Changes In Agitation Research Articles

Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment, cerebrovascular disease and Parkinson disease: A cross sectional and longitudinal study.

Neuropsychiatric symptoms (NPS) increase risk of developing dementia and are linked to various neurodegenerative conditions, including mild cognitive impairment (MCI due to Alzheimer's disease [AD]), cerebrovascular disease (CVD), and Parkinson's disease (PD). We explored the structural neural correlates of NPS cross-sectionally and longitudinally across various neurodegenerative diagnoses. The study included individuals with MCI due to AD, (n=74), CVD (n=143), and PD (n=137) at baseline, and at 2-years follow-up (MCI due to AD, n=37, CVD n=103, and PD n=84). We assessed the severity of NPS using the Neuropsychiatric Inventory Questionnaire. For brain structure we included cortical thickness and subcortical volume of predefined regions of interest associated with corticolimbic and frontal-executive circuits. Cross-sectional analysis revealed significant negative correlations between appetite with both circuits in the MCI and CVD groups, while apathy was associated with these circuits in both the MCI and PD groups. Longitudinally, changes in apathy scores in the MCI group were negatively linked to the changes of the frontal-executive circuit. In the CVD group, changes in agitation and nighttime behavior were negatively associated with the corticolimbic and frontal-executive circuits, respectively. In the PD group, changes in disinhibition and apathy were positively associated with the corticolimbic and frontal-executive circuits, respectively. The observed correlations suggest that underlying pathological changes in the brain may contribute to alterations in neural activity associated with MBI. Notably, the difference between cross-sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences.

The outcomes of a person-centered, non-pharmacological intervention in reducing agitation in residents with dementia in Australian rural nursing homes

BackgroundThere is limited best- practice evidence to address behavioral and psychiatric symptoms for those with dementia in Australian rural nursing homes. This study aims to evaluate the outcomes of a person-centered, non-pharmacological dementia care model, ‘Harmony in the Bush’, based on the Progressively Lowered Stress Threshold principles and person-centered music in rural Australia.MethodsA quasi-experimental (nonrandomized, pre-post) intervention study was conducted in five rural nursing homes in Queensland and South Australia. Seventy-four residents with dementia participated in this intervention study, which yielded a sample power of 80%. Eighty-seven staff completed the Caregiver Stress Inventory at pre-post four-weeks of intervention. Staff training workshops focused on the theory of the Progressively Lowered Stress Threshold principles and delivery of person-centered care plan with integrated music intervention. We used reported changes in agitation of the residents, measured using Cohen- Mansfield Agitation Inventory, and staff’s caregiving stress, using Caregivers Stress Inventory. This study adheres to the CONSORT guidelines.ResultsMean age of residents with dementia was 82.4 (7.7) years and 69% were females. The mean age of admission was 80.1(8.4) years. Baseline measures indicated that 32.7% had mild- severe pain and 30.5% reported mild-severe sadness. The results showed statistically significant decline in aggressive behaviors, physically non-aggressive behaviors, verbally agitated behavior and hiding and hoarding. There was similar reduction in staff stress in the domains of aggressive behaviors, inappropriate behaviors, resident safety, and resource deficiency.ConclusionsThe Harmony in the Bush model is effective in reducing agitation among dementia residents with significant reduction in staff stress levels in nursing homes in rural Australia.Trial registrationAustralian and New Zealand Clinical Trials Registry (ANZCTR) on 20/2/2018 (Registration No: ACTRN12618000263291p). https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374458

Biomarkers of agitation in moderate‐to‐severe Alzheimer's disease patients enrolled in an RCT with nabilone

AbstractBackgroundBrain cholesterol metabolism, neuroinflammation, and oxidative stress are processes altered during Alzheimer’s disease (AD), which may impede endocannabinoid signaling, and thus worsen agitation. We assessed whether the brain cholesterol metabolite, cerebrocholesterol (Cchol), proinflammatory cytokine, tumor necrosis factor (TNF), and oxidative stress marker, 4‐hydroxynonenal (4‐HNE) were associated with agitation severity and response to nabilone.MethodSerum Cchol, TNF and 4‐HNE, were collected from AD patients enrolled in a 14‐week, double‐blind cross‐over trial comparing 6 weeks of nabilone to placebo, at the start and end of each phase. We assessed the relationship between agitation (Cohen Mansfield Agitation Inventory (CMAI)) and baseline (BL) biomarker levels; the relationship between change in agitation and BL biomarker levels within each phase; and the relationship between change in agitation and change in biomarker levels within each phase. Exploratory analyses included adjustments for BL cognition (Mini‐Mental Status Exam (MMSE)), and analyses with CMAI subtotals consistent with the International Psychogeriatric Association (IPA) definition for agitation.ResultSerum was collected from thirty‐eight participants (mean±SD age=87±10, 77% male, CMAI=68±18, MMSE=6.3±6.3). Cchol was not associated with CMAI cross‐sectionally or longitudinally, before and after adjusting for MMSE. However, BL Cchol was negatively correlated with BL CMAI IPA (F(1,36)=4.95, p=.03). In placebo only, lower BL Cchol was associated with increases in CMAI IPA (b=‐35.2, p=.02), and decreases in Cchol were associated with increases in CMAI IPA (b=‐20.94, p=.03). After adjusting for MMSE, BL TNF was positively correlated with BL CMAI (F(2,25)=3.69, p=.04), and predicted improvements in CMAI during nabilone only (b=‐1.14, p=.045). Decreases in TNF were associated with improvements in CMAI during nabilone only (b=1.12, p=.006). BL 4‐HNE was positively correlated with BL CMAI (F(1,35)=6.41, p=.02), and predicted worsening in CMAI during placebo only (b=0.01, p=.01). Changes in 4‐HNE were not associated with changes in CMAI in either phase.ConclusionCchol, TNF, and 4‐HNE may be markers of agitation severity in AD. Though neither Cchol nor 4‐HNE predicted response to nabilone and did not change over time with nabilone, these markers may be associated with changes in agitation severity. Findings with TNF suggest that this marker predicts treatment response, and decreases with nabilone treatment.

Rumination in the Context of Anger and Sadness: Differential Effects on State Agitation

BackgroundAgitation is an important transdiagnostic factor for several mental health disorders and a significant risk factor for dangerous or maladaptive coping behaviors. How an individual responds to experiences of agitation itself may also play a crucial role in conferring risk towards maladaptive behaviors. Specifically, ruminating on high arousal emotions, such as anger, will also be more likely to initiate and maintain agitation, thereby increasing risk for impulsive and maladaptive behaviors. MethodsUndergraduate students (N=117) were randomly assigned to an emotion induction condition (i.e., control, sadness only, anger only, sadness and anger) followed by either a control condition or a rumination induction. They completed measures on subjective emotional state and agitation at baseline, after emotion induction, after rumination induction, and at the end of session. ResultsAgitation was influenced by negative affect broadly with each experimental condition leading to agitation. Anger influenced momentary change in agitation and sustained agitation when combined with rumination. LimitationsThe majority of participants in the current study were young, white females and the findings may not generalize to individuals of diverse genders and cultures who may have experience and cope with agitation differently. ConclusionsRecognizing and mitigating rumination during moments of anger may help decrease a clients’ use of problematic coping behaviors.

Prescribing Practices of Valproic Acid for Agitation and Delirium in the Intensive Care Unit.

Analgesics, sedatives, and antipsychotics are commonly prescribed for agitation and delirium in the intensive care unit (ICU), but their use is limited by adverse effects and lack of efficacy. Valproic acid is an alternative treatment option. The primary objective of this study was to describe valproic acid prescribing in our institution's ICUs when used for agitation or delirium. Measures of effectiveness and safety were also assessed. This was a single-center, retrospective, institutional review board-approved cohort study of adult inpatients admitted to the ICU between January 2018 and August 2018. Patients who received valproic acid for the treatment of agitation or delirium for ≥24 hours were included. Prescribing practices were evaluated for dose, frequency, and route of administration. Effectiveness was assessed via agitation and delirium assessment tools and quantity of adjunctive agents used. A total of 80 patients were included, with 35 receiving valproic acid alone and 45 in conjunction with antipsychotics. The most common valproic acid regimen was 250 mg orally 3 times daily. Delirium resolution occurred in 55% of patients: 24 in the valproic acid monotherapy group and 20 in the valproic acid plus antipsychotic group (69% vs 44%; P = 0.03). The incidence of delirium decreased from valproic acid day 0 to day 3 (93% vs 68%; P < 0.01), with no change in agitation (64% vs 63%; P = 0.28). Valproic acid is frequently prescribed in agitated, delirious patients at our institution and may have a role in the management of ICU delirium.

Comparative safety and efficacy of pharmacological and non-pharmacological interventions for the behavioral and psychological symptoms of dementia: protocol for a systematic review and network meta-analysis

BackgroundBehavioral and psychological symptoms of dementia (BPSD) are highly prevalent in patients with dementia. Both pharmacological and non-pharmacological strategies are commonly used to treat these symptoms, but their comparative safety and efficacy is unknown.MethodsWe will conduct a systematic review of the published and unpublished literature to retrieve all articles pertaining to outcomes of safety and efficacy associated with pharmacological and non-pharmacological treatments of BPSD for patients living in the community and institutionalized care settings. Our primary outcome of efficacy is a change in aggression. Our primary outcome of safety will be risk of fracture. These primary outcomes were chosen by stakeholders involved in the care of patients experiencing BPSD. Possible secondary outcomes of efficacy will include a change in agitation, depressive symptoms, and night-time behaviors. Possible secondary outcomes of safety will include the risk of stroke, falls, and mortality. All article screening, data abstraction, and risk of bias appraisal will be completed independently by two reviewers. If the assumption of transitivity is valid and the evidence forms a connected network, Bayesian random-effects pairwise and network meta-analyses (NMAs) will be conducted. Relative treatment rankings will be reported with mean ranks and the surface under the cumulative ranking curve.DiscussionWe will identify the safest and most efficacious treatment strategies for patients with BPSD from among our most highly ranked treatments. The results of this study will be used to guide decision-making and improve patient care.Systematic review registrationPROSPERO registry number CRD42017050130.

TIME - Targeted interdisciplinary model for evaluation and treatment of neuropsychiatric symptoms: protocol for an effectiveness-implementation cluster randomized hybrid trial.

BackgroundNearly all persons with dementia will experience neuropsychiatric symptoms (NPS) during the course of their disease. Clinicians and researchers emphasize the need for an evidence-informed standardized approach to managing NPS that integrates pharmacological and nonpharmacological treatments for real-world implementation. The Targeted Interdisciplinary Model for Evaluation and Treatment of Neuropsychiatric Symptoms (TIME) represents such an approach and is a multicomponent intervention based on the theoretical framework of cognitive behavioural therapy.Methods/designThe trial is a 3-month cluster randomized trial conducted in 30 nursing homes including 168 participants with dementia and a high level of agitation. Each nursing home defined as a cluster will be randomized to receive either the TIME intervention (the intervention group) or a brief education-only intervention regarding dementia and NPS (the control group). TIME is a manual-based, multicomponent programme that includes a rigorous assessment, one or more case conferences and the treatment and evaluation of NPS. Patient-level measurements are taken at baseline (prior to randomization) and 8 and 12 weeks later. The primary outcome measure is the change in agitation, as defined by the Neuropsychiatric Inventory-Nursing Home Version, at 8 weeks from baseline. Secondary outcome measures include change in agitation at 12 weeks from baseline, and change from baseline at 8 and 12 weeks in other NPS, quality of life, and the use of psychotropic and analgesic medications. Mixed methods will be used to follow, measure and explore the implementation process and the effect of the intervention at the individual staff level and the organization level. Combining measurements of clinical effectiveness and implementation outcomes define this trial as an effectiveness-implementation hybrid trial.DiscussionMeasuring the implementation and effect of complex interventions aimed at reducing NPS in nursing homes is challenging. In this study protocol, we describe a multicomponent program, TIME, and discuss how an effectiveness-implementation cluster randomized hybrid trial can meet these challenges.Trial registrationClinicalTrials.gov identifier NCT02655003. Registered 6 January 2016.

Effect of Aromatherapy Massage on Agitation and Depressive Mood in Individuals With Dementia.

The current study examined the effects of aromatherapy massage on alleviating agitation and depressive mood in individuals with dementia. A randomized controlled trial and repeated measures design was conducted. A total of 59 participants were randomly assigned to intervention or control groups. The intervention group received aromatherapy massage once per week for 8 weeks. Results indicated no significant changes over time in overall agitation for either group, but agitation decreased from Week 1 to Week 5 for the intervention group. In addition, the overall depressive symptoms decreased significantly over time for the intervention group compared to the control group (p < 0.001). However, changes in agitation within 24 hours following aromatherapy massage showed some significant changes in Weeks 5 and 9. Aromatherapy massage can be an effective and safe intervention to alleviate specific agitated behaviors and depressive mood in individuals with dementia. [Journal of Gerontological Nursing, 42(9), 38-46.].

Pharmacological treatment of acute agitation associated with psychotic and bipolar disorder: a systematic review and meta-analysis.

We used systematic review methodology to identify and evaluate short-term pharmacological interventions for agitation associated with schizophrenia or bipolar disorder. We searched electronic databases for randomised controlled trials involving comparisons between current treatments for agitation, benzodiazepines, antipsychotics and placebo. The patient population was adults with agitation associated with psychotic or bipolar disorder treated in specialist mental health services. The outcome of interest was change in agitation measured by accepted standard scales. Paired meta-analyses and network meta-analyses are presented. Seventeen randomised controlled trials were identified (n = 3841). Treatments included haloperidol, olanzapine, aripiprazole, risperidone and lorazepam. The primary outcome was change in Positive and Negative Syndrome Scale Excited Component scores. Pair-wise comparisons suggest that after 60 min, olanzapine is superior to haloperidol; no other treatment was more effective than any other. At 120 min, loxapine 10 mg is more effective than loxapine 5 mg, and olanzapine is more effective than lorazepam. In the network meta-analyses, no treatment was superior to any other. Because of limitations of available research, firm conclusions could not be drawn regarding the efficacy and safety of any identified intervention. Based on our results, there is no evidence that one drug is more effective or preferred over any other and treatment decisions could be made based on individual patient needs or costs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Principal components analysis of agitation outcomes in Alzheimer's disease

BackgroundWe developed a composite measure of agitation as a secondary outcome of change over time in the Citalopram for Agitation in Alzheimer's disease study (CitAD). CitAD demonstrated a positive effect of citalopram on agitation on the Neurobehavioral Rating Scale agitation subscale (NBRS-A). CitAD included additional agitation measures such as the Cohen-Mansfield Agitation Inventory and the Neuropsychiatric Inventory. MethodsWe performed principal components analyses on change in individual item of these scales for the same, original CitAD subjects. ResultsThe first principal component accounted for 12.6% of the observed variance and was composed of items that appear to reflect agitation. The effect size for citalopram calculated using this component was 0.53 (95% CI 0.22–0.83) versus 0.32 for the NBRS-A (95% CI 0.01–0.62). ConclusionsResults suggest that a composite measure of change in agitation might be more sensitive than change in a single primary agitation measure.

Change in agitation in Alzheimer's disease in the placebo arm of a nine-week controlled trial.

Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD). In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression. Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure. We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.

The effect of music therapy compared with general recreational activities in reducing agitation in people with dementia: a randomised controlled trial

This study aimed to compare the effects of music therapy with general recreational day activities in reducing agitation in people with dementia, residing in nursing home facilities. In a randomised controlled design, residents with dementia (n = 94) were allocated to either music therapy or recreational activities. Both music therapy and general activities were offered twice weekly for 4 months. Changes in agitation were measured with a modified Cohen-Mansfield Agitation Inventory (CMAI) at four intervals on each intervention day. A mixed model analysis was used to evaluate the effectiveness of music therapy, compared with general activities, on CMAI scores at 4 h after the intervention, controlled for CMAI scores at 1 h before the session and session number. Data were analysed for 77 residents (43 randomised to music therapy and 34 to general activities). In both groups, the intervention resulted in a decrease in agitated behaviours from 1 h before to 4 h after each session. This decrease was somewhat greater in the music therapy group than in the general activities group, but this difference was statistically not significant (F = 2.885, p = 0.090) and disappeared completely after adjustment for Global Deterioration Scale stage (F = 1.500; p = 0.222). Both music therapy and recreational activities lead to a short-term decrease in agitation, but there was no additional beneficial effect of music therapy over general activities. More research is required to provide insight in the effects of music therapy in reducing agitation in demented older people.

Serial changes in cerebral blood flow single photon emission computed tomography findings during memory retrieval in a case of psychogenic amnesia

acutely hospitalized after the earthquake to the Fukushima Medical University Hospital. Among 13 patients, five had bipolar I disorder, manic episode. We report a patient among these five patients who exhibited the most intense symptoms. The patient, a 26-year-old man, was diagnosed as having bipolar I disorder and continued regular follow up. His symptoms were stabilized with pharmacotherapy, mainly on lithium and valproate; however, immediately after the earthquake and the following nuclear plant accident, he had insomnia, marked hyperactivity, and talkativeness. Specifically, 3 days after the earthquake, that is, 2 days after the first hydrogen explosion at the plant, he was admitted to our hospital. After admission, he was placed in an isolation room. In addition to mood-stabilizers, antipsychotics, including haloperidol 10 mg/day and zotepine 125 mg/day, were given, but his manic state continued to worsen. The patient exhibited intense agitation, including violently kicking the door of the isolation room. This explosive agitation, peaking on day 7 after the earthquake, gradually decreased, and after day 14, he remarkably calmed down. The consecutive evaluation of the degree of agitation using the Positive and Negative Syndrome Scale-Excited Component showed a parallel change with the increase and reduction curve in the background radiation level measured in our hospital. The changes in agitation were thought not to be a direct response to fear triggered by radiation leakage being reported daily by the media because he was not informed about the reports. Thus, it was speculated to be possible that contact with the psychiatrists and nurses, whose anxiety was increased by the minute-to-minute news of the nuclear power plant accident, in turn affected the patient, thus contributing to the worsening of his symptoms. Previous studies have shown an unexpected worsening of conditions in patients with bipolar disorder after a catastrophic disaster. Such a mechanism may be plausible and bipolar I disorder patients, when they are confronted with threatening situations, switch into a manic mode in order to overcome the danger. Therefore, in bipolar I disorder patients, even when in a stable condition for many years, careful attention must be paid to any sign of worsening on the occasion of catastrophic disasters.

Treatment of delirium with risperidone in cancer patients

Antipsychotic medications have frequently been regarded as the treatment of choice for delirium. This study examined the clinical efficacy of risperidone for the treatment of delirium in cancer patients, combined with a repeated assessment of underlying medical severity levels. The study included consecutive referrals of 29 delirious cancer patients (mean age, 68.9 ± 12.5 years; male, 69%) to the psychiatric consultation service. Risperidone was given orally once per day (mean dosage, 1.4 ± 1.3 mg/day). Study participants were assessed using quantitative standardized scales of cognitive function, delirium, and physical impairment at baseline and at the end of the study (seventh day). Risperidone with routine clinical management was effective for the treatment of delirium: 48% of the patients responded and 38% achieved remission. The reduction of delirium severity occurred in 79% of the patients. Changes in delirium severity were unrelated to age, gender, general cognitive dysfunction, or to severity of attendant medical conditions. In addition to changes in agitation and perceptional disturbances, risperidone was also effective for other specific delirium symptoms. Risperidone with routine clinical management is effective in the treatment of delirium in advanced cancer patients, independent of changes in the underlying medical condition.

Relationship between symptoms of depression and agitation in nursing home residents with dementia

The aim of this study is to analyze modifiable factors related to agitation of nursing home residents with dementia. Relationship of agitation with three modifiable factors (depression, psychosis, and pain) was explored using longitudinal Minimum Data Set (MDS) information from 2032 residents of Dutch nursing homes. Presence of agitation and depression was ascertained using validated scales based on MDS information. Presence of psychosis and pain was ascertained from the individual MDS items. There was a significant correlation between MDS depression and agitation scores. Depression scores increased in residents whose agitation worsened and decreased in residents whose agitation improved. Psychosis scores (combination of delusions and hallucinations) also correlated with MDS depression scores, and psychosis scores increased in residents whose agitation worsened. Pain scores correlated with agitation scores, but the pain scores did not change with changes in agitation. Depression symptoms were present in 51% of residents, while psychotic symptoms were present only in 15% of residents, and two-thirds of these residents were also depressed. These results indicate that depression may be the most common factor associated with agitation in nursing home residents with dementia.

Changes in Nursing Burden Following Memantine for Agitation and Aggression in Long-Term Care Residents with Moderate to Severe Alzheimerʼs Disease

Agitation and aggression are common neuropsychiatric symptoms of Alzheimer's disease (AD) with a negative impact on caregivers. The aim of the study was to determine whether changes in agitation and aggression would follow memantine treatment and, if so, be associated with changes in nursing burden in institutionalized patients with moderate to severe AD. This was a 3-month open-label trial of memantine. The setting was two long-term care facilities. Thirty-one institutionalized patients with moderate to severe AD and significant behavioural and psychiatric symptoms were included in the study. Memantine was titrated to a target dose of 10 mg twice daily. Effectiveness was assessed by the change in the Neuropsychiatric Inventory-Nursing Home (NPI-NH) agitation/aggression subscale and Clinical Global Impression of Change (CGI-C) scale using the intent-to-treat population. To establish caregiver impact, the effect on nursing burden was measured by the Modified Nursing Care Assessment Scale (primary outcome). As a secondary analysis, the caregiver distress subscale of the NPI-NH was examined, as well as changes in as required (pro re nata [prn]) psychotropic medication use. Twenty-four patients completed the study. A significant decrease in agitation and aggression (F-test with 3 and 90 degrees of freedom [F(3,90)] = 3.721, p = 0.014) was demonstrated following memantine, with 48% of patients improving (either much improved or minimally improved) on the CGI-C scale. In addition, nursing burden (t-test with 30 degrees of freedom [t(30)] = 3.02, p = 0.005), caregiver distress (F(3,90) = 4.125, p = 0.009) and the use of prn psychotropics decreased following memantine treatment (Z = -1.99, p = 0.046). Fourteen patients experienced at least one adverse event during memantine treatment. The most common adverse event associated with treatment was somnolence (n = 5). The results of this study suggest that the decreased agitated and aggressive behaviour in institutionalized patients with moderate to severe AD following treatment with memantine was accompanied by improvements in nursing burden and decreased psychotropic use. These findings should be confirmed in a larger, controlled trial.

Impact of Underlying Depression on Treatment of Neuropsychiatric Symptoms in Older Adults with Dementia

This article examines the moderating effect of depression on interdisciplinary treatment approaches for behaviors in dementia. A secondary analysis of data collected on tailored treatment of 105 long-term care residents with dementia found a significant relationship between treatment and passivity (p < 0.001), treatment and agitation (p = 0.001), and the mediating effect of change in passivity on change in agitation (p < 0.001). The moderating effect of depression was found as a significant factor. For participants with depression and agitation, a significant change in passive behavior was related to significant change in agitated behavior. Thus, by focusing treatment on passivity, both types of neuropsychiatric behaviors improved. The implications of thoroughly assessing not only a behavior problem such as agitation but also other neuropsychiatric symptoms that complicate the delivery of the intervention are discussed.

Intramuscular olanzapine versus short-acting typical intramuscular antipsychotics: Comparison of real-life effectiveness in the treatment of agitation

Objective. To compare the effectiveness of intramuscular (IM) olanzapine and typical IM antipsychotics in naturalistically treated acutely agitated patients with schizophrenia or acute mania. Methods. During the acute phase, 2011 inpatients (including emergency settings) were assessed at 2, 24 and 72 h, and 7 days following initial injection and on oral antipsychotic transition. Mean change in agitation was assessed via Positive and Negative Symptom Scale-Excited Component (PANSS-EC) and Clinical Global Impressions-Severity (CGI-S) scores. Response (≥40% reduction in baseline PANSS-EC score) was analysed using logistic regression. Results. Significantly greater decreases in PANSS-EC and CGI-S scores were observed in patients receiving IM olanzapine (n=1294) as their first injection compared with patients receiving other IM antipsychotics (n=717) (P<0.05; 2 h: effect size 0.1); IM haloperidol treatment (all assessments, P<0.05); and IM zuclopenthixol treatment (2 h, P<0.001). Higher response rates were observed with IM olanzapine compared with other IM antipsychotics at 24 and 72 h, and 7 days (P<0.05). IM olanzapine was associated with fewer extrapyramidal side effects compared with other assessed IM antipsychotics. Conclusions. IM olanzapine provided somewhat more effective control of acute agitation than other assessed IM antipsychotics.

Propane hydrate nucleation: Experimental investigation and correlation

In this work the nucleation kinetics of propane gas hydrate has been investigated experimentally using a stirred batch reactor. The experiments have been performed isothermally recording the pressure as a function of time. Experiments were conducted at different stirring rates, but in the same supersaturation region. The experiments showed that the gas dissolution rate rather than the induction time of propane hydrate is influenced by a change in agitation. This was especially valid at high stirring rates when the water surface was severely disturbed. Addition of polyvinylpyrrolidone (PVP) to the aqueous phase was found to reduce the gas dissolution rate slightly. However the induction times were prolonged quite substantially upon addition of PVP. The induction time data were correlated using a newly developed induction time model based on crystallization theory also capable of taking into account the presence of additives. In most cases reasonable agreement between the data and the model could be obtained. The results revealed that especially the effective surface energy between propane hydrate and water is likely to change when the stirring rate varies from very high to low. The prolongation of induction times according to the model is likely to be due to a change in the nuclei–substrate contact angle.

The Efficacy of Divalproex Sodium in the Treatment of Agitation Associated With Major Depression

Agitation is both a feature of major depression and a common side effect of antidepressant treatment. Depressive agitation correlates with overall severity of illness and suicide risk, whereas treatment-emergent agitation may contribute to early discontinuation of pharmacotherapy. Thus, agitation merits investigation as a treatment target in clinical depression. In this study, adults with major depression were evaluated for change in agitation and other mood symptoms during adjunctive treatment with divalproex sodium. Twelve patients on antidepressants, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression, were given low doses of divalproex sodium and evaluated repeatedly for symptoms of depression, anxiety, and agitation. Agitation severity was evaluated using the Overt Agitation Severity Scale and the Stanford Scale for Agitation Symptoms. Mood symptoms were assessed with the Hamilton Anxiety and the Hamilton Depression Rating Scales. Nine of 12 patients completed 4 weeks of treatment. All agitation scores decreased sharply, whereas depression (Hamilton Depression Rating Scale) and anxiety (Hamilton Anxiety Rating Scale) symptoms decreased only modestly. Decreased agitation was not merely a function of decreases on the Hamilton Depression or Hamilton Anxiety Rating Scales. Relatively low doses of divalproex sodium appear to be useful in the treatment of agitation associated with major depression. The observation that decreases in agitation were not simply an artifact of overall change in depressive or anxiety symptoms is in keeping with the previous clinical impression that divalproex sodium has a specific effect on depressive agitation. Controlled clinical trials are needed to fully evaluate the utility and symptom specificity of divalproex sodium in depression.