Soenke Boettger

Haloperidol, risperidone, olanzapine and aripiprazole in the management of delirium: A comparison of efficacy, safety, and side effects

OBJECTIVE The aim of this study was to compare the efficacy and side-effect profile of the typical antipsychotic haloperidol with that of the atypical antipsychotics risperidone, olanzapine, and aripiprazole in the management of delirium. METHOD The Memorial Delirium Assessment Scale (MDAS), the Karnofsky Performance Status (KPS) scale, and a side-effect rating were recorded at baseline (T1), after 2-3 days (T2), and after 4-7 days (T3). Some 21 cases were case-matched by age, preexisting dementia, and baseline MDAS scores, and subsequently analyzed. RESULTS The baseline characteristics of the medication groups were not different: The mean age of the patients ranged from 64.0 to 69.6 years, dementia was present in between 23.8 and 28.6%, and baseline MDAS scores were 19.9 (haloperidol), 18.6 (risperidone), 19.4 (olanzapine), and 18.0 (aripiprazole). The doses of medication at T3 were 5.5 mg haloperidol, 1.3 mg risperidone, 7.1 mg olanzapine, and 18.3 mg aripiprazole. Over one week, the decline in MDAS scores between medications was equal, and no differences between individual MDAS scores existed at T2 or T3. After one week, the MDAS scores were 6.8 (haloperidol), 7.1 (risperidone), 11.7 (olanzapine), and 8.3 (aripiprazole). At T2, delirium resolution occurred in 42.9-52.4% of cases and at T3 in 61.9-85.7%; no differences in assessments between medications existed. Recorded side effects were extrapyramidal symptoms (EPSs) in haloperidol- and risperidone-managed patients (19 and 4.8%, respectively) and sedation with olanzapine (28.6%). SIGNIFICANCE OF RESULTS Haloperidol, risperidone, aripiprazole, and olanzapine were equally effective in the management of delirium; however, they differed in terms of their side-effect profile. Extrapyramidal symptoms were most frequently recorded with haloperidol, and sedation occurred most frequently with olanzapine.

Delirium and severe illness: Etiologies, severity of delirium and phenomenological differences.

OBJECTIVE Our aim was to examine the characteristics of delirium in the severely medically ill cancer population on the basis of sociodemographic and medical variables, delirium severity, and phenomenology, as well as severity of medical illness. METHOD All subjects in the database were recruited from psychiatric referrals at Memorial Sloan Kettering Cancer Center (MSKCC). Sociodemographic and medical variables, as well as the Karnofsky Performance Status (KPS) scale and Memorial Delirium Assessment Scale (MDAS) scores were recorded at baseline. Subsequently, these variables were analyzed with respect to the severity of the medical illness. RESULTS Out of 111 patients, 67 qualified as severely medically ill. KPS scores were 19.7 and 30.7 in less severe illness. There were no significant differences with respect to age, history of dementia, and MDAS scores. Although the severity of delirium did not differ, an increased frequency and severity of consciousness disturbance, disorientation, and inability to maintain and shift attention did exist. With respect to etiologies contributing to delirium, hypoxia and infection were commonly associated with severe illness. In contrast, corticosteroid administration was more often associated with less severe illness. There were no differences with respect to opiate administration, dehydration, and CNS disease, including brain metastasis. SIGNIFICANCE OF RESULTS Delirium in the severely medically ill cancer population has been characterized by an increased disturbance of consciousness, disorientation, and an inability to maintain and shift attention. However, the severity of illness did not predict severity of delirium. Furthermore, hypoxia and infection were etiologies more commonly associated with delirium in severe illness, whereas the administration of corticosteroids was associated with less severe illness.

Delirium in advanced age and dementia: A prolonged refractory course of delirium and lower functional status

OBJECTIVE The factors associated with persistent delirium, in contrast to resolved delirium, have not been studied well. The aim of our present study was to identify the factors associated with delirium resolution as measured by the Memorial Delirium Assessment Scale (MDAS) and functional improvement as measured by the Karnofsky Performance Status (KPS) scale. METHOD All subjects were recruited from psychiatric referrals at the Memorial Sloan Kettering Cancer Center (MSKCC). The two study instruments were performed at baseline (T1), at 2-3 days (T2), and at 4-7 days (T3). Subjects with persistent delirium were compared to those with resolved delirium in respect to sociodemographic and medical variables. RESULTS Overall, 26 out of 111 patients had persistent delirium. These patients were older, predominantly male, and had more frequently preexisting comorbid dementia. Among cancer diagnoses and stage of illness, brain cancer and terminal illness contributed to persistent delirium or late response, whereas gastrointestinal cancer was associated with resolved delirium. Among etiologies, infection responded late to delirium management, usually at one week. Furthermore, delirium was more severe in patients with persistent delirium from baseline through one week. At baseline, MDAS scores were 20.1 in persistent delirium compared to 17 to 18.8 in resolved delirium (T2 and T3), and at one week of management (T3), MDAS scores were 15.2 and 4.7 to 7.4, respectively. At one week of management, persistent delirium manifested in more severe impairment in the domains of consciousness, cognition, organization, perception, psychomotor behavior, and sleep-wake cycle. In addition, persistent delirium caused more severe functional impairment. SIGNIFICANCE OF RESULTS In this delirium sample, advanced age and preexisting dementia, as well as brain cancer, terminal illness, infection, and delirium severity contributed to persistent delirium or late response, indicating a prolonged and refractory course of delirium, in addition to more severe functional impairment through one week of management.

Assessment of decisional capacity: Prevalence of medical illness and psychiatric comorbidities.

OBJECTIVE Studies on decisional capacity have primarily focused on cognitive disorders, whereas noncognitive disorders remain understudied. The purpose of our study was to assess decisional capacity across a wide spectrum of medical and psychiatric disorders. METHOD More than 2,500 consecutive consults were screened for decisional capacity, and 336 consults were reviewed at Bellevue Hospital Center in New York. Sociodemographic and medical variables, medical and psychiatric diagnoses, as well as decisional capacity assessments were recorded and analyzed. RESULTS Consults for decisional capacity were most commonly called for in male patients with cognitive and substance abuse disorders. Less commonly, consults were called for patients with mood or psychotic disorders. Overall, about two thirds of patients (64.7%) were deemed not to have decisional capacity. Among medical diagnoses, neurological disorders contributed to decisional incapacity, and among the psychiatric diagnoses, cognitive disorders were most frequently documented in cases lacking decisional capacity (54.1%) and interfered more commonly with decisional capacity than substance abuse or psychotic disorders (37.2 and 25%). In contrast, patients with mood disorders usually retained their decisional capacity (32%). Generally, the primary treatment teams assessment was accurate and was confirmed by the psychiatric service. SIGNIFICANCE OF RESULTS Although decisional capacity assessments were most commonly requested for patients with substance abuse and cognitive disorders, the latter generally affected the ability to make healthcare decisions the most. Further, cognitive disorders were much more likely to impair the ability to make appropriate healthcare decisions than substance abuse or psychotic disorders.

Subsyndromal delirium in the intensive care setting: Phenomenological characteristics and discrimination of subsyndromal delirium versus no and full-syndromal delirium

OBJECTIVE Similar to delirium, its subsyndromal form has been recognized as the cause of diverse adverse outcomes. Nonetheless, the nature of this subsyndromal delirium remains vastly understudied. Therefore, in the following, we evaluate the phenomenological characteristics of this syndrome versus no and full-syndromal delirium. METHOD In this prospective cohort study, we evaluated the Delirium Rating Scale-Revised, 1998 (DRS-R-98) versus the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnostic criteria and examined the diagnosis of delirium with respect to phenomenological distinctions in the intensive care setting. RESULTS Out of 289 patients, 36 with subsyndromal delirium versus 86 with full-syndromal and 167 without delirium were identified. Agreement with respect to the DSM-IV-TR diagnosis of delirium was perfect. The most common subtype in those with subsyndromal delirium was hypoactive, in contrast to mixed subtype in those with full-syndromal delirium versus no motor alterations in those without delirium. By presence and severity of delirium symptoms, subsyndromal delirium was intermediate. The ability of the DRS-R-98 items to discriminate between either form of delirium was substantial. Between subsyndromal and no delirium, the cognitive domain and sleep-wake cycle were more impaired and allowed a distinction with no delirium. Further, between full- and subsyndromal delirium, the prevalence and severity of individual DRS-R-98 items were greater. Although the differences between these two forms of delirium was substantial, the items were not very specific, indicating that the phenomenology of subsyndromal delirium is closer to full-syndromal delirium. SIGNIFICANCE OF RESULTS Phenomenologically, subsyndromal delirium was found to be distinct from and intermediate between no delirium and full-syndromal delirium. Moreover, the greater proximity to full-syndromal delirium indicated that subsyndromal delirium represents an identifiable subform of full-syndromal delirium.

Delirium in the intensive care setting and the Richmond Agitation and Sedation Scale (RASS): Drowsiness increases the risk and is subthreshold for delirium

INTRODUCTION Sedation is a core concept in the intensive care setting, however, the impact of sedation on delirium has not yet been studied to date. METHODS In this prospective cohort study, 225 patients with Richmond Agitation and Sedation (RASS) scores of -1 - drowsiness and 0 - alert- and calmness were assessed with the Delirium Rating Scale-Revised 1998 (DRS-R-98) and DSM-IV-TR-determined diagnosis of delirium assessing drowsiness versus alertness. RESULTS By itself, drowsiness increased the odds for developing delirium eightfold (OR 7.88 p<0.001) and rates of delirium were 68.2 and 21.4%, respectively. Further, in the drowsy patient, delirium was more severe. In the presence of drowsiness, delirium was characterized by sleep-wake cycle disturbances and language abnormalities. These two features, in addition to psychomotor retardation, allowed the correct classification of delirium at RASS-1. The same features, in addition to thought abnormalities and the impairment in the cognitive domain, orientation, attention, short- and long-term memory representing the core domains of delirium, or the temporal onset were very sensitive towards delirium, however lacked specificity. Conversely, delusions, perceptual abnormalities and lability of affect representing the non-core domain were very specific for delirium in the drowsy, however, not very sensitive. In the absence of delirium, drowsiness caused attentional impairment and language abnormalities. CONCLUSION Drowsiness increased the odds for developing delirium eightfold and caused more severe delirium, which was characterized by sleep-wake cycle and language abnormalities. Further, drowsiness by itself caused attentional impairment and language abnormalities, thus, with its disturbance in consciousness was subthreshold for delirium.

Advanced age and decisional capacity: The effect of age on the ability to make health care decisions

OBJECTIVE Cognitive disorders, including dementia, have been shown to be predictors of decisional incapacity, even more than psychotic or substance use disorders. Nonetheless, the impact of advanced age on decisional capacity remains understudied. METHOD Out of more than 2500 consecutive psychiatric consultations performed by the Consultation-Liaison service at Bellevue Hospital Center in New York City, 266 completed decisional capacity assessments were identified and analyzed with respect to the indications for referral and the impact of age and other sociodemographic, medical and psychiatric variables on decisional capacity. RESULTS By itself, in this sample advanced age was not associated with impaired medical decision-making. In individuals ≥65years old, among whom only 27% were deemed to have decisional incapacity, cognitive disorders including dementia remained the strongest association with this incapacity; meanwhile, in patients <65, decisional impairment was evident in 62%, and delirium, psychosis and neurological disorders caused more decisional impairment. The main indications for referral were placement refusals in those ≥65, while young patients were largely seen due to their desire to leave the hospital against medical advice. CONCLUSION Advanced age by itself failed to be associated with decisional incapacity in this sample. In those ≥65, cognitive disorders remained the main association with such incapacity, versus psychosis, substance use and neurological disorders in younger patients.

Management of Gamma-Butyrolactone Dependence with Assisted Self-Administration of GBL

Gamma-hydroxybutyric acid (GHB) and its liquid precursor gamma-butyrolactone (GBL) have become increasingly popular beyond the clubbing culture resulting in daily consumption and dependence in the broader population. This case report illustrates the challenges of managing GHB-withdrawal and a possibly superior future approach of its management by titration and tapering of the addictive agent.

Brief assessment of delirium subtypes: Psychometric evaluation of the Delirium Motor Subtype Scale (DMSS)-4 in the intensive care setting.

OBJECTIVE The management of and prognosis for delirium are affected by its subtype: hypoactive, hyperactive, mixed, and none. The DMSS-4, an abbreviated version of the Delirium Motor Symptom Scale, is a brief instrument for the assessment of delirium subtypes. However, it has not yet been evaluated in an intensive care setting. METHOD We performed a prospective/descriptive cohort study in order to determine the internal consistency, reliability, and validity of the relevant items of the DMSS-4 versus the Delirium Rating Scale-Revised-98 (DRS-R-98) and the original DMSS in a surgical intensive care setting. RESULTS A total of 289 elderly, predominantly male patients were screened for delirium, and 122 were included in our sample. The internal consistency of the DMSS-4 items was excellent (Cronbachs α = 0.92), and between the DMSS-4 and DRS-R-98 the overall concurrent validity was substantial (Cramers V = 0.67). Within individual motor subtypes, concurrent validity remained at least substantial (Cohens κ = 0.65-0.81) and sensitivity high (69.8 to 82.2%), in contrast to those of the no-motor subtype, with less validity and sensitivity (κ = 0.28, 22%). Similarly, total concurrent validity between the DMSS-4 and the original DMSS reached perfection (Cramers V = 0.83), as did agreement between the subtypes (κ = 0.83-0.92), while sensitivity remained high (88.2-100%). Only in those with delirium with no-motor subtype was agreement moderate (κ = 0.56) and sensitivity lower (67%). Specificity was high across all subtypes (91.2-99.1%). The DMSS-4 yielded very sensitive ratings, particularly for hypoactive and hyperactive motor symptoms, and interrater agreement was excellent (Fleisss κ = 0.83). SIGNIFICANCE OF RESULTS We found the DMSS-4 to be a most reliable and valid brief assessment of delirium in characterizing the subtypes of delirium in an intensive care setting, with increased sensitivity to hypoactive and hyperactive motor alterations.

Severe Gamma-Hydroxy-Butyric Acid (GHB) Dependence with Repeated Withdrawal Syndrome and Induced Delirium

Gamma-Hydroxy-Butyric acid (GHB) and its liquid precursor Gamma-Butyro-Lactone (GBL) have become increasingly popular beyond the clubbing culture and daily consumption as well as dependence has become a more common problem. This case report illustrates the presentation and management of severe GHB-dependence and its sequelae, which are increasingly encountered in the addiction and general hospital setting.