A naturalistic study of intramuscular haloperidol versus intramuscular olanzapine for the management of acute agitation.

OBJECTIVE: Published research on agitation is limited by the difficulty in generalizing findings from trials using moderately agitated, carefully selected patients treated with single agents. More specifically, there are few comparative studies examining common intramuscular (IM) regimens (ie, haloperidol with or without benzodiazepines) with IM atypical antipsychotics. Therefore, we conducted a retrospective chart review to compare IM olanzapine and haloperidol in a "real-world" population with agitation. METHOD: We performed a retrospective evaluation of charts from 146 consecutive emergency department patients who received either IM haloperidol or IM olanzapine for agitation. We used a clinically oriented proxy marker of efficacy--the necessity for additional medication intervention for agitation (AMI)--as our primary outcome measure. RESULTS: Additional medication intervention for agitation was required by 43% (13/30) patients when haloperidol was given alone and by 18% (13/72) when haloperidol was given with a benzodiazepine. In the case of olanzapine, AMI was required by 29% (6/21) of patients receiving olanzapine alone and by 18% (2/11) of patients given olanzapine plus a benzodiazepine. A significant percentage of patients had clinical characteristics (nonpsychiatric triage complaint, drug/alcohol use, severe agitation) that differ from more selective samples. CONCLUSIONS: Overall, these finding suggest that in a naturalistic emergency department setting, haloperidol monotherapy is less effective--at least in requiring AMI--than olanzapine with or without a benzodiazepine or haloperidol plus a benzodiazepine. Moreover, these later 3 regimens seemed comparable. Prospective studies examining the treatment of real-world agitation, including head-to-head comparisons of the haloperidol-benzodiazepine combination with newer IM antipsychotics, are needed.

A Naturalistic, Single-blind Comparison of Rapid Dose Administration of Divalproex ER Versus Quetiapine in Patients with Acute Bipolar Mania.

OBJECTIVE: When treating acute bipolar mania, the speed of onset of anti-manic effects is crucial. Quetiapine and divalproex ER are widely used agents to treat acute mania. Rapid dose administration regimens for divalproex ER and for quetiapine have been described. We conducted a naturalistic, head-to-head, pilot study comparing the efficacy and safety of rapidly titrated divalproex ER and quetiapine in acutely manic inpatients, with the primary outcome being improvement within the first seven days. METHOD: Thirty consenting bipolar patients with acute mania (Young Mania Rating Scale >17 ) needing hospitalization due to acute mania were randomized to receive rapidly loaded divalproex ER (30mg/kg/day) or rapidly titrated quetiapine (200mg Day 1, raised by 200mg/day up to 800mg as tolerated). Assessments were made on Day 1 (baseline), Day 3, Day 7, Day 14, and Day 21 and included Young Mania Rating Scale, Clinical Global Impressions-Severity, Clinical Global Impressions-Improvement, and Montgomery-Asberg Depression Rating Scale. Raters but not patients or treating physicians were blinded (single-blinded study). RESULTS: Subjects in both treatment groups exhibited significant and rapid improvement in their mania starting at Day 3 with few significant adverse effects; however, there were no significant differences in the degree or rate of improvement between the two treatment groups in any of the efficacy or adverse effects scales. CONCLUSION: RESULTS of this small study indicate that rapid-dose administration of both quetiapine and divalproex ER produce rapid improvement in acute mania within the first seven days and both seem to be well tolerated.

Adjunctive intranasal oxytocin reduces symptoms in schizophrenia patients.

BACKGROUND: Both human and animal studies suggest oxytocin may have antipsychotic properties. Therefore, we conducted a clinical trial to directly test this notion. METHODS: Nineteen schizophrenia patients with residual symptoms despite being on a stable dose of at least one antipsychotic were enrolled in a randomized, double-blind, crossover study. They received 3 weeks of daily intranasal oxytocin (titrated to 40 IU twice a day) and placebo adjunctive to their antipsychotics. Order of intranasal treatment was randomly assigned and there was a 1-week washout between treatments. RESULTS: Analysis of the 15 subjects who completed all the study visits revealed that oxytocin significantly reduced scores on the Positive and Negative Symptom Scale (p < .001) and Clinical Global Impression-Improvement Scale (p < .001) compared with placebo at the 3-week end point. No benefit was seen at the early time points. Oxytocin was well tolerated and produced no adverse effects based upon patient reports or laboratory analysis. CONCLUSIONS: The results support the hypothesis that oxytocin has antipsychotic properties and is well tolerated. Higher doses and longer duration of treatment may produce larger benefits and should be evaluated in future studies.

Use of risperidone long-acting injectable in a rural border community clinic in southern california.

BACKGROUND: The rate of medication nonadherence among patients with chronic psychiatric conditions, such as schizophrenia and bipolar disorder, has been estimated to be between 40 and 60 percent. Poor adherence leads to clinical deterioration and increased disability in this population. Additionally, it adds to the burden cost of providing mental health services in underserved rural areas. Long-term injectable antipsychotics are considered a valuable tool to counteract medication nonadherence. OBJECTIVE: To describe the level of adherence and functioning among a group of patients, the majority of which were Hispanic, receiving risperidone long acting injectable (RLAI) in a community clinic in a border area of rural southern California. METHODOLOGY: A retrospective chart review was conducted from January, 2005, though December, 2006, of patients receiving RLAI, looking at adherence to their scheduled appointments and improvement in their global assessment of functioning (GAF). RESULTS: Fifty patients with schizophrenia and bipolar disorder were reviewed. Thirty-four received RLAI for at least one year, seven for at least six months, and seven for at least three months. For patients receiving RLAI, there was a significant improvement in patient adherence with appointments. Their no-show rate improved from 27 to 15 percent. Similar improvement was found for those patients receiving RLAI for six and three months. For those patients receiving RLAI for one year, their GAF improved from a mean of 40.8 to 57.2 (standard deviation [SD]=12.39, df=33, p<0.01). Similar improvement was found in those receiving RLAI for six months (mean GAF improvement from 36.4 to 51.8 [SD=9.7, df=6, p<0.01]) and three months (mean GAF improvement from 40.7-60.4 [SD=13.8, df=6, p<0.01]). CONCLUSION: Adherence among our group of majority Hispanics with disabling psychiatric conditions (schizophrenia and severe bipolar disorder) improved when they participate in a RLAI clinic with active case management. A longitudinal follow-up study is needed to determine improvement of their quality of life, comorbid substance use, and metabolic outcomes, and to evaluate long-term remission of symptoms among this specific population.