Co-occurring SAD symptomatology and schizophrenia at high latitude: a pilot study.

OBJECTIVES: Recent research investigates major depression with seasonal pattern, also called seasonal affective disorder (SAD), depression in schizophrenia and seasonality in schizophrenia, but there exits limited research investigating SAD in schizophrenia. This study documents co-occurring SAD symptomatology in patients with schizophrenia at high latitude. STUDY DESIGN: Clinical cross-sectional study of patients with schizophrenia attending treatment centres in Alaska. METHOD: Twenty-eight patients completed a structured interview assessing seasonal patterns in mood, depression, negative symptoms of schizophrenia and alcohol use. RESULTS: Thirty-six percent of patients with schizophrenia met the criteria for SAD used in previous general population research on SAD in Alaska. When a presence of major depressive episode was confirmed using a structured clinical interview for depression in schizophrenia, the rate was 25%. Severity of SAD symptoms was greatest among patients with alcohol-abuse history. CONCLUSIONS: Co-occurring SAD symptomatology was identified in this extreme latitude sample of patients with schizophrenia. The frequency and severity of symptomatology was greater than found in a general population study of SAD conducted in Alaska using identical criteria. SAD may be under-diagnosed in schizophrenia at moderate and extreme latitudes, highlighting clinical assessment considerations, potential utility of bright light therapy and the need for additional research.

A post hoc analysis of transitioning to oral treatment with olanzapine or haloperidol after 24-hour intramuscular treatment in acutely agitated adult patients with schizophrenia.

BACKGROUND: Acutely agitated patients with schizophrenia might require treatment with IM antipsychotics, followed by a transition to oral medication. OBJECTIVE: The aim of this study was to assess the relationship between 24-hour IM and transitional oral dosages of 2 antipsychotic medications, olanzapine and haloperidol. METHODS: This post hoc analysis used data from a multinational, double-blind, randomized, placebo-controlled study comparing the efficacy of olanzapine, haloperidol, and placebo in acutely agitated inpatients aged > or =18 years with schizophrenia conducted at hospitals in 13 countries. Patients received 1 to 3 IM injections of olanzapine 10 mg or haloperidol 7.5 mg over 24 hours (IM phase), followed by 4 days of oral treatment with 5 to 20 mg/d of either antipsychotic (oral phase). Study patients were grouped according to which drug they received, and subgrouped based on whether they received a single or multiple IM injections. Rates of transition to lower (5-10 mg/d) versus higher (15-20 mg/d) dosages were compared within and between treatments. RESULTS: Data from 236 patients were analyzed (olanzapine, 121 patients [76 men, 45 women; mean (SD) age, 38.4 (12.2) years; mean (SD) weight, 74.9 (18.5) kg]; haloperidol, 115 patients [80 men, 35 women; mean (SD) age, 38.0 (10.2) years; mean (SD) weight, 75.4 (18.7) kg]). At the end of the IM phase, the rate of haloperidol patients who were transitioned to lower oral doses was significantly higher in the single-injection subgroup compared with the multiple-injection subgroup (P = 0.03); this difference was not found in the group receiving olanzapine. At day 4 of oral treatment, the rates of patients in the olanzapine and haloperidol groups who were transitioned to higher oral doses were significantly higher in the single-injection subgroups compared with the multiple-injection subgroups (P = 0.002 and =0.003, respectively). CONCLUSION: In this study, the proportion of agitated patients with schizophrenia who transitioned to higher dosages (15-20 mg) of olanzapine or haloperidol by day 4 of the oral switch was significantly greater in patients who were previously treated with a single IM injection of olanzapine (10 mg) or haloperidol (7.5 mg).right.

Best clinical practice with ziprasidone IM: update after 2 years of experience.

Acute agitation is a common psychiatric emergency often treated with intramuscular (i.m.) medication when rapid control is necessary or the patient refuses to take an oral agent. Conventional i.m. antipsychotics are associated with side effects, particularly movement disorders, that may alarm patients and render them unreceptive to taking these medications again. Ziprasidone (Geodon) is the first second-generation, or atypical, antipsychotic to become available in an i.m. formulation. Ziprasidone IM was approved by the Food and Drug Administration in 2002 for the treatment of agitation in patients with schizophrenia. In October 2004, a roundtable panel of physicians with extensive experience in the management of acutely agitated patients met to review the first 2 years of experience with this agent. This monograph, a product of that meeting, discusses clinical experience to date with ziprasidone IM and offers recommendations on its use in various settings. In clinical trials, patients treated with ziprasidone IM demonstrated significant and rapid (within 15-30 minutes) reduction in agitation and improvement in psychotic symptoms, agitation, and hostility to an extent greater than or equal to that attained with haloperidol i.m. Tolerability of ziprasidone IM was superior to that of haloperidol IM, with a lower burden of movement disorders. Clinical trials have also shown that ziprasidone IM can be administered with benzodiazepines without adverse consequences. Transition from i.m. to oral ziprasidone has been well tolerated, with maintenance of symptom control. The most common adverse events associated with ziprasidone IM were insomnia, headache, and dizziness in fixed-dose trials and insomnia and hypertension in flexible-dose trials. No consistent pattern of escalating incidence of adverse events with escalating ziprasidone doses has been observed. Changes in QTc interval associated with ziprasidone at peak serum concentrations are modest and comparable to those seen with haloperidol IM. Results of randomized clinical trials of ziprasidone IM have been corroborated in studies in real-world treatment settings involving patients with extreme agitation or a recent history of alcohol or substance abuse. In these circumstances, clinically significant improvement was seen within 30 minutes of ziprasidone IM administration, without regard to the suspected underlying etiology of agitation. Agents with a good safety/tolerability profile, such as ziprasidone IM, may be more cost effective long term than older agents, due to reduced incidence of acute adverse effects (eg, acute dystonia) that often require extended periods of observation. Additional trials of ziprasidone IM in agitated patients in a variety of clinical setting are warranted to generate comparative risk/benefit data with conventional agents and other second-generation antipsychotics.

Ethical considerations in rural health care: a pilot study of clinicians in Alaska and New Mexico.

To investigate differences in the experiences of rural versus non-rural clinicians, we surveyed caregivers in New Mexico and Alaska regarding ethical aspects of care provision. Consistent with past literature, rural compared to non-rural clinicians perceived patients as having less access to health care resources. They reported more interaction with patients and less awkwardness in relationships with their patients outside of work. Rural clinicians also reported their patients expressed more concern about knowing them in both personal and professional roles, had more concerns over confidentiality, and experienced more embarrassment concerning stigmatizing illnesses. Ethical issues and implications of these results for providing care in rural areas are discussed.

Pharmacological management of acute agitation.

Acute agitation occurs in a variety of medical and psychiatric conditions, and when severe can result in behavioural dyscontrol. Rapid tranquillisation is the assertive use of medication to calm severely agitated patients quickly, decrease dangerous behaviour and allow treatment of the underlying condition. Intramuscular injections of typical antipsychotics and benzodiazepines, given alone or in combination, have been the treatment of choice over the past few decades. Haloperidol and lorazepam are the most widely used agents for acute agitation, are effective in a wide diagnostic arena and can be used in medically compromised patients. Haloperidol can cause significant extrapyramidal symptoms, and has rarely been associated with cardiac arrhythmia and sudden death. Lorazepam can cause ataxia, sedation and has additive effects with other CNS depressant drugs.Recently, two fast-acting preparations of atypical antipsychotics, intramuscular ziprasidone and intramuscular olanzapine, have been developed for treatment of acute agitation. Intramuscular ziprasidone has shown significant calming effects emerging 30 minutes after administration for acutely agitated patients with schizophrenia and other nonspecific psychotic conditions. Intramuscular ziprasidone is well tolerated and has gained widespread use in psychiatric emergency services since its introduction in 2002. In comparison with other atypical antipsychotics, ziprasidone has a relatively greater propensity to increase the corrected QT (QTc) interval and, therefore, should not be used in patients with known QTc interval-associated conditions. Intramuscular olanzapine has shown faster onset of action, greater efficacy and fewer adverse effects than haloperidol or lorazepam in the treatment of acute agitation associated with schizophrenia, schizoaffective disorder, bipolar mania and dementia. Intramuscular olanzapine has been shown to have distinct calming versus nonspecific sedative effects. The recent reports of adverse events (including eight fatalities) associated with intramuscular olanzapine underscores the need to follow strict prescribing guidelines and avoid simultaneous use with other CNS depressants. Both intramuscular ziprasidone and intramuscular olanzapine have shown ease of transition to same-agent oral therapy once the episode of acute agitation has diminished. No randomised, controlled studies have examined either agent in patients with severe agitation, drug-induced states or significant medical comorbidity. Current clinical experience and one naturalistic study with intramuscular ziprasidone suggest that it is efficacious and can be safely used in such populations. These intramuscular atypical antipsychotics may represent a historical advance in the treatment of acute agitation.

Calming versus sedative effects of intramuscular olanzapine in agitated patients.

Distinct calming rather than nonspecific sedation is desirable for the treatment of acute agitation. In 3 double-blind studies, acutely agitated patients with schizophrenia (N = 311), bipolar mania (N = 201), or dementia (N = 206) were treated with intramuscular (1-3 injections/24 hrs) olanzapine (2.5-10.0 mg), haloperidol (7.5 mg), lorazepam (2.0 mg), or placebo. The Agitation-Calmness Evaluation Scale (ACES; Eli Lilly and Co.) and treatment-emergent adverse events assessed sedation. Across all studies, 1 patient (lorazepam-treated, bipolar) became unarousable. There were no significant between-group differences in ACES scores of deep sleep or unarousable at any time across. Excluding asleep patients, agitation remained significantly more reduced with olanzapine than placebo (P <.05). The incidences of adverse events indicative of sedation were not significantly different with olanzapine versus comparators. For the treatment of acute agitation associated with schizophrenia, bipolar mania, or dementia, intramuscular olanzapine-treated patients experienced no more sedation than haloperidol- or lorazepam-treated patients and experienced distinct calming rather than nonspecific sedation.

Intramuscular olanzapine and intramuscular haloperidol in acute schizophrenia: antipsychotic efficacy and extrapyramidal safety during the first 24 hours of treatment.

OBJECTIVE: To determine the antipsychotic efficacy and extrapyramidal safety of intramuscular (i.m.) olanzapine and i.m. haloperidol during the first 24 hours of treatment of acute schizophrenia. METHOD: Patients (n = 311) with acute schizophrenia were randomly allocated (2:2:1) to receive i.m. olanzapine (10.0 mg, n = 131), i.m. haloperidol (7.5 mg, n = 126), or i.m. placebo (n = 54). RESULTS: After the first injection, i.m. olanzapine was comparable to i.m. haloperidol and superior to i.m. placebo for reducing mean change scores from baseline on the Brief Psychiatric Rating Scale (BRPS) Positive at 2 hours (-2.9 olanzapine, -2.7 haloperidol, and -1.5 placebo) and 24 hours (-2.8 olanzapine, -3.2 haloperidol, and -1.3 placebo); the BPRS Total at 2 hours (-14.2 olanzapine,-13.1 haloperidol, and -7.1 placebo) and 24 hours (-12.8 olanzapine, -12.9 haloperidol, and -6.2 placebo); and the Clinical Global Impressions (CGI) scale at 24 hours (-0.5 olanzapine, -0.5 haloperidol, and -0.1 placebo). Patients treated with i.m. olanzapine had significantly fewer incidences of treatment-emergent parkinsonism (4.3% olanzapine vs 13.3% haloperidol, P = 0.036), but not akathisia (1.1% olanzapine vs 6.5% haloperidol, P = 0.065), than did patients treated with i.m. haloperidol; they also required significantly less anticholinergic treatment (4.6% olanzapine vs 20.6% haloperidol, P < 0.001). Mean extrapyramidal symptoms (EPS) safety scores improved significantly from baseline during i.m. olanzapine treatment, compared with a general worsening during i.m. haloperidol treatment (Simpson-Angus Scale total score mean change: -0.61 olanzapine vs 0.70 haloperidol; P < 0.001; Barnes Akathisia Scale global score mean change: -0.27 olanzapine vs 0.01 haloperidol; P < 0.05). CONCLUSION: I.m. olanzapine was comparable to i.m. haloperidol for reducing the symptoms of acute schizophrenia during the first 24 hours of treatment, the efficacy of both being evident within 2 hours after the first injection. In general, more EPS were observed during treatment with i.m. haloperidol than with i.m. olanzapine.