Loxapine in the Treatment of Manic and Psychotic Symptoms in an Individual Intolerant to Multiple Mood-Stabilizing and Antipsychotic Medications.

First-line treatments for schizophrenia and schizoaffective disorder include antipsychotics and mood stabilizers, but their use may at times be limited due to severe adverse events. This case describes a 41-year-old male with a history of schizoaffective disorder and polysubstance use who was admitted to an inpatient psychiatry unit for acute manic and psychotic symptoms in the setting of absconding from his residential home and noncompliance with prescribed psychiatric medications. During his inpatient psychiatric hospitalization, he experienced DRESS (drug reaction with eosinophilia and systemic symptoms) with valproate, nephrogenic diabetes insipidus with lithium, potential neuroleptic malignant syndrome with risperidone, and orthostasis/tachycardia with clozapine. He ultimately achieved stabilization of manic and psychotic symptoms with loxapine without experiencing adverse events. This report highlights the potential utility of loxapine in individuals with schizoaffective disorder intolerant to standard mood-stabilizing and antipsychotic medications.

An update on recently approved long-acting injectable second-generation antipsychotics: Knowns and unknowns regarding their use.

There are now 9 available FDA-approved second-generation long-acting injectable antipsychotics including aripiprazole (3), olanzapine (1), paliperidone (3), and risperidone (2). These high-cost medications are commonly used with the goal of improving adherence and patient outcomes. With almost 2 decades of use, key aspects have been well studied, including population pharmacokinetics, CYP interactions and various clinical and economic outcomes. However, there are still unknowns with these medications. Issues including adherence, transition from oral antipsychotics, renal dosing, pharmacogenomics, and managing missed doses will be addressed in the context of 4 patient cases.

Akathisia and Newer Second-Generation Antipsychotic Drugs: A Review of Current Evidence.

Akathisia continues to present a significant challenge in clinical practice. As a class, so-called atypical, or second-generation, antipsychotics (SGAs) are the mainstay of treatment for schizophrenia and are commonly used to treat mood disorders. These medications have traditionally been distinguished from first-generation antipsychotics by their lowered risk of extrapyramidal side effects (EPS) such as dystonia, dyskinesia, akathisia, and pseudoparkinsonism. However, the occurrence of EPS, particularly akathisia, has been demonstrated to some degree in all commercially available SGAs. This review examines the incidence of akathisia in nine newer SGAs in patients with schizophrenia, bipolar disorder, and major depressive disorder (MDD). We performed a search of PubMed, ClinicalTrials.gov, Cochrane Central Register, and Google Scholar, as well as manufacturer websites and product labeling for published and unpublished clinical trials, meta-analyses, and systematic reviews. Studies evaluating adult patients with schizophrenia, bipolar disorder, or MDD were eligible for inclusion. Data on treatment-emergent akathisia rates were gathered from each study, and potential dose-response relationships were explored. A total of 177 studies were included in this review, comprising 58,069 patients across 414 treatment arms. Compared with placebo with a composite 3.7% incidence of akathisia, individual SGAs produced akathisia at total composite rates ranging from 2.9-13.0% across the included studies. High doses of an SGA were generally associated with an increased risk of akathisia. Clinicians should consider the risk of akathisia when choosing a treatment option and monitor for akathisia in patients beginning therapy with an SGA or following a dose increase of the SGA.

Adherence to evidence-based treatment guidelines for bipolar depression in an inpatient setting.

OBJECTIVE: The purpose of this study is to determine whether patients with a discharge diagnosis of bipolar depression were prescribed medications that are in accordance with evidence-based treatment guidelines and are FDA-approved for bipolar depression. METHODS: A retrospective study was conducted to assess prescribing of evidence-based therapies for patients discharged between November 2007 and August 2010 with a diagnosis code of BPD at the time of discharge. The primary objective of the study was to determine if evidence-based medications were prescribed at the time of discharge. Secondary objectives included analysis of other medications used, concomitant disease states and drug therapy, rate of readmission, and rate of therapeutic drug monitoring. RESULTS: Of 294 patients, 170 (58%) were prescribed evidence-based medications upon discharge. The most commonly used medication was quetiapine. The most commonly prescribed off-label medications were atypical antipsychotics. For patients on antipsychotics, rates of appropriate monitoring were variable. Seventy percent of patients receiving lithium had a therapeutic concentration prior to discharge. Differences in rates of readmission between groups were not significant. CONCLUSIONS: Rates of prescribing evidence-based medications at discharge for patients with BPD were low. Additionally, evidence-based monitoring for specific medications was variable. Future studies reviewing treatment course and illness severity may provide more information about appropriate medication use in patients with BPD.

Symptomatic bradycardia with oral aripiprazole and oral ziprasidone.

OBJECTIVE: To describe the case of a patient who developed symptomatic bradycardia upon initiation of oral ziprasidone and later with oral aripiprazole, both of which resolved shortly after discontinuation of therapy. CASE SUMMARY: An 18-year-old female with bipolar disorder was started on oral ziprasidone 80 mg at night and the dose was subsequently increased to 120 mg for management of acute mania and delusions. The patient developed symptomatic bradycardia (heart rate 31-35 beats/min), which resolved after ziprasidone was decreased to 80 mg. Three months later, the patient was readmitted for treatment of bipolar mania with psychotic features in the context of medication nonadherence. She was started on oral aripiprazole 15 mg daily (subsequently increased to 20 mg) in conjunction with 600 mg lithium carbonate twice daily. The patient again developed symptomatic bradycardia that resolved after discontinuation of aripiprazole. DISCUSSION: This is the first case report of symptomatic bradycardia associated with the use of ziprasidone or aripiprazole. The Naranjo probability scale suggests that the likelihood of the atypical antipsychotic as the cause of bradycardia is probable for both ziprasidone and aripiprazole. Symptomatic bradycardia with the use of other atypical antipsychotics has been reported in the literature. Little is known about the mechanisms that contribute to the antipsychotic-associated bradycardic response. CONCLUSIONS: Further studies are needed to better determine the relationship between antipsychotics and reflex bradycardia. Although bradycardia remains a relatively uncommon phenomenon seen with the use of these medications, the severity of this potential adverse effect warrants consideration when initiating antipsychotic therapy.

Serotonergic antidepressants and linezolid: a retrospective chart review and presentation of cases.

OBJECTIVE: To report the results from a retrospective chart review looking at the combination of linezolid and serotonergic antidepressants and to report two cases of serotonin syndrome which were identified at our hospital. CASE SUMMARY: During the retrospective chart review one case of serotonin syndrome was identified. A 65-year-old female was receiving escitalopram for the treatment of depression prior to admission. Linezolid therapy was initiated on admission and two days later the patient had a tonic-clonic seizure. Escitalopram was discontinued and the patient did not have any further seizure activity. In a second case, a 37-year-old male was receiving citalopram during hospitalization and was started on concomitant linezolid. The patient had myoclonus and was observed to be tremulous throughout therapy with linezolid. Ten days after discontinuation of linezolid the patient continued to have symptoms until the withdrawal of citalopram. The Naranjo probability scale scores the first case as possibly related and the second case as probably related to the combination. DISCUSSION: It has been well documented in the literature that the combination of linezolid and serotonergic antidepressants may cause serotonin syndrome. In this retrospective chart review only one patient of 53 (1.8%) had symptoms highly suggestive of serotonin syndrome. A second patient continued to have symptoms of serotonin syndrome even after withdrawal of linezolid. CONCLUSIONS: This retrospective review and subsequent case reports confirm the rare, but serious, potential of serotonin syndrome associated with the combination of linezolid and serotonergic antidepressants.

Risperidone- and quetiapine-induced cholestasis.

OBJECTIVE: To describe a case of a patient who developed drug-induced cholestasis after being on risperidone maintenance therapy for 8 years. CASE SUMMARY: A 30-year-old male with schizoaffective disorder, bipolar type, and insulin-dependent diabetes mellitus had been stable on risperidone 6 mg at night for 8 years. His other medications included lithium 900 mg twice daily and enalapril 5 mg daily, as well as regular insulin and NPH insulin as needed. The patient developed cholestasis that resolved once risperidone was discontinued. Over the next 11 months, he tolerated trials of ziprasidone and olanzapine. When quetiapine was initiated, the patient developed signs and symptoms of cholestasis within 3 weeks after starting this medication. The signs and symptoms of cholestasis resolved with removal of quetiapine. The Naranjo probability scale indicated that these atypical antipsychotics (risperidone and quetiapine) were the probable cause of cholestasis in this patient. DISCUSSION: It is well known that atypical antipsychotics can cause isolated asymptomatic increases in aminotransferase levels. Liver injury, both the hepatic and cholestatic type, has been described previously, although the incidence with atypical antipsychotics is rare. CONCLUSIONS: To our knowledge, this is the first case of cholestasis that developed after years of treatment and reappeared with another antipsychotic agent. Given that liver failure, of either the hepatic or cholestatic type, is a relatively rare phenomenon with atypical antipsychotics, it seems that the most reasonable approach to manage this risk is through education. By educating patients on early warning signs of hepatotoxicity, this rare but potentially fatal consequence could be detected early to allow appropriate intervention.