior group therapy and social skill training than cognitive- behavior group therapy, the negative symptoms of experimental group decreased significantly. Also, social skills of experimental group were significantly higher than the control group that causes the significant reduction of negative symptoms of schizophrenic patients.ConclusionsThe obtained results show that: on improvement of symptoms of schizophrenic patients, the efficacy of combination of cognitive -behavior group therapy and social skills is more than cognitive- behavior group therapy.

Engaging resistant adolescents in drug abuse treatment

In the first phase of a two-part treatment development study, families with a treatment-resistant drug-abusing adolescent ( n = 42) were offered 12 sessions of Community Reinforcement and Family Training (CRAFT). This parent-focused intervention was designed to help parents facilitate their adolescents' entry into treatment, to support adolescents' subsequent behavior change, and to improve parent and family functioning. In the second phase, successfully engaged adolescents ( n = 30) were offered 12 sessions of a multicomponent individual cognitive–behavioral therapy (CBT) targeting substance use and related problem behaviors. For parents and adolescents, measures were collected on pretreatment and posttreatment, with an additional follow-up assessment for parents at 3 months after treatment. Parents on CRAFT intervention experienced a significant reduction in negative symptoms, and 71% of parents were successful in engaging their resistant youths in treatment. The CBT intervention for engaged youths was associated with a statistically significant, but not clinically significant, reduction in marijuana use.

Randomized, Double-blind 6-Month Comparison of Olanzapine and Quetiapine in Patients With Schizophrenia or Schizoaffective Disorder With Prominent Negative Symptoms and Poor Functioning

This study compared the effects of olanzapine (OLZ) with those of quetiapine (QUE) for improving negative symptoms in patients diagnosed with schizophrenia or schizoaffective disorder who had prominent negative symptoms and marked deficits in social or occupational functioning. In this 6-month, multicenter, double-blind clinical trial, patients were randomized to treatment with OLZ (n = 171, 10-20 mg/d) or QUE (n = 175, 300-700 mg/d). Patients were treated at community mental health centers and assigned case managers who developed individualized psychosocial treatment plans. The primary efficacy measure was the reduction in negative symptoms using the Scale for the Assessment of Negative Symptoms. Secondary measures assessed changes in functioning, psychopathology, and treatment tolerability. Treatment with OLZ or QUE led to a significant reduction in negative symptoms, with no between-group difference (P = 0.09). Both treatment groups also showed significant improvement on most efficacy measures. Olanzapine-treated patients showed significantly greater improvement on positive symptoms and on several measures of functioning including Global Assessment of Functioning Scale, Quality of Life Instrumental Role domain, and level of effort in psychosocial or occupational rehabilitation programs. Significantly more OLZ-treated patients completed the study (52.6% OLZ, 37.7% QUE, P = 0.007). Treatment differences in safety were relatively small and not thought to be clinically relevant. Patients with schizophrenia who manifest prominent negative symptoms and marked functional deficits demonstrated significant improvement in negative symptoms after treatment with OLZ or QUE. Greater improvement in positive symptoms and a greater study completion rate may hold relevance to enhanced functional outcomes observed after OLZ therapy.

Transcranial magnetic stimulation for the deficit syndrome of schizophrenia: A pilot investigation

In an open study, four subjects with a stable deficit syndrome of schizophrenia received high frequency repetitive transcranial magnetic stimulation (15 Hz at 90% of motor threshold, 1800 pulses each session, daily for 20 sessions over 4 weeks) over the left dorsolateral prefrontal cortex. Subjects showed a significant reduction in negative symptoms and improvement in function, with no change in positive symptoms. This improvement was maintained at the 1 month follow up. Repetitive transcranial magnetic stimulation as a treatment of the deficit syndrome of schizophrenia is feasible, safe and may be beneficial. A systematic study in randomized control trials would be appropriate.

High-frequency repetitive transcranial magnetic stimulation in schizophrenia: a combined treatment and neuroimaging study

Repetitive transcranial magnetic stimulation (rTMS) of frontal brain regions is under study as a non-invasive method in the treatment of affective disorders. Recent publications provide increasing evidence that rTMS may be useful in treating schizophrenia. Results are most intriguing, demonstrating a reduction of negative symptoms following high-frequency rTMS. In this context, disentangling of negative and depressive symptoms is of the utmost importance when understanding specific rTMS effects on schizophrenic symptoms. Using a sham-controlled parallel design, 20 patients with schizophrenia were included in the study. Patients were treated with high-frequency 10 Hz rTMS over 10 days. Besides clinical ratings, ECD-SPECT (technetium-99 bicisate single photon emission computed tomography) imaging was performed before and after termination of rTMS treatment. High-frequency rTMS leads to a significant reduction of negative symptoms combined with a trend for non-significant improvement of depressive symptoms in the active stimulated group as compared with the sham stimulated group. Additionally, a trend for worsening of positive symptoms was observed in the actively treated schizophrenic patients. In both groups no changes in regional cerebral blood flow could be detected by ECD-SPECT. Beneficial effects of high-frequency rTMS on negative and depressive symptoms were found, together with a trend for worsening positive symptoms in schizophrenic patients.

D-Cycloserine added to risperidone in patients with primary negative symptoms of schizophrenia

Background. d-Cycloserine, a partial agonist at the glycine recognition site of the NMDA receptor has previously been shown to improve negative symptoms when added to conventional antipsychotics and to worsen negative symptoms when added to clozapine. The purpose of this study was to examine the effects of d-cycloserine when added to risperidone on negative symptoms of schizophrenia. Method. Ten patients with schizophrenia who were treated with risperidone completed consecutive two week trials of placebo and four doses of d-cycloserine. Clinical assessments were videotaped and were scored by a rater who was blind to temporal sequence. Results. d-Cycloserine at a dose of 50 mg/day was associated with significant reduction in negative symptoms (mean=10%). Ratings of depression, extrapyramidal side effects, and cognitive function were unchanged. Serum concentrations of glutamate and serine increased significantly on this dose of d-cycloserine. Conclusions. This preliminary study suggests that combination of d-cycloserine, 50 mg/day, with risperidone may improve negative symptoms of schizophrenia over a narrow dose range. The degree of improvement appears to be intermediate between improvement of negative symptoms observed with combination of d-cycloserine with conventional antipsychotics and worsening of negative symptoms observed with combination of d-cycloserine with clozapine in previous trials of identical design.

Course of treatment response in first-episode and chronic schizophrenia.

The timing and clinical correlates of symptom change following antipsychotic treatment were examined in first-episode and chronic schizophrenia. The subjects were 36 first-episode schizophrenic patients who had received minimal or no neuroleptics and 34 patients with chronic illness whose neuroleptics had been withdrawn. They were followed for 2 years and assessed with the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. Treatment decisions during follow-up were made clinically by the treating physicians. At 6-month follow-up, both the neuroleptic-naive and previously treated patients showed significant improvement in positive symptoms (52% and 44% reductions from baseline, respectively). The previously treated but not the neuroleptic-naive patients also showed a significant reduction in negative symptoms (19% from baseline). A longer duration of illness before baseline assessment and inconsistent treatment during follow-up were independently associated with poorer treatment outcome in terms of positive symptoms in both groups. There were no significant changes on the outcome measures in either group after the 6-month follow-up. The results suggest that maximum symptomatic improvement occurs within the first 6 months of treatment and that disease progression may blunt treatment efficacy in both first-episode and chronic schizophrenia.