Benzodiazepines for psychosis-induced aggression or agitation. Rapid tranquillisation in psychiatric emergency settings in Brazil: pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol plus promethazine A retrospective analysis of intramuscular haloperidol and intramuscular olanzapine in the treatment of agitation in drug- and alcohol-using patients. The expert consensus guideline series. Treatment of behavioral emergencies 2005. A Naturalistic Study of Intramuscular Haloperidol Versus Intramuscular Olanzapine for the Management of Acute Agitation Treatment of Behavioral Emergencies: A Summary of the Expert Consensus Guidelines Initial treatment of severe acute psychosis with fast orally disintegrating risperidone tablets. Intramuscular ziprasidone, 2 mg versus 10 mg, in the short-term management of agitated psychotic patients. Intramuscular (IM) ziprasidone 20 mg is effective in reducing acute agitation associated with psychosis: a double-blind, randomized trial Persisting low use of antipsychotics in the treatment of major depressive disorder with psychotic features. Prescribing for inpatients with schizophrenia: an international multi-center comparative study. The expert consensus guideline series. Optimizing pharmacologic treatment of psychotic disorders. Introduction: methods, commentary, and summary. Psychotic vs. nonpsychotic depression: comparison of treatment response. Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting. Pragmatic randomised trial of intramuscular lorazepam v. haloperidol plus promethazine. Efficacy of combinations of intramuscular antipsychotics and sedative-hypnotics for control of psychotic agitation. Acute mania: haloperidol dose and augmentation with lithium or lorazepam. A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia Olanzapine in the treatment of depression with psychotic features: A prospective open-label study Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study. Early onset of antipsychotic response in the treatment of acutely agitated patients with psychotic disorders The expert consensus guideline series. Treatment of dementia and its behavioral disturbances. Introduction: methods, commentary, and summary. Dementia and antipsychotic drugs. [Effectiveness results of olanzapine in acute psychotic patients with agitation in the emergency room setting: results from NATURA 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 Objective To determine whether haloperidol alone results in swifter and safer tranquillisation and sedation than haloperidol plus promethazine . Design Pragmatic r and omised open trial ( January-July 2004 ) . Setting Psychiatric emergency room , Rio de Janeiro , Brazil . Participants 316 patients who needed urgent intramuscular sedation because of agitation , dangerous behaviour , or both . Interventions Open treatment with intramuscular haloperidol 5 - 10 mg or intramuscular haloperidol 5 - 10 mg plus intramuscular promethazine up to 50 mg ; doses were at the discretion of the prescribing clinician . Main outcome measures The primary outcome was proportion tranquil or asleep by 20 minutes . Secondary outcomes were asleep by 20 minutes ; tranquil or asleep by 40 , 60 , and 120 minutes ; physically restrained or given additional drugs within 2 hours ; severe adverse events ; another episode of agitation or aggression ; additional visit from the doctor during the subsequent 24 hours ; overall antipsychotic load in the first 24 hours ; and still in hospital after 2 weeks . Results Primary outcome data were available for 311 ( 98.4 % ) people , 77 % of whom were thought to have a psychotic illness . Patients allocated haloperidol plus promethazine were more likely to be tranquil or asleep by 20 minutes than those who received intramuscular haloperidol alone ( relative risk 1.30 , 95 % confidence interval 1.10 to 1.55 ; number needed to treat 6 , 95 % confidence interval 4 to 16 ; P=0.002 ) . No differences were found after 20 minutes . However , 10 cases of acute dystonia occurred , all in the haloperidol alone group . Conclusions Haloperidol plus promethazine is a better option than haloperidol alone in terms of speed of onset of action and safety . Enough data are now available to change guidelines that continue to recommend treatments that leave people exposed to longer periods of aggression than necessary and patients vulnerable to distressing and unsafe adverse effects . Trial registration Current Controlled Trials IS RCT N83261243 OBJECTIVE The treatment of agitation in drug- and alcohol-using emergency patients is understudied . METHOD We performed a retrospective chart review of 105 agitated emergency department patients who received either intramuscular ( IM ) haloperidol or IM olanzapine  , comparing prescribing patterns , level of agitation , response to treatment and side effects in patients positive for drugs or alcohol [ D/A(+ ) ] and patients negative for drugs or alcohol [ ( D/A(- ) ] . RESULTS The haloperidol-benzodiazepine combination was the most frequently prescribed treatment in both groups , although alcohol(+ ) status biased clinicians toward using haloperidol alone . Overall , D/A(+ ) and D/A(- ) patients responded to the initial intervention at similar rates , although D/A(+ ) patients were rated as more agitated and had more posttreatment sedation than D/A(- ) patients . In D/A(+ ) patients , haloperidol+benzodiazepine and IM olanzapine performed better than haloperidol alone . There were no serious adverse events with any treatment . CONCLUSION Findings support the generalization of efficacy data from more rarified agitated sample s to population s with high rates of substance use and highlight the need for prospect i ve , inclusive , r and omized trials comparing the commonly used haloperidol-benzodiazepine combination with newer injectable antipsychotics 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 Published research on agitation is limited by the difficulty in generalizing findings from trials using moderately agitated , carefully selected patients treated with single agents . More specifically , there are few comparative studies examining common intramuscular ( IM ) regimens ( ie , haloperidol with or without benzodiazepines ) with IM atypical antipsychotics . Therefore , we conducted a retrospective chart review to compare IM olanzapine and haloperidol in a “ real-world ” population with agitation . Method We performed a retrospective evaluation of charts from 146 consecutive emergency department patients who received either IM haloperidol or IM olanzapine for agitation . We used a clinical ly oriented proxy marker of efficacy — the necessity for additional medication intervention for agitation (AMI)—as our primary outcome measure . Results Additional medication intervention for agitation was required by 43 % ( 13/30 ) patients when haloperidol was given alone and by 18 % ( 13/72 ) when haloperidol was given with a benzodiazepine . In the case of olanzapine , AMI was required by 29 % ( 6/21 ) of patients receiving olanzapine alone and by 18 % ( 2/11 ) of patients given olanzapine plus a benzodiazepine . A significant percentage of patients had clinical characteristics ( nonpsychiatric triage complaint , drug/alcohol use , severe agitation ) that differ from more selective sample s. Conclusions Overall , these finding suggest that in a naturalistic emergency department setting , haloperidol monotherapy is less effective — at least in requiring AMI — than olanzapine with or without a benzodiazepine or haloperidol plus a benzodiazepine . Moreover , these later 3 regimens seemed comparable . Prospect i ve studies examining the treatment of real-world agitation , including head-to-head comparisons of the haloperidol-benzodiazepine combination with newer IM antipsychotics , are needed Objectives . Behavioral emergencies are a common and serious problem for consumers , their communities , and the healthcare setting s on which they rely , but there is little research to guide provider responses to this challenge . Key constructs such as agitation have not been adequately operationalized so that the criteria defining a behavioral emergency are vague . A significant number of deaths of patients in restraint has focused government and regulators on these issues , but a consensus about key elements in the management of behavioral emergencies has not yet been articulated by the provider community . The authors assembled a panel of 50 experts to define the following elements : the threshold for emergency interventions , the scope of assessment for varying levels of urgency and cooperation , guiding principles in selecting interventions , and appropriate physical and medication strategies at different levels of diagnostic confidence and for a variety of etiologies and complicating conditions . Method . A written  survey with 808 decision points was completed by 50 experts . A modified version of the R AND Corporation 9-point scale for rating appropriateness of medical decisions was used to score options . Consensus on each option 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 choice , second line/ alternate choice , third line/usually inappropriate ) to each option based on the 95 % confidence interval around the mean rating . Guideline tables were constructed describing the preferred strategies in key clinical situations . Results . The expert panel reached consensus on 83 % of the options . The relative appropriateness of emergency interventions was ascertained for a continuum of behaviors . When asked about the frequency with which emergency interventions  ( parenteral medication , restraint , seclusion ) were required in their services , 47 % of the experts reported that such interventions were necessary for 1%–5 % of patients seen in their services and 32 % for 6%–20 % . In general , the consensus of this panel lends support to many elements of recent regulations from the Health Care Financing Administration ( now the Centers for Medicare and Medicaid Services ) , including the timing of clinician assessment and re assessment and the intensity of nursing care . However , the panel did not endorse the concept of “ chemical restraint , ” instead favoring the idea that medications are treatments for target behaviors in behavioral emergencies even when the causes of these behaviors are not well understood . Control of aggressive behavior emerged as the highest priority during the emergency ; however , preserving the physician-patient relationship was rated a close second and became the top priority in the long term . Oral medications , particularly concentrates , were clearly preferred if it is possible to use them . Benzodiazepines alone were top rated in 6 of 12 situations . High-potency conventional antipsychotics used alone never received higher ratings than benzodiazepines used alone . A combination of a benzodiazepine and an antipsychotic was preferred for patients with suspected schizophrenia , mania , or psychotic depression . There was equal support for high-potency conventional or atypical antipsychotics  ( particularly liquids ) in oral combinations with benzodiazepines .  Droperidol emerged in fourth place in some situations requiring an injection . Conclusions . To evaluate many of the treatment options in this survey , the experts had to extrapolate beyond controlled data . Within the limits of expert opinion and with the expectation that future research data will take precedence , these guidelines provide some direction for addressing common clinical dilemmas in the management of psychiatric emergencies and can be used to inform clinicians in acute care setting s regarding the relative merits of various strategies INTRODUCTION Although the use of atypical antipsychotics is the st and ard of care in the maintenance treatment of psychosis , most clinicians still rely on conventional neuroleptics to treat acutely agitated psychotic patients . The objective of this study was to evaluate the effectiveness and safety of a fast orally disintegrating tablet formulation of risperidone in the initial treatment of a large sample of very acutely ill psychotic patients . METHODS In this multi-center , prospect i ve , open-label observational trial , 191 schizophrenic patients were treated upon admission to hospital with fast orally disintegrating risperidone tablets for up to seven days . Co-medication was per usual clinical practice and at physician 's discretion . Psychopathology was rated at baseline , 2 , 24 and 48 hours and 4 and 7 days after initiation of therapy . RESULTS A mean PANSS total score of 114.3+/-23.4 at baseline reflected a severely exacerbated patient population . The PANSS total score was significantly reduced to 83.6+/-26.8 ( p<0.0001 ) and the CGI from 5.6+/-0.7 to 4.5+/-1.1 ( p<0.0001 ) after 7 days . The median time to calmness was 70 min and the associated PANSS item 4 ( excitation ) dropped two hours after the first intake of the study medication from 4.3+/-1.5 to 3.1+/-1.5 ( p<0.0001 ) . A total of 172 patients ( 90.1 % ) out of 191 completed the study . The median risperidone dose was 2 mg/d at the initiation of therapy and 4 mg/d after one week . CONCLUSION Oral treatment of acutely exacerbated schizophrenic patients with fast orally disintegrating risperidone tablets , alone or in combination with benzodiazepines , was associated with a rapid onset of action and a significant and clinical ly relevant improvement of acute symptoms BACKGROUND There is a clear need for effective , well-tolerated intramuscular ( i.m . ) agents for the acute control of agitated psychotic patients . Currently used agents , including conventional antipsychotics and /or benzodiazepines , may be associated with distressing side effects such as extrapyramidal side effects and excessive sedation . OBJECTIVE The objective of this study was to evaluate the efficacy and tolerability of the rapid-acting i.m . formulation of the novel antipsychotic ziprasidone in the treatment of in patients with psychosis and acute agitation ( DSM-IV diagnoses ) . METHOD In a 24-hour , double-blind , fixed-dose clinical trial , patients were r and omly assigned to receive up to 4 injections ( every 2 hours p.r.n . ) of 2 mg ( N = 54 ) or 10 mg ( N = 63 ) of ziprasidone i.m . The Behavioral Activity Rating Scale measured behavioral symptoms at baseline and the response to treatment up to 4 hours after the first i.m . injection . RESULTS Ziprasidone i.m . , 10 mg , rapidly reduced symptoms of acute agitation and was significantly more effective ( p < .01 ) than the 2-mg dose up to 4 hours after the first injection . Patients were calmed but not excessively se date d , and over half were classed as responders 2 hours after the 10-mg dose . No acute dystonia or behavioral disinhibition was reported . One patient who received the 10-mg dose experienced the extrapyramidal side effect akathisia . CONCLUSION Ziprasidone i.m . , 10 mg , is rapidly effective and well tolerated in the short-term management of the agitated psychotic patient . Comparison with a study of identical design comparing 2-mg with 20-mg doses in patients with similar levels of psychopathology suggests that efficacy with 10 mg or 20 mg of ziprasidone i.m . is significant and dose related Abstract Rationale : Intramuscular ( IM ) conventional antipsychotics and /or benzodiazepines are effective in the short-term treatment of acutely agitated psychotic patients but may be associated with adverse effects . A short-acting IM formulation of the novel antipsychotic , ziprasidone , which may offer advantages over conventional agents , has been developed . Objective : To compare ziprasidone IM 2 mg ( n=38 ) and 20 mg ( n=41 ) in the acute control and short-term management of agitated psychotic patients . Methods : A prospect i ve , r and omized , double-blind , 24-h study assessed efficacy using the  Behavioral Activity Rating Scale ( BARS ) and the PANSS . The BARS is a vali date d rating scale for the assessment of treatment response in acute agitation associated with psychosis . Following the initial dose , three more doses could be given 4 h apart if needed during the 24-h period . Results : The mean BARS score had decreased 15 min after the first 20 mg IM dose and was statistically significantly lower than the 2 mg group at 30 min post-dose . The improvement with the 20 mg dose increased until 2 h , and was maintained until at least 4 h post-dose ( P<0.001 ) . Two hours after the first injection , almost all of the patients receiving ziprasidone 20 mg were BARS responders compared with just one-third of those receiving 2 mg ziprasidone ( P<0.001 ) . The calming effect of ziprasidone was also evident by the significant reduction in PANSS agitation items ( P<0.05 ) and CGI-severity at 4 h ( P=0.008 ) . Both ziprasidone doses were very well tolerated .  Ziprasidone IM 20 mg was not associated with EPS , dystonia , akathisia , respiratory depression or with excessive sedation . Conclusions : Ziprasidone IM 20 mg substantially and significantly reduced the symptoms of acute agitation in patients with psychotic disorders .  Ziprasidone 20 mg IM was very well tolerated and produced no dystonia or akathisia OBJECTIVE Practice guidelines recommend the use of a combination of an antidepressant and an antipsychotic for the pharmacologic treatment of major depressive disorder with psychotic features ( MD-Psy ) . We assessed the extent to which the  pharmacotherapy  received by patients with MD-Psy under usual care conforms to these recommendations . METHOD We assessed the  pharmacotherapy  received under usual care conditions by 100 patients with MD-Psy prior to enrollment in STOP-PD ( Study of the Pharmacotherapy of Psychotic Depression ) , a 12-week r and omized , controlled trial comparing olanzapine plus sertraline to olanzapine plus placebo . Our assessment took place from January 2003 to May 2004 . The strength of antidepressant trials was rated using the Antidepressant Treatment History Form ( ATHF ) . The strength of antipsychotic trials or combinations of antidepressants and antipsychotics was rated using a modified version of the ATHF . We also determined whether the strength of antipsychotic or combination trials was associated with age , the duration of the current depressive episode , medical burden , cognitive status , or the severity of depressive or psychotic symptoms . RESULTS Most patients with MD-Psy were treated with antidepressants ( N = 82 , 82 % ) or antipsychotics ( N = 65 , 65 % ) . About half of the patients ( N = 48 , 48 % ) received therapeutic doses of an antidepressant ; 10 % ( N = 10 ) received an intermediate dose of an antipsychotic , and 6 % ( N = 6 ) received a high dose . Overall , only 5 % ( N = 5 ) received a combination of an adequate dose of an antidepressant and a high dose of an  antipsychotic .  The strength of both antipsychotic trials ( p = .021 ) and combination trials ( p = .039 ) was significantly associated only with a longer duration of the current depressive episode . CONCLUSIONS These findings show a persisting low use of  antipsychotics  in the treatment of MD-Psy . Given the high morbidity rates associated with MD-Psy , it is important to continue to educate clinicians regarding its identification and treatment . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00056472 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 A growing number of atypical antipsychotics are available for clinicians to choose from in the treatment of psychotic disorders . However , a number of important questions concerning medication selection , dosing and dose equivalence , and the management of inadequate response , compliance problems , and relapse have not been adequately addressed by clinical trials . To aid clinical decision-making , a consensus survey of expert opinion on the pharmacologic treatment of psychotic disorders was undertaken to address questions not definitively answered in the research literature . METHOD Based on a literature review , a written survey was developed with 60 questions and 994 options . Approximately half of the options were scored using a modified version of the R AND 9-point scale for rating the appropriateness of medical decisions . For the other options , the experts were asked to write in answers ( e.g. , average doses ) or check a box to indicate their preferred answer . The survey was sent to 50 national experts on the pharmacologic treatment of psychotic disorders , 47 ( 94 % ) of whom completed it . In analyzing the responses to items rated on the 9-point scale , consensus on each option 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 choice , second line/alternate choice , third line/usually inappropriate ) to each option based on the 95 % confidence interval around the mean rating . Guideline tables indicating preferred treatment strategies were then developed for key clinical situations . RESULTS The expert panel reached consensus on 88 % of the options rated on the 9-point scale . The experts overwhelmingly endorsed the atypical antipsychotics for the treatment of psychotic disorders . Risperidone was the top choice for first-episode and multi-episode patients , with the other newer atypicals rated first line or high second line depending on the clinical situation . Clozapine and a long-acting injectable atypical ( when available)were other high second line options for multi-episode patients . The expert 's dosing recommendations agreed closely with the package inserts for the drugs , and their estimates of dose equivalence among the antipsychotics followed a linear pattern . The experts considered 3 - 6 weeks an adequate antipsychotic trial , but would wait a little longer ( 4 - 10 weeks ) before making a major change in treatment regimen if there is a partial response . The experts recommended trying to improve response by increasing the dose of atypical and depot antipsychotics before switching to a different agent ; there was less agreement about increasing the dose of conventional antipsychotics before switching , probably because of concern about side effects at higher doses . If it is decided to switch because of inadequate response , risperidone was the expert 's first choice to switch to , no matter what drug was initially tried . Although there was some disparity in the expert 's recommendations concerning how many agents to try before switching to clozapine , the expert 's responses suggest that switching to clozapine should be Clozapine was also the antipsychotic of choice for patients with suicidal behavior . When switching oral antipsychotics , the experts considered cross-titration the preferred strategy . When switching to an injectable antipsychotic , the experts stressed the importance of continuing the oral antipsychotic until therapeutic levels of the injectable agent are achieved . The experts considered psychosocial interventions the first choice strategy for partially compliant patients , with pharmacologic interventions the first choice for patients with clear evidence of noncompliance . However , because it can be difficult to distinguish partially compliant from noncompliant patients , the editors recommended combining psychosocial and pharmacologic interventions to improve compliance whenever possible . When patients relapse because of compliance problems or if there is any doubt about compliance , the experts recommended the use of a long-acting injectable antipsychotic and would select an injectable atypical when this option becomes available . The experts would also consider using an injectable atypical antipsychotic ( when available ) in many clinical situations that do not involve compliance problems . The experts stressed the importance of monitoring for health problems-especially obesity , diabetes , cardiovascular problems , HIV risk behaviors , medical complications of substance abuse , heavy smoking and its effects , hypertension , and amenorrhea-in patients being treated with antipsychotics . Although many patients are prescribed adjunctive treatments , multiple antipsychotics , and combinations of different classes of drugs ( e.g. , antipsychotics plus mood stabilizers or antidepressants ) in an effort to enhance response , the experts gave little support to any of these strategies , with the exception of antidepressants for patients with  dysphoria/depression  , antidepressants or ECT for patients with suicidal behavior , and mood stabilizers for patients with aggression/violence . When asked about indicators of remission and recovery , the experts considered acute improvement in psychotic symptoms the most important indicator of remission , whereas they considered more sustained improvement in multiple outcome domains ( e.g. , occupational/educational functioning , peer relationships , independent living ) important in assessing recovery . CONCLUSIONS The experts reached a high level of consensus on many of the key treatment questions in the survey . Within the limits of expert opinion and with the expectation that future research data will take precedence , these guidelines provide direction for addressing common clinical dilemmas that arise in the pharmacologic treatment of psychotic disorders . They can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions . Clinicians should keep in mind that no guidelines can address the complexities involved in the care of each individual patient and that sound clinical judgment based on clinical experience should be used in applying these recommendations This retrospective study compared the treatment responses of 34 primary , unipolar depressives without psychotic features and 30 with psychotic features . Patients were diagnosed by Research Diagnostic Criteria and received trials of tricyclic antidepressants , antipsychotics , the combination of the two , electroconvulsive therapy , or placebo and psychotherapy . Only three of 18 psychotic patients vs. 17 of 23 nonpsychotic patients responded to antidepressants alone . Electroconvulsive therapy and the combination of antipsychotic and antidepressant medication gave better responses . These data suggest that major depressive disorder with psychotic features is best considered as a distinct subtype rather than a severe variant of major depression BACKGROUND The pharmacological management of violence in people with psychiatric disorders is under- research ed . AIMS To compare interventions commonly used for controlling agitation or violence in people with serious psychiatric disorders . METHOD We r and omised 200 people to receive intramuscular lorazepam ( 4 mg ) or intramuscular haloperidol  ( 10 mg ) plus promethazine ( 25 - 50 mg mix ) . RESULTS At blinded assessment s 4 h later ( 99.5 % follow-up ) , equal numbers in both groups ( 96 % ) were tranquil or asleep . However , 76 % given the haloperidol-promethazine mix were asleep compared with 45 % of those allocated lorazepam ( RR=2.29,95 % CI 1.59 - 3.39 ; NNT=3.2,95 % CI 2.3 - 5.4 ) . The haloperidol-promethazine mix produced a faster onset of tranquillisation/sedation and more clinical improvement over the first 2 h. Neither intervention differed significantly in the need for additional intervention or physical restraints , numbers absconding , or adverse effects . CONCLUSIONS Both interventions are effective for controlling violent/agitated behaviour . If speed of sedation is required , the haloperidol-promethazine combination has advantages over lorazepam The combination of haloperidol , 5 mg , and lorazepam , 4 mg , was both effective and safe for managing agitated behavior in an open trial with acutely psychotic patients . The combination also appeared to be superior to its individual components when studied in a r and omized , nonblind trial . The principle of the combined use of antipsychotics and sedative-hypnotics was further tested by comparing two new combinations : thiothixene , 5 mg , and lorazepam , 4 mg , versus haloperidol , 5 mg , and phenobarbital sodium , 130 mg . These combinations had comparable efficacy and safety , and the level of transquilization approached that produced by the haloperidol-lorazepam combination in the preceding studies Antipsychotic dosing for acute mania has not been well studied . Combined treatment with lithium and an antipsychotic is the most common treatment , but additional antimanic efficacy of a lithium-antipsychotic combination beyond that of an antipsychotic alone has not been well demonstrated . Furthermore , the possibility that lithium could affect antipsychotic dose requirement is believed to have never been studied . In this study , 63 acutely psychotic bipolar manic in patients were r and omly assigned to receive double-blind treatment with 1 of 2 haloperidol doses , 25 mg/day or 5 mg/day , for 21 days . In addition to haloperidol , subjects were r and omly assigned to receive concomitant treatment with placebo , st and ard lithium , or lorazepam 4 mg/day . The high haloperidol dose produced greater improvement and more side effects than did the low dose . Lithium added to the low dose produced a markedly greater clinical response than did the low dose alone . Lorazepam did not improve the outcome for the patients receiving low-dose haloperidol . The clinical response produced by high-dose haloperidol was not enhanced by adding either lithium or lorazepam . All treatment effects emerged by the fourth day of treatment and persisted . Used alone , a haloperidol dose of 5 mg/day is too low for most manic patients , but concomitant lithium produces a dose-dependent enhancement of haloperidol response .  Lorazepam 4 mg/day was insufficient to produce an advantage when added to low-dose haloperidol 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 Objective . Depression with psychotic features is a severe subtype of major depression associated with the presence of delusions , hallucinations and specific neurobiological features . Despite clinical consensus and guideline recommendations , data comparing the efficacy of combining antipsychotics with antidepressants compared to antidepressants alone remain inconclusive . The aim of the study was to investigate effectiveness and tolerability of the atypical antipsychotic olanzapine in acute depression with psychotic features . Methods . Seventeen in patients with major depressive disorder with psychosis ( MDDp ) were treated with a combination of an antidepressant and olanzapine for 6 weeks in a prospect i ve open-label study . Depressive and psychotic symptoms , extrapyramidal and general side effects were assessed every 2 weeks . Sixteen patients were eligible for final analysis . Results . The Brief Psychiatric Rating Scale ( BPRS ) showed a 30 % symptom reduction after week 2 , a 45 % symptom reduction after week 4 and no considerable improvement thereafter . Depressive symptoms ( Bech – Rafaelsen Melancholia Scale , BRMS ) receded by 37 % after week 2 and 50 % after week 4 . No extrapyramidal side effects occurred . Conclusion . Olanzapine is effective and tolerable in combination with an antidepressant in an MDDp inpatient sample . The results concur with data supporting good efficacy in negative and depressive symptoms of patients with schizophrenic and schizoaffective diseases Rapid tranquilization is a routinely practice d method of calming agitated psychotic patients by use of neuroleptics , benzodiazepines , or both in combination . Although several studies have examined the efficacy of the three approaches , none have compared these treatments in a prospect i ve , r and omized , double-blind , multicenter trial . Ninety-eight psychotic , agitated , and aggressive patients ( 73 men and 25 women ) were prospect ively enrolled during an 18-month period in emergency departments in five university or general hospitals . Patients were r and omly assigned to receive intramuscular injections of lorazepam ( 2 mg ) , haloperidol ( 5 mg ) , or both in combination . Patients in each treatment group received 1 to 6 injections of the same study drug within 12 hours , based on clinical need . They were evaluated hourly after the first injection until at least 12 hours after the last . Efficacy was assessed on the Agitated Behavior Scale ( ABS ) , a modified Brief Psychiatric Rating Scale ( MBPRS ) , Clinical Global impressions ( CGI ) scale , and an Alertness Scale . Effective symptom reduction was achieved in each treatment group with significant ( P < .01 ) mean decreases from baseline at every hourly ABS evaluation . Significant ( P < .05 ) mean differences on the ABS ( hour 1 ) and MBPRS ( hours 2 and 3 ) suggest that tranquilization was most rapid in patients receiving the combination treatment . Study event incidence ( side effects ) did not differ significantly between treatment groups , although patients receiving haloperidol alone tended to have more extrapyramidal system symptoms . The superior results produced by the combination treatment support the use of lorazepam plus haloperidol as the treatment of choice for acute psychotic agitation 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 OBJECTIVES New treatment options for dementia and its behavioral disturbances have become available since publication of The Expert Consensus Guidelines on the Treatment of Agitation in Older Persons with Dementia in 1998 . While only 2 cholinesterase inhibitors , donepezil and tacrine , were available in 1998 , 3 new cognitive-enhancing agents have been introduced since that time as well as several new atypical antipsychotics and antidepressants . However , there are still limited data from controlled studies to guide clinicians in choosing among these agents and sequencing and combining treatments . We therefore conducted a new survey study of expert opinion on the treatment of cognitive impairment and behavioral disturbances associated with dementia . METHODS Based on a literature review , a 61- question survey was developed with 1,225 options . Most options were scored using a modified version of the R AND 9-point scale for rating appropriateness of medical decisions . For other options , the experts were asked to write in answers . The survey was sent to 50 North American experts on dementia , 100 % of whom completed it . In analyzing responses to items rated on the 9-point scale , consensus was defined as a nonr and om distribution of scores by chi-square " goodness-of-fit " test . Based on the 95 % confidence interval around the mean , we assigned a categorical rank ( first line/preferred , second line/alternate , third line/usually inappropriate ) to each option . Guidelines indicating preferred treatment strategies were then developed for selected clinical situations . RESULTS For patients at risk for dementia , the experts recommended control of hypertension and diabetes . They also recommended aspirin and would consider a lipid-lowering agent in patients at risk for vascular dementia . Cholinesterase inhibitors were an option for patients with mild cognitive impairment ( i.e. , at risk for Alzheimer 's dementia [ AD ] ) . To slow cognitive impairment in mild/moderate AD , the experts recommended a cholinesterase inhibitor alone or combined with vitamin E. Donepezil and  galantamine  were the preferred cholinesterase inhibitors . The experts recommended combining a cholinesterase inhibitor with a N-methyl-D-aspartate ( NMDA ) antagonist ( e.g. , memantine ) if a patient with mild/moderate dementia has an inadequate response to monotherapy . Control of hypertension and diabetes was the treatment of choice , in patients with mild/moderate vascular or mixed AD/vascular dementia , with aspirin another first-line option . Cholinesterase inhibitors were also a first-line option for mild/moderate mixed AD/vascular dementia . Among nonpharmacological interventions for mild/moderate dementia , the experts recommended caregiver education , supportive therapy for caregivers , referral to day treatment , exercise programs , and respite care . For moderate/severe AD or mixed AD/vascular dementia , the experts recommended combining an NMDA antagonist with a cholinesterase inhibitor . For moderate/severe vascular or mixed AD/vascular dementia , they recommended control of hypertension and diabetes . The experts ' ratings underscore the importance of nonpharmacological strategies aim ed at reducing caregiver burden in more severe dementia . Management of agitation and other behavioral disturbances was another focus of this study . The experts recommended using an atypical antipsychotic for agitation associated with delirium , psychosis , aggression , or anger . They would also consider divalproex to manage anger with a risk of physical aggression . Selective serotonin reuptake inhibitors were recommended for the treatment of depression or anxiety in patients with dementia . Benzodiazepines or atypical antipsychotics were viewed as short-term options for acute anxiety .  Trazodone was recommended for insomnia . The experts also gave recommendations concerning dosage levels , duration of treatment , and choice of medications for patients with different complicating conditions . CONCLUSIONS The experts reached high levels of consensus on key steps in treating dementia and associated behavioral disturbances . Within the limits of expert opinion and with the expectation that new research data will take precedence , these guidelines may provide direction for clinicians offering care to patients with dementia Introduced in the 1950s , antipsychotic agents have been found to improve symptomatology and function in young and middle-aged psychotic schizophrenics . Three decades of research , however , have not made clear these agents ' usefulness in demented elderly patients . A review of placebo-controlled studies suggests a definite but limited role for antipsychotic medication in behaviorally disturbed elderly dementia patients with agitated behavior . Studies also suggest that cognitive function needs careful monitoring when these drugs are prescribed to treat behavioral symptoms of dementia 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
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 .