Rifampin-divalproex drug-drug interaction in an adult patient: A case report.

The divalproex (DVP) package insert states that rifampin may increase the oral clearance of valproate by 40% and that valproic acid derivative dose adjustments may be required when starting or stopping rifampin. However, the overall clinical significance of this drug-drug interaction remains unclear given that limited clinical outcome data has been published. This case describes a 52-year-old female with bipolar disorder, borderline personality disorder, and PTSD who was previously stable on a medication regimen consisting of DVP delayed-release 500 mg every morning and 1500 mg every evening (baseline steady-state trough 99.8 mcg/mL). Throughout rifampin therapy for latent tuberculosis treatment, she required an increase in both the frequency of DVP administration, from 2 to 3 times daily, and DVP dose by 75% to maintain clinical stability. Valproic acid trough concentrations ranged from 56.4 to 75.9 mcg/mL during the 4-month course of rifampin. This report supports that the DVP-rifampin interaction may be clinically significant and of a greater magnitude than suggested by the package insert.

Risk Factors for Utilization of Acute Care Services for Lithium Toxicity.

OBJECTIVE: This study evaluated risk factors for utilization of acute care services (ACS) (hospitalization or emergency department or urgent care visit) for lithium toxicity and the prevalence of lithium toxicity in a large, ambulatory population. METHODS: A nested case-control study compared lithium users with ACS utilization for lithium toxicity (case group) to lithium users without toxicity (control group) by using data from Kaiser Permanente Colorado for patients with at least one lithium prescription purchase. Patients in the case group were matched 1:5 with patients in the control group who had purchased lithium within 39 days of the ACS encounter. Possible lithium toxicity, identified by lithium level or diagnosis, was confirmed by chart review. Multivariable, conditional logistic regression analysis was used to identify patient and prescription characteristics associated with ACS utilization for lithium toxicity. The prevalence of lithium toxicity was determined. RESULTS: Of 3,115 individuals who took lithium, 70 experienced lithium toxicity, with or without ACS utilization, for a prevalence of 2.2%. Identified risk factors for ACS utilization for lithium toxicity included a newly initiated potentially interacting medication (odds ratio [OR]=30.30, 95% confidence interval [CI]=2.32-394.95), a higher number of treated chronic diseases (OR=1.28, CI=1.12-1.45), older age (OR=1.05, CI=1.02-1.09), and higher total daily lithium dose (OR=1.00, CI=1.00-1.00). CONCLUSIONS: Newly initiated, potentially interacting medications are a major preventable driver of ACS use for lithium toxicity, whereas age, chronic disease, and total daily lithium dose are small but significant factors. Clinicians should use extra caution when initiating a potentially interacting medication.

Pregabalin as adjunctive therapy in benzodiazepine discontinuation.

PURPOSE: The available evidence for the use of pregabalin as adjunctive therapy in the discontinuation of benzodiazepines is reviewed. SUMMARY: Pregabalin has been studied as an adjunctive pharmacologic treatment for the discontinuation of long-term benzodiazepine use. Unlike carbamazepine, pregabalin has little potential for drug interactions, and its adverse effects are mostly mild and transient. Pregabalin reduces the release of excitatory neurotransmitters by binding to regulatory subunits of voltage-activated calcium channels. The majority of studies evaluated failed to find a significant difference in benzodiazepine discontinuation rates between pregabalin and comparator groups. The long-term efficacy of pregabalin in benzodiazepine discontinuation is also unknown, as patients were only followed for 0-12 weeks after discontinuing the benzodiazepines. Most studies, however, did observe consistent improvement in withdrawal symptoms, anxiety symptoms, and cognitive function with pregabalin use in benzodiazepine discontinuation. Studies varied in design elements, such as whether past benzodiazepine discontinuation attempts occurred, baseline benzodiazepine use characteristics (agent, dose, duration), benzodiazepine discontinuation strategies previously used, and the use of comorbid psychiatric diagnoses and concurrent psychotropics as exclusion criteria. In addition, the literature does not clearly describe whether patients successfully discontinued pregabalin, for which there are reports of substance abuse. CONCLUSION: Based on the current available evidence, pregabalin is not recommended for use in benzodiazepine discontinuation, as the majority of studies did not find a significant difference in benzodiazepine discontinuation rates between pregabalin and comparatory groups despite an improvement in withdrawal and anxiety symptoms.

Review of cariprazine in management of psychiatric illness.

Schizophrenia and bipolar disorder are severe and debilitating psychiatric disorders. Despite the availability of numerous antipsychotic drugs, many patients still experience poor outcomes and treatment-limiting adverse side effects. Cariprazine is a novel antipsychotic with unique pharmacodynamic and pharmacokinetic properties. It is both a dopamine type 2 and dopamine type 3 partial agonist with 2 equipotent metabolites, desmethyl cariprazine and didesmethyl cariprazine, of which didesmethyl cariprazine has a half-life of 1 to 3 weeks. The objective of this article is to review the literature regarding efficacy and tolerability of cariprazine in the management of psychiatric disorders to determine its current place in therapy.

Cost-avoidance and qualitative analysis of clinical pharmacy interventions by psychiatric pharmacy residents at state psychiatric facilities.

PURPOSE: The cost avoidance and quality of clinical interventions made by postgraduate year 2 (PGY2) psychiatric pharmacy residents are analyzed. METHODS: A retrospective database review of clinical interventions made by PGY2 psychiatric pharmacy residents in two state psychiatric facilities from July 1, 2007 through June 30, 2014, was conducted using a clinical intervention documentation software system. Cost avoidance was calculated by multiplying the mean cost of an adverse drug reaction (ADR) by the probability of an ADR occurring had the intervention not occurred. Sensitivity analyses were performed to identify a conservative estimate of cost avoidance and an upper limit estimate of cost avoidance. The significance of an intervention was determined based on the potential of the intervention type to impact patient care. RESULTS: A total of 2,329 clinical interventions were documented by 10 residents during the seven-year study period, with a mean of 233 interventions made per resident. Interventions were largely accepted (70.1%), were of moderate significance (61.9%), were associated with management of psychiatric conditions (48.7%), and primarily involved medication adjustments (13.7%), particularly for antipsychotics (24.6%). The estimated overall cost avoidance associated with PGY2 psychiatric pharmacy resident interventions was $406,944 over the study period, with a mean cost avoidance of $40,694 per resident. CONCLUSION: A detailed qualitative analysis revealed that PGY2 psychiatric pharmacy residents' interventions were largely accepted, focused on medication adjustments for psychiatric conditions, and were of moderate significance at two state psychiatric facilities. Antipsychotics were associated with the greatest cost avoidance and total number of interventions.

Fatty Acid desaturase gene polymorphisms and metabolic measures in schizophrenia and bipolar patients taking antipsychotics.

Atypical antipsychotics have become a common therapeutic option in both schizophrenia and bipolar disorder. However, these medications come with a high risk of metabolic side effects, particularly dyslipidemia and insulin resistance. Therefore, identification of patients who are at increased risk for metabolic side effects is of great importance. The genetics of fatty acid metabolism is one area of research that may help identify such patients. Therefore, in this present study, we aimed to determine the effect of one commonly studied genetic polymorphism from both fatty acid desaturase 1 (FADS1) and FADS2 gene on a surrogate measure of insulin resistance and lipid levels in a metabolically high-risk population of patients largely exposed to atypical antipsychotics. This study used a cross-sectional design, fasting blood draws, and genetic analysis to investigate associations between polymorphisms, haplotypes, and metabolic measures. A total of 320 subjects with schizophrenia (n = 226) or bipolar disorder (n = 94) were included in this study. The mean age of the population was 42.5 years and 45% were male. A significant association between FADS1 and FADS2 haplotypes was found with insulin resistance while controlling for confounders. Further investigation is required to replicate this finding.

Antipsychotic treatment response in schizophrenia.

PURPOSE: Research supporting the "early-onset" theory of antipsychotic activity is reviewed, with an emphasis on psychometric assessment of early response to antipsychotic agents as a tool for optimizing schizophrenia treatment outcomes. SUMMARY: A growing body of evidence indicates that a poor response to antipsychotic therapy in the first weeks of schizophrenia treatment may justify a prompt switch to alternative medication in some cases. In placebo-controlled trials of both first- and second-generation antipsychotics, nonresponse at week 1 or 2, as determined with assessment instruments such as the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS), was found highly predictive of nonresponse at week 4 or later; however, an early favorable response to a particular antipsychotic agent does not appear to be a similarly strong predictor of continued responsiveness. While the available evidence indicates that the BPRS, PANSS, and other scoring tools can be useful in guiding schizophrenia treatment decisions, it also emphasizes the importance of patient-specific factors (e.g., severity of illness at diagnosis, age at symptom onset, premorbid adolescent functioning) as determinants of both initial and longer-term antipsychotic response. CONCLUSION: The current evidence suggests that early nonresponse to antipsychotic treatment may predict subsequent non-response, though early response is not necessarily indicative of future response. If patients do not respond to treatment within the first two weeks of an acute exacerbation, clinicians (being cognizant of patient-specific factors) should consider switching antipsychotic agents, except in patients with first-episode psychosis, for whom a longer trial of the initially prescribed therapy appears to be appropriate.