A randomized comparison of divalproex oral loading versus haloperidol in the initial treatment of acute psychotic mania. Combination of a mood stabilizer with risperidone or haloperidol for treatment of acute mania: a double-blind, placebo-controlled comparison of efficacy and safety. Psychoactive drugs in mania. A controlled comparison of lithium carbonate, chlorpromazine, and haloperidol. Haloperidol Blood Levels in Acute Mania With Psychosis A 12-week, double-blind comparison of olanzapine vs haloperidol in the treatment of acute mania. A Double-Blind, Randomized, Prospective Evaluation of the Efficacy and Safety of Risperidone Versus Haloperidol in the Treatment of Schizoaffective Disorder Comparative study of the effectiveness of zuclopenthixol acetate and haloperidol in acutely disturbed psychotic patients. Adjunctive antipsychotic treatment is necessary for adolescents with psychotic mania. Flupenthixol versus haloperidol in acute psychosis. A comparison of haloperidol, lithium carbonate and their combination in the treatment of mania. Acute mania: haloperidol dose and augmentation with lithium or lorazepam. Olanzapine or chlorpromazine plus lithium in first episode psychotic mania: An 8-week randomised controlled trial. A controlled Nordic multicentre study of zuclopenthixol acetate in oil solution, haloperidol and zuclopenthixol in the treatment of acute psychosis Allopurinol for mania: a randomized trial of allopurinol versus placebo as add-on treatment to mood stabilizers and/or antipsychotic agents in manic patients with bipolar disorder. Allopurinol as an adjunct to lithium and haloperidol for treatment of patients with acute mania: a double-blind, randomized, placebo-controlled trial. Calming versus sedative effects of intramuscular olanzapine in agitated patients. [Flupenthixol versus haloperidol in acute psychotic episodes]. Rapid tranquillisation in psychiatric emergency settings in Brazil: pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol plus promethazine Acute and continuation risperidone monotherapy in bipolar mania: a 3-week placebo-controlled trial followed by a 9-week double-blind trial of risperidone and haloperidol Quetiapine or haloperidol as monotherapy for bipolar mania—a 12-week, double-blind, randomised, parallel-group, placebo-controlled trial A Pilot Study of Risperidone, Olanzapine, and Haloperidol in Psychotic Youth: A Double-Blind, Randomized, 8-Week Trial Effectiveness of aripiprazole v. haloperidol in acute bipolar mania: double-blind, randomised, comparative 12-week trial. A comparison of the central nervous system effects of haloperidol, chlorpromazine and sulpiride in normal volunteers. Topiramate monotherapy in the management of acute mania: results of four double-blind placebo-controlled trials. Carbamazepine compared to haloperidol in acute mania. Risperidone in the treatment of acute mania: double-blind, placebo-controlled study.
BACKGROUND Uncontrolled evidence suggests that divalproex administered via the oral loading strategy of 20 mg/kg/day may produce clinical ly significant antimanic response within 3 days of treatment in some patients . We conducted a prospect i ve study to compare the antimanic response of divalproex oral loading with that of haloperidol in the initial treatment of acute psychotic mania . METHOD After a < or = 1-day screening period , 36 consecutive hospitalized patients with bipolar disorder , manic or mixed phase and with psychotic features , were r and omly assigned to receive either divalproex 20 mg/kg/day or haloperidol 0.2 mg/kg/day for 6 full days , without other psychotropic agents except lorazepam up to 4 mg/day for management of agitation . Serum valproate concentrations were measured after 1 day of treatment . Response was measured daily by a blind rater using the Young Mania Rating Scale and the Scale for Assessment of Positive Symptoms . RESULTS Divalproex oral loading and haloperidol were equally effective in acutely reducing manic and psychotic symptoms . The greatest rate of improvement for both drug regimens occurred over the first 3 full days of treatment . Side effects were infrequent and minor for both treatments , except for extrapyramidal side effects which were significantly more common with haloperidol . CONCLUSION Divalproex oral loading may produce rapid onset of antimanic and antipsychotic response comparable to that of haloperidol and with minimal side effects in the initial treatment of acute psychotic mania in a subset of bipolar patients OBJECTIVE The study assessed the efficacy and safety of risperidone as an adjunctive agent to mood stabilizers in the treatment of acute mania .  METHOD This 3-week r and omized , double-blind , placebo-controlled study included 156 bipolar disorder patients with a current manic or mixed episode who received a mood stabilizer ( lithium or divalproex ) and placebo , risperidone , or haloperidol .  The primary efficacy measure was the Young Mania Rating Scale . Other assessment s used the Brief Psychiatric Rating Scale , the Clinical Global Impression scale , and safety measures . RESULTS The trial was discontinued by 25 ( 49 % ) of the 51 placebo group patients , 18 ( 35 % ) of the 52 risperidone group patients , and 28 ( 53 % ) of the 53 haloperidol group patients . Mean modal doses were 3.8 mg/day ( SD=1.8 ) of risperidone and 6.2 mg/day ( SD=2.9 ) of haloperidol . Significantly greater reductions in Young Mania Rating Scale scores at endpoint and over time were seen in the risperidone group and in the haloperidol group , compared with the placebo group . Young Mania Rating Scale total scores improved with risperidone and with haloperidol both in patients with psychotic features and in those without psychotic features at baseline . Extrapyramidal Symptom Rating Scale total scores at endpoint were significantly higher in the haloperidol patients than in the placebo patients . Antiparkinsonian medications were received by 8 % , 17 % , and 38 % of patients in the placebo , risperidone , and haloperidol groups , respectively . CONCLUSIONS Risperidone plus a mood stabilizer was more efficacious than a mood stabilizer alone , and as efficacious as haloperidol plus a mood stabilizer , for the rapid control of manic symptoms and was well tolerated Lithium carbonate , haloperidol , and chlorpromazine hydrochloride were compared in a double-blind controlled study with severely ill hospitalized manics .  Lithium carbonate and haloperidol produced a highly significant improvement of manic symptoms without sedation . Although producing considerable sedation , chlorpromazine did little to alter the underlying mania qualitatively . Qualitative differences between lithium carbonate and haloperidol indicate that , while haloperidol has a more dramatically rapid impact on behavior-motor activity , lithium carbonate acted more evenly on the entire manic picture , with total normalization realized during active treatment . The majority of lithium carbonate-treated patients met discharge criteria at study termination , but not the patients receiving either neuroleptic drug . The rating scales are not sensitive enough to monitor manic psychopathology ; this accounts for the lack of statistically significant differences among drug groups at treatment termination , despite the widely disparate discharge rates In this study , the authors examined the relationship between steady-state haloperidol  blood levels and clinical response in patients with acute psychotic mania . Fifty-four in patients with acute mania were r and omly assigned to receive either haloperidol 25 mg/day or haloperidol 5 mg/day . Each subject also received a concomitant medication : lorazepam 4 mg/day , lithium , or placebo . The relationship between steady-state  haloperidol blood levels and clinical improvement was studied using analysis of covariance . There was wide interindividual variation in the  haloperidol blood level – dose ratio . Haloperidol blood levels ( log-transformed ) were found to significantly correlate with clinical response in acute mania . Low-dose haloperidol with concomitant lithium may produce an optimal response in acute mania .  Haloperidol blood levels may be clinical ly useful in identifying patients who are nonresponsive because of low drug levels and , hence , in enhancing optimal haloperidol dosing for acute mania with psychosis BACKGROUND This r and omized controlled trial compares the efficacy and safety of olanzapine vs haloperidol , as well as the quality of life of patients taking these drugs , in patients with bipolar mania . METHODS The design consisted of 2 successive , 6-week , double-blind periods and compared flexible dosing of olanzapine ( 5 - 20 mg/d , n = 234 ) with haloperidol ( 3 - 15 mg/d , n = 219 ) . RESULTS Rates of remission ( Young-Mania Rating Scale score of < or = 12 and 21-item Hamilton Rating Scale for Depression score of < or = 8 at week 6 ) were similar for  olanzapine- and haloperidol-treated patients ( 52.1 % vs 46.1 % , respectively ; P = .15 ) . For the subgroup of patients whose index episode did not include psychotic features , rates of remission were significantly greater for the olanzapine group compared with the haloperidol group ( 56.7 % vs 41.6 % , P = .04 ) . Relapse into an affective episode ( mania and /or depression ) occurred in 13.1 % and 14.8 % of olanzapine- and haloperidol-treated patients , respectively ( P = .56 ) . Switch to depression occurred significantly more rapidly with haloperidol than with olanzapine when using survival analysis techniques ( P = .04 ) , and significantly more haloperidol-treated patients experienced worsening of extrapyramidal symptoms , as indicated by several measures . Weight gain was significantly greater in the olanzapine group compared with the haloperidol group ( 2.82 vs 0.02 kg , P<.001 ) . The olanzapine group had significant improvement in quality of life on several dimensions compared with the haloperidol group . CONCLUSIONS These data suggest that olanzapine does not differ from haloperidol in achieving overall remission of bipolar mania . However , haloperidol carries a higher rate of extrapyramidal symptoms , whereas olanzapine is associated with weight gain The relative efficacy and safety of risperidone versus haloperidol in the treatment of schizoaffective disorder was studied . Sixty-two patients ( 29 depressed type ; 33 bipolar type ) entered a three-site , r and omized , double-blind , 6-week trial of risperidone ( up to 10 mg/day ) or haloperidol ( up to 20 mg/day ) . Trained raters assessed baseline , weekly , and end-of- study levels of psychopathology with the Positive and Negative Syndrome Scale ( PANSS ) , the 24-item Hamilton Rating Scale for Depression ( HAM-D-24 ) and the Clinician-Administered Rating Scale for Mania ( CARS-M ) . The authors were unable to statistically distinguish between risperidone and haloperidol in the amelioration of psychotic and manic symptoms . In addition , there was no difference in worsening of mania between the two agents in either subgroup ( i.e. , depressed or bipolar subgroups ) . For the total PANSS , risperidone produced a mean decrease of 16 points from baseline compared with a 14-point decrease with haloperidol . For the total CARS-M scale , risperidone and haloperidol produced mean change scores of 5 and 8 points , respectively , and for the CARS-M Mania subscale , 3 and 7 points , respectively . Additionally , risperidone produced a mean decrease of 13 points from the baseline 24-item HAM-D , compared with an 8-point decrease with haloperidol . In those patients who had more severe depressive symptoms ( i.e. , HAM-D baseline score > 20 ) , risperidone produced at least a 50 % mean improvement in 12 ( 75 % ) of 16 patients in comparison to 8 ( 38 % ) of 21 patients receiving haloperidol . Haloperidol produced significantly more extrapyramidal side effects and result ed in more dropouts caused by any side effect . There was no difference between risperidone and haloperidol in reducing both psychotic and manic symptoms in this group of patients with schizoaffective disorder .  Risperidone did not demonstrate a propensity to precipitate mania and was better tolerated than haloperidol . In those subjects with higher baseline HAM-D scores ( i.e. , > 20 ) , risperidone produced a greater improvement in depressive symptoms than haloperidol OBJECTIVES To study the effectiveness , frequency of administration and side effects of zuclopenthixol acetate ( ZPTA ) and haloperidol ( HAL ) in the treatment of acute psychotic disturbance with aggression . METHOD Purposive sampling method was employed in a group of psychotic patients with aggression admitted to Songkla Neuropsychiatric Hospital , they were r and omly divided into 2 groups :  ZPTA  group and HAL group . All of the patients were evaluated daily for 7 consecutive days using the Brief Psychiatric Rating Scale ( BPRS ) and the Clinical Global Impression Scale ( CGI ) . Statistical analysis was performed by using the Student t-test and Linear regression . RESULTS There were 70 patients with diagnosis of schizophrenia , mania and acute psychosis . Thirty-eight patients were r and omly assigned to the ZPTA group and were given 50 - 100 mg of the drug , while 32 patients received HAL 5 - 10 mg . The result showed a significant reduction in BPRS or CGI scores in both groups . Patients treated with ZPTA required less frequent administration than did those on HAL ( p < 0.05 ) . There was no statistically significant difference in the reduction in scores between the two groups . Nor was there a statistical difference in reduction of aggression based on BPRS rating . Each group of patients showed a few side effects of mild degree . CONCLUSION Both ZPTA and HAL were effective in the treatment of acute psychosis with aggression , but frequency of administration was lower in the ZPTA Adolescents with acute psychotic mania were treated with lithium and adjunctive haloperidol as part of a lithium efficacy study . If the psychosis completely resolved , haloperidol was discontinued after 1 week of therapeutic lithium levels . Our first five subjects experienced a rapid exacerbation of symptoms , which responded to restarting haloperidol . A longer duration of adjunctive antipsychotic treatment is necessary in adolescents with bipolar psychosis Forty acutely psychotic patients were treated either with flupenthixol drops or haloperidol drops in an open , 28-day controlled study . The flupenthixol  group comprised 11 schizophrenic , 8 manic , and 1 paranoid patient and there were 10 schizophrenic , 5 manic , and 5 paranoid patients in the haloperidol group . Mean daily dosage was approximately 112 mg flupenthixol and 18 mg haloperidol . Clinical ly , both drugs showed an antipsychotic effect . In the schizophrenic patients there was a definite trend towards a more rapid relief of the psychotic symptoms after flupenthixol treatment . In contrast to haloperidol , flupenthixol showed a mood elevating effect and an effect on the negative symptoms , e.g. emotional withdrawal , motor retardation , blunted affect , and disorientation . With both drugs , the most troublesome side-effects were extrapyramidal in nature . Initially , they were more common in the flupenthixol group : later the incidence was similar Previous investigations of the treatment of mania have result ed in uncertainty about the efficacy of lithium versus a neuroleptic . In addition there have been reports of toxicity with a haloperidol -- lithium combination . In order to determine the comparative efficacy of lithium vs haloperidol vs a combination of haloperidol -- lithium , we studied 21 severely ill manic patients who all met rigorous criteria for bipolar illness and who required in hospital treatment . Subjects were r and omly assigned to 3 groups : ( A ) Lithium plus placebo ( B ) Placebo plus haloperidol and ( C ) Lithium plus haloperidol . The study was conducted in double blind fashion for 3 weeks with the dosages of the medications varied according to clinical response or untoward effects . Subjects on haloperidol and placebo or the haloperidol -- lithium combination were significantly improved after 7 days in comparison to the lithium-treated group . Groups B and C did not differ from each other , either in degree of improvement or in side effects . Inspite of the relatively small sample size the results suggest ( 1 ) that haloperidol is superior to lithium for treating severely ill acute mania and ( 2 ) that while a haloperidol -- lithium combination does not result in a significant increase in side effects , it is not superior to haloperidol alone 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 BACKGROUND Treatment strategies for mental disorders may vary according to illness stage . However no data currently exist to guide treatment in first episode psychotic mania . The aim of this study was to compare the safety and efficacy profile of chlorpromazine and olanzapine , as add-on to lithium , in patients with a first episode of psychotic mania , expecting better safety profile and adherence to olanzapine but similar efficacy for both treatments . METHODS Data from 83 patients were collected in an 8-week r and omised controlled trial on clinical variables , side effects , vital signs , and weight . Analyses of treatment differences over time were based on intent-to-treat principles . Kaplan-Meier estimated survival curves were used to analyse time-to-event data and mixed effects models repeated measures analysis of variance were used to determine treatment group differences over time on safety and efficacy measures . RESULTS Ethics committee approval to delay informed consent procedure until recovery from the acute episode allowed the inclusion of 83 patients highly representative of those treated in the public sector . Contrary to our hypotheses , safety profile of both medications was similar . A signal for higher rate ( P=.032 ) and earlier occurrence ( P=.043 ) of mania remission was observed in the olanzapine group which did not survive correction for multiple comparisons . CONCLUSIONS Olanzapine and chlorpromazine have a similar safety profile in a uniquely representative cohort of patients with first episode psychotic mania . The possibility for a greater impact of olanzapine on manic symptoms leading to earlier remission of the episode needs exploration in a large sample Zuclopenthixol acetate — a new injectable formulation with a duration of action of 2–3 days — was compared with conventional intramuscular and oral formulations of haloperidol and zuclopenthixol in the initial treatment of acutely disturbed , psychotic patients . The patients were stratified into 3 diagnostic categories : acute psychoses ( 48 patients ) , mania ( 22 patients ) , and exacerbation of chronic psychoses ( 73 patients ) . The patients were rated on the Brief Psychiatric Rating Scale ( BPRS ) , the Bech‐Rafaelsen Mania Rating Scale ( brmas ) ( only manic patients ) and globally on the Clinical Global Impression ( CGI ) . The study was an open , r and omized multicentre trial with a 6‐day treatment period . The zuclopenthixol acetate patients received 1–4 doses , the haloperidol patients 1–26 and the zuclopenthixol patients 1–22 doses . The assessment s on the CGI showed that all 3 treatments caused a clear reduction of the severity of illness scores in all 3 diagnostic categories , with no differences between treatments . The ratings of the acute and chronic psychotic patients on the BPRS also showed significant reductions in scores with no differences between treatments . All 3 treatments caused a rapid remission of symptoms on the BRMAS .  Haloperidol  induced hypokinesia in significantly more patients than zuclopenthixol acetate after 24 h. Later there were no significant differences between treatments . Zuclopenthixol acetate fulfils many desires for an amended neuroleptic formulation for the initial treatment of acutely disturbed psychotic patients OBJECTIVE An emerging body of evidence supports a role for dysfunctional purinergic neurotransmission in mood disorders . Adenosine agonists have been shown to have properties similar to those of dopamine antagonists ; there is a well-characterized interaction between adenosine and dopamine receptors in the ventral striatum , and increasing adenosinergic transmission has been demonstrated to reduce the affinity of dopamine agonists for dopamine receptors . Allopurinol increases adenosine levels in the brain , and hence is hypothesized to reduce the symptoms of mania . Two r and omized , placebo-controlled trials administering add-on allopurinol to manic patients showed significantly greater improvements in Young Mania Rating Scale ( YMRS ) scores for drug compared to placebo , while a more recent , relatively small , add-on study showed negative results . Based on these data , our objective was to examine the efficacy of allopurinol as add-on treatment to mood stabilizers and /or antipsychotic agents in manic patients with bipolar disorder . METHODS We performed a large , well-powered , multicenter , six-week , r and omized , placebo-controlled trial of allopurinol added to mood stabilizers and /or antipsychotic agents in 180 patients with bipolar disorder in an acute manic episode . RESULTS Both groups showed improvement on the YMRS ( effect size of 1.5 for placebo and 1.6 for allopurinol ) , with no difference observed between groups on YMRS scores ( t = 0.28 , p = 0.78 ) . There was no difference in the proportion of patients who responded to treatment ( defined as showing at least 50 % improvement in YMRS score ) between the two groups ( p = 0.92 ) , or in dropout rates ( p = 0.84 ) . LIMITATIONS None of our patients received lithium . However , the side effects of lithium and its narrow therapeutic index made the use of lithium less common and , therefore , our study results reflect common current clinical practice . In the present study , we used a variety of antipsychotic and /or mood stabilizing treatments , to which we added allopurinol ; one might hypothesize that add-on allopurinol has a different effect in combination with different antipsychotic agents or mood stabilizers . CONCLUSIONS The findings of this large , well-powered study do not support add-on allopurinol as a treatment for acute mania . This study did not test the efficacy of allopurinol as monotherapy OBJECTIVE Allopurinol , a hypouricemic agent , has been shown to present therapeutic effects in mania associated with hyperuricemia . This study assessed the efficacy and safety of risperidone as an adjunctive agent to lithium and haloperidol for the treatment of acute mania in hospitalized bipolar patients . METHODS Eighty-two patients aged between 18 and 49 were eligible to participate , as they met the DSM-IV criteria for a current manic episode , on the basis of a clinical interview by two academician psychiatrists . In addition , a score of at least 20 points on the Young Mania Rating Scale was required representing at least a moderate-to-severe mania . Forty-one patients were r and omly allocated to lithium ( 1 - 1.2 mEq/L ) + haloperidol ( 10 mg/day ) + allopurinol ( 300 mg/day ) ( group A ) or lithium ( 1 - 1.2 mEq/L ) + haloperidol ( 10 mg/day ) + placebo ( group B ) for an 8-week , double-blind , placebo-controlled study . Patients were assessed by a third-year resident of psychiatry at baseline and at 7 , 14 , 28 , 42 , and 56 days after the medication started . The mean decrease in the Young Mania Rating Scale score from baseline was used as the main outcome measure of response of mania to treatment . The extrapyramidal symptoms were assessed using the Extrapyramidal Symptoms Rating Scale ( ESRS ) . Side effects were systematic ally recorded throughout the study and were assessed using a checklist . RESULTS Young Mania Rating Scale scores improved with allopurinol . The difference between the two protocol s was significant as indicated by the effect of the group , the between-subjects factor ( F = 5.22 , df = 1 , p = 0.008 ) . The mean ESRS scores for the placebo group were higher than the allopurinol group . However , the differences were not significant over the trial . The difference between the two groups in the frequency of side effects was not significant except for agitation that was more often in the placebo group . CONCLUSIONS The efficacy of allopurinol to obtain a greater improvement in patients with mania seems to support the purinergic dysfunction in mania Distinct calming rather than nonspecific sedation is desirable for the treatment of acute agitation . In 3 double-blind studies , acutely agitated patients with schizophrenia ( N = 311 ) , bipolar mania ( N = 201 ) , or dementia ( N = 206 ) were treated with intramuscular ( 1 - 3 injections/24 hrs ) olanzapine ( 2.5 - 10.0 mg ) , haloperidol ( 7.5 mg ) , lorazepam ( 2.0 mg ) , or placebo . The Agitation-Calmness Evaluation Scale ( ACES ; Eli Lilly and Co. ) and treatment-emergent adverse events assessed sedation . Across all studies , 1 patient ( lorazepam-treated , bipolar ) became unarousable . There were no significant between-group differences in ACES scores of deep sleep or unarousable at any time across . Excluding asleep patients , agitation remained significantly more reduced with olanzapine than placebo ( P < .05 ) . The incidences of adverse events indicative of sedation were not significantly different with olanzapine versus comparators . For the treatment of acute agitation associated with schizophrenia , bipolar mania , or dementia , intramuscular olanzapine-treated patients experienced no more sedation than haloperidol- or lorazepam-treated patients and experienced distinct calming rather than nonspecific sedation The aim of this study is to evaluate the activity of flupentixol oral high concentration and to define the profile of the drug according to the administered dose . The trial includes 40 acute patients ( 21 schizophrenics , 13 manic patients and 6 other psychotics ) . The study was open , but the patients were treated at r and om either by haloperidol or by flupentixol . Both substances showed a strong antipsychotic and antimanic effect . The differences according to the administered doses were : a quicker onset of action for flupentixol in schizophrenic patients ; a more pronounced activity of flupentixol in the same patients , as far as anxiety , depressive tendencies and defect symptoms are concerned . Extrapyramidal side effects are the most common ones amongst the two drugs 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 In a r and omized , double-blind trial , patients with acute bipolar mania received 1 - 6 mg/day of risperidone , 2 - 12 mg/day of haloperidol , or placebo for 3 weeks , followed by double-blind risperidone or haloperidol for 9 weeks . Of 438 patients , 154 were r and omized to risperidone , 144 to haloperidol , and 140 to placebo .  The mean+/-S.D. modal doses were 4.2+/-1.7 mg/day of risperidone and 8.0+/-3.6 mg/day of haloperidol during the initial 3-week phase and 4.1+/-1.8 and 7.4+/-3.7 mg/day during the 12-week period . At week 3 , mean Young Mania Rating Scale ( YMRS ) score reductions from baseline were significantly greater in patients receiving risperidone than placebo ( p<0.001 ) . Differences between risperidone and haloperidol on this efficacy measure were not significant . Further reductions in YMRS scores were seen in patients receiving risperidone or haloperidol during the subsequent 9 weeks . No unexpected adverse events were reported . Extrapyramidal disorder and hyperkinesias , the most commonly reported adverse events with antipsychotic use , occurred less frequently with risperidone than haloperidol . We conclude that risperidone monotherapy was an effective and well-tolerated treatment for bipolar mania and that efficacy was maintained over the long term METHODS Patients ( n=302 ) with bipolar I disorder ( manic episode ) were r and omised to 12 weeks ' double-blind treatment with quetiapine ( flexibly dosed up to 800 mg/day ) , placebo , or haloperidol ( up to 8 mg/day ) . The primary efficacy outcome variable was change from baseline to Day 21 in Young Mania Rating Scale ( YMRS ) score . RESULTS YMRS score improved with quetiapine at Day 21 ( -12.29 versus -8.32 for placebo ; P<0.01 ) . The difference in favor of quetiapine increased by Day 84 ( -17.52 versus -9.48 ; P<0.001 ) . Haloperidol also showed an advantage over placebo at Days 21 and 84 ( P<0.001 ) . There was no significant difference in efficacy measures between quetiapine and haloperidol groups at any assessment except Day 21 . The only common adverse event with quetiapine was somnolence ( 12.7 % ) . Extrapyramidal symptoms ( EPS ) , including akathisia , occurred at 59.6 % with haloperidol , 12.7 % with quetiapine , 15.8 % with placebo . Most quetiapine responders ( 84 % ) received a dose of 400 - 800 mg/day . CONCLUSIONS Quetiapine was effective and well tolerated . The efficacy and tolerability profile of haloperidol ( including its propensity for EPS ) supported study validity This pilot study was undertaken to estimate the acute antipsychotic effect size and side effect propensity of risperidone and olanzapine in the pediatric population , in comparison to haloperidol , a conventional antipsychotic with established efficacy . Risperidone and olanzapine are widely used as first-line treatments to ameliorate psychotic symptoms in youth , but their abilities to specifically treat children and adolescents presenting due to psychotic symptoms have not been rigorously studied . Subjects , selected because of prominent positive psychotic symptoms , were r and omly assigned to double-blind , parallel treatment with risperidone , olanzapine , or haloperidol for 8 weeks . The primary outcome was reduction in the Brief Psychiatric Rating Scale for Children total score from baseline to termination . An exploratory , descriptive analysis was done to compare the three treatments . A total of 50 patients , 8–19 years , participated . All treatments reduced symptoms significantly with p-values ( corrected for multiple comparisons ) of 0.0018 for each of the atypical agents and 0.012 for haloperidol . In all , 88 % of subjects treated with olanzapine  , 74 % treated with  risperidone , and 53 % treated with haloperidol met response criteria . The primary side effects observed in all patients were mild to moderate sedation , extrapyramidal symptoms , and weight gain .  Risperidone and olanzapine  acutely reduced psychotic symptoms in this pediatric sample . Exploratory comparisons indicate the magnitude of the antipsychotic response with these atypical agents is comparable to that observed with haloperidol . However , youth treated with risperidone and olanzapine experienced weight gain and extrapyramidal effects that appear more prevalent and severe than reported in adults BACKGROUND Despite several treatmentoptions , adherenceto therapy is poor in patients with bipolar disorder . AIMS A double-blind , controlled comparison of aripiprazole and haloperidol in patients with bipolar I disorder experiencing acute manic or mixed episodes . METHOD Patients ( n=347 ) were r and omised to receive aripiprazole or haloperidol  in this 12-week , multicentre study . The primary outcome measure was the number of patients in response ( greater , similar 50 % improvement from baseline in Young Mania Rating Scale score ) and receiving therapy at week 12 . RESULTS At week 12 , significantly more patients taking aripiprazole ( 49.7 % ) were in response and receiving therapy compared with those taking haloperidol ( 28.4 % ; P < 0.001 ) . Continuation rates differed markedly between treatments ( week 12 : aripiprazole , 50.9 % ; haloperidol , 29.1 % ) . Extrapyramidal adverse events were more frequent with haloperidol than aripiprazole ( 62.7 % v. 24.0 % ) . CONCLUSIONS Aripiprazole showed superior levels of response and tolerability to haloperidol in the treatment of an acute manic episode for up to 12 weeks 1 . Twelve healthy male volunteers participated in four experimental occasions during each of which they were dosed with one of the following anti-psychotic drugs : chlorpromazine ( 50 mg ) , haloperidol ( 3 mg ) , sulpiride ( 400 mg ) and placebo . Drugs were allocated to subjects in a double-blind , crossover fashion . 2 . The subject 's mood state , psychometric performance and electroencephalogram ( EEG ) were assessed pre-dose , and at 2 , 4 , 6 , 8 , 24 and 48 h post-dose . Mood states were assessed using 16 visual analogue scales and psychomotor performance was measured using the following tests : elapsed time estimation , tapping rate , choice reaction times , a rapid information processing task , flash fusion threshold , a manipulative motor task , digit span , body sway and tremor . 3 . Chlorpromazine and haloperidol significantly reduced subjective ratings of ' alertness ' and ' contentedness ' , and haloperidol significantly reduced feelings of ' calmness ' .  Sulpiride did not significantly affect any of the visual analogue scales . 4 . All three anti-psychotic drugs had similar EEG effects with peak effect 2 to 4 h postdose . The profile was characterised by an increase in the proportion of slow wave activity ( delta and theta ) as well as decreased alpha ( 8 - 14 Hz ) and faster ( beta ) wave activity . 5 . Chlorpromazine reduced tapping rate and increased choice reaction movement times . Haloperidol reduced the flash fusion threshold frequency at 6 h post-dose . Sulpiride prolonged the duration of the manipulative motor task , particularly at 48 h post-dose . 6 . All three anti-psychotic drugs impaired performance on the rapid information processing task . Chlorpromazine significantly reduced the number of correct letter pair identification s at 2 , 4 and 6 h post-dose , haloperidol at 4 , 6 , 8 , 24 and 48 h post-dose , and sulpiride at 24 h post-dose . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To evaluate the efficacy and tolerability of topiramate monotherapy in adults with acute manic or mixed episodes of bipolar I disorder . METHODS In four trials , adults hospitalized with acute mania , a diagnosis of bipolar I disorder , history of > or = 1 previous manic or mixed episodes , and > or = 20 Young Mania Rating Scale ( YMRS ) score were r and omized to double-blind treatment with topiramate ( target doses : 200 , 400 , or 600 mg/day ) or placebo ; two trials included an active comparator ( lithium , 1500 mg/day ) . The core study duration in all trials was 3 weeks ; three trials also had 9-week double-blind extensions . The primary efficacy variable was mean change from baseline in YMRS in the core 3-week study . RESULTS Changes in YMRS score during 3 weeks were not significantly different for topiramate versus placebo ( mean YMRS reductions , -5.1 to -8.4 ) . Mean YMRS reductions in lithium-treated groups were significantly greater ( p < or = 0.001 versus placebo and topiramate ) . A similar pattern was observed after 12 weeks of double-blind treatment in studies with double-blind extensions . Paresthesia , appetite decrease , dry mouth , and weight loss were more frequently associated with topiramate than with placebo . CONCLUSIONS These studies do not support the efficacy of topiramate as monotherapy in acute mania or mixed episodes in adults with bipolar I disorder . Topiramate was not associated with mood destabilization measured as mania exacerbation or treatment-emergent depression . Lithium was confirmed as an effective therapy in this population In a double-blind , between-patient clinical trial carbamazepine ( CBZ ) ( n = 8) was compared to haloperidol ( HP ) ( n = 9 ) in patients presenting with mania ( DSM III ) . Seven patients on HP and 2 on CBZ  failed to complete 4 weeks treatment . In 4 of the  HP  group this was because of extrapyramidal side-effects ( EPS ) . Two patients on CBZ and 2 on HP were withdrawn because of lack of efficacy . Statistically significant clinical improvement was seen in both groups within the first 2 weeks of treatment with HP acting more quickly . In addition to EPS which occurred in HP patients , drowsiness was experienced in 4 on CBZ and 3 on HP , and gastrointestinal symptoms in 3 on CBZ . No serious haematological changes , nor abnormalities in clinical chemistry occurred in either group . We conclude that CBZ appears to be a potentially useful drug in the treatment of acute mania BACKGROUND Severe mania is life-threatening , carries an increased risk of suicide and has a serious impact on patients and their families . Efficient and rapid control of episodes of acute mania is needed . AIMS To evaluate the safety and efficacy of risperidone monotherapy for acute mania . METHOD In a 3-week , r and omised , double-blind trial , 290 in- patients with bipolar I disorder with current manic or mixed episode and a baseline Young Mania Rating Scale ( YMRS ) score of 20 or more received flexible doses of risperidone ( 1 - 6 mg per day ) or placebo . RESULTS Risperidone was received by 146 patients and placebo by144 . Their mean baseline YMRS score was 37.2 ( s.e.=0.5 ) . Significantly greater improvements were observed with risperidone than with placebo at weeks 1 and 2 and at end-point ( total YMRS : P < 0.01 ) . Extrapyramidal symptoms were the most frequently reported adverse events in the risperidone group . CONCLUSIONS In patients with severe manic symptoms , risperidone produced significant improvements in YMRS scores as early as week 1 and substantial changes at end-point . Treatment was well tolerated
There is some evidence that haloperidol is an effective treatment for  acute mania .
From the limited data available , there was no difference in overall efficacy of treatment between haloperidol and olanzapine or risperidone .
Some evidence suggests that haloperidol could be less effective than aripiprazole .
BACKGROUND The main objectives in treating mania are to control dangerous behaviour , reduce suicide , produce appropriate acute sedation and shorten the episode of mood disturbance .
Among different drugs , haloperidol has for many years been used in treating psychotic patients , but it has a troublesome side effect profile .
OBJECTIVES To assess the effects of haloperidol for the treatment of mania in comparison with placebo or other active drugs , either as monotherapy or add-on treatment .