Are Low Doses of Antipsychotics Effective in the Management of Psychomotor Agitation? A Randomized, Rated-Blind Trial of 4 Intramuscular Interventions TREC-Rio trial: a randomised controlled trial for rapid tranquillisation for agitated patients in emergency psychiatric rooms [ISRCTN44153243] Psychomotor agitation in major depressive disorder is a predictive factor of mood-switching. Incorrect use of thromboprophylaxis for venous thromboembolism in medical and surgical patients: results of a multicentric, observational and cross-sectional study in Brazil. Does psychomotor agitation in major depressive episodes indicate bipolarity? Predictors of an acute antidepressant response to fluoxetine and sertraline. Non-pharmacological management of behavioural symptoms in nursing homes. Aromatherapy as a safe and effective treatment for the management of agitation in severe dementia: the results of a double-blind, placebo-controlled trial with Melissa. Acupuncture and Acupressure for Dementia Behavioral and Psychological Symptoms: A Scoping Review. A Prospective Cohort Study of Emergence Agitation in the Pediatric Postanesthesia Care Unit Efficacy of Topiramate, Valproate, and Their Combination on Aggression/Agitation Behavior in Patients With Psychosis Agitation in nursing home residents with dementia (VIDEANT trial): effects of a cluster-randomized, controlled, guideline implementation trial. Effects of dexmedetomidine on delirium duration of non-intubated ICU patients (4D trial): study protocol for a randomized trial The impact of reboxetine and mirtazapine on driving simulator performance and psychomotor function in depressed patients. Is Baseline Agitation a Relative Contraindication for a Selective Serotonin Reuptake Inhibitor: A Comparative Trial of Fluoxetine Versus Imipramine Information needs in the management of osteoporosis in family practice: an illustration of the failure of the current guideline implementation process [Effect of a non-pharmacological intervention, Voix d'Or(®), on behavior disturbances in Alzheimer disease and associated disorders]. Medication development for agitation and aggression in Alzheimer disease: review and discussion of recent randomized clinical trial design. Current practices in managing acutely disturbed patients at three hospitals in Rio de Janeiro-Brazil: a prevalence study A randomized crossover trial to study the effect of personalized, one-to-one interaction using Montessori-based activities on agitation, affect, and engagement in nursing home residents with Dementia. [Principles of clinical pharmacology]. Comparative trial of intravenous lorazepam and clonazepam im status epilepticus. Rapid tranquillisation in psychiatric emergency settings in Brazil: pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol plus promethazine
Background Psychomotor agitation can be associated with a wide range of medical conditions . Although clinical practice advocates the use of several drugs for the management of psychomotor agitation , there are still very few controlled studies comparing the profiles of action and the adverse effects of different drugs that induce tranquilization . Objectives The purpose of this study was to compare the efficacy and safety of 4 low-dose pharmacological interventions used to control psychomotor agitation guided by the clinical response . Methods Using a r and omized , rated-blind design , 100 agitated patients were assigned to receive 1 of 4 treatments : haloperidol ( 2.5 mg ) + promethazine ( 25 mg ) ( HLP + PMZ ) , haloperidol ( 2.5 mg ) + midazolam ( 7.5 mg ) ( HLP + MID ) , ziprasidone ( 10 mg ) ( ZIP ) , or olanzapine ( 10 mg ) ( OLP ) . Patients were evaluated just before the intervention and after 30 , 60 , and 90 minutes , using the Agitation-Calmness Evaluating Scale . Adverse effects were assessed within 24 hours after the intervention , using selected items from the UKU Scale ( Ugvalg Klinisk Undersgelser Side Effect Scale ) . According to the clinical indication , medication could be repeated twice after the first injection . Data were analyzed using general linear model with repeated measures and logistic regression . Results All treatment options promoted a reduction in agitation , without causing excessive sedation , although a lower reduction in agitation was observed with HLP + PMZ and ZIP compared with HLP + MID and OLZ . The need for an additional dose of medication was observed in 22 patients , and only 8 remained agitated during the entire 90-minute period . A higher risk for the development of extrapyramidal symptoms within the following 24 hours was observed with HLP + PMZ . Discussion Low doses of haloperidol combined with midazolam can be as effective as olanzapine in reducing psychomotor agitation without increasing the risk of extrapyramidal effects . Because of the higher risk for the occurrence of extrapyramidal symptoms , the combination of haloperidol with promethazine should be considered a second-line treatment option Background Agitated or violent patients constitute 10 % of all emergency psychiatric treatment . Management guidelines , the preferred treatment of clinicians and clinical practice all differ . Systematic review s show that all relevant studies are small and none are likely to have adequate power to show true differences between treatments . Worldwide , current treatment is not based on evidence from r and omised trials . In Brazil , the combination haloperidol-promethazine is frequently used , but no studies involving this mix exist . Methods TREC-Rio ( Tranquilização Rápida-Ensaio Clínico [ Translation : Rapid Tranquillisation- Clinical Trial ] ) will compare midazolam with haloperidol-promethazine mix for treatment of agitated patients in emergency psychiatric rooms of Rio de Janeiro , Brazil . TREC-Rio is a r and omised , controlled , pragmatic and open study . Primary measure of outcome is tranquillisation at 20 minutes but effects on other measures of morbidity will also be assessed . TREC-Rio will involve the collaboration of as many health care professionals based in four psychiatric emergency rooms of Rio as possible . Because the design of this trial does not substantially complicate clinical management , and in several aspects simplifies it , the study can be large , and treatments used in everyday practice can be evaluated BACKGROUND The relationship between psychomotor agitation in unipolar depression and mood-switching from depression to manic , hypomanic and mixed states has been controversial . We investigated the future risk of initial mood-switching as a function of psychomotor agitation in unipolar depression . METHODS We identified 189 participants diagnosed with major depressive disorder ( MDD ) . We divided all patients with MDD into two categories ( 1 ) agitated patients ( n=74 ) , and ( 2 ) non-agitated patients ( n=115 ) . These groups were prospect ively followed and compared by time to mood-switching . Kaplan-Meier survival curves , log-rank test for trend for survivor functions , and Cox proportional hazard ratio estimates for a multivariate model were conducted to examine the risk of mood-switching by psychomotor agitation . RESULTS During follow-up , mood-switching occurred in 20.3 % of the agitated patients and 7.0 % of the non-agitated patients . In the Kaplan-Meier survival estimates for time to incidence of mood-switching with agitated or non-agitated patients , the cumulative probability of developing mood-switching for agitated patients was higher than those for non-agitated patients ( log-rank test : χ(2)=7.148 , df=1 , p=0.008 ) . Survival analysis was also performed using Cox proportional hazards regression within a multivariate model . The agitation remained significantly associated with incidence of mood-switching ( HR=2.98 , 95 % CI : 1.18 - 7.51 ) . LIMITATIONS We did not make a clear distinction between antidepressant-induced mood-switching and spontaneous switching . CONCLUSIONS The main finding demonstrated that MDD patients with agitation were nearly threefold as likely to experience mood-switching , suggesting that psychomotor agitation in MDD may be related to an indicator of bipolarity OBJECTIVES Although effective strategies for the prevention of venous thromboembolism ( VTE ) are widely available , a significant number of patients still develop VTE because appropriate thromboprophylaxis is not correctly prescribed . We conducted this study to estimate the risk profile for VTE and the employment of adequate thromboprophylaxis procedures in patients admitted to hospitals in the state of São Paulo , Brazil . METHODS Four hospitals were included in this study . Data on risk factors for VTE and prescription of pharmacological and non-pharmacological thromboprophylaxis were collected from 1454 r and omly chosen patients ( 589 surgical and 865 clinical ) . Case report forms were filled according to medical and nursing records . Physicians were unaware of the survey . Three risk assessment models were used : American College of Chest Physicians ( ACCP ) Guidelines , Caprini score , and the International Union of Angiololy Consensus Statement ( IUAS ) . The ACCP score classifies VTE risk in surgical patients and the others classify VTE risk in surgical and clinical patients . Contingency tables were built presenting the joined distribution of the risk score and the prescription of any pharmacological and non-pharmacological thromboprophylaxis ( yes or no ) . RESULTS According to the Caprini score , 29 % of the patients with the highest risk for VTE were not prescribed any thromboprophylaxis .  Considering the patients under moderate , high or highest risk who should be receiving prophylaxis , 37 % and 29 % were not prescribed thromboprophylaxis according to ACCP ( surgical patients ) and IUAS risk scores , respectively . In contrast , 27 % and 42 % of the patients at low risk of VTE , according to Caprini and IUAS scores , respectively , had thromboprophylaxis prescribed . CONCLUSION Despite the existence of several guidelines , this study demonstrates that adequate thromboprophylaxis is not correctly prescribed : high-risk patients are under-treated and low-risk patients are over-treated . This condition must be changed to insure that patients receive adequate treatment for the prevention of thromboembolism Abstract Background Kraepelin ’s partial interpretation of agitated depression  as a mixed state of “ manic-depressive insanity ” ( including the current concept of bipolar disorder ) has recently been the focus of much research . This paper tested whether , how , and to what extent both psychomotor symptoms , agitation and retardation in depression are related to bipolarity and anxiety . Method The prospect i ve Zurich Study assessed psychiatric and somatic syndromes in a community sample of young adults ( N = 591 ) ( aged 20 at first interview ) by six interviews over 20 years ( 1979–1999 ) .  Psychomotor symptoms of agitation and retardation were assessed by professional interviewers from age 22 to 40 ( five interviews ) on the basis of the observed and reported behaviour within the interview section on depression . Psychiatric diagnoses were strictly operationalised and , in the case of bipolar-II disorder , were broader than proposed by DSM-IV-TR and ICD-10 . As indicators of bipolarity , the association with bipolar disorder , a family history of mania/hypomania/cyclothymia , together with hypomanic and cyclothymic temperament as assessed by the general  behavior inventory  ( GBI ) [ 15 ] , and mood lability ( an element of cyclothymic temperament ) were used . Results Agitated and retarded depressive states were equally associated with the indicators of bipolarity and with anxiety . Longitudinally , agitation and retardation were significantly associated with each other ( OR = 1.8 , 95 % CI = 1.0–3.2 ) , and this combined group of major depressives showed stronger associations with bipolarity , with both hypomanic/cyclothymic and depressive temperamental traits , and with anxiety . Among agitated , non-retarded depressives , unipolar mood disorder was even twice as common as bipolar mood disorder . Conclusion Combined agitated and retarded major depressive states are more often bipolar than unipolar , but , in general , agitated depression ( with or without retardation ) is not more frequently bipolar than retarded depression ( with or without agitation ) , and pure agitated depression is even much less frequently bipolar than unipolar . The findings do not support the hypothesis that agitated depressive syndromes are mixed states . Limitations The results are limited to a population up to the age of 40 ; bipolar-I disorders could not be analysed ( small N ) Sertraline and fluoxetine have different pharmacologic and pharmacokinetic profiles which may be of clinical relevance in the determination of response in different subtypes of depression . A r and omized , double-blind , 6-week study comparing sertraline ( 50 - 100 mg/day ) with fluoxetine ( 20 - 40 mg/day ) in 286 out patients with major depression , who had demonstrated comparable efficacy and tolerability for the two drugs , was analysed by subgroups of patients at baseline with melancholia , severe depression , single depressive episode , multiple depressive episodes , high anxiety , low anxiety , psychomotor retardation and psychomotor agitation . Multiple logistic regression with regressors including treatment-by-subgroup variables revealed that , within certain subgroups , the efficacy might differ substantially from that of the whole treatment group . However , the only treatment-by-subgroup interaction term that was significant was anxiety ( P < 0.05 ) . There was no evidence of interaction in single or recurrent episode subgroups , and these were not included in subsequent analyses . Subsequent two- sample statistical comparison tests of response ( i.e. Hamilton Depression Scale reduction > or = 50 % ) rates at study endpoint between treatment groups demonstrated that patients with melancholic depression and those with symptoms of psychomotor agitation yielded a significantly greater proportion of responders with sertraline compared to fluoxetine ( P < 0.05 ) . Response rates in sertraline- and fluoxetine-treated patients , respectively , were : overall study 59 % , 51 % ; melancholia 59 % , 44 % ; severe depression 59 % , 41 % ; low anxiety 71 % , 55 % ; high anxiety 47 % , 48 % ; psychomotor retardation , 48 % , 46 % ; and psychomotor agitation 62 % , 39 % . Multiple logistic regression adjusting for possible confounding factors , that included a treatment by anxiety interaction term , also led to similar findings . In particular , the analysis showed that significant differences existed in favour of sertraline in patients with low anxiety in the melancholia and severe depression subgroups ( P < 0.05 ) , indicating that these characteristics predicted a superior response to 6 weeks of treatment with sertraline relative to fluoxetine . Sertraline also demonstrated advantages over fluoxetine on parameters such as sleep and weight disturbance in severely depressed patients , and sleep disturbance , weight , cognitive disturbance and retardation in melancholic patients BACKGROUND Behavioural and psychological symptoms of dementia ( BPSD ) are often reported in institutions for the elderly . OBJECTIVE To evaluate the effectiveness of a staff education intervention to manage BPSD in older people with a diagnosis of dementia . METHODS The trial was conducted in 16 nursing homes ; 306 patients with a diagnosis of dementia and presenting BPSD were selected . Nursing homes were r and omly allocated to an intervention group or a control group . An 8-week staff education and training programme was conducted in the nursing homes in the intervention group . The main outcome measures were the Cohen-Mansfield Agitation Inventory ( CMAI ) and an Observation Scale ( OS ) score . Assessment s were done at baseline ( W0 ) , at the end of the ' intervention ' period ( W8 ) and 12 weeks after ( W20 ) . RESULTS There was a significant decrease in the global CMAI score between baseline and W8 ( -7.8 ; p > 0.01 ) and between baseline and W20 ( -6.5 ; p > 0.01 ) in the intervention group but not in the control group . Results of mixed linear models showed that the CMAI global score , the CMAI physically non-aggressive behaviours subscale score and verbally non-aggressive behaviours subscale score significantly decreased in the intervention group ( p < 0.001 ) although there was no significant evolution in the control group . Direct assessment with the OS produced the same pattern of results , with a significant decrease only in the intervention group . CONCLUSION The intervention reduced BPSD in severely demented nursing home residents and this effect was still present 3 months after the end of the programme BACKGROUND Behavioral and psychological symptoms in dementia are frequent and are a major management problem , especially for patients with severe cognitive impairment . Preliminary reports have indicated positive effects of aromatherapy using select essential oils , but there are no adequately powered placebo-controlled trials . We conducted a placebo-controlled trial to determine the value of aromatherapy with essential oil of Melissa officinalis ( lemon balm ) for agitation in people with severe dementia . METHOD Seventy-two people residing in National Health Service ( U.K. ) care facilities who had clinical ly significant agitation in the context of severe dementia were r and omly assigned to aromatherapy with Melissa essential oil ( N = 36 ) or placebo ( sunflower oil ) ( N = 36 ) . The active treatment or placebo oil was combined with a base lotion and applied to patients ' faces and arms twice a day by caregiving staff . Changes in clinical ly significant agitation ( Cohen-Mansfield Agitation Inventory [ CMAI ] ) and quality of life indices ( percentage of time spent socially withdrawn and percentage of time engaged in constructive activities , measured with Dementia Care Mapping ) were compared between the 2 groups over a 4-week period of treatment . RESULTS Seventy-one patients completed the trial . No significant side effects were observed . Sixty percent ( 21/35 ) of the active treatment group and 14 % ( 5/36 ) of the placebo-treated group experienced a 30 % reduction of CMAI score , with an overall improvement in agitation ( mean reduction in CMAI score ) of 35 % in patients receiving Melissa balm essential oil and 11 % in those treated with placebo ( Mann-Whitney U test ; Z = 4.1 , p < .0001 ) . Quality of life indices also improved significantly more in people receiving essential balm oil ( Mann-Whitney U test ; percentage of time spent socially withdrawn : Z = 2.6 , p = .005 ; percentage of time engaged in constructive activities : Z = 3.5 , p = .001 ) . CONCLUSION The finding that aromatherapy with essential balm oil is a safe and effective treatment for clinical ly significant agitation in people with severe dementia , with additional benefits for key quality of life parameters , indicates the need for further controlled trials Due to the dangers associated with psychotropic medications , there is an urgent need for non-pharmacologic therapies to treat behavioral and psychological symptoms of dementia ( BPSD ) . Acupuncture and acupressure are safe and well-tolerated non-pharmacologic therapies for this population , but currently no review has explored acutherapy for management of distressing dementia symptoms . This review synthesizes research on acupuncture and acupressure for BPSD . Upon search ing five data bases , 15 studies met inclusion /exclusion criteria . Nine examined acupressure , six acupuncture , and eight were r and omized controlled trials . The percent of studies demonstrating statistically significant improvements in symptoms were : activities of daily living ( ADLs ; 75 % ) , agitation ( 100 % ) , anxiety ( 67 % ) , depression ( 100 % ) , mood ( 100 % ) , neuropsychological disturbances ( 67 % ) , and sleep disturbances ( 100 % ) . Variations in study design , intervention procedures , and outcomes limit interpretations about effectiveness . It is recommended that further research be done to examine the efficacy of these therapies and promote generalizability Emergence agitation ( EA ) is a postanesthetic problem that interferes with a child ’s recovery and presents a challenge in terms of assessment and management . In this prospect i ve cohort study , we sought to determine the incidence of EA , evaluate factors associated with and predictive of EA , and describe associated outcomes in healthy children . Children aged 3–7 yr who were undergoing general anesthesia for elective outpatient procedures were included . All perioperative care was documented , and postoperative behaviors in the postanesthesia care unit were recorded . Parents completed the Behavioral Style Question naire for 3- to 7-yr-olds . Five-hundred-twenty-one children were studied , of whom 96 ( 18 % )  had EA . Agitation lasted up to 45 min in some cases ( range , 3–45 min ; mean , 14 ± 11 min ) , required pharmacologic intervention in 52 % of children , and was associated with a prolonged postanesthesia care unit stay ( 117 ± 66 min versus 101 ± 61 min for nonagitated children ; P = 0.02 ) . Ten factors were found to be associated with EA , including age , previous surgery , adaptability , ophthalmology and otorhinolaryngology procedures , sevoflurane , isoflurane , sevoflurane/isoflurane , analgesics , and time to awakening . Of these , otorhinolaryngology procedures , time to awakening , and isoflurane were shown to be independent risk factors . IMPLICATION S : Children may become agitated after general anesthesia . This study describes several factors that may increase the risk for agitation . These data are important in planning anesthesia care for young children Abstract : Topiramate is an antiepileptic drug , recently also used in the treatment of psychiatric diseases . Inasmuch as topiramate and valproate , which are currently used for aggressive behavior , share several pharmacological mechanisms ( positive modulatory effect on the GABA activity and negative modulatory effect on glutamatergic neurotransmission ) , the objective of the present study was to compare the pharmacological effects of topiramate with those of valproate and their combination in patients with psychiatric disorders showing marked aggression and agitation . A retrospective , case-controlled , mirror-image study was carried out in a sample of 45 in patients affected by schizophrenia , schizoaffective and bipolar disorder , and hospitalized in a maximum-security Canadian psychiatry hospital .  Overt Aggression Scale , Agitation-Calmness Evaluation Scale , number and intensity of psychotic episodes , number of episodes of withdrawal from group activities per week , and number of therapeutic isolation per week and of strict surveillance intervention per week were evaluated before and after the treatments . Results indicate that patients treated with topiramate show a decrease in the average score of the Overt Aggression Scale , a decrease of episodes of agitation and of strict surveillance interventions . This effect was similar to the group treated with valproate or with the combination of valproate-topiramate . However , valproate therapy , but not topiramate therapy , decreased the intensity of agitation episodes measured by the Agitation-Calmness Evaluation Scale ;  valproate and the combination topiramate-valproate decreased the number of psychotic disorganization episodes as well . These results suggest that topiramate could be a valid medicine in the control of aggression in psychosis . Double-blind , r and omized , placebo-controlled studies need to further assess this pharmacological indication OBJECTIVE To test the effect of a complex guideline -based intervention on agitation and psychotropic prescriptions . DESIGN , SETTING , PARTICIPANTS Cluster r and omized controlled trial ( VIDEANT ) with blinded assessment of outcome in 18 nursing homes in Berlin , Germany , comprising 304 dementia patients . INTERVENTION Training , support , and activity therapy intervention , delivered at the level of each nursing home , focusing on the management of agitation in dementia . Control group nursing homes  received treatment as usual . MEASUREMENTS Levels of agitated and disruptive behavior ( Cohen-Mansfield agitation inventory [ CMAI ] ) as the primary outcome . Number of neuroleptics , antidepressants , and cholinesterase inhibitors ( ChEIs ) prescribed in defined daily dosages ( DDDs ) . RESULTS Of 326 patients screened , 304 ( 93.3 % ) were eligible and cluster-r and omized to 9 intervention ( n = 163 ) and 9 control ( n = 141 ) nursing homes . Data were collected from 287 ( 94.4 % ) patients at 10 months . At 10 months , compared with controls , nursing home residents with dementia in the intervention group exhibited significantly less agitation as measured with the CMAI ( adjusted mean difference , 6.24 ; 95 % CI 2.03 - 14.14 ; P = .009 ; Cohen 's d = 0.43 ) , received fewer neuroleptics ( P < .05 ) , more  ChEIs  ( P < .05 ) , and more antidepressants ( P < .05 ) . CONCLUSION Complex guideline -based interventions are effective in reducing agitated and disruptive behavior in nursing home residents with dementia . At the same time , increased prescription of ChEIs and antidepressants together with decreased neuroleptic prescription suggests an effect toward guideline -based pharmacotherapy Background Delirium during intensive care unit ( ICU ) stay is frequent and associated with significant morbidity , mortality and healthcare-related costs . International guidelines suggest its prevention . However , curative treatment remains unclearly established . Despite contradictory and ambiguous academic literature , international guidelines suggest the use of second-generation ( atypical ) antipsychotics over haloperidol . However , haloperidol remains the most widely used neuroleptic worldwide as a first-line treatment of agitation and /or delirium . Dexmedetomidine , an alpha2-adrenergic receptors agonist , has shown its efficiency in the treatment of delirium in intubated patients but also in its prevention . Dexmedetomidine represents a widely used alternative to haloperidol . Only few studies have compared the efficacy of dexmedetomidine in non-intubated ICU patients as a first-line curative treatment of delirium . The main objective of the 4D trial is to demonstrate that dexmedetomidine  decreases delirium duration compared to placebo . Methods / design The 4D trial is an investigator-initiated , prospect i ve , multicenter , r and omized , double-blinded , two-arm trial , r and omizing 300 non-intubated ICU patients with a diagnosis of agitated delirium to receive  dexmedetomidine or placebo as a cure . In case of agitation ( RASS≥ + 2 ) , immediate haloperidol administration will be allowed , to protect patient and staff in charge , while waiting for study treatment action . The primary outcome measure is a composite of duration of agitation or delirium or the use of intubation with deep sedation and mechanical ventilation . Secondary outcomes include mortalities at 7 and 30 days , ICU length of stay and occurrence of adverse effects related to dexmedetomidine use ( bradycardia or hypotension requesting any treatment ; or haloperidol use ( neuroleptic malignant syndrome , extrapyramidal syndrome , prolonged QTc ) . The sample size will allow the detection of a 50 % decrease of agitation duration ( 120 min ) , of an absolute reduction of delirium duration ( 1 day ) and of a 50 % relative decrease of intubation and mechanical ventilation , with a type 1 error rate of 1.8 % ( error risk inflation due to components of composite ) and power of 90 % , assuming a 15 % incidence of intubation and mechanical ventilation requirements , an agitation duration of 240 min and a delirium duration of 3 days . One hundred and ten patients by group will be needed . An intermediate analysis is scheduled and requires the inclusion of 150 patients . Discussion The 4D trial may provide important data on the safety of commonly used sedative dexmedetomidine and could have a significant impact on future treatment of non-intubated ICU patients presenting with agitated delirium . Trial registration Clinical Trials.gov , ID : NCT 03317067 . Registered on 23 October 2017 OBJECTIVE The aim of the present study was to examine the influence of reboxetine and mirtazapine on psychomotor functions related to driving skills and on driving simulator performance in depressed in patients . METHOD Forty depressed in patients diagnosed according to DSM-IV-TR criteria were r and omly assigned to treatment with either reboxetine ( N = 20 ) or mirtazapine ( N = 20 ) . To control for retest effects in psychomotor measures , a group of 10 healthy controls was examined on the same time schedule . Participants were tested once before pharmacologic treatment and twice after initiation of treatment ( days 7 and 14 ) with computerized tests related to car-driving skills .  Data were collected with the Act and React Testsystem ART-90 and the Wiener Testsystem , measuring visual perception , reactivity , stress tolerance , concentration , and vigilance . In addition , patients went through various risk simulations on a static driving simulator . Data were analyzed with nonparametric statistics and repeated- measures analysis of variance . The study was conducted from June 2004 through June 2006 . RESULTS Before onset of treatment with antidepressants , about 65 % of patients did not reach the threshold criterion according to the German guidelines for road and traffic safety . After 14 days of treatment with reboxetine or mirtazapine , patients improved in driving ability skills . Controlling for retest effects in psychomotor measures , data indicate that both patient groups significantly improved in tests measuring selective attention and reactivity ( all p < .01 ) . Furthermore , the frequency of accidents in the risk simulations markedly decreased in patients receiving mirtazapine and reboxetine ( all p < .05 ) . Statistically significant differences between treatment groups could not be shown . CONCLUSION Our results indicate that partially remitted depressed in patients treated with reboxetine or mirtazapine show a better performance on tasks related to driving skills than do untreated depressives A common presentation for major depression includes psychomotor agitation . However , this subtype has been the infrequent subject of controlled investigation during depression trials . Yet , the subcategorization of agitated depression has historically been associated with the belief that older , sedating compounds have a superior risk : benefit profile . In the 8-week , double-blind , r and omized , parallel trial , 124 subjects with Research Diagnostic Criteria -compatible agitated depression were r and omized to either imipramine ( IMI ) or fluoxetine ( FLU ) . Both compounds proved to be similarly effective as measured by change in HAM-D17 , HAM-D17 response , and HAM-D17 remission rates . Similar comparability was seen in secondary measures of agitation , anxiety , suicidality , and global impressions . However , of note , a statistically significant difference in early discontinuations because of intolerable adverse events emerged . Whereas 43.5 % of IMI subjects discontinued early , only 9.7 % of FLU subjects ( p < 0.001 ) did . Significantly more central nervous system events characterized the IMI than the FLU subgroup ( IMI , 24.2 % , vs. FLU , 6.5 % ; p = 0.006 ) . In conclusion , among subjects with major depression , subtype agitated , the risk : benefit profile favored FLU over IMI . This was driven by the superior tolerance of FLU . No evidence emerged in support of the clinical hypothesis that a “ sedating ” agent is the treatment of choice for this group . The results are important when striving to maximize compliance with pharmacotherapy in order to minimize recidivism and associated psychological and economic morbidity . ( J Clin Psychopharmacol 1994;14:385–391 The objectives of this study were to determine information needs of family physicians around issues in the management of osteoporosis and preferences for dissemination of this information . A mailed survey was sent to a stratified r and om sample of 1000 family physicians in Ontario in May 2001 . Female physicians and those practicing in rural communities were over- sample d from the College of Family Physicians ' data base . Among the 505 respondents , 364 were still practicing ( 182 males and 182 females ) and completed the full question naire . There were no statistically significant differences in responses by sex or region of practice . Over 80 % of family physicians wanted to be more informed about bone density testing and the pharmacological and non-pharmacological management of osteoporosis .  The presence of risk factors was one of the most influential factors ( 72 % ) for ordering bone density testing . Information in peer- review ed journals was thought to be the most credible , with 80 % rating the CMAJ as very credible compared to 47 % for the Osteoporosis Society of Canada ( OSC ) . Sixty-two percent found the OSC guidelines ( 1996 ) to be useful even though much of that information is now out of date . Almost 70 % had not read the more recently published treatment guidelines from the Ontario Program for Optimal Therapeutics ( 2000 ) . Over 80 % were interested in a decision aid , which incorporates information on risk factors , fracture risk and a treatment algorithm . The perceived need and the lack of availability of clinical ly useful information on osteoporosis for the family practice setting highlights the failure of the current guideline implementation process and provides insight into where the process has to be improved An innovative non-pharmacological intervention called Voix d'Or ( ® ) ( Golden Voice ) was proposed in the Cognitive behavioral unit ( CBU ) of the Memory center at the Hospices civils in Lyon .  Voix d'Or ( ® ) offers eight sound activities disseminated via an audio device based on different approaches sociotherapeutic ( music therapy , reminiscence , relaxation , reorientation in reality ) . The aim of this study was to test the effects of the Voix d'Or ( ® ) program on behavioral and psychological symptoms of dementia ( BPSD ) in patients with Alzheimer 's disease hospitalized in the CBU . Twenty four patients with agitation and /or apathy and /or anxiety and /or depression were included . Patients were r and omly selected in the intervention group exposed to Voix d'Or versus a control group exposed to usual occupational activities . Patients were assessed before ( T0 ) and after ( T1 ) the intervention period . Several variables were measured : frequency and severity of behavioral disorders , anxiety , depression , agitation and apathy . A significant improvement of anxiety level between T0 and T1was observed in the group with Voix d'Or ( ® ) compared to the control group . This study suggests that this non-pharmacological intervention may be beneficial on anxiety in patients with Alzheimer 's disease ABSTRACT Background : The management of disruptive neuropsychiatric symptom ( NPS ) such as agitation and aggression ( A/A ) is a major priority in caring for people with Alzheimer 's disease ( AD ) . Few effective pharmacological or non-pharmacological options are available . Results of r and omized clinical trials ( RCTs ) of drugs for A/A have been disappointing . This may result from the absence of biological efficacy for medications tested in treating A/A. It may also be related to method ological issues such as the choice of outcomes . The aim of this review was to highlight key method ological issues pertaining to RCTs of current and emerging medications for the treatment of A/A in AD . Methods : We search ed PubMed / Medline , Cochrane Central Register of Controlled Trials , and Clinical Trials.gov for RCTs comparing medications with either placebo or other drugs in the treatment of A/A in AD , between January 2008 and December 2013 . Results : We identified a total of 18 RCTs ; of these , 11 were completed and 7 ongoing . Of the ongoing RCTs , only one is in Phase III . Seven of 10 completed RCTs with reported results did not report greater benefit from drug than placebo . Each of the completed RCTs used a different definition of " clinical ly significant A/A. " There was considerable heterogeneity in study design . The primary endpoints were largely proxy-based but a variety of scales were used . The definition of caregiver and scales used to assess caregiver outcomes were similarly heterogeneous . Placebo response was notable in all trials . Conclusions : This review highlights a great heterogeneity in RCTs design of drugs for A/A in AD and some key method ological issues such as definition of A/A , choice of outcome measures and caregiver participation that could be addressed by an expert consensus to optimize future trials design Background The medical management of aggressive and violent behaviour is a critical situation for which there is little evidence . In order to prepare for a r and omised trial , due to start in the psychiatric emergency rooms of Rio de Janeiro in 2001 , a survey of current practice was necessary . Methods A seven day survey of pharmacological management of aggressive people with psychosis in the emergency rooms of all four public psychiatric hospitals in Rio de Janeiro , Brazil . Results In one hospital data were not available . Of the 764 people with psychosis attending these ERs , 74 were given IM medication for rapid tranquillisation ( 9.7 % , 2.1/week/100,000 ) . A haloperidol-promethazine mix ( with or without other drugs ) was used for the majority of patients ( 83 % ) . Conclusion The haloperidol-promethazine mix , given intramuscularly for rapid tranquilization , is prevalent in Rio , where it is considered both safe and efficient . However , scientific evaluation of all pharmacological approaches to rapid tranquilization of psychotic people is inadequate or incomplete and a r and omized trial of IM haloperidol-promethazine is overdue BACKGROUND Increasingly more attention has been paid to non-pharmacological interventions as treatment of agitated behaviors  that accompany dementia . The aim of the current study is to test if personalized one-to-one interaction activities based on Montessori principles will improve agitation , affect , and engagement more than a relevant control condition . METHODS We conducted a r and omized crossover trial in nine residential facilities in metropolitan Melbourne , Australia ( n = 44 ) .  Personalized one-to-one activities that were delivered using Montessori principles were compared with a non-personalized activity to control for the non-specific benefits of one-to-one interaction . Participants were observed 30 minutes before , during , and after the sessions . The presence or absence of a selected physically non-aggressive behavior was noted in every minute , together with the predominant type of affect and engagement . RESULTS Behavior counts fell considerably during both the Montessori and control sessions relative to beforeh and . During Montessori activities , the amount of time spend actively engaged was double compared to during the control condition and participants displayed more positive affect and interest as well . Participants with no fluency in English ( all from non-English speaking background s ) showed a significantly larger reduction in agitation during the Montessori than control sessions . CONCLUSION Our results show that even non-personalized social contact can assist in settling agitated residents . Tailoring activities to residents ' needs and capabilities elicit more positive interactions and are especially suitable for people who have lost fluency in the language spoken predominantly in their residential facility . Future studies could explore implementation by family members and volunteers to avoid dem and s on facilities ' re sources . TRIAL REGISTRATION Australian New Zeal and Clinical Trials Registry - ACTRN12609000564257 626 pages , 2012 , Academic Press , 2012 , Arthur J. Atkinson ( Jr. ) , Shiew-Mei Huang , Principles of Clinical Pharmacology , 0123854717 , 9780123854711 , Principles of Clinical Pharmacology is a successful survey covering the pharmacologic principles underlying the individualization of patient therapy and contemporary drug development . This essential reference continues to focus on the basics of clinical pharmacology for the development , evaluation , and clinical use of pharmaceutical products while also addressing the most recent advances in the field . Written by leading experts in academia , industry , clinical and regulatory setting s , the third edition has been thoroughly up date d to provide readers with an ideal reference covering the wide range of important topics impacting clinical pharmacology as the discipline plays an increasingly significant role in drug development and regulatory science . The Third Edition has been endorsed by the American Society for Clinical Pharmacology and Therapeutics * Includes new chapters on imaging and the pharmacogenetic basis of adverse drug reactions . * Offers an exp and ed regulatory section that addresses US and international issues and guidelines . * Provides extended coverage of earlier chapters on transporters , pharmacogenetics and biomarkers and also illustrates the impact of gender on drug response . * Presents a broadened discussion of clinical trials from Phase 1 to incorporate Phases II and III . file download The primary use of lorazepam , when administered intravenously ( IV ) , has been in the treatment of acute attacks of anxiety and agitation . Recent studies have investigated its efficacy in patients with status epilepticus . The present study compared the efficacy and tolerability of lorazepam and clonazepam in the treatment of status epilepticus . Lorazepam , 4 to 10 mg IV , and /or clonazepam , 1 mg IV , was administered in 61 hospitalized epileptic patients . If needed , the dose of each agent was repeated in 20 minutes . Twenty-two patients were given lorazepam , nine were given  clonazepam , and 30 were given both drugs at different times . Improvement in EEG was greater with lorazepam while the clinical symptoms responded more completely to clonazepam . Both drugs were most effective in patients with secondary generalized epilepsy .  Drowsiness followed either drug . Psychomotor agitation followed either drug in 12 % of patients 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
Verbal de-escalation techniques have been shown to decrease agitation and reduce the potential for associated violence in the emergency setting .
OBJECTIVE To present the essential guidelines for non-pharmacological management of patients with psychomotor agitation in Brazil .