Stephanie V. Phan

Adjunct mirtazapine for negative symptoms of schizophrenia.

Negative symptoms of schizophrenia are characterized by affective flattening, alogia, avolition, and anhedonia and are often nonresponsive to antipsychotic therapy. Because negative symptoms are predictive of poor occupational and social functioning, as well as poor global outcomes, numerous studies evaluating adjunct therapy to antipsychotics have been conducted. This review focuses on the use of the antidepressant mirtazapine as adjunct therapy to antipsychotics for the treatment of negative symptoms of schizophrenia. A literature search of the MEDLINE database (from inception‐March 2011) identified eight relevant articles: six were randomized, double‐blind, placebo‐controlled trials, and two were open‐label trials. Of the six randomized trials reviewed, four studies assessed add‐on mirtazapine to second‐generation antipsychotics, whereas two studies examined add‐on mirtazapine to firstgeneration antipsychotics. Five of the six randomized trials supported the use of mirtazapine for negative symptoms of schizophrenia. Of the two open‐label trials, one naturalistic study demonstrated that mirtazapine add‐on therapy to clozapine was not associated with improvements in negative symptoms; however, this study focused primarily on improvements in cognition, not negative symptoms. An open‐label extension phase to a randomized controlled trial showed that mirtazapine continued to produce significant improvement in negative symptoms over a longer duration of time, when added to first‐generation antipsychotic therapy. Overall, mirtazapine appears to be well tolerated and associated with few drug interactions. Although adjunct mirtazapine to antipsychotics has been shown to be effective at doses of 30 mg/day in most of the trials, limitations of these studies include short study duration and small sample sizes. To improve generalizability, larger multicenter studies with broader inclusion criteria should be conducted. In addition, studies of longer duration that use different mirtazapine dosages are needed to further assess the benefits of mirtazapine for negative symptoms of schizophrenia.

Medication adherence in patients with schizophrenia

Medication nonadherence is common among patients with schizophrenia and due to a variety of factors including lack of insight, psychopathology, substance use disorder, issues associated with treatment, stigma, fragmentation of care, cultural influences, and socioeconomic status. Among this population, nonadherence is problematic because it can lead to decompensation or exacerbation of symptoms, relapse, rehospitalization or greater use of emergency psychiatric services, functional decline, and increased risk of death. Psychoeducational approaches alone are ineffective, but in combination with behavioral interventions, appear to be effective. Involving the patient’s support system, in addition to other interventions, can improve treatment adherence. Many medication-related factors, such as effectiveness and tolerability of antipsychotics, regimen complexity, and past medication trials impact appropriate medication use. Therefore, optimizing the patient’s pharmacotherapeutic regimens can improve adherence. Additional factors favorably influencing adherence include involving the patient in their treatment, fostering a therapeutic alliance, implementing/using reminder systems, and addressing substance use disorder. Medication nonadherence arises from multiple reasons that vary between patients. Thus, the most effective strategies to improve adherence are multifactorial and may involve both psychoeducational and behavioral techniques, as well as previously listed approaches. Strategies should be targeted toward the patient and their support system, whenever possible, to further improve the chances of appropriate medication use. Recognizing that all patients with schizophrenia are at risk for medication nonadherence is important. No one technique has been shown to be most effective; therefore, the risk for nonadherence should continually be assessed and multiple strategies should be targeted to the patient (and caregiver) and repeatedly implemented throughout the course of the patient’s illness.

A literature review of quetiapine for generalized anxiety disorder.

To evaluate the efficacy and tolerability of quetiapine for the treatment of generalized anxiety disorder (GAD), a literature search of the Medline database was conducted from inception to May 2014. The search was not restricted by language. Keywords used in the search were quetiapine and generalized anxiety disorder or anxiety. All studies assessing the use of quetiapine as monotherapy or adjunct therapy for the primary management of GAD in adults 18–65 years of age were included in this review. The nine studies included in this review were three studies evaluating the use of quetiapine extended release (XR) as monotherapy for acute GAD treatment, one study evaluating quetiapine XR monotherapy for maintenance treatment of GAD, and five studies evaluating quetiapine (2 XR, 3 immediate release) as adjunct therapy for acute GAD treatment. Quetiapine displayed both efficacy and tolerability in all monotherapy trials evaluating its use for acute and long‐term treatment of GAD. Despite some limitations to and heterogeneity among the five adjunct therapy studies, three studies showed that quetiapine resulted in statistically significant changes in the Hamilton Anxiety Rating Scale or Clinical Global Impressions‐Severity of Illness Scale scores. Although future studies of longer duration with broader inclusion criteria are needed to further evaluate the benefits and risks of quetiapine for GAD, in patients failing to respond to conventional antidepressant therapy, quetiapine may be a potential treatment option. With appropriate monitoring and management of adverse effects, the potential benefits of quetiapine in patients with treatment‐refractory GAD may outweigh the risks associated with its use.

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.

Acute Hyperglycemia Associated with Short-term Use of Atypical Antipsychotic Medications

The prevalence of metabolic disturbances associated with long-term use of antipsychotic medications has been widely reported in the literature. The use of atypical antipsychotics for the treatment of delirium in the intensive care unit (ICU) has gained popularity due to a lower potential for adverse effects compared with conventional antipsychotics. However, current studies evaluating safety and efficacy of antipsychotics in the ICU setting do not include metabolic parameters as a potential adverse effect that requires monitoring. It is thought that long-term adverse effects of antipsychotics may be out of context for the intensive care setting. A literature review was conducted to investigate the prevalence of acute hyperglycemia associated with short-term use of antipsychotics, with the purpose of reviewing evidence that hyperglycemia may occur even with short-term use of atypical antipsychotics. A MEDLINE search for acute hyperglycemia from short-term use of antipsychotics resulted in studies involving animal models and healthy volunteers. These studies indicate that acute hyperglycemia may occur after short-term treatment. A review of the literature shows preliminary evidence to suggest that atypical antipsychotics impact glucose sensitivity and induce insulin resistance even after a single dose. Although no studies have been conducted evaluating the impact of hyperglycemia in critically ill patients from the short-term use of atypical antipsychotics for the treatment of delirium, the potential to affect clinical outcomes exist and warrants further research in this area.

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

Prolonged sinus pauses with hydromorphone in the absence of cardiac conduction disease.

A 49-year-old male had open sigmoid colectomy with colorectal anastomosis for sigmoid diverticulitis. The patient was given patient-controlled analgesia (PCA) hydromorphone and subsequently developed bradycardia with prolonged sinus pauses up to 7.1 seconds. The pauses resolved shortly after the hydromorphone was discontinued. This is the first case report to our knowledge of reversible prolonged sinus pauses associated with the use of hydromorphone. Animal studies support a role for opioid signaling at the sinoatrial (SA) node. Hydromorphone is a potential cause of prolonged sinus pauses and should be taken into consideration when monitoring a patient on hydromorphone for pain control.

Glucose Disturbances and Atypical Antipsychotic Use in the Intensive Care Unit

Purpose: Chronic use of atypical antipsychotics may lead to metabolic abnormalities including hyperglycemia. Although evidence supports acute hyperglycemic episodes associated with atypical antipsychotic use, the acute use of atypical antipsychotics in the intensive care unit (ICU) setting has not been studied. The purpose of this study is to evaluate the occurrence of hyperglycemia in ICU patients receiving newly prescribed atypical antipsychotic. Summary: Of the 273 patient charts reviewed, 50 patients were included in this study. Approximately 45% of patients experienced at least 1 hyperglycemic episode (blood glucose >180 mg/dL) after the initiation of an atypical antipsychotic in the ICU. Of the patients experiencing at least 1 hyperglycemic episode, 60% experienced multiple distinct hyperglycemic episodes. In this study, quetiapine was the most commonly used atypical antipsychotic, 19 (38%) patients were discharged from the ICU on the atypical antipsychotic, 6 (12%) patients died in the ICU, and 31 (62%) patients were treated with an antihyperglycemic agent. Logistic regression analysis showed that women and ICU patients with a higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score were significantly more likely to have multiple hyperglycemic episodes. Conclusion: Patients admitted to the ICU and initiated on an atypical antipsychotic may develop hyperglycemia independent of other glucose-elevating factors. The direct correlation of these agents to resulting acute hyperglycemia is unknown. Further studies are needed to investigate the link between atypical antipsychotics and acute hyperglycemia and the clinical significance of the impact on patient outcomes.

Ziconotide-induced psychosis: a case report

Ziconotide is used intrathecally in the management of severe chronic pain that contains a warning against neuropsychiatric adverse events. The definition of psychiatric events is broad and management strategies are vague. This case report describes a 49-year-old female who was admitted to the acute psychiatric unit to address auditory hallucinations and paranoid ideation persisting for 3 weeks. Approximately 3 months ago, an intrathecal pump with ziconotide was implanted to treat pain. Upon hospital admission, the pump was infusing at a rate of 4.9 mcg/24 hours. Because the drug could not be immediately discontinued, risperidone 0.5 mg nightly was initiated and subsequently, the pump was drained of ziconotide, rinsed, and refilled with normal saline. The patient reported no hallucinations or apparent delusions several hours later and was eventually discharged with resolution of psychotic symptoms and continuation of risperidone for 10 days. Despite the identification of neuropsychiatric effects, limited information is available to characterize the presentation and guide specific management aside from recommendations to discontinue the infusion and possible use of psychotropic medications or necessity for hospitalization. This case report characterizes one presentation of hallucinations and paranoia associated with ziconotide intrathecal infusion. Clinicians should be aware of the management strategies to mediate these adverse effects, including expected time to adverse effect resolution, removal of ziconotide from the pump, and role for short-term use of antipsychotics.