Suicidality and hospitalization as cause and outcome of pediatric psychiatric emergency room visits.

The aim of this study was to identify predictors of suicidality in youth presenting to a pediatric psychiatric emergency room service (PPERS). To this end, we conducted a retrospective cohort study of youth aged <18 years consecutively assessed by a PPERS 01.01.2002-12.31.2002, using a 12-page semi-structured institutional evaluation form and the Columbia Classification Algorithm for Suicide Assessment. Multivariate regression analyses were conducted to identify correlates of suicidal thoughts and attempts/preparation and their relationship to outpatient/inpatient disposition. Of 1,062 youth, 265 (25.0%) presented with suicidal ideation (16.2%) or attempt/preparation (8.8%). Suicidal ideation was associated with female sex, depression, adjustment disorder, absent referral by family/friend/self, school referral, precipitant of peer conflict, and no antipsychotic treatment (p < 0.0001). Suicidal attempt/preparation was associated with female sex, depression, lower GAF score, past suicide attempt, precipitant of peer conflict, and no stimulant treatment (p < 0.0001). Compared to suicidal attempt/preparation, suicidal ideation was associated with school referral, and higher GAF score (p < 0.0001). Of the 265 patients with suicidality, 58.5% were discharged home (ideation = 72.1% vs. attempt/preparation = 33.7%, p < 0.0001). In patients with suicidal ideation, outpatient disposition was associated with higher GAF score, school referral, and adjustment disorder (p < 0.0001). In patients with suicidal attempt/preparation, outpatient disposition was associated with higher GAF score, lower acuity rating, and school referral (p < 0.0001). Suicidality is common among PPERS evaluations. Higher GAF score and school referral distinguished suicidal ideation from suicidal attempt/preparation and was associated with outpatient disposition in both presentations. Increased education of referral sources and establishment of different non-PPERS evaluation systems may improve identification of non-emergent suicidal presentations and encourage more appropriate outpatient referrals.

The QTc interval and its dispersion in patients receiving two atypical antipsychotics.

OBJECTIVE: Treatment with atypical antipsychotics may prolong the rate-corrected Q-T interval (QTc) on electrocardiogram and increase the risk of dangerous ventricular arrhythmias. Polytherapy with atypical antipsychotics is becoming common, but the effect of this practice on the QTc has not been explored in detail. METHODS: Among 364 adults treated with atypical antipsychotics randomly selected from consecutive admissions to a single hospital, electrocardiograms with measurable Q-T intervals in at least six leads were available for 38 of 49 patients receiving polytherapy with two atypical antipsychotics. Daily chlorpromazine equivalent, QTc duration and QTc dispersion were assessed in this group and in 73 closely matched patients receiving atypical antipsychotic monotherapy. RESULTS: The daily chlorpromazine equivalent of atypical antipsychotics was significantly greater in the polytherapy group (525.2 vs. 244.7 mg, P = 0.0003). Polytherapy and monotherapy patients were similar with regard to QTc duration, QTc dispersion and proportion of patients with gender-adjusted QTc prolongation (7.9% vs. 9.6%). The QTc duration had only a modest correlation with the total antipsychotic dose (P = 0.064). The presence of hypokalemia (3.0-3.5 mEq/l) was not associated with longer QTc intervals. CONCLUSIONS: The common practice of polytherapy with two atypical antipsychotics does not seem to lead to significant QTc prolongation compared to monotherapy.

Equally increased risk for metabolic syndrome in patients with bipolar disorder and schizophrenia treated with second-generation antipsychotics.

OBJECTIVE: Although second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and bipolar disorder, their effects on dyslipidemia, glucose intolerance, metabolic syndrome (MetS), and coronary heart disease (CHD) risk are less well documented for bipolar disorder. We compared bipolar disorder and schizophrenia patients receiving SGAs to determine whether MetS prevalence is influenced by the primary psychiatric diagnosis or concomitant mood stabilizer treatment. METHODS: Admission assessment of MetS criteria (abdominal obesity, fasting hypertriglyceridemia, low high-density lipoprotein cholesterol, hyperglycemia, arterial hypertension) and the calculated 10-year CHD risk in bipolar disorder and schizophrenia patients treated with SGAs and closely matched for age, sex, and race. RESULTS: Compared to schizophrenia patients (n = 111), those with bipolar disorder (n = 74) had lower body mass index (27.1 +/- 5.3 versus 29.9 +/- 8.1, p = 0.0053), were more likely treated with mood stabilizers (60.8 versus 36.0, p = 0.0009), and less likely treated with clozapine (1.3% versus 15.3%, p = 0.0017) or two antipsychotics (10.8% versus 34.2%, p = 0.0003). Despite these differences, bipolar disorder and schizophrenia patients had comparable rates of MetS (43.2% versus 45.9%, p = 0.71) and predicted CHD events (10-year risk >10%: 18.9% versus 23.4%, p = 0.47). Using >or=100 mg/dL as the adapted glucose criterion, MetS rates were 54.0% in both diagnostic groups (p = 1.0). Mood stabilizer co-treatment was not associated with MetS or its individual criteria. CONCLUSIONS: Patients with bipolar disorder and schizophrenia who are treated with SGAs have similarly high rates of MetS. These findings suggest a shared susceptibility to antipsychotic-related metabolic dysregulations that is not primarily related to psychiatric diagnosis or concomitant mood stabilizer treatment.

Does antipsychotic polypharmacy increase the risk for metabolic syndrome?

OBJECTIVE: To determine whether the coprescribing of two or more antipsychotics, a relatively frequent practice with little data to support its safety and efficacy, is associated with an increased prevalence of metabolic syndrome. METHODS: 364 newly admitted adults treated with second-generation antipsychotics underwent assessments evaluating antipsychotic polytherapy, and of the presence of metabolic syndrome and triglycerides/high-density lipoprotein cholesterol ratio>3.5 (TG/HDL), a sensitive marker of insulin resistance. The correlates of antipsychotic polytherapy and associations with metabolic syndrome and TG/HDL were determined by univariate comparisons and multiple logistic regression analyses. RESULTS: Antipsychotic polytherapy was present in 70 patients (19.2%) and was significantly more likely in patients with schizophrenia and those treated with clozapine, quetiapine or ziprasidone (p<0.0001). Compared with antipsychotic monotherapy, polytherapy was associated with elevated rates of metabolic syndrome (50.0% vs. 34.3%, p=0.015) and TG/HDL (50.7% vs. 35.0%, p=0.016). However, in logistic regression analyses, metabolic syndrome was significantly associated with higher body mass index (BMI), older age, a diagnosis of bipolar disorder or schizophrenia, and cotreatment with a first-generation antipsychotic (r(2): 0.25, p<0.0001). The TG/HDL marker of insulin resistance was associated with higher BMI, male sex, Caucasian race and absence of aripiprazole treatment (r(2): 0.14, p<0.0001). Antipsychotic polypharmacy dropped out of both multivariate models. CONCLUSIONS: Compared with patients receiving antipsychotic monotherapy, patients on antipsychotic polytherapy have higher rates of metabolic syndrome and lipid markers of insulin resistance. However, antipsychotic polytherapy is not independently associated with the prevalence of these abnormalities, which are related to known demographic, clinical and anthropometric risk factors.

Low-density lipoprotein cholesterol in patients treated with atypical antipsychotics: missed targets and lost opportunities.

BACKGROUND: The treatment of psychotic disorders with second-generation antipsychotics (SGAs) has been linked to an increased risk of coronary heart disease (CHD). Lowering low-density lipoprotein-cholesterol (LDL-C) to individualized targets of 100, 130 or 160 mg/dl reduces the risk of CHD. We determined the prevalence of above-target LDL-C and its management during psychiatric hospitalization. METHODS: 364 hospitalized adults receiving SGAs underwent LDL-C target assessments. Records of patients with above-target LDL-C were searched for dietary or pharmacologic treatments and referrals for medical consultation. RESULTS: Above-target LDL-C levels were present in 100 (27.5%) patients and were associated with higher total cholesterol, lower high-density lipoprotein cholesterol, older age, higher systolic blood pressure, smoking and male gender (r(2): 0.53; p<0.0001). Only 32.0% of these patients received appropriate interventions during hospital stays of 27.6+/-23.3 days. CONCLUSIONS: A substantial number of SGA-treated patients have above-target LDL-C, but do not receive interventions to reduce the risk of CHD.

Differentiation in the preonset phases of schizophrenia and mood disorders: evidence in support of a bipolar mania prodrome.

OBJECTIVE: The presence and specificity of a bipolar prodrome remains questioned. We aimed to characterize the prodrome prior to a first psychotic and nonpsychotic mania and to examine the phenotypic proximity to the schizophrenia prodrome. METHODS: Using a semi-structured interview, the Bipolar Prodrome Symptom Scale-Retrospective, information regarding the mania prodrome was collected from youth with a research diagnosis of bipolar I disorder and onset before 19 years of age, and/or their caregivers. Only newly emerging, at least moderately severe, symptoms were analyzed. Prodromal characteristics were compared between patients with and without subsequent psychotic mania and with published bipolar and schizophrenia prodrome data. RESULTS: In 52 youth (age at first mania: 13.4 +/- 3.3 years), the prodrome onset was predominantly "insidious" (>1 year, 51.9%) or "subacute" (1-12 months, 44.2%), while "acute" presentations (<1 month, 3.8%) were rare. The prodrome duration was similar in patients with (1.7 +/- 1.8 years, n = 34) and without (1.9 +/- 1.5 years, n = 18) subsequent psychotic mania (P = .70). Attenuated positive symptoms emerging late in the prodrome and increased energy/goal-directed activity were significantly more common in patients with later psychotic mania. Mania and schizophrenia prodrome characteristics overlapped considerably. However, subsyndromal unusual ideas were significantly more likely part of the schizophrenia prodrome, while obsessions/compulsions, suicidality, difficulty thinking/communicating clearly, depressed mood, decreased concentration/memory, tiredness/lack of energy, mood lability, and physical agitation were more likely part of the mania prodrome. CONCLUSIONS: A lengthy and symptomatic prodrome makes clinical high-risk research a feasible goal for bipolar disorder. The phenotypic overlap with the schizophrenia prodrome necessitates the concurrent study of both illness prodromes.

Metabolic syndrome and the risk of coronary heart disease in 367 patients treated with second-generation antipsychotic drugs.

OBJECTIVE: To examine the relationship between presence of metabolic syndrome and the risk of coronary heart disease (CHD) events (angina pectoris, myocardial infarction, and sudden cardiac death) in patients treated with second-generation antipsychotic medications. METHOD: 367 adults treated with second-generation antipsychotics randomly selected from consecutive psychiatric admissions to a single hospital between August 1, 2004, and March 1, 2005, underwent assessments evaluating the presence of metabolic syndrome. The 10-year risk of CHD events was calculated according to the Framingham scoring system for age, smoking, total cholesterol, high-density lipoprotein (HDL)-cholesterol, blood pressure, and history of diabetes and was compared in patients with and without the metabolic syndrome. RESULTS: Metabolic syndrome, present in 137 patients (37.3%), was associated with a significantly greater age- and race-adjusted 10-year risk of CHD events, i.e., 11.5% vs. 5.3% for men (risk ratio = 2.18, 95% CI = 1.88 to 2.48, p < .0001) and 4.5% vs. 2.3% for women (risk ratio = 1.94, 95% CI = 1.65 to 2.23, p = .0005). The increased risk of CHD events in patients with metabolic syndrome remained significant after the exclusion of diabetic patients. In a logistic regression analysis of variables independent of the Framingham scoring system, triglyceride levels (p < .0001), waist circumference (p = .035), and white race (p = .047) were significantly associated with the 10-year risk of CHD events (R2 = 0.134; p < .0001). CONCLUSIONS: These data confirm the high prevalence of metabolic syndrome in patients receiving second-generation anti-psychotics, indicate that metabolic syndrome doubles the 10-year risk of CHD events in this population, and emphasize the importance of the "hypertriglyceridemic waist" for the identification of psychiatric patients at high risk of CHD.

Clozapine: its impact on aggressive behavior among children and adolescents with schizophrenia.

OBJECTIVE: To evaluate the effectiveness of clozapine on aggressive behavior for treatment-refractory adolescents (age range 8.5-18) with schizophrenia (295.x) at Bronx Children's Psychiatric Center. METHOD: Clozapine treatment was administered in an open-label fashion using a flexible titration schedule. The frequency of administration of emergency oral and injectable medications and the frequency of seclusion events 3 months immediately before and from 12 to 24 weeks of clozapine treatment (when optimal clozapine levels were achieved) were compared. RESULTS: Twenty clozapine-treated children (mean +/- SD dose at week 24, 476 +/- 119 mg) were included. A statistically significant decrease in the frequency of the administration of emergency oral medications, the administration of emergency injectable medications, and seclusion events was found in adolescents during weeks 12 to 24 of clozapine treatment compared with their baseline condition before clozapine initiation. CONCLUSIONS: These preliminary data indicate the benefits of clozapine treatment in adolescents with treatment-refractory schizophrenia for aggressive behaviors. Although open data limit conclusions from this study, it is important that there was a clinically significant improvement in aggressive behaviors that enabled patients to be discharged to a less restrictive setting. Additional controlled clinical trials of clozapine are needed in treatment-refractory children and adolescents.

Hematological adverse events in clozapine-treated children and adolescents.

OBJECTIVE: To retrospectively examine rates of hematological adverse events (HAEs) in psychiatrically ill, hospitalized children treated with clozapine. METHOD: Clozapine treatment was administered in an open-label fashion using a flexible titration schedule, and data from weekly complete blood counts was obtained. The rate of neutropenia and agranulocytosis (HAEs) development was determined for 172 eligible patients (mean age at clozapine initiation, 15.03 +/- 2.13 years) with a median observation period of 8 months. RESULTS: Neutropenia (absolute neutrophil count <1,500/mm) developed in 23 (13%) patients and agranulocytosis (absolute neutrophil count <500/mm) in one (0.6%) patient. The cumulative probability of developing an initial HAE at 1 year of clozapine treatment was 16.1% (95% confidence interval 9.7%-22.5%). Eleven (48%) of 24 patients who developed an HAE were successfully rechallenged on clozapine. Eight (5%) of 172 patients from this sample eventually discontinued clozapine because of an HAE (one agranulocytosis, seven neutropenia). CONCLUSIONS: The occurrence of HAEs is a significant risk associated with the administration of clozapine. However, in this sample, few children actually discontinued therapy because of an HAE and the incidence of agranulocytosis does not appear higher than what has been reported in the adult literature.

Frequency and correlates of inappropriate pediatric psychiatric emergency room visits.

BACKGROUND: Despite increasing pediatric psychiatric emergency room service (PPERS) visits, data are lacking regarding visit characteristics and appropriateness. METHOD: This retrospective cohort study consecutively assessed youngsters aged < 18 years between January 1 and December 31, 2002, utilizing data from a 12-page semistructured institutional evaluation form. Appropriateness, severity, acuity, and harm potential of PPERS visits were rated on a Likert scale. RESULTS: Of 1,062 PPERS patient visits (mean +/- SD age: 13.5 +/- 3.1 years, 51.1% male, and 51.2% white), 305 (28.7%) led to hospitalization. Although most patients (68.7%) were in outpatient care, only 21.9% sought and 11.5% completed an outpatient evaluation prior to reaching the emergency room. As many as 34.4% of PPERS visits were somewhat/very inappropriate (optimal care: outpatient evaluation/treatment, even if delayed), 26.6% were somewhat appropriate/neutral (best served by outpatient evaluation/treatment, but timely appointment unavailable), and only 39.0% were fully appropriate. Main reasons for inappropriate PPERS visits were direct emergency room referral from school (P = .0056) or mental health provider (P = .0438) without prior psychiatrist evaluation, or unavailable appointment (P = .0304). Multivariate predictors of inappropriate PPERS visits (r(2) = .296, P < .0001) included current Global Assessment of Functioning score > 48 (P < .0001), absent suicidal ideation/attempt (P < .0001), low harm potential (< 4.4, P < .0001) and severity (< 4.8, P = .0136) (1- to 7-point scale) of presenting complaint, and absent psychosis (P = .0008). CONCLUSIONS: Over one third of PPERS visits were inappropriate, characterized by better functioning, low harm potential or severity of presenting complaint, and absent suicidality or psychosis. Development of and improved access to urgent child and adolescent psychiatric outpatient care services in the community and referral agent educational programs may minimize inappropriate PPERS visits.