Benzodiazepines for psychosis-induced aggression or agitation. Use of antipsychotics and benzodiazepines in patients with psychiatric emergencies: Results of an observational trial A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Rapid Tranquilization of Severely Agitated Patients With Schizophrenia Spectrum Disorders: A Naturalistic, Rater-Blinded, Randomized, Controlled Study With Oral Haloperidol, Risperidone, and Olanzapine Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder. Effectiveness of atypical antipsychotic medications in reducing violent behavior among persons with schizophrenia in community-based treatment. Comparison of antipsychotic medication effects on reducing violence in people with schizophrenia. The expert consensus guideline series. Treatment of behavioral emergencies 2005. Early onset of antipsychotic response in the treatment of acutely agitated patients with psychotic disorders Effects of antipsychotic medications on quality of life and psychosocial functioning in patients with early-stage schizophrenia: 1-year follow-up naturalistic study. Randomised clinical trial comparing oral versus depot formulations of zuclopenthixol in patients with schizophrenia and previous violence. [Effectiveness results of olanzapine in acute psychotic patients with agitation in the emergency room setting: results from NATURA study]. Intramuscular olanzapine vs. intramuscular short-acting antipsychotics: safety, tolerability and the switch to oral antipsychotic medication in patients with schizophrenia or acute mania. Benzodiazepine use and abuse among patients with severe mental illness and co-occurring substance use disorders. Prescribing for inpatients with schizophrenia: an international multi-center comparative study. Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment. Acute psychotic disorders treated with 5% zuclopenthixol acetate in 'Viscoleo' ('Cisordinol-Acutard'), a global assessment of the clinical effect: an open multi-centre study.
BACKGROUND Acute psychotic illness , especially when associated with agitated or violent behaviour , can require urgent pharmacological tranquillisation or sedation . In several countries , clinicians often use benzodiazepines ( either alone or in combination with antipsychotics ) for this outcome . OBJECTIVES To estimate the effects of benzodiazepines , alone or in combination with antipsychotics , when compared with placebo or antipsychotics , alone or in combination with antihistamines , to control disturbed behaviour and reduce psychotic symptoms . SEARCH METHODS We search ed the Cochrane Schizophrenia Group 's register ( January 2012 ) , inspected reference lists of included and excluded studies and contacted authors of relevant studies . SELECTION CRITERIA We included all r and omised clinical trials ( RCTs ) comparing benzodiazepines alone or in combination with any antipsychotics , versus antipsychotics alone or in combination with any other antipsychotics , benzodiazepines or antihistamines , for people with acute psychotic illnesses . DATA COLLECTION AND ANALYSIS We reliably selected studies , quality assessed them and extracted data . For binary outcomes , we calculated st and ard estimates of relative risk ( RR ) and their 95 % confidence intervals ( CI ) using a fixed-effect model . For continuous outcomes , we calculated the mean difference ( MD ) between groups . If heterogeneity was identified , this was explored using a r and om-effects model . MAIN RESULTS We included 21 trials with a total of n = 1968 participants . There was no significant difference for most outcomes in the one trial that compared benzodiazepines with placebo , although there was a higher risk of no improvement in people receiving placebo in the medium term ( one to 48 hours ) ( n = 102 , 1 RCT , RR 0.62 , 95 % CI 0.40 to 0.97 , very low quality evidence ) . There was no difference in the number of participants who had not improved in the medium term when benzodiazepines were compared with antipsychotics ( n = 308 , 5 RCTs , RR 1.10 , 95 % CI 0.85 to 1.42 , low quality evidence ) ; however , people receiving benzodiazepines were less likely to experience extrapyramidal effects ( EPS ) in the medium term ( n = 536 , 8 RCTs , RR 0.15 , 95 % CI 0.06 to 0.39 , moderate quality of evidence ) . Data comparing combined benzodiazepines and antipsychotics versus benzodiazepines alone did not yield any significant results . When comparing combined benzodiazepines/antipsychotics ( all studies compared haloperidol ) with the same antipsychotics alone ( haloperidol ) , there was no difference between groups in improvement in the medium term ( n = 155 , 3 RCTs , RR 1.27 , 95 % CI 0.94 to 1.70 , very low quality evidence ) but sedation was more likely in people who received the combination therapy ( n = 172 , 3 RCTs , RR 1.75 , 95 % CI 1.14 to 2.67 , very low quality evidence ) . However , more participants receiving combined benzodiazepines and haloperidol had not improved by medium term when compared to participants receiving olanzapine ( n = 60,1 RCT , RR 25.00 , 95 % CI 1.55 to 403.99 , very low quality evidence ) or ziprasidone ( n = 60 , 1 RCT , RR 4.00 , 95 % CI 1.25 to 12.75very low quality evidence ) . When haloperidol and midazolam were compared with olanzapine , there was some evidence the combination was superior in terms of improvement , sedation and behaviour . AUTHORS ' CONCLUSIONS The evidence from trials for the use of benzodiazepines alone is not good . There were relatively little good data and most trials are too small to highlight differences in either positive or negative effects . Adding a benzodiazepine to other drugs does not seem to confer clear advantage and has potential for adding unnecessary adverse effects . Sole use of older antipsychotics unaccompanied by anticholinergic drugs seems difficult to justify . Much more high quality research is needed in this area Background Conventional antipsychotics augmented with benzodiazepines have been the st and ard acute treatment for psychiatric emergencies for more than 50 years . The inability of patients to give informed consent limits r and omised , controlled studies . This observational study on immediate therapy for aggression and impulse control in acutely agitated patients ( IMPULSE ) evaluated the short-term effectiveness and tolerability of atypical and typical antipsychotic medications ( AP ) in a non-interventional setting . Methods This was a comparative , non-r and omised , prospect i ve , open-label , observational study . Treatment over the first 5 days was classified according to whether any olanzapine , risperidone , or haloperidol was included or not . Documentations ( PANSS-excited component , CGI-aggression , CGI-suicidality , tranquilisation score ) were at baseline ( day 1 ) and days 2–6 after start of AP . Results During the short treatment-period , PANSS-EC and CGI-aggression scores improved in all cohorts . 68.7 % of patients treated with olanzapine , 72.2 % of patients treated with risperidone , and 83.3 % of patients treated with haloperidol received concomitant benzodiazepines ( haloperidol vs. non-haloperidol : p < 0.001 ) . More patients treated with olanzapine ( 73.8 % ) were fully alert according to a tranquilisation score and active at day 2 than patients treated with risperidone ( 57.1 % ) or haloperidol ( 58.0 % ) . Conclusion Current medication practice s for immediate aggression control are effective with positive results present within a few days . In this study , concomitant benzodiazepine use was significantly more frequent in patients receiving haloperidol OBJECTIVE Data on the effectiveness of antipsychotics in the early phase of schizophrenia are limited . The authors examined the risk of rehospitalization and drug discontinuation in a nationwide cohort of 2,588 consecutive patients hospitalized for the first time with a diagnosis of schizophrenia between 2000 and 2007 in Finl and . METHOD The authors linked national data bases of hospitalization , mortality , and antipsychotic prescriptions and computed hazard ratios , adjusting for the effects of sociodemographic and clinical variables , the temporal sequence of the antipsychotics used , and the choice of the initial antipsychotic for each patient . RESULTS Of 2,588 patients , 1,507 ( 58.2 % ) collected a prescription for an antipsychotic during the first 30 days after hospital discharge , and 1,182 ( 45.7 % , 95 % confidence interval [CI]=43.7 - 47.6 ) continued their initial treatment for 30 days or longer . In a pairwise comparison between depot injections and their equivalent oral formulations , the risk of rehospitalization for patients receiving depot medications was about one-third of that for patients receiving oral medications ( adjusted hazard ratio=0.36 , 95 % CI=0.17 - 0.75 ) . Compared with oral risperidone , clozapine ( adjusted hazard ratio=0.48 , 95 % CI=0.31 - 0.76 ) and olanzapine ( adjusted hazard ratio=0.54 , 95 % CI=0.40 - 0.73 ) were each associated with a significantly lower rehospitalization risk . Use of any antipsychotic compared with no antipsychotic was associated with lower mortality ( adjusted hazard ratio=0.45 , 95 % CI=0.31 - 0.67 ) . CONCLUSIONS In Finl and , only a minority of patients adhere to their initial antipsychotic during the first 60 days after discharge from their first hospitalization for schizophrenia . Use of depot antipsychotics was associated with a significantly lower risk of rehospitalization than use of oral formulations of the same compounds . Among oral antipsychotics , clozapine and olanzapine were associated with more favorable outcomes . Use of any antipsychotic was associated with lower mortality Introduction Agitation is a major problem in acute schizophrenia . Only a few studies have tested antipsychotic agents in severely agitated patients , mainly because of legal issues . Furthermore , most studies were limited to the first 24 hours . We aim ed to investigate the efficacy of oral haloperidol , risperidone , and olanzapine in reducing psychotic agitation in severely agitated patients with schizophrenia or schizophreniform or schizoaffective disorder over 96 hours using a prospect i ve , r and omized , rater-blinded , controlled design within a naturalistic treatment regimen . Methods In total , 43 severely agitated patients at acute care psychiatric units were enrolled . Participants were r and omly assigned to receive either daily haloperidol 15 mg , olanzapine 20 mg , or risperidone 2 to 6 mg over 5 days . Positive and Negative Syndrome Scale psychotic agitation subscale score was the primary outcome variable . A mixed-model analysis was applied . Results All drugs were effective for rapid tranquilization within 2 hours . Over 5 days , the course differed between agents ( P < 0.001 ) , but none was superior . Dropouts occurred only in the risperidone and olanzapine groups . Men responded better to treatment than did women during the initial 2 hours ( P = 0.046 ) as well as over the 5-day course ( P < 0.001 ) . No difference between drug groups was observed regarding diazepam or biperiden use . Conclusions Oral haloperidol , risperidone , and olanzapine seem to be suitable for treating acute severe psychotic agitation in schizophrenia spectrum disorders . Response to oral antipsychotics demonstrated a gender effect with poorer outcome in women throughout the study CONTEXT Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community . Finding appropriate treatment of violent behaviors is of primary importance . OBJECTIVE To compare the efficacy of 2 atypical antipsychotic agents , clozapine and olanzapine , with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder . DESIGN AND SETTING R and omized , double-blind , parallel-group , 12-week trial . Physically assaultive subjects with schizophrenia or schizoaffective disorder who were in patients in state psychiatric facilities were r and omly assigned to treatment with clozapine ( n = 37 ) , olanzapine ( n = 37 ) , or haloperidol ( n = 36 ) . MAIN OUTCOME MEASURES Number and severity of physical assaults as measured by the Modified Overt Aggression Scale ( MOAS ) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score . Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale ( PANSS ) . RESULTS Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score . Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures . There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales . CONCLUSIONS Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior . This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications This study prospect ively compared the effectiveness of atypical antipsychotic medications to that of conventional neuroleptics in reducing violent behavior  among patients with schizophrenia under " usual care " conditions in the community . Participants ( n = 229 ) were adults with schizophrenia spectrum disorders receiving inpatient or outpatient services in public sector mental health systems in North Carolina . Subjects were followed for 2 years in an observational study using multiple methods of data collection at 6-month intervals to assess treatment , sociodemographic characteristics , clinical features , and violence outcomes . Treatment with atypical antipsychotic medications ( clozapine , risperidone , or olanzapine ) was found to significantly reduce the risk of violent behavior , whereas treatment with conventional neuroleptics did not have this same beneficial effect . A cumulative effect on reduced violence was attributable to consistent compliance with atypical antipsychotic medications over a 2-year period . Concurrent reductions in psychotic symptoms , substance abuse , and adverse medication side effects were found to mediate the association between adherence with atypicals and lower violence risk . Treatment with atypical antipsychotic medications should be considered as an important component of violence risk management for schizophrenia patients at risk for violent behavior BACKGROUND Violence is an uncommon but significant problem associated with schizophrenia . AIMS To compare antipsychotic medications in reducing violence among patients with schizophrenia over 6 months , identify prospect i ve predictors of violence and examine the impact of medication adherence on reduced violence . METHOD Participants ( n=1445 ) were r and omly assigned to double-blinded treatment with one of five antipsychotic medications . Analyses are presented for the intention-to-treat sample and for patients completing 6 months on assigned medication . RESULTS Violence declined from 16 % to 9 % in the retained sample and from 19 % to 14 % in the intention-to-treat sample . No difference by medication group was found , except that perphenazine showed greater violence reduction than quetiapine in the retained sample . Medication adherence reduced violence , but not in patients with a history of childhood antisocial conduct . Prospect i ve predictors of violence included childhood conduct problems , substance use , victimisation , economic deprivation and living situation . Negative psychotic symptoms predicted lower violence . CONCLUSIONS Newer antipsychotics did not reduce violence more than perphenazine . Effective antipsychotics are needed , but may not reduce violence unrelated to acute psychopathology OBJECTIVES Due to inherent dangers and barriers to research in emergency setting s , few data are available to guide clinicians about how best to manage behavioral emergencies . Key constructs such as agitation are poorly defined . This lack of empirical data led us to undertake a survey of expert opinion , results of which were published in the 2001 Expert Consensus Guidelines on the Treatment of Behavioral Emergencies . Several second-generation ( atypical ) antipsychotics ( SGAs ) are now available in new formulations for treating behavioral emergencies ( e.g. , intramuscular [ i.m . ] olanzapine and ziprasidone ; rapidly dissolving tablets of olanzapine and risperidone ) . Critical questions face the field . The SGAs are significantly different from the FGAs and from each other and have not been studied in unselected patients as were the FGAs . Can the SGAs can be thought of as a class , do all antipsychotics have similar anti-agitation effects in different conditions , and , if equally effective , what limits might their safety profiles impose ? Should antipsychotics be used more specifically to treat psychotic conditions , while benzodiazepines ( BNZs ) alone are used nonspecifically ? Few data are available concerning combinations of SGAs and BNZs , and findings concerning the traditional combination of haloperidol plus a BNZ may not be relevant to combinations with SGAs . The culture is also evolving with more emphasis on patient involvement in treatment decisions . An international consensus has been developing that calming rather than sedation is the appropriate endpoint of behavioral emergency interventions . We undertook a new survey of expert opinion to up date recommendations from the earlier survey . METHOD A written survey of 61 questions ( 1,020 options ) was mailed to 50 experts in the field , 48 ( 96 % ) of whom completed it . The survey sought to define level of agitation at which emergency interventions are appropriate , scope of assessment depending on urgency and patients ' ability to cooperate , guiding principles for selecting interventions , and appropriate physical and medication strategies at different levels of diagnostic confidence for a variety of provisional diagnoses and complicating conditions . A modified version of the R AND Corporation 's 9-point scale for rating appropriateness of medical decisions was used to score most options . Consensus was defined as a non-r and om distribution of scores by chi-square " goodness-of-fit " test . We assigned a categorical rank ( first line/preferred , second line/alternate , third line/usually inappropriate ) to each option based on the 95 % confidence interval around the mean . Ratings were used to develop guidelines for preferred strategies in key clinical situations . This study received financial support from multiple sponsors , with the panel kept blind to sponsorship to reduce possible bias . Medication ratings were based on responses of only those respondents with direct experience with each drug . In reporting practice patterns , the panel was asked to respond based on actual data rather than estimates . RESULTS The expert panel reached consensus on 78 % of the options rated on the 9-point scale . The responses suggest that physicians can make provisional diagnoses with some confidence and that pharmacological and nonpharmacological interventions are selected differentially based on diagnosis and other salient demographic and medical features . BNZs are recommended when no data are available , when there is no specific treatment ( e.g. , personality disorder ) , or when they may have specific benefits ( e.g. , intoxication ) . No single SGA emerges as a nonspecific replacement for haloperidol ; instead , different SGAs are preferred in various circumstances consistent with current evidence . To the degree that haloperidol is recommended , it is almost always in combination with a BNZ ; haloperidol alone is preferred only in the medically compromised . In contrast , the SGAs are more often recommended for use alone , and the panel would avoid combining BNZs with some SGAs . Oral risperidone alone or combined with a BNZ receives strong support in a variety of situations . Oral olanzapine was rated very similarly to risperidone , with slightly higher ratings than risperidone in situations where it has been studied ( e.g. , schizophrenia , mania ) and slightly lower ratings where it has not been studied or safety may be a concern ; there was less support for combining oral olanzapine with a BNZ . For oral treatment of agitation related to schizophrenia or mania , olanzapine alone , risperidone alone or combined with a BNZ , and haloperidol plus a BNZ are first line , with strong support also for combining divalproex with the antipsychotic for presumed mania . Oral ziprasidone and quetiapine generally received similar second-line ratings in most situations . If a parenteral agent is needed , i.m . olanzapine alone received somewhat more support than i.m . ziprasidone alone ; however , there was more support for i.m . ziprasidone alone or combined with a BNZ than for i.m . olanzapine plus a BNZ , probably reflecting safety concerns . For example , for a provisional diagnosis of schizophrenia , first-line parenteral options are i.m . olanzapine or ziprasidone alone or i.m . haloperidol or ziprasidone combined with a BNZ . Neither of the new parenteral formulations received as much support as traditional agents ( i.m . BNZs , i.m . haloperidol ) when no data are available or the diagnosis involves medical comorbidity or intoxication . When initial intervention with risperidone , ziprasidone , or haloperidol is unsuccessful , the panel recommended adding a BZD to the antipsychotic . However , when initial treatment with olanzapine or quetiapine is unsuccessful , increasing the dosage is recommended . Perphenazine was consistently rated second line and droperidol and chlorpromazine received third-line ratings throughout . CONCLUSIONS Within the limits of expert opinion and with the expectation that future research data will take precedence , these guidelines suggest that the SGAs are now preferred for agitation in the setting of primary psychiatric illnesses but that BNZs are preferred in other situations OBJECTIVE While the efficacy of antipsychotic medications for the treatment of psychosis is generally established , the speed of onset of antipsychotic action remains controversial . The objective of this study was to evaluate the early response ( within the first 24 h ) in psychosis with ziprasidone IM treatment , and to determine whether this early effect is distinct from a reduction in agitation symptoms . METHODS In a 24-h , double-blind study , hospitalized patients with psychotic disorder and acute agitation were r and omized to treatment with fixed doses of IM ziprasidone : 2 mg ( N=38 ) or 20 mg ( N=41 ) . Efficacy assessment s were based on the PANSS positive subscale and PANSS early psychosis factor score ( conceptual disorganization , hallucinatory behavior , and unusual thought content ) at 4 and 24 h. RESULTS Ziprasidone IM demonstrated a significant dose-related effect ( 20 mg vs. 2 mg ) on both the PANSS early psychosis factor score and the PANSS positive subscale at the first post-baseline time point ( 4 h ) , and at 24 h ( all p<0.05 ) . There was a significant direct effect of ziprasidone IM on early psychosis at 24 h ( p<0.05 ) , distinct from improvement in agitation symptoms . CONCLUSIONS These findings suggest , in addition to an early reduction in acute agitation , ziprasidone IM may be associated with a more rapid improvement in psychotic symptoms than previously reported , thus lending further support to the emergent hypothesis of early psychosis improvement in antipsychotic treatment BACKGROUND The relative effects of the atypical antipsychotic drugs and conventional agent on quality of life and psychosocial functioning in patients with early-stage schizophrenia is still uncertain because of an insufficient number of studies examining this issue . METHODS In a 12 months open-label , prospect i ve observational , multicenter study , 1029 subjects with schizophrenia or schizophreniform disorder within 5 years of onset were monotherapy with chlorpromazine , sulpiride , clozapine , risperidone , olanzapine , quetiapine or aripiprazole . The health-related quality of life and psychosocial functioning were assessed using Medical Outcomes Study 36-Item Short Form Health Survey ( SF-36 ) , the Global Assessment Scale ( GAS ) and the Activities of Daily Living Scale ( ADL ) , respectively . RESULTS At 12 months , treatment result ed in significant improvements in all 8 domain scores of SF-36 , GAS and ADL score ( all P-values < .001 ) . However , only olanzapine and quetiapine groups demonstrated greater improvement in the role-psychical score of SF-36 and GAS score than did the chlorpromazine group ( all P-values ≤ .002 ) . CONCLUSIONS All antipsychotics may improve quality of life and social function in patients with early-stage schizophrenia , but further studies are needed to determine whether atypical antipsychotics are superior to conventional agents PURPOSE The aim of this longitudinal study was to determine whether the depot formulation of an antipsychotic reduces violence in out patients with schizophrenia as compared to oral administration of the same antipsychotic . METHODS Forty-six previously violent patients with schizophrenia were r and omised to receive treatment with oral or depot zuclopenthixol for 1 year . Clinicians interviewed patients at baseline and every month thereafter to assess treatment adherence . An interviewer blinded to treatment assignments interviewed an informant about any violent behaviour during the previous month . RESULTS Violence during the follow-up year was inversely proportional to treatment adherence , better compliance , and greater reduction of positive symptoms . Lower frequency of violent acts was observed in the depot group . The level of insight at baseline was not significantly associated with violence recidivism . Regardless of route of administration , treatment non-adherence was the best predictor of violence . CONCLUSIONS Some patients with schizophrenia and prior violent behaviour  may benefit from the depot formulation of antipsychotic medication INTRODUCTION Patterns of use of antipsychotics are not well described in emergency units . The objective of this study was to describe the effectiveness and safety of use of olanzapine in patients with acute psychosis and agitation in the emergency rooms . METHODS In this prospect i ve observational study 278 patients with acute psychosis and agitation were consecutively admitted in 16 psychiatric emergency wards and treated with any oral psychopharmacology treatment , including olanzapine  , according to investigators clinical criteria . Data were collected prospect ively including demographics , diagnosis , concomitant medications , utilization of mechanical restraints , and severity of agitation . Clinical evolution during emergency room stay was assessed with PANSS-Excitement Component , CGI-S and Agitation and Calmness Evaluation Scale ( ACES ) at baseline , before any re-intervention ( if needed ) and at discharge from the emergency room . Safety was also evaluated . RESULTS Olanzapine alone was used in 148 ( 53.2 % ) patients . Most of them ( 77.7 % ) were diagnosed of Schizophrenia and related psychoses . Up to 38 patients ( 25.7 % ) required mechanical restraints . Mean change ( confidence interval [ CI ] 95 % ) from baseline to discharge was significant in all rating scales ; PANSS-EC : -7.46 ( -8.2 , -6.7 ) ; CGI-S : -1.82 ( -2 , -1.6 ) ACES : 1.28 ( 1.1 , 1.5 ) . At discharge 70.3 % of patients went to inpatient units . Five patients ( 3.4 % ) reported adverse events including : bradycardia , dry mouth , sedation , hypertension , hypotension , and orthostatic hypotension . None of them was serious . CONCLUSIONS The utilization of olanzapine alone decreased agitation in psychotic patients in emergency room setting s. Incidence of adverse events was low and it was well tolerated BACKGROUND This study compared the safety , tolerability and switch to oral medication in patients with bipolar disorder or schizophrenia who received intramuscular ( IM ) olanzapine or other IM antipsychotics for the treatment of acute agitation . METHODS Patients ( N = 2011 ) from 15 countries participated in this prospect i ve , observational , non-interventional study . In patients requiring treatment with at least one IM injection of a short-acting antipsychotic  were assessed at baseline and within 7 days after the first IM injection . Treatment groups comprised : ( i ) patients prescribed IM olanzapine at baseline ; and ( ii ) patients prescribed any other IM antipsychotic medication at baseline . Outcome measures included : treatment-emergent adverse events , concomitant psychotropic medication and the time taken to switch to oral medication . RESULTS Fewer patients in the IM olanzapine group experienced an adverse event than patients in the other IM antipsychotic group ( 34.4 % vs. 46.2 % , p < 0.001 ) . The most frequently reported adverse events in both groups were : sedation , Parkinsonism , disturbance in attention , akathisia , dystonia and orthostatic hypotension . Fewer patients in the IM olanzapine group used anticholinergics ( 13.9 % vs. 42.5 % , p < 0.001 ) or anxiolytics/hypnotics ( 47.6 % vs. 51.6 % , p = 0.023 ) . Patients in the IM olanzapine group switched to oral medication earlier than patients in the other IM antipsychotic group ( median time = 46.5 vs. 48.0 h , p = 0.009 ) . CONCLUSIONS These findings suggest that IM olanzapine may have a favourable impact on individual patients . However , the high rate of oral concomitant medication used throughout the study limits these findings from being associated with IM olanzapine alone OBJECTIVES Because use of benzodiazepines may exacerbate existing substance use disorders or become abused substances , prescription of benzodiazepines for patients with severe mental illness ( schizophrenia or bipolar disorder ) and co-occurring substance use disorders ( abuse or dependence ) is controversial . The authors examined benzodiazepine use and associated psychiatric , substance abuse , and institutional outcomes in a six-year longitudinal study of patients with co-occurring disorders . METHODS At baseline and yearly follow-up for six years , 203 patients with co-occurring severe mental illness and substance use disorder were prospect ively assessed for medication use , substance use , psychiatric symptoms , use of hospitalization , and quality of life . RESULTS Almost one-half of the patients ( 43 percent ) reported taking prescribed benzodiazepines at the time of at least one assessment . Patients taking prescribed benzodiazepines were more likely to have high scores on measures of overall symptoms and affective symptoms ( anxiety and depression ) and low ratings for general quality of life throughout the study . Benzodiazepine use was unrelated to remission of substance use disorder or hospitalization , but a greater proportion of patients who were prescribed benzodiazepines developed  benzodiazepine abuse , compared with those who were not prescribed benzodiazepines ( 15 percent compared with 6 percent ) . CONCLUSIONS Prescription benzodiazepine use was common among patients with co-occurring severe mental illness and a substance use disorder and was not associated with any of the measured outcomes other than increasing the likelihood of benzodiazepine abuse . Physicians should consider other treatments for anxiety in this population BACKGROUND This study compares prescription practice s for acute in patients with schizophrenia among six academic departments located in China , Japan , Hungary , and the U.S. METHODS Prescription data for a sample of 429 in patients from six academic departments were collected on a r and omly chosen census day . All patients met criteria for schizophrenia according to DSM-IV and had a length of illness of at least two years . RESULTS While patients at the different centers varied in their demographic and clinical characteristics , i. e. , age , sex , and length of illness , a great variation in prescription patterns for antipsychotic and other psychotropic drugs among centers was observed even within the same country for all the variables studied ( i. e. , number and dose antipsychotics , atypical and depot antipsychotics , other psychotropic drugs , multiple antipsychotics , and daily dose ) except antidepressant use . In most cases these differences persisted even after adjusting for demographic and clinical characteristics ( age , sex , and length of illness ) of the subjects . Antipsychotics were usually prescribed in divided daily doses in combination with one or more other psychotropic drugs , including anticholinergics , anticonvulsants , benzodiazepines , and non-benzodiazepine hypnotics .  Anticholinergic use was more common with typical antipsychotics . Rates of atypical antipsychotic drug use were lowest in the Japanese center . The Japanese center had by far the highest mean daily dose of antipsychotics .  CONCLUSIONS The results indicate that prescription patterns in different centers do not follow any specific guidelines for the treatment of schizophrenia . The results also confirm previous findings that prescribing practice s for schizophrenia vary greatly among centers and countries . A common prescribing pattern found was the use of atypical antipsychotic drugs in combination with psychotropic drugs , such as anticholinergics , hypnotics , anticonvulsants , and benzodiazepines , administered in multiple daily doses OBJECTIVES To determine the clinical and cost-effectiveness of different classes of antipsychotic drug treatment in people with schizophrenia responding inadequately to , or having unacceptable side-effects from , their current medication . DESIGN Two pragmatic , r and omised controlled trials ( RCTs ) were undertaken . The first RCT ( b and 1 ) compared the class of older , inexpensive conventional drugs with the class of new atypical drugs in people with schizophrenic disorders , whose current antipsychotic drug treatment was being changed either because of inadequate clinical response or owing to side-effects . The second RCT ( b and 2 ) compared the new ( non-clozapine ) atypical drugs with clozapine in people whose medication was being changed because of poor clinical response to two or more antipsychotic drugs . Both RCTs were four-centre trials with concealed r and omisation and three follow-up assessment s over 1 year , blind to treatment . SETTING Adult mental health setting s in Engl and . PARTICIPANTS In total , 227 participants aged 18 - 65 years ( 40 % of the planned sample ) were r and omised to b and 1 and 136 ( 98 % of the planned sample ) to b and 2 . INTERVENTIONS Participants were r and omised to a class of drug . The managing clinician selected the individual drug within that class , except for the clozapine arm in b and 2 . The new atypical drugs included risperidone , olanzapine , quetiapine and amisulpride . The conventional drugs included older drugs , including depot preparations . As in routine practice , clinicians and participants were aware of the identity of the prescribed drug , but clinicians were asked to keep their participating patient on the r and omised medication for at least the first 12 weeks . If the medication needed to be changed , the clinician was asked to prescribe another drug within the same class , if possible . MAIN OUTCOME MEASURES The primary outcome was the Quality of Life Scale ( QLS ) . Secondary clinical outcomes included symptoms [ Positive and Negative Syndrome Scale ( PANSS ) ] , side-effects and participant satisfaction . Economic outcomes were costs of health and social care and a utility measure . RESULTS Recruitment to b and 1 was less than anticipated ( 40 % ) and diminished over the trial . This appeared largely due to loss of perceived clinical equipoise ( clinicians progressively becoming more convinced of the superiority of new atypicals ) . Good follow-up rates and a higher than expected correlation between QLS score at baseline and at follow-up meant that the sample as recruited had 75 % power to detect a difference in QLS score of 5 points between the two treatment arms at 52 weeks . The recruitment to b and 2 was approximately as planned . Follow-up assessment s were completed at week 52 in 81 % of b and 1 and 87 % of b and 2 participants . B and 1 data showed that , on the QLS and symptom measures , those participants in the conventional arm tended towards greater improvements . This suggests that the failure to find the predicted advantage for new atypicals was not due to inadequate recruitment and statistical power in this sample . Participants reported no clear preference for either class of drug . There were no statistically significant differential outcomes for participants entering b and 1 for reasons of treatment intolerance to those entering because of broadly defined treatment resistance . Net costs over the year varied widely , with a mean of 18,850 pounds sterling in the conventional drug group and 20,123 pounds sterling in the new atypical group , not a statistically significant difference . Of these costs , 2.1 % and 3.8 % were due to antipsychotic drug costs in the conventional and atypical group , respectively . There was a trend towards participants in the conventional drug group scoring more highly on the utility measure at 1 year . The results for b and 2 showed an advantage for commencing clozapine in quality of life ( QLS ) at trend level ( p = 0.08 ) and in symptoms ( PANSS ) , which was statistically significant ( p = 0.01 ) , at 1 year . Clozapine showed approximately a 5-point advantage on PANSS total score and a trend towards having fewer total extrapyramidal side-effects . Participants reported at 12 weeks that their mental health was significantly better with clozapine than with new atypicals ( p < 0.05 ) . Net costs of care varied widely , but were higher than in b and 1 , with a mean of 33,800 pounds sterling in the clozapine group and 28,400 pounds sterling in the new atypical group . Of these costs , 4.0 % and 3.3 % , respectively , were due to antipsychotic drug costs . The increased costs in the clozapine group appeared to reflect the licensing requirement for inpatient admission for commencing the drug . There was a trend towards higher mean participant utility scores in the clozapine group . CONCLUSIONS For b and 1 , there is no disadvantage in terms of quality of life and symptoms , or associated costs of care , over 1 year in commencing conventional antipsychotic drugs rather than new atypical drugs . Conventional drugs were associated with non-significantly better outcomes and lower costs . Drug costs represented a small proportion of the overall costs of care ( < 5 % ) . For b and 2 , there is a statistically significant advantage in terms of symptoms but not quality of life over 1 year in commencing clozapine rather than new atypical drugs , but with increased associated costs of care . The results suggest that conventional antipsychotic drugs , which are substantially cheaper , still have a place in the treatment of patients unresponsive to , or intolerant of , current medication . Further analyses of this data set are planned and further research is recommended into areas such as current antipsychotic treatment guidance , valid measures of utility in serious mental illness , low-dose ' conventional ' treatment in first episode schizophrenia , QLS validity and determinants of QLS score in schizophrenia , and into the possible financial and other mechanisms of rewarding clinician participation in trials In an open clinical multi-centre trial carried out in five Danish psychiatric departments , patients suffering from acute psychosis including mania or exacerbation of chronic psychosis were given injections of 5 % zuclopenthixol acetate in ' Viscoleo ' . The object of the trial was to evaluate the treatment by means of a global assessment of the severity of the psychosis , the therapeutic effect and the side-effects . The results showed that the treatment was rapidly effective in reducing the severity of psychotic symptoms combined with an advantageous unspecific sedation . The side-effect profile was similar to that after other neuroleptics . Special attention should be paid , however , to a possible occurrence of acute dystonia which was observed particularly in young men with acute psychosis
When haloperidol and midazolam were compared with olanzapine , there was some evidence the combination was superior in terms of improvement , sedation and behaviour .
There were relatively little good data and most trials are too small to highlight differences in either positive or negative effects .
Adding a benzodiazepine to other drugs does not seem to confer clear advantage and has potential for adding unnecessary adverse effects .
Sole use of older antipsychotics unaccompanied by anticholinergic drugs seems difficult to justify .
BACKGROUND Acute psychotic illness , especially when associated with agitated or violent behaviour , can require urgent pharmacological tranquillisation or sedation .
In several countries , clinicians often use benzodiazepines ( either alone or in combination with antipsychotics ) for this outcome .
OBJECTIVES To estimate the effects of benzodiazepines , alone or in combination with antipsychotics , when compared with placebo or antipsychotics , alone or in combination with antihistamines , to control disturbed behaviour and reduce psychotic symptoms .