Mr. B, age 44, presents to the clinic with increased anxiety and difficult-to-treat recurrent migraine headaches. His history is significant for migraines without aura, generalized anxiety disorder, major depressive disorder, and chronic insomnia. His current medications include aripiprazole 10 mg by mouth daily,
Posttraumatic stress disorder (PTSD) in children and adolescents has a high prevalence of accompanying sleep disturbances. Currently, pediatric treatment of PTSD-related nightmares is extrapolated from adult studies. This study aims to determine the effectiveness and safety of clonidine and guanfacine compared with prazosin for the treatment of PTSD-related nightmares.
Methods
This was a retrospective, single-center, medical record review of patients 5 to 17 years old admitted to an inpatient psychiatric unit from January 2015 to September 2021. Patients with a new initiation of an alpha-2 agonist (clonidine or guanfacine) or an alpha-1 antagonist (prazosin) with a diagnosis of PTSD, other trauma- or stressor-related disorder or unspecified anxiety disorder were included. The primary endpoint was the percentage of patients with a decrease in the frequency of nightmares.
Results
A total of 59 patients were included in the study: 37 in the alpha-2 agonist group and 22 in the alpha-1 antagonist group. There was no statistically significant difference in reduction of nightmares with both groups having a high percentage of patients showing response (alpha-2 agonist: 91.9%, alpha-1 antagonist: 86.4%). Time to decrease in nightmares was comparable between groups with a relatively quick onset. Within the alpha-2 agonist group, clonidine (1.59 ± 1.06 days) compared with guanfacine (3.18 ± 1.74 days) had a statistically significant faster time to reduction in nightmares (p = .005).
Discussion
Both pharmacologic classes of medications were effective treatment options for pediatric PTSD-associated nightmares with a low incidence of adverse effects. There was a quick time to onset seen with all agents.
Clozapine is the only antipsychotic approved for treatment-resistant schizophrenia, but without appropriate monitoring, it can be associated with potentially fatal outcomes. An International Adult Clozapine Titration Guideline categorizes patients into normal or slow metabolizers. Categorization provides clozapine titration schedules and recommends regular c-reactive protein (CRP) and clozapine concentration monitoring to reduce the risk of adverse drug reactions (ADRs). The impact of the guideline on clozapine ADRs has not been evaluated.
Methods
A retrospective chart review assessed clozapine titrations, laboratory monitoring, ADRs, and discontinuations for clozapine-naive adult inpatients at a single center from January 1, 2013, to June 1, 2022. Each patient’s cumulative weekly clozapine dosage was compared with their guideline recommended dosage to create a percent accordance. Linear logistic regression evaluated the relationship between titration speed and the presence of an ADR, while descriptive statistics analyzed laboratory monitoring.
Results
Forty-three patients were included, with the majority being White males with schizophrenia. An inverse relationship existed between the last inpatient week clozapine dose percent accordance and the probability of an ADR. Nonobese patients were less likely than obese patients to experience an ADR (odds ratio = 0.17; 95% CI, 0.03-0.99). CRP and clozapine concentration monitoring was suboptimal.
Discussion
Based on our small retrospective review of primarily White males, more aggressive clozapine titrations did not increase ADRs. Future studies with more diverse samples are needed and should focus on specific ADRs, which may have increased occurrence with rapid titrations. Obese patients were at higher risk of ADRs, correlating with the guideline-recommended slower titrations for these patients.
Aripiprazole has been linked to the development of impulse control problems (ICPs), most commonly gambling. Aripiprazole’s effect on serotonergic and dopaminergic pathways has had mixed results on drinking behaviors. A male patient receiving outpatient psychiatric care presented with ongoing symptoms of depression on his current regimen of mirtazapine and gabapentin. Aripiprazole was chosen for augmentation after multiple failed trials of alternative medications. Within 3 weeks the patient discontinued the medication due to escalating binge-drinking behavior. This behavior resolved within 3 days after discontinuing aripiprazole. Individuals who engage in binge drinking demonstrate consistent impulse control deficits that are unrelated to the rewarding effects of alcohol. Aripiprazole may be related to this patient’s return to binge drinking from an ICP standpoint rather than driven by alcohol cravings as other psychosocial factors remained stable throughout this time.
Catatonia is a syndrome characterized by psychomotor and behavioral disturbances and is associated with a substantially increased mortality risk in adolescent patients. There is a dearth of published literature describing treatment strategies for pediatric patients with catatonia. This dual-case series will describe the treatment course of 2 adolescent patients with catatonia at our pediatric inpatient psychiatric facility.
Case Series
This case series presents 2 adolescent patients (a 17-year-old male and a 16-year-old female) who initially presented with worsening agitation and paranoia, later developing catatonia. Both patients required long durations of hospitalization and were treated with high-dose lorazepam before requiring the addition of electroconvulsive therapy (ECT).
Discussion
Treatment of pediatric patients with catatonia creates a significant burden on patients, families, and the healthcare system. Treatment with high-dose benzodiazepines is high risk, while ECT is both difficult to access and comes with its own risks. Both patients discussed are transitional age, meaning they will soon be young adults who will continue to require high-level psychiatric care. Psychiatric pharmacists have a large role to play in ensuring safe medication management for these complex patients.
Conclusions
This case series of 2 adolescent patients with catatonia demonstrates marginal reduction in symptoms with high-dose lorazepam in conjunction with ECT, with minimal side effects. This case series adds to the limited available literature regarding treatment of catatonia in pediatric patients and highlights the need for further study into effective treatment alternatives.
Clozapine is primarily metabolized via cytochrome P450(CYP)1A2 and to a lesser extent CYP3A4, CYP2C19, and CYP2D6. Metabolic inhibitors of clozapine, such as fluvoxamine and ciprofloxacin, are important to recognize to avoid adverse drug events. Estrogen-containing oral contraceptives (eOCPs) are weaker CYP1A2 and CYP2C19 inhibitors but are associated with a 2-fold increase of clozapine concentrations. The potential for phenoconversion due to a CYP genetic polymorphism can add additional complexities when considering drug interactions. A case report is presented of a suspected interaction between newly initiated clozapine and a prescribed eOCP for which the patient’s pharmacogenomic status was known. A 17-year-old, nonsmoking, White female with a history of schizophrenia was initiated on clozapine 12.5 mg at bedtime with a plan to increase by 25 mg every 4 days in the outpatient setting. The patient was a known rapid CYP1A2 metabolizer without identified sources of CYP1A2 induction and a CYP2C19 rapid metabolizer. Based on pharmacogenomic testing, there was no suspicion for significant gene-drug interactions. Yet, as the patient was prescribed an eOCP, a clozapine concentration was obtained after reaching 150 mg at bedtime. This steady-state clozapine concentration was found to be 560 ng/mL, correlating with worsening sedation and constipation. Given ongoing side effects, clozapine was lowered to 100 mg at bedtime; however, ongoing intolerance ultimately led to clozapine discontinuation. This case highlights the potential interaction between clozapine and eOCP in a CYP1A2 and CYP2C19 rapid metabolizer, leading to clozapine intolerance and discontinuation. The concomitant use of clozapine and eOCPs should be undertaken judiciously.
Drug overdose death rates in the United States remain high despite efforts to mitigate this risk. Many communities and hospitals across the country have implemented overdose review teams, including local overdose fatality review teams or postoverdose intervention programs, to address the opioid crisis. The goal of most of these teams is to identify missed opportunities or patient-specific interventions to prevent future opioid overdose fatalities. Few overdose review teams review a combination of both fatal and nonfatal overdose events. The Veterans Affairs Tennessee Valley Healthcare System implemented a novel overdose review team (ORT) that collaboratively reviews all overdose incidents regardless of fatality, intent, or substance involved. This practice description characterizes reported facility overdose events and patient-specific risk-mitigation strategies recommended by the ORT, highlights the implementation rate and time to implementation of ORT recommendations, and discusses potential areas for process improvement. This practice highlights the potential impact of a pharmacist-led, interdisciplinary ORT following accidental or intentional overdose events involving any substance or medication. Key patient-specific interventions implemented following ORT recommendations included overdose prevention education and naloxone distribution, prescribing of medications for opioid use disorder and/or alcohol use disorder, reducing medication supply to limit lethal means access, and facilitation of mental health and/or substance use disorder specialty appointments. Further research to evaluate clinical outcomes related to specific ORT interventions should be considered.
Patients with schizophrenia often experience symptoms such as poor insight and disorganized thought, which limit their ability to seek and receive care consistently. In rural settings, systemic factors, including limited resources and transportation, further contribute to difficulties in health care access. Long-acting injectable antipsychotics (LAIs) can improve medication adherence and reduce hospitalizations from relapse. Opportunities exist for pharmacists to provide individualized care and improved health care access. The pilot service took place in ambulatory care clinics and home care settings. Pharmacists performed weekly reviews of patients with active orders for LAIs, coordinated care with nonadherent patients, and offered follow-up appointments in the Patient Centered Medical Home (PCMH). For patients unable to be reached, outreach pharmacists provided psychiatric assessment and LAI medication administration at home visits. There were 10 patients with LAI prescriptions in the past year selected for review. The period reviewed was 90 days before and after start of service. Pharmacist interventions resulted in 4 patients reestablished with care who were previously lost to follow-up. The percentage of days covered by LAI fills increased from an average 26% to 67% of days covered (P = .06). Total emergency room visits related to mental health episodes decreased from 11 to 2 visits (P = .03). Four patients who did not have metabolic lab monitoring in more than 1 year received lab monitoring as indicated. PCMH pharmacy services, including home visits by outreach pharmacists, may improve access and bridge care gaps for patients on LAIs by providing community-based services in addition to traditional clinic-based care.
