Amy VandenBerg

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.

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 oflinezolid 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.

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 bradycardia 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.

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.

Evaluating the Quality of Performance of Medication Reconciliation on Hospital Admission

Purpose To assess the quality of the performance of the medication reconciliation process during hospital admission. Methods Subjects were randomized by facility over a 30-day period. Standardized questionnaires were utilized to obtain demographic information, drug allergies, and medication histories. This information was compared with medication reconciliation forms completed upon hospital admission. The primary outcome was the percent of accurate forms completed by the admitting clinician. Secondary outcomes were the accuracy of individual components of the medication order and the time required to accurately reconcile medications. Results One hundred fourteen medication reconciliation forms were audited; over half the subjects were white males with a mean age of 51 years and a median of 7 home medications. Accurate medication reconciliation was documented on 13% of forms. Allergies were consistent among providers in 59% of patients. Of 742 medication orders, the number of inaccuracies was as follows: wrong dose (108, 14.6%), wrong frequency (108, 14.6%), wrong route (54, 7.3%), and wrong medication (25, 3.4%). Omissions (204) and commissions (98) occurred at a rate of 1.79 and 0.86, respectively (114 forms evaluated). The majority of patient/caregiver, outpatient provider, and retail pharmacy interviews required 15 minutes or less to complete. Conclusions Though a national benchmark does not exist for the quality of medication reconciliation performed on hospital admission, there are opportunities to increase the accuracy of medication information obtained during hospital admission.

Financial impact of a pharmacist-managed clinic for long-acting injectable antipsychotics

Nonadherence or partial adherence to antipsychotic medications contributes to long-term dysfunction and loss of autonomy. It has been associated with relapse and rehospitalization, which significantly increases the cost of treatment, as hospitalization is responsible for up to 40% of direct costs

Clinical Management of Bleeding Risk With Antidepressants

Objective: This nonsystematic review describes risk of bleeding in treatment with serotonin reuptake inhibitors (SRIs) and provide recommendations for the management of patients at risk of bleeding. Data Sources: Articles were identified by English-language MEDLINE search published prior to June 2018 using the terms SRI, serotonin and noradrenaline reuptake inhibitors, OR antidepressive agents, AND hemorrhage OR stroke. Study Selection and Data Extraction: Meta-analyses were utilized to identify information regarding risk of bleeding with antidepressants. Individual studies were included if they had information regarding bleeding risk with specific SRIs, timing of risk, or risk with medications of interest. Data Synthesis: SRIs increase risk of bleeding by 1.16- to 2.36-fold. The risk is synergistic between SRIs and nonsteroidal anti-inflammatory drugs (NSAIDs; odds ratio [OR] range between studies 3.17-10.9). Acid-reducing medications may mitigate risk of gastrointestinal bleeds in chronic NSAIDs and SRI users (OR range between studies 0.98-1.1). Antidepressants with low or no affinity for the serotonin transporter, such as bupropion or mirtazapine, may be appropriate alternatives for patients at risk of bleeding. Relevance to Patient Care and Clinical Practice: This review includes data regarding bleeding risk for specific antidepressants, concomitant medications, and risk related to duration of SRI use. Considerations and evidence-based recommendations are provided for management of SRI users at high bleeding risk. Conclusions: Clinicians must be aware of the risk of bleeding with SRI use, especially for patients taking NSAIDs. Patient education is prudent for those prescribed NSAIDs and SRIs concurrently.

Pharmacologic Options for the Management and Prevention of Migraines

Objective: To review available pharmacologic options for the management and prevention of migraine headaches. Data Sources: A PubMed literature search (1985–December 2010) was conducted using the following MeSH search terms: migraine, aura, headache, triptans, ergot derivatives, NSAIDs, opioids, analgesics, antiepileptics, antidepressants, β-blockers, calcium channel blockers, and prophylaxis. Tertiary references and prescribing information for included medications were used for dosing recommendations. Study Selection and Data Extraction: English-language reviews, tertiary references, guidelines, and clinical trials of newly released medications were reviewed for inclusion. Articles using pharmacotherapy in human models were reviewed. Data Synthesis: Migraine headaches are a costly and painful problem that affects 12% of the US population. Current treatment options may be divided into either acute treatments or preventive therapy. Nonpharmacologic therapy, such as the identification of triggers and maintenance of a headache diary, is an important addition to either medication regimen. Patients experiencing mild-to-moderate migraine pain may be able to manage the pain using nonsteroidal antiinflammatory drugs or analgesics. More severe migraine pain may require the use of different medications, such as opioid pain relievers or a triptan. Patients who report frequent migraines or migraines that significantly affect their activities of daily life may become candidates for migraine prophylaxis. Agents for migraine prophylaxis include antiepileptics, β-adrenergic antagonists, antidepressants, and calcium channel blockers. Conclusions: There are several options available for both the management and prevention of migraine headaches. Choice of pharmacotherapy depends on the intensity and frequency of a patients migraines. In addition, patients should be encouraged to avoid triggers and to keep a log of migraine symptoms in order to best manage their migraines.