The Use of Omega-3 Fatty Acids in Mental Illness

Purpose: This article will summarize the current evidence on the effects of omega-3 fatty acids on prevention and treatment of mental illness. Background: Omega-3 fatty acids are involved in many physiologic processes. Since they cannot be made de novo in the body, they are considered essential nutrients. As the Western diet evolved, dietary intake of fatty acids has shifted to increased omega-6 fatty acids and decreased omega-3 fatty acids intake. These changes have been correlated with numerous differences in prevalence and course of mental illnesses. Methods: A MEDLINE search from 1966 to December 2010 was completed to identify studies comparing changes in symptoms, functioning, other outcomes, and/or side effects in patients treated with omega-3 fatty acids for mental illness. The studies were reviewed and reported by specific psychiatric disorder studied. Conclusions: Omega-3 fatty acids play a role in many biologic functions. Epidemiologic data implicate omega-3 fatty acid deficiencies in many mental illnesses. Data are most robust for omega-3 fatty acids’ role in affective disorders. However, data are conflicting, negative, or absent for most mental illnesses

Infection and Inflammation Leading to Clozapine Toxicity and Intensive Care: A Case Series

Objective: To describe 3 cases of clozapine toxicity associated with infectious and/or inflammatory processes. Case Summaries: 3 patients stable on clozapine therapy prior to a medical hospital admission developed clozapine toxicity. It was suspected that an acute infectious and/or inflammatory process in each patient was related to abrupt mental status changes, onset of sialorrhea, myoclonus, and/or need for ventilatory support. Investigations of altered mental status did not reveal alterative causes and presentations were not consistent with neuroleptic malignant syndrome, other acute neurologic complications, or psychiatric decompensation. All patients improved after clozapine dose reductions allowing for transfer from intensive care units. Using the Naranjo ADR Probability Scale for each case, a probable relation between clozapine toxicity and the infectious and/or inflammatory process was determined. Discussion: Clozapine toxicity may manifest with multiple symptoms including sedation, sialorrhea, and hypotension. In addition to overdose and drug interactions; infection and/or inflammation may precipitate clozapine toxicity. This may be related to cytokine-mediated inhibition of cytochrome P450 1A2. The likelihood of toxicity via this mechanism has not been well-characterized, thus careful monitoring is required for medically ill patient receiving clozapine. Clozapine is extensively bound to the acute phase reactant, alpha-1 acid glycoprotein, which may unpredictably protect against clinical toxicity. C-reactive protein has also been investigated to relate clozapine toxicity to infection and/or inflammation. Conclusion: Clozapine toxicity developed in 3 patients admitted to a medical setting suspected to be related to infection and/or inflammation. Clinicians should be aware of this potential adverse drug event with clozapine

Development and Delivery of a Quality Improvement Program to Reduce Antipsychotic Polytherapy

BACKGROUND: Although antipsychotic polytherapy is considered appropriate in limited circumstances (e.g., during a brief “cross-titration” period when switching medications), its increasing prevalence indicates use beyond this limited scope. Despite absence of support in the medical literature and higher costs, antipsychotic polytherapy is common in the treatment of schizophrenia and related disorders. The highest utilization of antipsychotic polytherapy occurs on psychiatric inpatient units, and in 2008, the Joint Commission released the first set of 7 hospital-based inpatient psychiatric services (HBIPS) core measures, 2 of which assess antipsychotic polytherapy at time of discharge. OBJECTIVE: To describe the effect on antipsychotic polytherapy at time of discharge of a 2-part quality improvement program composed of educational seminars and prescriber-specific feedback provided to 11 psychiatrists in 4 acute inpatient psychiatric units in 2 hospitals. METHODS: In a regional academic health care system, we determined the prevalence of antipsychotic monotherapy and polytherapy at time of discharge for all patients discharged on standing antipsychotic medications during 3 periods: (a) a 3-month baseline period (August 2006 through October 2006); (b) in July 2007, after delivery of 4 educational luncheon seminars to 11 psychiatrists from November 2006 through June 2007; and (c) in June 2008, following the provision of monthly prescriber-specific audit feedback from August 2007 through June 2008. To prepare nurses for the change and address possible safety concerns, an educational module was delivered to the psychiatric nursing staff at “best practice” day lectures held in the first quarter of 2007. General themes in the educational presentations included literature-based reviews of (a) safety and efficacy of antipsychotic polytherapy, (b) medical risks of antipsychotic medications, (c) specific versus nonspecific effects of these medications, and (d) effectiveness of first- versus second-generation antipsychotic medications. The prescriber-specific audit feedback was provided in paper form and masked the identity of the other prescribers. The chief of service reviewed audit feedback individually with each psychiatrist on a quarterly basis. The primary outcome measure was the percentage of patients prescribed 2 or more antipsychotics at discharge. A secondary outcome measure was the percentage of patients prescribed 3 or more antipsychotics at discharge. Differences in the primary outcome measure, comparing (a) July 2007 with the baseline period and (b) June 2008 with July 2007, were analyzed using Fisher’s Exact tests. The Cochran-Armitage test for trend was used to assess the relationship between the primary outcome measure and the extent of the intervention, measured as the 3 time periods. For the secondary outcome measure, the Goodman-Kruskal gamma test for ordered categorical data was calculated to examine the association between the proportion of patients receiving 1, 2, or 3 or more antipsychotics at discharge and the 3 time periods. RESULTS: The percentage of patients prescribed 2 or more antipsychotics at discharge declined from 33.9% at baseline (132 of 389 patients), to 21.8% after delivery of the educational modules (44 of 202 patients, P = 0.002), and to 12.2% after audit feedback (18 of 147 patients, P = 0.023; Cochran-Armitage test for trend P \u3c 0.001). When antipsychotic use was classified as 1, 2, or 3 or more antipsychotic medications, more extensive intervention was associated with decreased combination use (Goodman-Kruskal gamma = 0.39, P \u3c 0.001). In the baseline period, 5.9% of patients were prescribed 3 or more antipsychotics at discharge. Following completion of the educational and audit components, respectively, the proportion of patients prescribed 3 or more antipsychotics declined to 2.5% and then to 0.0%. CONCLUSION: Educational modules presented to psychiatrists and nurses in group settings were associated with a decrease in the rate of prescribing 2 or more antipsychotics at discharge from acute psychiatric inpatient units. Addition of monthly audit feedback provided to psychiatrists was associated with further decreases

Multiple Versus Single Antipsychotic Agents for Hospitalized Psychiatric Patients: Case-Control Study of Risks Versus Benefits

OBJECTIVE: Since use of multiple drugs to treat psychiatric patients is increasing, and research on this practice is rare, the authors carried out a retrospective case-control study of multiple versus single antipsychotic treatment in psychiatric inpatients. METHOD: Inpatient treatment groups receiving either antipsychotic monotherapy or polytherapy were matched in terms of age, sex, diagnostic category, and admission clinical ratings (Global Assessment of Functioning [GAF] and Clinical Global Impression [CGI]), which yielded 70 subject pairs. They were compared in terms of total chlorpromazine-equivalent daily dose, changes in total daily dose, length of hospitalization, incidence of adverse effects, and changes in clinical ratings (CGI, GAF, Positive and Negative Syndrome Scale score) between admission and discharge. RESULTS: Initial doses were closely similar at admission for both treatment groups, but the median total final antipsychotic dose was 78% higher for those receiving antipsychotic polytherapy versus monotherapy. Also, median length of stay in the hospital was 55% (8.5 days) longer, and risk of adverse effects was 56% higher with polytherapy, whereas clinical improvement scores were similar (within 11%) for both treatments. CONCLUSIONS: Short-term treatment with multiple antipsychotics was associated with major increases in drug exposure, adverse events, and time in the hospital but with no apparent gain in clinical benefit. These findings require further testing in controlled prospective studies

Inpatient Antipsychotic Drug Use in 1998, 1993, and 1989

OBJECTIVE: Patterns of clinical use of antipsychotic agents have changed greatly in the past decade. The authors’ goal was to examine these patterns. METHOD: They evaluated medication use in all McLean Hospital inpatients treated with antipsychotic drugs during 3 months in 1998 (N=349) and compared the results with McLean Hospital inpatients treated with antipsychotics in 1993 (N=299) and Boston area inpatients in 1989 (N=50). RESULTS: The most commonly prescribed antipsychotics in 1998 were atypical agents; olanzapine was prescribed more often than risperidone or quetiapine, which were prescribed more often than other antipsychotics. Two or more antipsychotics were prescribed at some time during their hospitalization for 150 (43%) of the patients in 1998. The total discharge dose in chlorpromazine equivalents for the 349 patients for whom antipsychotics were prescribed at discharge was 371 mg/day, 29% higher than the total discharge dose for patients in 1993 and 46% greater than the dose in 1989. The dose of antipsychotics was greater for patients with psychotic illnesses than for those with affective illnesses. Higher doses were associated with greater clinical improvement, polypharmacotherapy, and younger patient age. CONCLUSIONS: Emerging trends toward higher total antipsychotic doses and polypharmacotherapy require critical assessments of cost-benefit relationships

Organizational Characteristics of High- and Low-Clozapine-Utilization Clinics in the Veterans Health Administration

Objective: Treatment-resistance schizophrenia occurs in 20-30% of patients. Clozapine is the only medication proven effective for treatment-resistant schizophrenia. However, less than 25% of treatment-resistant schizophrenia patients receive clozapine in most settings. Therefore, this study was conducted to identify facilitators and barriers to clozapine use, to inform development of interventions to maximize appropriate clozapine-utilization. Methods: Seventy semi-structured phone interviews were conducted with five high- and five low-utilization VA Medical Centers, from different US regions including urban and rural areas. Interviewees were key informants of clozapine processes, including mental health leadership, psychiatrists, clinical pharmacists and advanced practice nurses. Interviews were analyzed using an emergent thematic strategy to identify barriers and facilitators to clozapine prescribing. Results: Key elements associated with high-utilization included integration of non-physician psychiatric providers and clear organizational processes and infrastructure for treatment of severe mental illness (e.g. clozapine clinics, larger mental health intensive case management services). Low-utilization was associated with lack of champions to support clozapine processes and limited-capacity care systems. Obstacles identified at both high- and low-utilization sites included complex time-consuming paperwork, reliance on few individuals to facilitate processes, and issues related to transportation for patients living far from care facilities. Conclusions: Implementation efforts to organize, streamline and simplify clozapine processes, development of a multidisciplinary clozapine clinic, increasing the size and capacity of existing clinics, and provision of transportation are reasonable targets to increase clozapine utilization

Antipsychotic Prescribing Pathways, Polypharmacy, and Clozapine Use in Treatment of Schizophrenia

Objective To ensure optimal care for patients with schizophrenia, antipsychotic medications must be appropriately prescribed and used. Therefore, the primary objectives of this study were to identify and describe pathways for antipsychotic prescribing, assess the consistency of observed pathways with treatment guidelines, and describe variability across facilities. Methods Data from Veterans Affairs administrative data sets from fiscal year (FY) 2003 to FY 2007 were gathered for analysis in this retrospective cohort study of antipsychotic prescribing pathways among 13 facilities across two regional networks. Patients with a new episode of care for schizophrenia or schizoaffective disorder in FY 2005 were identified, and antipsychotic prescribing history was obtained for two years before and after the index diagnosis. Demographic characteristics and distribution of comorbidities were assessed. Median medical center rates of polypharmacy were calculated and compared with Fisher’s exact test. Results Of 1,923 patients with a new episode of schizophrenia care, 1,003 (52%) had complete data on prescribing pathways. A majority (74%) of patients were prescribed antipsychotic monotherapy, and 19% received antipsychotic polypharmacy. Of patients receiving antipsychotic polypharmacy, 65% began polypharmacy within 90 days of starting any antipsychotic treatment. There was a fourfold difference in polypharmacy across facilities. Antipsychotic polypharmacy was not associated with geographic location or medical center patient volume. Clozapine utilization was low (0%–2%). Conclusions Retrospective examination of longitudinal prescribing patterns identified multiple antipsychotic prescribing pathways. Although most patients received guideline-concordant care, antipsychotic polypharmacy was commonly used as initial treatment, and there was substantial variability among facilities. Study findings suggest the utility of secondary data to assess treatment adaptation or switching for practical clinical trials

When Is Antipsychotic Polypharmacy Supported by Research Evidence? Implications for QI

Background: Concurrent use of multiple standing antipsychotics (antipsychotic polypharmacy) is increasingly common among both inpatients and outpatients. Although this has often been cited as a potential quality-of-care problem, reviews of research evidence on antipsychotic polypharmacy have not distinguished between appropriate versus inappropriate use. Methods A MEDLINE search from 1966 to December 2007 was completed to identify studies comparing changes in symptoms, functioning, and/or side effects between patients treated with multiple antipsychotics and patients treated with a single antipsychotic. The studies were reviewed in two groups on the basis of whether prescribing was concordant with guideline recommendations for multiple-antipsychotic use. Results A review of the literature, including three randomized controlled trials, found no support for the use of antipsychotic polypharmacy in patients without an established history of treatment resistance to multiple trials of monotherapy. In patients with a history of treatment resistance to multiple monotherapy trials, limited data support antipsychotic polypharmacy, but positive outcomes were primarily found in studies of clozapine augmented with a second-generation antipsychotic. Discussion Research evidence is consistent with the goal of avoiding antipsychotic polypharmacy in patients who lack guideline-recommended indications for its use. The Joint Commission is implementing a core measure set for Hospital-Based Inpatient Psychiatric Services. Two of the measures address antipsychotic polypharmacy. The first measure assesses the overall rate. The second measure determines whether clinically appropriate justification has been documented supporting the use of more than one antipsychotic medication