Relationship of Cognition to Clinical Response in First-Episode Schizophrenia Spectrum Disorders. Feasibility and Effectiveness of a Multi-Element Psychosocial Intervention for First-Episode Psychosis: Results From the Cluster-Randomized Controlled GET UP PIANO Trial in a Catchment Area of 10 Million Inhabitants Ethyl-eicosapentaenoic acid in first-episode psychosis: a randomized, placebo-controlled trial. Omega-3 fatty acids in first-episode schizophrenia - a randomized controlled study of efficacy and relapse prevention (OFFER): rationale, design, and methods The effect of extract of ginkgo biloba addition to olanzapine on therapeutic effect and antioxidant enzyme levels in patients with schizophrenia. Predictive value of prospective memory for remission in first-episode schizophrenia. Preventing progression to first-episode psychosis in early initial prodromal states. Oxidative–antioxidative systems and their relation with serum S100 B levels in patients with schizophrenia: Effects of short term antipsychotic treatment Prediction of functional remission in first-episode psychosis: 12-month follow-up of the randomized-controlled trial on extended early intervention in Hong Kong Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial. A Randomized Controlled Trial of Clinician-Supported Problem-Solving Bibliotherapy for Family Caregivers of People With First-Episode Psychosis Cognitive improvement after treatment with second-generation antipsychotic medications in first-episode schizophrenia: is it a practice effect? Vitamin B6 as add-on treatment in chronic schizophrenic and schizoaffective patients: a double-blind, placebo-controlled study. A randomized controlled study of the efficacy of six-month supplementation with concentrated fish oil rich in omega-3 polyunsaturated fatty acids in first episode schizophrenia. Supplementation of vitamin C with atypical antipsychotics reduces oxidative stress and improves the outcome of schizophrenia Prevention of antipsychotic-induced weight gain with early behavioural intervention in first-episode psychosis: 2-year results of a randomized controlled trial A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia
First-episode schizophrenia ( FES ) spectrum disorders are associated with pronounced cognitive dysfunction across all domains . However , less is known about the course of cognitive functioning , following the first presentation of psychosis , and the relationship of cognition to clinical course during initial treatment . The present longitudinal study examined the magnitude of neurocognitive impairment , using the MATRICS Consensus Cognitive Battery , in patients experiencing their first episode of psychosis at baseline and after 12 weeks of r and omized antipsychotic treatment with either aripiprazole or risperidone .  At baseline , FES patients evidence d marked impairments in cognitive functioning . Notably , performance on the mazes task of planning and reasoning significantly predicted the likelihood of meeting stringent criteria for positive symptom remission during the first 12 weeks of the trial . Performance on indices of general cognitive function , working memory , and verbal learning improved over time , but these improvements were mediated by improvements in both positive and negative symptoms . We did not detect any differential effects of antipsychotic medication assignment ( aripiprazole vs risperidone ) on cognitive functioning . Our results suggest that a brief paper- and -pencil measure reflecting planning/reasoning abilities may index responsivity to antipsychotic medication . However , improvements in cognitive functioning over time were related to clinical symptom improvement , reflecting " pseudospecificity . Integrated multi-element psychosocial interventions have been suggested to improve the outcomes of first-episode psychosis ( FEP ) patients , but they have been studied primarily in experimental setting s and in nonepidemiologically representative sample s. Thus , we performed a cluster-r and omized controlled trial , comparing an integrated multi-element psychosocial intervention , comprising cognitive behavioral therapy , family intervention , and case management , with treatment as usual ( TAU ) for FEP patients in 117 community mental health centers ( CMHCs ) in a large area of northern Italy ( 10 million inhabitants ) . The r and omized units ( clusters ) were the CMHCs , and the units of observation the patients ( and , when available , their family members ) . The primary hypotheses were that add-on multicomponent intervention : ( 1 ) results in greater improvements in symptoms , as assessed with positive and negative syndrome scale and ( 2 ) reduces in-hospital stay , based on days of hospitalization over the 9-month follow-up . Four hundred and forty-four FEP patients received the intervention or TAU  and were assessed at baseline and 9 months . Based on the retention rates of patients ( and families ) in the experimental arm , multi-element psychosocial interventions can be implemented in routine mental health services . Regarding primary outcomes , patients in the experimental arm showed greater reductions in overall symptom severity , while no difference could be found for days of hospitalization . Among the secondary outcomes , greater improvements were detected in the experimental arm for global functioning , emotional well-being , and subjective burden of delusions . No difference could be found for service disengagement and subjective burden of auditory hallucinations . These findings support feasibility and effectiveness of early interventions for psychosis in generalist mental health services OBJECTIVE To investigate if ethyl-eicosapentaenoic acid ( E-EPA ) augmentation improves antipsychotic efficacy and tolerability in first-episode psychosis ( FEP ) . METHOD We performed a 12-week , r and omized , double-blind , placebo-controlled trial of 2-g E-EPA augmentation in 80 FEP patients . Sixty-nine patients were eligible for analysis ; a post hoc analysis was computed for a subgroup of nonaffective FEP patients ( N = 53 ) . The first participant was included in November 2000 and the last participant completed the trial in August 2003 . Primary outcome measures were symptom change scores and time to first response , while tolerability measures and cumulative antipsychotic dose were secondary outcome measures . RESULTS Analysis of covariance controlling for baseline symptoms found no significant mean difference between E-EPA and placebo at week 12 for symptom change scores . Cox regression analysis revealed a significant treatment by diagnosis interaction ( p = .024 ) for time to first response favoring E-EPA in nonaffective psychosis . Post hoc analysis for cumulative response rates further confirmed a higher response rate at week 6 ( 42.9 % [ 15/35 ] vs. 17.6 % [ 6/34 ] for all participants , p = .036 ; 54.2 % [ 13/24 ] vs. 17.2 % [ 5/29 ] for the nonaffective psychosis subset , p = .008 ) ; however , the difference at week 12 was no longer significant . Analysis of secondary outcome measures revealed that E-EPA-augmented participants needed 20 % less antipsychotic medication between weeks 4 through 6 ( p = .03 ) , had less extrapyramidal side effects in the initial 9 weeks ( p < .05 for all participants and for all timepoints ) , and reported less constipation ( p = .011 ) and fewer sexual side effects ( p = .016 ) than those treated with antipsychotic medication alone . CONCLUSION The findings suggest that E-EPA may accelerate treatment response and improve the tolerability of antipsychotic medications . However , it was not possible to demonstrate a sustained symptomatic benefit of E-EPA in early psychosis , possibly due to a ceiling effect , since a high proportion of first-episode patients already achieve symptomatic remission with antipsychotic medication alone . Further controlled trials in nonaffective early psychosis seem warranted . TRIAL REGISTRATION Australian Clinical Trials Registry identifier 12605000267651 ( http://actr.org.au ) Background Polyunsaturated fatty acid ( PUFA ) metabolism abnormalities have been long implicated in the etiology of schizophrenia . Although several r and omized clinical trials have been carried out to assess the efficacy of omega-3 PUFA as add-on therapy in reducing psychopathology in population s of chronic patients with schizophrenia , only a few concern first-episode schizophrenia . The majority of these studies used a 12-week intervention based on ethyl-eicosapentaenoic acid ( ethyl-EPA ) , however , with conflicting results . An intervention based on docosahexaenoic acid plus EPA has not been used in first-episode schizophrenia studies so far . No add-on supplementation studies have been carried out in medicated first-episode schizophrenia patients to assess the efficacy of omega-3 PUFA in preventing relapses . Methods A r and omized placebo-controlled one-center trial will be used to compare the efficacy of 26-week intervention , composed of either 1320 mg/day of EPA and 880 mg/day of DHA , or olive oil placebo with regard to symptom severity and relapse rate in first-episode schizophrenia patients . Eighty-two patients ( aged 16–35 ) will be recruited for the study . Eligible patients will be r and omly allocated to one of two intervention arms : an active arm or a placebo arm ( olive oil ) . The primary outcome measure of the clinical evaluation is schizophrenia symptom severity measured by the Positive and Negative Syndrome Scale ( PANSS ) . Other outcomes include depressive symptoms , patient functioning and the level of insight . Correlates of change measured during the study will include structural brain changes , oxidative stress and defense , as well as neuroplasticity indicators . Metabolic syndrome components will also be assessed throughout the study . Discussion By comparing 26-week administration of EPA + DHA or ( placebo ) olive oil as add-on therapy in reducing symptom severity and one-year relapse rate in patients with first episode schizophrenia , it is intended to provide new insights into the efficacy of omega-3 PUFA and correlates of change , and contribute to the improvement of mental health care for individuals suffering from schizophrenia . Trial registration This study has been registered at Clinical Trials.gov with the following number : NCT02210962 It has been suggested that the extract of gingko biloba ( EGb ) may enhance the efficiency of the classic antipsychotic haloperidol in patients with chronic schizophrenia , especially on positive symptoms , and reduce serum superoxide dismutase ( SOD ) levels . Therefore , we decided to evaluate the therapeutic effect of EGb and to examine the effect of it on the levels of antioxidant enzymes in schizophrenic patients on olanzapine treatment . We hypothesized that EGb would have the beneficial effects on schizophrenic symptoms and might cause reductions in antioxidant enzymes . The subjects were r and omly assigned to the two groups : olanzapine plus EGb  ( group I ) ( n=15 ) and olanzapine alone  ( group II ) ( n=14 ) . The patients were evaluated at baseline and at week 8 with respect to the Positive and Negative Syndrome Scale ( PANSS ) , serum SOD , catalase ( CAT ) , and glutathion peroxidase ( GPX ) levels . At baseline , no statistically significant difference regarding the mean total PANSS scores between treatment groups was found . At the evaluation of week 8 , a significant difference in mean Scale for the Assessment of Postive Symptoms ( SAPS ) scores but not in Scale for the Assessment of Negative Symptoms scores between groups was found . Total patients had statistically significant higher serum SOD , CAT and GPX levels compared to control groups at baseline . At 8 weeks , there were significant differences in the mean decrease in SOD and CAT levels but not in GPX levels between treatment groups . The changes in SOD and CAT levels were correlated with the change in SAPS in group I , but not in the group II . The present study supported the findings of the previous study demonstrating that EGb might enhance the efficiency of antipsychotic in patients with schizophrenia , particularly on positive symptoms of the disorder PURPOSE The study examined the rate of remission in individuals experiencing a first episode of schizophrenia ( FES ) in China and explored predictors of remission in the acute phase of the illness . DESIGN AND METHODS Fifty-five FES patients were r and omly treated with risperidone , olanzapine , or aripiprazole at therapeutic doses for 8 weeks , and their clinical profiles and cognition were assessed using st and ardized assessment instruments at entry and the end of the study . FINDINGS Of the 55 patients , 30 ( 54.5 % ) remitted by the end of the 8-week study . In univariate analyses , shorter duration of untreated psychosis , higher scores on both the time-based prospect i ve memory ( TBPM ) and event-based prospect i ve memory tasks and the Hopkins Verbal Learning Test-revised , and less severe negative symptoms were significantly associated with remission . In stepwise multiple logistic regression analyses , only higher scores on the TBPM significantly predicted remission . Individuals having higher scores reflecting better TBPM at baseline were more likely to achieve remission after 8 weeks of optimized antipsychotic treatment . PRACTICE IMPLICATION S TPBM may be useful in helping clinicians identify those FES patients most likely to achieve a favorable treatment response BACKGROUND Young people with self-experienced cognitive thought and perception deficits ( basic symptoms ) may present with an early initial prodromal state ( EIPS ) of psychosis in which most of the disability and neurobiological deficits of schizophrenia have not yet occurred . AIMS To investigate the effects of an integrated psychological intervention ( IPI ) , combining individual cognitive-behavioural therapy , group skills training , cognitive remediation and multifamily psychoeducation , on the prevention of psychosis in the EIPS . METHOD A r and omised controlled , multicentre , parallel group trial of 12 months of IPI v. supportive counselling ( trial registration number : NCT00204087 ) . Primary outcome was progression to psychosis at 12- and 24-month follow-up . RESULTS A total of 128 help-seeking out- patients in an EIPS were r and omised .  Integrated psychological intervention was superior to supportive counselling in preventing progression to psychosis at 12-month follow-up ( 3.2 % v. 16.9 % ; P = 0.008 ) and at 24-month follow-up ( 6.3 % v. 20.0 % ; P = 0.019 ) . CONCLUSIONS Integrated psychological intervention appears effective in delaying the onset of psychosis over a 24-month time period in people in an EIPS Oxidative stress may be a contributing factor in the etiopathophysiology of schizophrenia , which may be exacerbated by the treatment with antipsychotics with pro-oxidant properties . Increased levels of S100 B are associated with neurodegenerative disorders , including schizophrenia . The aim of the present study was to investigate the role of oxidative cell damage in the pathogenesis of schizophrenia . Forty patients who fully met the fourth Diagnostic and Statistical Manual of Mental Disorders criteria for schizophrenia and 35 healthy control subjects were included in the study .  Serum S100 B level was determined to investigate brain damage . Plasma malondialdehyde ( MDA ) levels and susceptibility of red blood cell ( RBC ) to oxidation were determined to investigate the oxidative status and plasma vitamin E , vitamin C , serum total carotenoid levels and total antioxidant capacity and RBC superoxide dismutase ( SOD ) and whole blood glutathione peroxidase activities were measured to investigate the antioxidative defence before and after 6 weeks of antipsychotic treatment .  Plasma MDA and serum S100 B levels and RBC-SOD activity were significantly higher in the schizophrenia group than those of the control group . Treatment did not modify any of the oxidative-antioxidative system parameters or serum S100 B levels . S100 B level was significantly higher in patients with negative symptoms than the patients with positive symptoms and the control subjects . S100 B levels were significantly reduced after 6 weeks of treatment in patients with negative symptoms . The results of the present study might support the oxidative cell injury hypothesis of the schizophrenia . Furthermore , the underlying mechanisms of the subgroups of schizophrenia might be different as suggested by the increased S100 B levels and its decrement after treatment in patients with negative symptoms BACKGROUND Functional remission ( FR ) is an intermediate and necessary step toward recovery , but is understudied in first-episode psychosis ( FEP ) . We aim ed to examine the rate and predictors of FR in FEP patients in the context of a r and omized-controlled trial ( RCT ) comparing a 1-year extension of early intervention ( Extended EI , 3-year EI ) with step-down psychiatric care ( SC , 2-year EI ) . METHODS One hundred sixty Chinese patients were recruited from a specialized EI program for FEP in Hong Kong after they have completed this 2-year EI service , r and omly allocated to Extended EI or SC , and followed up for 12 months . Assessment s on premorbid adjustment and personality , clinical profiles , functioning , and treatment characteristics were conducted . FR was operationalized as simultaneous fulfillment of attaining adequate functional levels ( measured by Social and Occupational Functioning Scale and Role Functioning Scale ) and competitive employment at 6 and 12 months . Data analysis was based on 156 subjects who completed follow-up functional assessment s. RESULTS Thirty-one ( 19.9 % ) patients achieved FR status . Multivariate binary regression analysis showed that female gender , lower degrees of premorbid schizoid-schizotypal traits , Extended EI treatment condition , lower levels of positive symptoms at intake , and better baseline functioning independently predicted FR . CONCLUSION This is the first RCT providing supportive evidence to an extension of EI service beyond 2-year treatment duration on further enhancing the likelihood of FR attainment in FEP . Our findings that only approximately 20 % of patients achieved FR indicate an unmet therapeutic need for promoting sustained adequate functional improvement in the early stage of psychotic illness IMPORTANCE Short-term outcome studies of antipsychotic dose-reduction/discontinuation strategies in patients with remitted first-episode psychosis ( FEP ) showed higher relapse rates but no other disadvantages compared with maintenance treatment ; however , long-term effects on recovery have not been studied before . OBJECTIVE To compare rates of recovery in patients with remitted FEP after 7 years of follow-up of a dose reduction/discontinuation ( DR ) vs maintenance treatment ( MT ) trial . DESIGN Seven-year follow-up of a 2-year open r and omized clinical trial comparing MT and DR . SETTING One hundred twenty-eight patients participating in the original trial were recruited from 257 patients with FEP referred from October 2001 to December 2002 to 7 mental health care services in a 3.2 million- population catchment area . Of these , 111 patients refused to participate and 18 patients did not experience remission . PARTICIPANTS After 7 years , 103 patients ( 80.5 % ) of 128 patients who were included in the original trial were located and consented to follow-up assessment . INTERVENTION After 6 months of remission , patients were r and omly assigned to DR strategy or MT for 18 months . After the trial , treatment was at the discretion of the clinician . MAIN OUTCOMES AND MEASURES Primary outcome was rate of recovery , defined as meeting the criteria of symptomatic and functional remission . Determinants of recovery were examined using logistic regression analysis ; the treatment strategy ( MT or DR ) was controlled for baseline parameters . RESULTS The DR patients experienced twice the recovery rate of the MT patients ( 40.4 % vs 17.6 % ) . Logistic regression showed an odds ratio of 3.49 ( P = .01 ) . Better DR recovery rates were related to higher functional remission rates in the DR group but were not related to symptomatic remission rates . CONCLUSIONS AND RELEVANCE Dose reduction/discontinuation of antipsychotics during the early stages of remitted FEP shows superior long-term recovery rates compared with the rates achieved with MT . To our knowledge , this is the first study showing long-term gains of an early-course  DR strategy in patients with remitted FEP . Additional studies are necessary before these results are incorporated into general practice . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N16228411 Family interventions for first-episode psychosis ( FEP ) are an integral component of treatment , with positive effects mainly on patients ’ mental state and relapse rate . However , comparatively little attention has been paid to the effects of family interventions on caregivers ’ stress coping and well-being , especially in non-Western countries . We aim ed to test the effects of a 5-month clinician-supported problem-solving bibliotherapy ( CSPSB ) for Chinese family caregivers of people with FEP in improving family burden and carers ’ problem-solving and caregiving experience , and in reducing psychotic symptoms and duration of re-hospitalizations , compared with those only received usual outpatient family support ( UOFS ) . A r and omized controlled trial was conducted across 2 early psychosis clinics in Hong Kong , where there might be inadequate usual family support services for FEP patients . A total of 116 caregivers were r and omly selected , and after baseline measurement , r and omly assigned to the CSPSB or UOFS . They were also assessed at 1-week and 6- and 12-month post-intervention . Intention-to-treat analyses were applied and indicated that the CSPSB group reported significantly greater improvements in family burden and caregiving experience , and reductions in severity of psychotic symptoms and duration of re-hospitalizations , than the UOFS group at 6- and 12-month follow-up . CSPSB produces moderate long-term benefits to caregivers and FEP patients , and is a low-cost adjunct to UOFS CONTEXT Cognitive impairment in schizophrenia is frequent , involves multiple domains , and is enduring . Numerous recent clinical trials have suggested that second-generation antipsychotic medications significantly enhance cognition in schizophrenia . However , none of these studies included healthy controls undergoing repeated testing to assess the possibility that improvements might reflect simple practice effects . OBJECTIVE To report the results on cognition of a r and omized comparison of 2 widely prescribed second-generation antipsychotic medications , olanzapine and risperidone , in patients with first-episode schizophrenia and a healthy control group . DESIGN R and omized clinical trial . SETTING Hospital-based research units . Patients A total of 104 participants with first-episode schizophrenia and 84 healthy controls . MAIN OUTCOME MEASURES Cognitive assessment of all study participants occurred at baseline , 6 weeks later , and 16 weeks later . Neurocognitive tests included measures of working memory and attention , speed , motor function , episodic memory , and executive function . RESULTS No differential drug effects were observed . Of 16 cognitive measures , 9 demonstrated improvement over time and only 2 demonstrated greater rates of change than those observed in the healthy control group undergoing repeated assessment . The composite effect size for cognitive change was 0.33 in the healthy control group ( attributed to practice ) and 0.36 in the patients with first-episode schizophrenia . Improvements in cognition in the first-episode schizophrenia group could not be accounted for by medication dose , demographic variables , or intellectual level . CONCLUSIONS The cognitive improvements observed in the trial were consistent in magnitude with practice effects observed in healthy controls , suggesting that some of the improvements in cognition in the first-episode schizophrenia group may have been due to practice effects ( ie , exposure , familiarity , and /or procedural learning ) . Our results also indicated that differential medication effects on cognition were small . We believe that these findings have important implication s for drug discovery and the design of registration trials that attempt to demonstrate cognitive enhancement BACKGROUND Vitamin B6 , or pyridoxine , plays an intrinsic role in the synthesis of certain neurotransmitters that take part in development of psychotic states . Several reports indicate that vitamin B6 may be a factor in a number of psychiatric disorders and related conditions , such as autism , Alzheimer 's disease , hyperactivity , learning disability , anxiety disorder , and depression . Moreover , there are anecdotal reports of a reduction in psychotic symptoms after vitamin B6 supplementation of psychopharmacologic treatment of patients suffering from schizophrenia or organic mental disorder . The aim of this study was to examine whether vitamin B6 therapy influences psychotic symptoms in patients suffering from schizophrenia and schizoaffective disorder . METHOD The effects of the supplementation of vitamin B6 to antipsychotic treatment on positive and negative symptoms in 15 schizophrenic and schizoaffective patients ( DSM-IV criteria ) were examined in a double-blind , placebo-controlled , crossover study spanning 9 weeks . All patients had stable psychopathology for at least 1 month before entry into the study and were maintained on treatment with their pre study  psychoactive and antiparkinsonian medications  throughout the study . All patients were assessed using the Positive and Negative Syndrome Scale ( PANSS ) for schizophrenia on a weekly basis . Patients r and omly received placebo or vitamin B6 , starting at 100 mg/day in the first week and increasing to 400 mg/day in the fourth week by 100-mg increments each week . RESULTS PANSS scores revealed no differences between vitamin B6- and placebo-treated patients in amelioration of their mental state . CONCLUSION Further studies with larger population s and shorter duration of illness are needed to clarify the question of the possible efficacy of vitamin B6 in treatment of psychotic symptoms in schizophrenia Short-term clinical trials of omega-3 polyunsaturated fatty acids ( n-3 PUFA ) as add-on therapy in patients with schizophrenia revealed mixed results . The majority of these studies used an 8- to 12-week intervention based on ethyl-eicosapentaenoic acid . A r and omized placebo-controlled trial was design ed to compare the efficacy of 26-week intervention , composed of either 2.2 g/day of n-3 PUFA , or olive oil placebo , with regard to symptom severity in first-episode schizophrenia patients . Seventy-one patients ( aged 16 - 35 ) were enrolled in the study and r and omly assigned to the study arms . The primary outcome measure of the clinical evaluation was schizophrenia symptom severity change measured by the Positive and Negative Syndrome Scale ( PANSS ) . Mixed models repeated measures analysis revealed significant differences between the study arms regarding total PANSS score change favouring n-3 PUFA ( p = 0.016 ; effect size ( ES ) = 0.29 ) . A fifty-percent improvement in symptom severity was achieved significantly more frequently in the n-3 PUFA group than in the placebo group ( 69.4 vs 40.0 % ; p = 0.017 ) . N-3 PUFA intervention was also associated with an improvement in general psychopathology , measured by means of PANSS ( p = 0.009 ; ES = 0.32 ) , depressive symptoms ( p = 0.006 ; ES = 0.34 ) , the level of functioning ( p = 0.01 ; ES = 0.31 ) and clinical global impression ( p = 0.046 ; ES = 0.29 ) . The findings suggest that 6-month intervention with n-3 PUFA may be a valuable add-on therapy able to decrease the intensity of symptoms and improve the level of functioning in first-episode schizophrenia patients Rationale Several investigators implicated role of free radical-mediated pathology in schizophrenia . No study has ever examined the effect of vitamin C with atypical antipsychotics in the treatment of schizophrenia . Objective The aim of this study was to examine the effect of oral vitamin C with atypical antipsychotics on serum malondialdehyde ( MDA ) , plasma ascorbic acid levels , and brief psychiatric rating scale ( BPRS ) score in schizophrenic patients . Method Forty schizophrenic patients participated in a prospect i ve , double-blind , placebo-controlled , noncrossover , 8-week study . The patients with schizophrenia were divided r and omly into placebo and vitamin C group of 20 each . Serum MDA and plasma ascorbic acid were estimated by methods of Nischal and Aye , respectively . Result Increased serum MDA and decreased plasma ascorbic acid levels were found in schizophrenic patients . These levels were reversed significantly after treatment with vitamin C along with atypical antipsychotics compared to placebo with atypical antipsychotics .  BPRS change scores at 8 weeks improved statistically significant with vitamin C as compared to placebo . Conclusion Oral supplementation of vitamin C with atypical antipsychotic reverses ascorbic acid levels , reduces oxidative stress , and improves BPRS score , hence both the drugs in combination can be used in the treatment of schizophrenia While weight-management interventions are effective in attenuating antipsychotic-induced weight , there is no available evidence on their long-term effectiveness . This study sought to investigate the 2-year effects of an early behavioural intervention ( EBI ) design ed to prevent antipsychotic-induced weight gain in first-episode psychosis ( FEP ) patients . Sixty-one FEP patients were r and omized to receive either EBI or treatment-as-usual .  Intention-to-treat and observed-cases analysis showed that patients in the EBI group gained significantly less weight than those allocated to routine care at intervention completion ( 3-month follow-up ) with treatment effects maintained over 3months . Differences between groups were no longer significant by 12months . Weight-management interventions may need to be offered for longer periods to maintain preventative effects . Alternatively , booster sessions may need to be regularly delivered after intervention completion Membrane lipid metabolism and redox regulation may be disturbed in schizophrenia . We examined the clinical effect of adding an omega-3 fatty acid and /or vitamins E+C to antipsychotics . It was hypothesized that lower baseline levels of polyunsaturated fatty acids ( PUFAs ) would predict more benefit from the add-on treatment . The trial had a multicenter , r and omized , double-blind , placebo-controlled 2 × 2 factorial design . Patients aged 18–39 years with schizophrenia or related psychoses were consecutively included at admission to psychiatric departments in Norway . They received active or placebo ethyl-eicosapentaenoate ( EPA ) 2 g day−1 and active or placebo vitamin E 364 mg day−1+vitamin C 1000 mg day−1 ( vitamins ) for 16 weeks . The main outcome measures were Positive and Negative Syndrome Scale ( PANSS ) total and subscales scores , analyzed by linear mixed models . Ninety-nine patients were included . At baseline , erythrocyte PUFA were measured in 97 subjects . Given separately , EPA and vitamins  increased drop-out rates , whereas when combined they did not differ from placebo . In low PUFA patients , EPA alone impaired the course of total PANSS ( Cohen ’s d=0.29 ; P=0.03 ) and psychotic symptoms ( d=0.40 ; P=0.003 ) , especially persecutory delusions ( d=0.48 ; P=0.0004 ) . Vitamins alone impaired the course of psychotic symptoms ( d= 0.37 ; P=0.005 ) , especially persecutory delusions ( d=0.47 ; P=0.0005 ) . Adding vitamins to EPA neutralized the detrimental effect on psychosis ( interaction d=0.31 ; P=0.02 ) . In high PUFA patients , there were no significant effects of trial drugs on PANSS scales . In conclusion , given separately during an acute episode , EPA and vitamins E+C  induce psychotic symptoms in patients with low levels of PUFA . Combined , these agents seem safe
However , mechanistic studies found significant improvements in hippocampal neuronal health and brain glutathione .
CONCLUSION There is preliminary evidence that taurine improves outcomes in FEP , whereas effects of omega-3 and antioxidant vitamins/amino-acids are inconsistent ; perhaps mainly benefitting patients with high levels of oxidative stress .
AIM The effects of nutrient-based treatments , including adjunctive vitamin or antioxidant supplementation , have been explored extensively in long-term schizophrenia .
However , no systematic evaluation of trials in " first-episode psychosis " ( FEP ) has been conducted , despite the potential benefits of using these treatments during the early stages of illness .
Therefore , we aim ed to review all studies examining efficacy , tolerability and the biological mechanisms of action , of nutrient supplementation in FEP .