Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial Randomized trial to evaluate the efficacy of cognitive therapy for low-functioning patients with schizophrenia. Predictors of treatment response from a first episode of schizophrenia or schizoaffective disorder. Effects of clozapine, olanzapine, risperidone, and haloperidol on hostility among patients with schizophrenia. Adjunctive divalproex and hostility among patients with schizophrenia receiving olanzapine or risperidone. MECHANISM OF THE ANTIPSYCHOTIC EFFECT IN THE TREATMENT OF ACUTE SCHIZOPHRENIA [Clozapine in the treatment of schizophrenia]. [A pilot study on the effectiveness of a group-based cognitive-behavioral therapy program for coping with auditory hallucinations]. Subanesthetic Doses of Ketamine Stimulate Psychosis in Schizophrenia VR-Based Conversation Training Program for Patients with Schizophrenia: A Preliminary Clinical Trial Identification of clinically meaningful relationships among cognition, functionality, and symptoms in subjects with schizophrenia or schizoaffective disorder Etiological and clinical features of childhood psychotic symptoms: results from a birth cohort. Sleep deprivation as an experimental model system for psychosis: Effects on smooth pursuit, prosaccades, and antisaccades Examining transcranial direct-current stimulation (tDCS) as a treatment for hallucinations in schizophrenia. Effect of Antipsychotic Withdrawal on Negative Symptoms in Schizophrenia Symptoms of psychoses. A factor-analytic study. Cognitive-behavioural therapy for refractory psychotic symptoms of schizophrenia resistant to atypical antipsychotic medication. Randomised controlled trial. A long-term study of penfluridol in chronic schizophrenia. Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia. A Randomized Clinical Trial. Pimavanserin, a Serotonin2A Receptor Inverse Agonist, for the Treatment of Parkinson's Disease Psychosis What are the effects of group cognitive behaviour therapy for voices? A randomised control trial Independent frontal-system deficits in schizophrenia: cognitive, clinical, and adaptive implications Change in level of productivity in the treatment of schizophrenia with olanzapine or other antipsychotics
Schizophrenia is a chronic , complex and heterogeneous mental disorder , with pathological features of disrupted neuronal excitability and plasticity within limbic structures of the brain . These pathological features manifest behaviorally as positive symptoms ( including hallucinations , delusions and thought disorder ) , negative symptoms ( such as social withdrawal , apathy and emotional blunting ) and other psychopathological symptoms ( such as psychomotor retardation , lack of insight , poor attention and impulse control ) . Altered glutamate neurotransmission has for decades been linked to schizophrenia , but all commonly prescribed antipsychotics act on dopamine receptors . LY404039 is a selective agonist for metabotropic glutamate 2/3 ( mGlu2/3 ) receptors and has shown antipsychotic potential in animal studies . With data from rodents , we provide new evidence that mGlu2/3 receptor agonists work by a distinct mechanism different from that of olanzapine . To clinical ly test this mechanism , an oral prodrug of LY404039 ( LY2140023 ) was evaluated in schizophrenic patients with olanzapine  as an active control in a r and omized , three-armed , double-blind , placebo-controlled study . Treatment with LY2140023 , like treatment with olanzapine , was safe and well-tolerated ; treated patients showed statistically significant improvements in both positive and negative symptoms of schizophrenia compared to placebo ( P < 0.001 at week 4 ) . Notably , patients treated with LY2140023 did not differ from placebo-treated patients with respect to prolactin elevation , extrapyramidal symptoms or weight gain . These data suggest that mGlu2/3 receptor agonists have antipsychotic properties and may provide a new alternative for the treatment of schizophrenia CONTEXT Low-functioning patients with chronic schizophrenia have high direct treatment costs and indirect costs incurred due to lost employment and productivity and have a low quality of life ; antipsychotic medications and psychosocial interventions have shown limited efficacy to promote improved functional outcomes . OBJECTIVE To determine the efficacy of an 18-month recovery-oriented cognitive therapy program to improve psychosocial functioning and negative symptoms ( avolition-apathy , anhedonia-asociality ) in low-functioning patients with schizophrenia . Design , Setting , and PARTICIPANTS A single-center , 18-month , r and omized , single-blind , parallel group trial enrolled 60 low-functioning , neurocognitively impaired patients with schizophrenia ( mean age , 38.4 years ; 33.3 % female ; 65.0 % African American ) . INTERVENTIONS Cognitive therapy plus st and ard treatment vs st and ard treatment alone . MAIN OUTCOME MEASURES The primary outcome measure was the Global Assessment Scale score at 18 months after r and omization . The secondary outcomes were scores on the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms at 18 months after r and omization . RESULTS Patients treated with cognitive therapy showed a clinical ly significant mean improvement in global functioning from baseline to 18 months that was greater than the improvement seen with st and ard treatment ( within-group Cohen d , 1.36 vs 0.06 , respectively ; adjusted mean [ SE ] , 58.3 [ 3.30 ] vs 47.9 [ 3.60 ] , respectively ; P = .03 ; between-group d = 0.56 ) . Patients receiving cognitive therapy as compared with those receiving st and ard treatment also showed a greater mean reduction in avolition-apathy ( adjusted mean [ SE ] , 1.66 [ 0.31 ] vs 2.81 [ 0.34 ] , respectively ; P = .01 ; between-group d = -0.66 ) and positive symptoms ( hallucinations , delusions , disorganization ) ( adjusted mean [ SE ] , 9.4 [ 3.3 ] vs 18.2 [ 3.8 ] , respectively ; P = .04 ; between-group d = -0.46 ) at 18 months . Age was controlled in the analyses , and there were no meaningful group differences in baseline antipsychotic medications ( class or dosage ) or in medication changes during the course of the trial . CONCLUSION Cognitive therapy can be successful in promoting clinical ly meaningful improvements in functional outcome , motivation , and positive symptoms in low-functioning patients with significant cognitive impairment . Trial Registration clinical trials.gov Identifier : NCT00350883 OBJECTIVE This study examined the treatment response of patients with first-episode schizophrenia and schizoaffective disorder and potential predictors of response . METHOD First-episode patients were assessed on measures of psychopathology , cognition , social functioning , and biological parameters and treated according to a st and ardized algorithm . RESULTS One hundred eighteen patients ( 52 % male , mean age 25.2 years ) entered the study . The cumulative percentage of patients responding by 1 year was 87 % ; the median time to response was 9 weeks . The following variables were significantly associated with less likelihood of response to treatment : male sex , obstetric complications , more severe hallucinations and delusions , poorer attention at baseline , and the development of parkinsonism during antipsychotic treatment . Variables not significantly related to treatment response were diagnosis ( schizophrenia versus schizoaffective disorder ) , premorbid functioning , duration of psychotic symptoms prior to study entry , baseline disorganization , negative and depressive symptoms , baseline motor function , akathisia and dystonia during treatment , growth hormone and homovanillic acid measures , psychotic symptom activation to methylpheni date , and magnetic resonance measures . CONCLUSIONS Patients with first-episode schizophrenia and schizoaffective disorder have high rates of response to antipsychotic treatment ; there are specific clinical and pathobiologic predictors of response OBJECTIVE This study compared the specific antiaggressive effects of clozapine with those of olanzapine , risperidone , and haloperidol . METHODS A total of 157 in patients with schizophrenia or schizoaffective disorder and a history of suboptimal treatment response were r and omly assigned to receive clozapine , olanzapine , risperidone , or haloperidol in a double-blind 14-week trial . The trial was divided into two periods : eight weeks during which the dosage was escalated and then fixed , and six weeks during which variable dosages were used . The hostility item of the Positive and Negative Syndrome Scale ( PANSS ) was the principal outcome measure . Covariates included the items that reflect positive symptoms of schizophrenia ( delusions , suspiciousness or feelings of persecution , gr and iosity , unusual thought content , conceptual disorganization , and hallucinations ) and the sedation item of the Nurses Observation Scale for Inpatient Evaluation ( NOSIE ) . RESULTS Patients differed in their treatment response as measured by the hostility item of the PANSS . The scores of patients taking clozapine indicated significantly greater improvement than those of patients taking haloperidol or risperidone . The effect on hostility appeared to be independent of the antipsychotic effect of clozapine on other PANSS items that reflect delusional thinking , a formal thought disorder , or hallucinations and independent of sedation as measured by the NOSIE . Neither risperidone nor olanzapine showed superiority to haloperidol . CONCLUSION Clozapine has a relative advantage over other antipsychotics as a specific antihostility agent OBJECTIVE This study compared the specific antihostility effects of atypical antipsychotic monotherapy ( olanzapine or risperidone ) with that of combination treatment with divalproex sodium among patients with schizophrenia experiencing an acute psychotic episode . METHODS A total of 249 in patients with schizophrenia were r and omly assigned to receive olanzapine plus placebo , olanzapine plus divalproex , risperidone plus placebo , or risperidone plus divalproex in a double-blind , 28-day multicenter trial . The target daily dose was 15 milligrams for olanzapine , 6 milligrams for risperidone , and up to 30 milligrams per kilogram ( minimum , 15 milligrams per kilogram ) for divalproex . The hostility item of the Positive and Negative Syndrome Scale ( PANSS ) was the principal outcome measure . Covariates included the PANSS items reflecting positive symptoms of schizophrenia ( delusions , suspiciousness/persecution , gr and iosity , unusual thought content , conceptual disorganization , and hallucinatory behavior ) . RESULTS Combination treatment with risperidone or olanzapine plus divalproex was associated with different scores on the hostility item of the PANSS compared with antipsychotic monotherapy . Combination therapy had a significantly greater antihostility effect at days 3 and 7 than monotherapy . This result was not seen beyond the first week of treatment , but there was a trend toward a difference in effect for the entire treatment period . The effect on hostility appears to be statistically independent of antipsychotic effect on other PANSS items reflecting delusional thinking , a formal thought disorder , or hallucinations . CONCLUSIONS Divalproex sodium may be useful as an adjunctive agent in specifically reducing hostility in the first week of treatment with risperidone or olanzapine among patients with schizophrenia experiencing an acute psychotic episode In a double-blind trial in which 45 patients with acute schizophrenia took part the alpha-isomer of flupenthixol  ( which blocks the dopamine receptor ) was found to be significantly more effective than both beta-flupenthixol ( which does not ) and placebo . The drug effect was confined to the " positive " symptoms -- delusions , hallucinations , and though disorder-- and appeared only in the 3rd and 4th weeks of the trial . It was as great in patients with evidence of deterioration ( Feighner-positive patients ) as in patients without deterioration and was less in patients who had affective disturbance in addition to schizophrenia symptoms . The findings are consistent with the hypothesis that dopamine-receptor blockade is the only requirement for antipsychotic activity and suggest that the antipsychotic effect occurs in patients with typically schizophrenic illnesses but may be limited to positive symptoms Schizophrenia is associated with brain abnormalities and is typically evidence d by disorganized speech and behavior , delusions , and hallucinations ; it usually requires extended hospitalization . Its incidence in the western world is estimated at 4 - 7 cases/10,000/year . A method of shortening hospitalization and improving level of functioning is the use of unique medication , including clozapine , which has been in use in Israel for the past 6 years . We report 327 patients who participated in a community rehabilitation program and were treated with clozapine .  They were compared with 417 patients who corresponded to the guidelines of the Director of Mental Health Services for treatment with clozapine , but were not treated with it for reasons not defined in the guidelines . The study included those 25 - 44 and 45 - 64 years of age and according to the division of the population of patients hospitalized in both government and private hospitals . The project demonstrates the savings from use of clozapine as opposed to the alternative of hospitalizing these patients . It also shows the complexity and difficulty in assimilating new technologies , in relation to the influence of social considerations and supplier/insurer accounting on the patterns of technological assimilation OBJECTIVE The aim of this study was to prepare a group-based cognitive-behavioral therapy program for patients with schizophrenia and other psychotic disorders coping with auditory hallucinations , and to evaluate the effectiveness of the program . METHOD The study included 12 male in patients aged between 18 and 55 years from the Manisa Mental Health and Illnesses Hospital that were diagnosed with schizophrenia or schizoaffective disorder according to DSM-IV diagnostic criteria ( SCID-I ) . The inclusion criteria were the diagnosis of schizophrenia or schizoaffective disorder , at least 1 hospitalization , the presence of auditory hallucinations , and the absence of alcohol/drug abuse/dependence , organic deficit , and mental/physical disability . In all , 7 patients received routine care plus group CBT and 5 patients received routine care alone . The group treatment program was conducted for 9 - 10 sessions twice a week . The patients were assessed using SAPS , SANS , the Problem/Symptom Checklist , and the Knowledge of Schizophrenia Question naire pre-treatment , post-treatment , and at the 1-year follow-up . The outcomes were analyzed using the Wilcoxon signed rank test . RESULTS There was a significant reduction in the severity and frequency of hallucinations , delusions , distress and occupation with auditory hallucinations , negative symptoms , and anxiety in the CBT group after treatment . Additionally , post-treatment outcome in the treatment group did n't change at 1 year follow-up . In the control group , there was no difference between pre-treatment and post-treatment outcome ( P<0.05 ) . CONCLUSION The therapy program was considered to be effective in increasing the ability to cope with auditory hallucinations and reducing their frequency for the patients with schizophrenia and schizoaffective disorder We administered ketamine to schizophrenic individuals in a double-blind , placebo-controlled design using a range of subanesthetic doses ( 0.1 , 0.3 , and 0.5 mg/kg ) to evaluate the nature , dose characteristics , time course , and neuroleptic modulation of N-methyl-D-aspartate ( NMDA ) antagonist action on mental status in schizophrenia . Ketamine induced a dose-related , short ( < 30 minutes ) worsening in mental status in the haloperidol-treated condition , reflected by a significant increase in BPRS total score for the 0.3 mg/kg ( p = . 005 ) and 0.5 mg/kg ( p = . 01 ) challenges . Positive symptoms ( hallucinations , delusions , thought disorder ) , not negative symptoms accounted for these changes . These ketamine-induced psychotic symptoms were strikingly reminiscent of the subject 's symptoms during active episodes of their illness . Results from six patients who were retested in the same design after being neuroleptic-free for 4 weeks failed to indicate that haloperidol blocks ketamine-induced psychosis . Several subjects evidence d delayed or prolonged ( 8–24 hours ) psychotomimetic effects such as worsening of psychosis with visual hallucinations . These data suggest that antagonism of NMDA-sensitive glutamatergic transmission in brain exacerbates symptoms of schizophrenia Schizophrenia is a devastating mental illness and is characterized by hallucinations and delusions as well as social skills deficits . Generally , social skills training design ed to help patients develop social skills includes role-playing , but this form of training has typical shortcomings , which are largely due to a trainer 's difficulties to project emotion . Virtual reality (VR)-based techniques have the potential to solve these difficulties , because they provide a computer-generated but realistic three-dimensional world and humanlike avatars that can provide emotional stimuli . In this paper , we report on a method of implementing virtual environments ( VEs ) in order to train people with schizophrenia to develop conversational skills in specific situations , which could overcome the shortcomings of or complement conventional role-playing techniques . The paper reports the efficacy of the proposed approach in a preliminary clinical trial with 10 patients with schizophrenia INTRODUCTION Cognitive impairment in schizophrenia and schizoaffective disorder is a major determinant of disability . This study explored the relationships among cognitive functioning , clinical symptoms , overall functionality , and demographic characteristics . METHODS This was a post hoc analysis of a 52-week , prospect i ve , r and omized , double-blind study ( N=323 ) comparing 2 doses of risperidone long-acting injectable ( RLAI ) in stable subjects with schizophrenia or schizoaffective disorder . Cognitive evaluations were performed and st and ardized using a healthy age- and sex-matched comparison group . Simple and multiple regression models were used to identify relationships among neurocognitive composite scores ( NCS ) , clinical symptom end points ( Positive and Negative Syndrome Scale [ PANSS ] total and factor scores ) , overall functionality ( Personal and Social Performance [ PSP ] score ) , and demographics . RESULTS A simple regression model identified significant relationships between the NCS at end point and PANSS total score , PANSS disorganized thoughts factor score , functioning ( PSP ) and age . A 1-point decrease on PANSS total score and PANSS disorganized thoughts factor score corresponded to an increase in NCS of 0.126-point , and 0.81-point increases , respectively . A 1-point increase on the PSP corresponded to a 0.186-point increase in the NCS T-score . Among the demographic variables , only age correlated significantly with cognition ( 10-year increase in age corresponded to 1.1-point decrease in NCS T-score ) in a multiple regression model . CONCLUSION Improved cognition was associated with beneficial changes in functional status and clinical symptoms ( particularly disorganization symptoms ) in subjects with schizophrenia/schizoaffective disorder . Older subjects showed less overall cognitive improvement . Improved cognitive and functional outcome is correlated with symptom improvements in RLAI-treated  patients with schizophrenia CONTEXT It has been reported that childhood psychotic symptoms are common in the general population and may signal neurodevelopmental processes that lead to schizophrenia . However , it is not clear whether these symptoms are associated with the same extensive risk factors established for adult schizophrenia . OBJECTIVE To examine the construct validity of children 's self-reported psychotic symptoms by testing whether these symptoms share the risk factors and clinical features of adult schizophrenia . DESIGN Prospect i ve , longitudinal cohort study of a nationally representative birth cohort in Great Britain . PARTICIPANTS A total of 2232 twelve-year-old children followed up since age 5 years ( retention , 96 % ) . Main Outcome Measure Children 's self-reported hallucinations and delusions . RESULTS Children 's psychotic symptoms are familial and heritable and are associated with social risk factors ( eg , urbanicity ) ; cognitive impairments at age 5 ; home-rearing risk factors ( eg , maternal expressed emotion ) ; behavioral , emotional , and educational problems at age 5 ; and comorbid conditions , including self-harm . CONCLUSIONS The results provide a comprehensive picture of the construct validity of children 's self-reported psychotic symptoms . For research ers , the findings indicate that children who have psychotic symptoms can be recruited for neuroscience research to determine the pathogenesis of schizophrenia . For clinicians , the findings indicate that psychotic symptoms in childhood are often a marker of an impaired developmental process and should be actively assessed Current antipsychotic medications fail to satisfactorily reduce negative and cognitive symptoms and produce many unwanted side effects , necessitating the development of new compounds . Cross-species , experimental behavioural model systems can be valuable to inform the development of such drugs . The aim of the current study was to further test the hypothesis that controlled sleep deprivation is a safe and effective model system for psychosis when combined with oculomotor biomarkers of schizophrenia . Using a r and omized counterbalanced within-subjects design , we investigated the effects of 1 night of total sleep deprivation in 32 healthy participants on smooth pursuit eye movements ( SPEM ) , prosaccades ( PS ) , antisaccades ( AS ) , and self-ratings of psychosis-like states . Compared with a normal sleep control night , sleep deprivation was associated with reduced SPEM velocity gain , higher saccadic frequency at 0.2 Hz , elevated PS spatial error , and an increase in AS direction errors . Sleep deprivation also increased intra-individual variability of SPEM , PS , and AS measures . In addition , sleep deprivation induced psychosis-like experiences mimicking hallucinations , cognitive disorganization , and negative symptoms , which in turn had moderate associations with AS direction errors . Taken together , sleep deprivation result ed in psychosis-like impairments in SPEM and AS performance . However , diverging somewhat from the schizophrenia literature , sleep deprivation additionally disrupted PS control . Sleep deprivation thus represents a promising but possibly unspecific experimental model that may be helpful to further improve our underst and ing of the underlying mechanisms in the pathophysiology of psychosis and aid the development of antipsychotic and pro-cognitive drugs OBJECTIVE Some 25%–30 % of patients with schizophrenia have auditory verbal hallucinations that are refractory to antipsychotic drugs . Outcomes in studies of repetitive transcranial magnetic stimulation suggest the possibility that application of transcranial direct-current stimulation ( tDCS ) with inhibitory stimulation over the left temporo-parietal cortex and excitatory stimulation over the left dorsolateral prefrontal cortex could affect hallucinations and negative symptoms , respectively . The authors investigated the efficacy of tDCS in reducing the severity of auditory verbal hallucinations as well as negative symptoms . METHOD Thirty patients with schizophrenia and medication-refractory auditory verbal hallucinations were r and omly allocated to receive 20 minutes of active 2-mA tDCS or sham stimulation twice a day on 5 consecutive weekdays . The anode was placed over the left dorsolateral prefrontal cortex and the cathode over the left temporo-parietal cortex . RESULTS Auditory verbal hallucinations were robustly reduced by tDCS relative to sham stimulation , with a mean diminution of 31 % ( SD=14 ; d=1.58 , 95 % CI=0.76–2.40 ) . The beneficial effect on hallucinations lasted for up to 3 months . The authors also observed an amelioration with tDCS of other symptoms as measured by the Positive and Negative Syndrome Scale ( d=0.98 , 95 % CI=0.22–1.73 ) , especially for the negative and positive dimensions . No effect was observed on the dimensions of disorganization or gr and iosity/excitement . CONCLUSIONS Although this study is limited by the small sample size , the results show promise for treating refractory auditory verbal hallucinations and other selected manifestations of schizophrenia Although it is generally accepted that antipsychotic treatment improves the negative symptoms of schizophrenia  in the context of improvement of positive symptoms , exactly how and to what extent they effect “ primary ” negative symptoms remains controversial . Antipsychotic treatment may reduce only those negative symptoms secondary to positive or depressive symptoms , and may have minimal , if any effect , on negative symptoms that represent a primary psychopathological trait manifestation of schizophrenia . In an effort to further examine this issue , we prospect ively assessed negative , positive , depressive , and extrapyramidal symptoms following the discontinuation of antipsychotic medication . Fifty-nine DSM III-R schizophrenic patients underwent a three-week drug wash as part of our neuroimaging protocol s. We assessed psychopathological status and adverse effects utilizing various rating instruments ( i.e. , Scale for Assessment of Positive Symptoms [ SAPS ] , Scale for Assessment of Negative Symptoms [ SANS ] , Hamilton Rating Scale for Depression , and Simpson-Angus Extrapyramidal ) at baseline and weekly during this three-week period . Negative symptoms , as measured by the SANS , worsened significantly during the three-week drug wash . Positive symptoms showed a less consistent change with symptoms of disorganization worsening and with psychotic symptoms remaining the same . The changes in negative symptoms during the drug-free period were correlated with the changes in psychosis and disorganization , but not with changes in depression or extrapyramidal side effects . We were not able to substantiate if the worsening in negative symptoms was a direct result of the worsening of positive symptoms or if they were changing simultaneously , but independent of each other BACKGROUND The literature on the statistical analysis of symptoms of psychoses was limited to positive and negative symptoms in schizophrenia . The present study explored the relationship between positive and negative symptoms as well as affective symptoms in a wider category of psychotic disorders . METHOD The symptoms of 584 psychiatric patients , consecutively admitted to any of the 95 mental hospitals in Japan , were studied . They manifested at least one of the following : ( a ) delusions , ( b ) hallucinations , ( c ) formal thought disorder , ( d ) catatonic symptoms , or ( e ) negative ( defect ) symptoms . RESULTS Factor analysis yielded five factors interpretable as ( a ) manic symptoms , ( b ) depressive symptoms , ( c ) negative ( defect ) symptoms and formal thought disorders , ( d ) positive ( psychotic ) symptoms , and ( e ) catatonic symptoms . CONCLUSION These results suggest that although major symptoms seen among psychotic patients can be categorised into positive , negative , manic , and depressive groups , corresponding to current knowledge of phenomenology , catatonic symptoms constitute a discrete syndrome , while formal thought disorders merge into the negative syndrome BACKGROUND There is increasing evidence that cognitive-behavioural therapy can be an effective intervention for patients experiencing drug-refractory positive symptoms of schizophrenia . AIMS To investigate the effects of cognitive-behavioural therapy on in- patients with treatment-refractory psychotic symptoms . METHOD Manualised therapy was compared with supportive counselling in a r and omised controlled study . Both interventions were delivered by experienced psychologists over 16 sessions of treatment . Therapy fidelity was assessed by two independent raters . Participants underwent masked assessment at baseline , after treatment and at 6 months ' follow-up . Main outcome measures were the Positive and Negative Syndrome Scale and the Psychotic Symptoms Rating Scale . The analysis was by intention to treat . RESULTS Participants receiving cognitive cognitive-behavioural therapy had improved with regard to auditory hallucinations and illness insight at the post-treatment assessment , but these findings were not maintained at follow-up . CONCLUSIONS Cognitive-behavioural therapy showed modest short-term benefits over supportive counselling for treatment-refractory positive symptoms of schizophrenia Penfluridol , a member of the novel diphenylbutylpiperidine class of antipsychotic drugs , is the first long-acting oral neuroleptic . The population of the present study consisted of 24 chronic schizophrenic patients ( 14 males , ten females ) whose treatment with penfluridol was initiated in our previous open/double-blind trial lasting 32 weeks 1 ; mean age was 42.2 years and mean duration of illness , 15.4 years . During one additional year in an uncontrolled clinical study , penfluridol in the form of 20-mg capsuent procedures included BPRS , CGI , NOSIE , vital signs , and laboratory measurements . During this long-term treatment with penfluridol , the scores of a cluster of BPRS items that included emotional withdrawal , conceptual disorganization , motor retardation , uncooperativeness , and blunted affect showed a progressively significant improvement . This indicated that the Bleulerian primary symptoms in chronic schizophrenics can be improved by the long-term administration of this long-acting neuropleptic with concomitant betterment of social adaptation and activity . The percentage of failure was very low ( four patients ) and was marked by instability of psychopathology with periods of excitation . The incidence of extrapyramidal reactions necessitating the administration of an antiparkinsonian drug during the length of trial was 35 per cent . No serious effects nor significant laboratory test changes were observed IMPORTANCE Long-acting , injectable , second-generation antipsychotic medication has tremendous potential to bring clinical stability to persons with schizophrenia . However , long-acting medications are rarely used following a first episode of schizophrenia . OBJECTIVE To compare the clinical efficacy of the long-acting injectable formulation of risperidone with the oral formulation in the early course of schizophrenia . DESIGN , SETTING , AND PARTICIPANTS A r and omized clinical trial performed at a university-based research clinic , between 2005 and 2012 . Eighty-six patients with recent onset of schizophrenia were r and omized to receive long-acting injectable risperidone or oral risperidone . Half of each group was simultaneously r and omized to receive cognitive remediation to improve cognitive functioning or healthy-behaviors training to improve lifestyle habits and well-being . An intent-to-treat analysis was performed between October 4 , 2012 , and November 12 , 2014 . INTERVENTIONS A 12-month trial comparing the long-acting injectable vs oral risperidone and cognitive remediation vs healthy-behaviors training . MAIN OUTCOMES AND MEASURES Psychotic relapse and control of breakthrough psychotic symptoms . RESULTS Of the 86 patients r and omized , 3 refused treatment in the long-acting injectable risperidone group . The psychotic exacerbation and /or relapse rate was lower for the long-acting risperidone group compared with the oral group ( 5 % vs 33 % ; χ21 = 11.1 ; P < .001 ; relative risk reduction , 84.7 % ) . Long-acting injectable risperidone better controlled mean levels of hallucinations and delusions throughout follow-up ( β = -0.30 ; t68 = -2.6 , P = .01 ) . The cognitive remediation and healthy-behaviors training groups did not differ significantly regarding psychotic relapse , psychotic symptom control , or hospitalization rates , and there were no significant interactions between the 2 medications and the 2 psychosocial treatments . Discontinuations owing to inadequate clinical response were more common in the oral group than in the long-acting risperidone group ( χ21 = 6.1 ; P = .01 ) . Adherence to oral risperidone did not appear to differ before r and omization but was better for the long-acting risperidone group compared with the oral group ( t80 = 5.3 ; P < .001 ) . Medication adherence was associated with prevention of exacerbation and /or relapse ( χ21 = 11.1 ; P = .003 ) and control of breakthrough psychotic symptoms ( β = 0.2 ; t79 = 2.1 ; P = .04 ) . CONCLUSIONS AND RELEVANCE The use of long-acting injectable risperidone after a first episode of schizophrenia has notable advantages for clinical outcomes . The key clinical advantages are apparently owing to the more consistent administration of the long-acting injectable . Such formulations should be offered earlier in the course of illness . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00333177 Psychotic symptoms occur in up to 40 % of patients with Parkinson 's disease ( PD ) .  Clozapine and quetiapine , two atypical antipsychotic drugs , at doses markedly lower than those effective in schizophrenia , which , nevertheless , still cause sedation , hypotension , and other side effects , are widely used to treat psychotic symptoms in patients with PD psychosis ( PDP ) , although quetiapine has never been shown to be effective in a placebo-controlled study . The demonstrated efficacy of clozapine in PDP has been attributed to serotonin ( 5-HT2A ) receptor blockade . We postulated that pimavanserin ( ACP-103 ) , a highly selective 5-HT2A inverse agonist , would attenuate psychosis in patients with PDP , but avoid motoric worsening and non-motoric side effects . In this double-blind , r and omized multicenter 28-day study , the tolerability and efficacy of pimavanserin was compared with placebo in 60 patients with L-DOPA or dopamine ( DA ) agonist-induced PDP .  Motor function was evaluated using the Unified Parkinson 's Disease Rating Scale ( UPDRS ) Parts II and III . Antipsychotic efficacy was evaluated using multiple measures from the Scale for the Assessment of Positive Symptoms ( SAPS ) and a UPDRS Part I psychosis-relevant item . Pimavanserin did not differentiate from placebo with regard to motor impairment , sedation , hypotension , or other side effects . The principal measures of efficacy of antipsychotic response to pimavanserin , the SAPS total domain score , only showed a trend . However , the pimavanserin-treated patients showed significantly greater improvement in some but not all measures of psychosis , including SAPS global measures of hallucinations and delusions , persecutory delusions , and the UPDRS measure of delusions and hallucinations .  Pimavanserin showed significantly greater improvement in psychosis in patients with PDP at a dose which did not impair motor function , or cause sedation or hypotension Thus , pimavanserin may represent a novel treatment for PDP . Furthermore , these results support the hypothesis that attenuation of psychosis secondary to DA receptor stimulation in PDP may be achieved through selective 5-HT2A receptor antagonism BACKGROUND Little evidence exists for the effects of psychological treatment on voices even though it is clear that CBT does affect delusions and symptoms overall . This study tested whether a group based on cognitive behavioural principles could produce beneficial effects on hallucinations . AIM To test the effectiveness of group CBT on social functioning and severity of hallucinations . METHOD Participants were included if they had a diagnosis of schizophrenia and experienced distressing auditory hallucinations ( rated on the PANSS ) . They were r and omly allocated to group CBT ( N = 45 ) or a  control group who received treatment as usual ( N = 40 ) . The two main outcomes were social functioning as measured by the Social Behaviour Schedule and the severity of hallucinations as measured by the total score on the Hallucinations Scale of PSYRATS . Assessment s were carried out at baseline , 10 weeks ( post therapy ) and 36 weeks ( six months following therapy ) . RESULTS Mixed r and om effects models revealed significant improvement in social functioning ( effect size 0.63 six months after the end of therapy ) . There was no general effect of group CBT on the severity of hallucinations . However , there was a large cluster effect of therapy group on the severity of hallucinations such that they were reduced in some but not all of the therapy groups . Improvement in hallucinations was associated with receiving therapy early in the trial and having very experienced therapists ( extensive CBT training which included expert supervision for a series of individual cases for at least a year following initial training ) . CONCLUSION Group CBT does improve social functioning but unless therapy is provided by experienced CBT therapists hallucinations are not reduced This study examined whether frontal-system impairments in schizophrenia occur independently of one another and whether they have distinct implication s for information processing , symptom severity , and adaptive functioning . We assessed 26 medication-free schizophrenic out patients and 18 normal control subjects on eight frontally mediated tasks , semantic information processing , IQ , the BPRS , and long-term psychosocial adaptation . Schizophrenic subjects showed three types of deficits , which were uncorrelated with one another : ( 1 ) Executive dysfunction ( inflexible problem solving ) was related to decreased use of expectancy during controlled semantic priming , lower intelligence , more severe negative symptoms and stereotyped mannerisms . ( 2 ) Disinhibition of responses ( to irrelevant stimuli ) was associated with increased automatic priming , a trend for more severe hallucinations , and was unrelated to intelligence . ( 3 ) Motor dyscoordination ( inaccurate , dysfluent motor sequencing ) was not related to semantic processing , intelligence , or symptoms . Furthermore , all three impairments were unrelated to generalized slowness , age , sex , illness length , or pre-washout neuroleptic dose . Two deficits accounted for aspects of long-term psychosocial adaptation , even after statistical correction for IQ : Executive dysfunction was associated with younger illness onset , poor purpose fulness and planning , impaired social relations , and lower global functioning . Motor dyscoordination was associated with poor treatment outcome and restricted educational advancement . Furthermore , executive and motor deficits interacted significantly ; subjects who had both deficits showed the least favorable treatment outcome . These findings are neither consistent with generalized impairment nor with a unitary ' frontal syndrome ' in schizophrenia . They provide preliminary evidence for at least three frontal-system deficits ( dorsolateral , orbital , and premotor ) , which are dissociable from one another , can occur without general intellectual impairment , and have distinct implication s for long-term adaptive functioning Background When treating schizophrenia , improving patients ' productivity level is a major goal considering schizophrenia is a leading cause of functional disability . Productivity level has been identified as the most preferred treatment outcome by patients with schizophrenia . However , little has been done to systematic ally investigate productivity levels in schizophrenia . We set out to better underst and the change in productivity level among chronically ill patients with schizophrenia treated with olanzapine compared with other antipsychotic medications .  We also assessed the links between productivity level and other clinical outcomes . Methods This post hoc analysis used data from 6 r and omized , double-blind clinical trials of patients with schizophrenia or schizoaffective disorder , with each trial being of approximately 6 months duration . Change in productivity level was compared between  olanzapine-treated patients ( HGBG , n = 172 ; HGHJ , n = 277 ; HGJB , n = 171 ; HGLB , n = 281 ; HGGN , n = 159 ; HGDH , n = 131 ) and patients treated with other antipsychotic medications ( separately vs. haloperidol [ HGGN , n = 97 ; HGDH , n = 132 ] , risperidone [ HGBG , n = 167 ; HGGN , n = 158 ] , quetiapine [ HGJB , n = 175 ] , ziprasidone [ HGHJ , n = 271 ] and aripiprazole [ HGLB , n = 285 ] ) . Productivity was defined as functional activities/work including working for pay , study ing , housekeeping and volunteer work . Productivity level in the prior 3 months was assessed on a 5-point scale ranging from no useful functioning to functional activity/work 75 % to 100 % of the time . Results Chronically ill patients treated with olanzapine ( OLZ ) experienced significantly greater improvement in productivity when compared to patients treated with risperidone ( RISP ) ( OLZ = 0.22 ± 1.19 , RISP = -0.03 ± 1.17 , p = 0.033 ) or ziprasidone ( ZIP ) ( OLZ = 0.50 ± 1.38 , ZIP = 0.25 ± 1.27 , p = 0.026 ) , but did not significantly differ from the quetiapine , aripiprazole or haloperidol treatment groups . Among first episode patients , OLZ therapy was associated with greater improvements in productivity levels compared to haloperidol ( HAL ) , during the acute phase ( OLZ = -0.31 ± 1.59 , HAL = -0.69 ± 1.56 , p = 0.011 ) and over the long-term ( OLZ = 0.10 ± 1.50 , HAL = -0.32 ± 1.91 , p = 0.008 ) . Significantly more chronically ill and first episode patients treated with olanzapine showed moderately high ( > 50%-75 % of the time ) and high levels of productivity ( > 75%-100 % of the time ) at endpoint , when compared to risperidone or haloperidol-treated patients ( p < .05 ) , respectively . Higher productivity level was associated with significantly higher study completion rates and better scores on the positive , negative , disorganized thoughts , hostility and depression subscales of the Positive and Negative Symptom Scale ( PANSS ) . Conclusions Some antipsychotic medications significantly differed in beneficial impact on productivity level in the long-term treatment of patients with schizophrenia . Findings further highlight the link between clinical and functional outcomes , showing significant associations between higher productivity , lower symptom severity and better persistence on therapy . Trial Registration clinical trials.gov identifier NCT00088049 ;
At the time of this review , seven AAPs were available in Canada : aripiprazole clozapine olanzapine paliperidone quetiapine risperidone ziprasidone
Schizophrenia is a mental illness that requires lifelong treatment and is associated with symptoms that include hallucinations , delusions , cognitive impairment , disorganized thoughts , social withdrawal , and low motivation .
Antipsychotic medications are effective at relieving the symptoms of schizophrenia , and they form the foundation of treatment .