Leigh Anne Nelson

Analysis of Cost Avoidance From Pharmacy Students' Clinical Interventions at a Psychiatric Hospital

Objective. To analyze the cost avoidance resulting from clinical interventions made by pharmacy students completing an advanced pharmacy practice experience (APPE) at a psychiatric hospital. Methods. A retrospective database review of documented clinical interventions by pharmacy students was conducted to classify interventions by type and significance. Interventions were assigned a cost avoidance value determined by an evaluation of the literature. Results. Three hundred-twenty interventions were documented by 15 pharmacy students during the 1-year study period. The majority of interventions were related to psychiatric medication classes and most (n = 197; 61.6%) were classified as being of moderate significance. The most common interventions included patient education (13.1%), order clarification (11.6%), therapeutic dosing adjustments (10.9%), and laboratory order monitoring (8.8%). The estimated cost avoidance from all interventions made by pharmacy students was approximately

Ramelteon: A Novel Approach in the Treatment of Insomnia

23,000. Conclusions. Pharmacy students completing APPEs at a psychiatric hospital contributed to a variety of significant clinical interventions and provided considerable cost avoidance value to the institution.

Role of Mirtazapine in the Treatment of Antipsychotic-Induced Akathisia

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of ramelteon in the treatment of primary insomnia in adults, including elderly adults. Data Sources: MEDLINE (1966–July 2008) and PsyclNFO (1985–July 2008) literature searches were conducted to idontify clinical data involving ramelteon. The manufacturer provided a summary of clinical data and abstracts of unpublished studies. Study Selection And Data Extraction: All primary literature, including abstracts, focusing on the pharmacology and pharmacokinetics of ramelteon and clinical trials evaluating its use was reviewed. Information deemed most relevant was incorporated. Our search revealed 5 controlled trials evaluating the short-term efficacy and safety of ramelteon in the treatment of primary insomnia: 3 in adults and 2 in geriatric patients. Additionally, 2 studies in abstract form that evaluated the long-term effects of ramelteon were included. Data Synthesis: Ramelteon is the first selective melatonin receptor agonist approved by the Food and Drug Administration. It has no affinity for the γ-aminobutyric acid receptor complex or for receptors that bind acetylcholine, cytokines, dopamine, norepinephrine, neuropeptides, opiates, and serotonin. In the only published Phase 3 trial in adults, investigators found that latency to persistent sleep decreased with ramelteon to 31.5 ± 2.91 minutes with 8 mg and 29.5 ± 2.96 minutes with 16 mg compared with 42.5 ± 2.97 minutes with placebo (p = 0.007 and p = 0.002, respectively). Total sleep time was not significantly different from that with placebo. Safety data from short-term studies showed advantages of ramelteon over other sleep agents including no potential for abuse, no rebound insomnia, and lack of effect on motor and cognitive function. The adverse effects seen most frequently in ramelteon clinical trials were headache, somnolence, fatigue, nausea, dizziness, and insomnia. The overall incidence was similar to that of placebo. Conclusions: Ramelteon offers a novel mechanism of action for the treatment of insomnia. Studies support its short- and long-term use in adults and elderly adults for the treatment of primary insomnia characterized by difficulty with sleep initiation. Efficacy studies comparing ramelteon with other sleep agents are needed to further solidify the role of ramelteon in the treatment of insomnia.

Varenicline use in patients with mental illness: an update of the evidence

Objective: To evaluate the role of mirtazapine in the treatment of antipsychotic-induced akathisia. Data Sources: MEDLINE (1966–February 2008) and PsycINFO (1967–February 2008) were searched using the terms akathisia and mirtazapine. A bibliographic search was conducted as well. Study Selection and Data Extraction: All English-language articles identified from the search were evaluated. All primary literature was included in the review. Data Synthesis: Antipsychotic-induced akathisia can be difficult to manage and may respond to mirtazapine based on its antagonist activity at the serotonin 5-HT2A/5-HT2C receptors. Three case reports (N = 9 pts.>, 1 placebo-controlled trial (N = 26), and 1 placebo- and propranolol-controlled study (N = 90) that evaluated mirtazapine for antipsychotic-induced akathisia have been published. Mirtazapine demonstrated a response rate of 53.8% compared with a 7.7% response rate for placebo, based on at least a 2-point reduction on the Barnes Akathisia Scale (global subscale; p = 0.004). Using the same criterion, mirtazapine and propranolol demonstrated efficacy based on response rates of 43.3% and 30.0% compared with placebo (6.7%; p = 0.0051). Mirtazapine was better tolerated than propranolol. In both studies, drowsiness was the most common adverse event associated with mirtazapine. Conclusions: Mirtazapine may be considered a treatment option for antipsychotic-induced akathisia. It may be especially useful for patients with contraindications or intolerability to β-blockers and for those with comorbid depression or negative symptoms. Additional studies should be conducted to provide further evidence of mirtazapines effectiveness in treating akathisia.

Historical Review of Carbamazepine for the Treatment of Bipolar Disorder

Importance of the field: Patients with a psychiatric diagnosis have a higher prevalence of smoking compared to the general population. Varenicline is a first-line pharmacotherapy option to assist in smoking cessation. Clinical trials during drug development excluded patients with active psychiatric illnesses leaving the risks associated with varenicline use in this patient population unknown. Areas covered in this review: Literature published in English up to December 2009 were identified and include neuropsychiatric adverse drug events reported in pre-marketing trials and post-marketing surveillance, varenicline case reports, evidence surrounding the use of varenicline in patients with psychiatric diagnoses, and varenicline and suicidality. What the reader will gain: Although the risk of potential neuropsychiatric events is evident through voluntary reporting systems and reported cases in the literature, multiple studies and case reports support the use of varenicline in the mental health population. Reviewing the literature will enable clinicians to optimize patient care by weighing the risks and benefits associated with varenicline use against the risk of continued smoking. Take home message: Cautious treatment initiation, patient education, and close follow-up, monitoring for mood and behavior changes during therapy are recommended, especially in the psychiatric setting.

Adherence to Antihyperlipidemic Medication and Lipid Control in Diabetic Veterans Affairs Patients with Psychotic Disorders

The management of bipolar disorder has seen significant evolution in terms of the number of treatment options now approved for both the acutely manic phase and the maintenance stages of the illness. In addition, new formulations of traditional agents are available for clinicians to use in their treatment approach. One such example is carbamazepine, which has approval by the United States Food and Drug Administration for the treatment of acute and mixed mania in an extended‐release formulation that uses a three‐bead delivery system. Although the parent compound has been available for decades, its approval for bipolar disorder is recent despite numerous clinical trials that have supported its use in both the acute and maintenance phases of bipolar disorder. Advantages of the new formulation include less fluctuation in plasma concentration and, in general, improved tolerability. However, issues remain with regard to cytochrome P450 drug‐related interactions and the need for therapeutic drug monitoring (e.g., drug concentrations, epoxide metabolite concentrations, hematology, and liver function tests) as part of the treatment and monitoring process. We review the current body of literature describing the use of carbamazepine in bipolar disorder during both the acute and maintenance phases of the disorder, including trials of both monotherapy and combination therapy, as well as findings from trials that included patients with rapid cycling and mixed episodes.

Medication adherence and glycemic control in patients with psychotic disorders in the Veterans Affairs healthcare system

BACKGROUND Medication adherence for chronic medical illnesses has been studied extensively, but there is limited data evaluating medication adherence for comorbid medical illnesses in a psychiatric population. Furthermore, only one study has evaluated both medication adherence and clinical outcomes between the two populations. Examining medication adherence rates and clinical outcomes are important as chronic medical illnesses occur commonly in psychiatric patients, can be drug-induced, and have negative long-term consequences. OBJECTIVES To compare antihyperlipidemic medication adherence and lipid control between individuals with psychotic disorders and those without a psychiatric illness. METHODS This was a retrospective medical record review of 124 subjects with hyperlipidemia and diabetes (62 subjects with schizophrenia or a related psychotic disorder and 62 randomly selected, age-matched individuals without a psychiatric illness) receiving medical and psychiatric care through the Veterans Affairs Medical Center during 2008. Cumulative mean gap ratio (CMGR) was used to determine adherence. Lipid values were utilized to compare lipid control between groups. RESULTS A significant difference in CMGR was detected. Subjects with psychotic disorders were without antihyperlipidemic therapy for 44 days compared with 62 days for the nonpsychiatric comparison group (P = 0.034). Antipsychotic adherent subjects (≥80% adherent) were more likely to adhere to their antihyperlipidemic medication (P = 0.0007). There were no significant differences between the groups for lipid control. CONCLUSION Antihyperlipidemic medication adherence differed with the psychotic disorder group having fewer days without drug therapy. However, there was no significant difference in lipid control between subjects with a psychotic disorder and those without a psychiatric illness.

Adverse Drug Reactions: A Retrospective Review of Hospitalized Patients at a State Psychiatric Hospital

Objective To compare antihyperglycemic medication adherence and glycemic control between individuals with schizophrenia and related psychotic disorders and a nonpsychiatric comparison group. Methods This was a retrospective medical record review. A total of 124 subjects with diabetes (62 patients with schizophrenia or a related psychotic disorder and 62 randomly selected, age-matched patients without a psychiatric illness) receiving their medical and psychiatric care exclusively through the Kansas City Veterans Affairs healthcare system during 2008 were included in the study. Adherence to antihyperglycemic and antipsychotic medication was determined by refill records obtained through the computerized patient record system to calculate the cumulative mean gap ratio. Hemoglobin A1C values were utilized to compare glycemic control between groups and compared to glycemic goals established by diabetes treatment guidelines. Results Antihyperglycemic medication adherence was poor for both groups as approximately 60% of the psychotic disorder group and 75% of the nonpsychiatric comparison group were without antihyperglycemic medication for greater than 30 days during the 12-month period but adherence did not differ between the groups (p=0.182). Antipsychotic adherent subjects (≥80% adherent) were more likely to be adherent to their antihyperglycemic medication (p=0.0003). There were no significant differences between groups in glycemic control. Conclusions Antihyperglycemic medication adherence and glycemic control was less than optimal for both groups. There were no significant differences in antihyperglycemic medication adherence and glycemic control between patients with a psychotic disorder and those without a psychiatric illness.

Inconsistency in risperidone long-acting injection steady-state plasma levels when switching from deltoid to gluteal administration.

Background There is a paucity of information regarding adverse drug reactions (ADRs) in psychiatric patients. Information on common and preventable ADRs (pADRs) in psychiatric patients will allow for targeted improvement projects. Objective To characterize reported ADRs and pharmacist interventions to prevent ADRs in an extended-care state psychiatric hospital. Methods Four years of ADR reports were assessed for probability, reaction severity, pharmacological class of medication involved, preventability, change in therapy, and transfers to a medical facility. The pharmacist intervention database was queried for interventions classified as “prevention of ADR.” The interventions were assessed for type of medication and recommendation acceptance. Results Medication classes responsible for ADRs included mood stabilizers (30%), typical antipsychotics (25%), atypical antipsychotics (25%), and antidepressants (8%). Nine percent resulted in transfer to a medical facility. Of all ADRs, 34.4% were pADRs; mood stabilizers (41%) and atypical antipsychotics (27%) were the most common pADRs. The most common causes of pADRs were supratherapeutic serum concentrations, drug-drug interactions, and history of reaction. There were 87 pharmacist interventions that were classified as “prevention of ADR,” and the acceptance rate of pharmacists’ recommendations was 96.5%. Mood stabilizers (20%), atypical antipsychotics (17%), and typical antipsychotics (11%) were commonly associated with prevented ADRs. Lithium accounted for 13.8% of prevented ADRs; these ADRs were most often due to a drug–drug interaction with a nonsteroidal anti-inflammatory drug. Conclusions ADRs were most commonly associated with mood stabilizers and antipsychotics, and pADRs were common. There is an opportunity to provide education to medical staff on therapeutic drug monitoring and drug–drug interactions for these classes, particularly lithium.

The Role of Selegiline in the Treatment of Negative Symptoms Associated with Schizophrenia

721 2010 50 721-724 R long-acting injection (RLAI) is a second-generation antipsychotic (SGA) administered intramuscularly every 2 weeks for the treatment of schizophrenia. RLAI is the first SGA to come to market in the United States as a long-acting injectable dosage formulation targeted to improve medication adherence. RLAI is an aqueous suspension of microspheres containing risperidone in a copolymer matrix. The copolymer undergoes gradual hydrolysis at the injection site to allow a slow and steady release of risperidone over a period of several weeks, resulting in stable plasma concentrations of risperidone and its active metabolite, 9-hydroxy-risperidone. The release profile of RLAI following a single intramuscular injection consists of a small initial release of drug (<1% of the dose), followed by a lag time of approximately 3 weeks. The main release of drug begins in the third week and is maintained from week 4 to 6 and subsides by week 7. Steady-state plasma concentrations are achieved after 4 injections. Following multiple doses of RLAI, plasma concentrations of risperidone and 9-hydroxy-risperidone demonstrate linear kinetics. At the time RLAI was initially approved in 2003, it was approved only for gluteal muscle (GM) injection. In October 2008, the drug received approval for deltoid muscle (DM) administration. It is thought that DM injection may be preferred over GM injection by many patients and clinicians and allows for a choice between administration sites, thus potentially increasing patient acceptance. A literature search was performed to validate this claim, which produced no publications directly addressing patient or clinician preference for one injection site over another. Regardless, many patients will be switched from RLAI GM to DM administration, and under some circumstances, some patients may be switched from DM to GM administration. Although one study demonstrated that GM and DM injections of RLAI were bioequivalent routes of administration and thus interchangeable, we report a case of a patient switched from DM and GM injection resulting in inconsistent risperidone and 9-hydroxy-risperidone levels. To our knowledge, this is the first case reporting a difference in steady-state levels between RLAI DM and GM administration.