Reduction of benztropine use duration in acute psychiatry: A quality improvement initiative.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Secondary to the risk of antipsychotic-induced acute dystonia, prophylactic use of benztropine is occasionally warranted but is recommended for no longer than 7 days after initiating an antipsychotic, correlating to the period of highest dystonia risk. Despite the associated increased anticholinergic burden, many clinicians continue to order benztropine for periods exceeding the recommended prophylactic duration. We investigated the reduction of benztropine use duration subsequent to implementation of truncated electronic entry orders to improve benztropine prescribing within an acute psychiatric facility. METHODS: Data were collected for psychiatric inpatients admitted between January and June 2020 who were prescribed scheduled benztropine. In a quality improvement initiative implemented in April 2022, electronic orders for benztropine were modified from a 180-day to a 7-day duration, with subsequent postintervention data collection. The primary outcomes included a change in the duration of benztropine use for any indication in the hospital, and a change in the percentage of patients meeting predetermined "unnecessary use" criteria. Secondary analyses included the percentage of patients with discharge prescriptions for scheduled benztropine (either for prophylaxis or for other indications) in the pre- and postintervention periods. RESULTS: 73 pre- and 77 postintervention individual patients/encounters were included. Following the intervention, in-hospital duration of benztropine use for any indication decreased from a median of 14 days to a median of 7.5 days (P < 0.05), and appropriate use increased by 92.9%. The percentage of patients with prescriptions for scheduled benztropine decreased from 67.1% in the preintervention group to 29.9% in the postintervention group. CONCLUSION: Decreased benztropine use duration, by means of truncated order entry sentences, during inpatient psychiatric admissions, appears feasible regardless of dual antipsychotic or first-generation antipsychotic use, and may reduce the rates of benztropine prescriptions written for discharge.

Sublingual asenapine for agitation in malabsorptive states: three patient cases.

Gastric malabsorptive conditions may prevent patients from deriving benefit from orally administered medications intended for enteric absorption. While malabsorption is an increasingly common issue, current data on alternative oral options for agitation in these patients are very sparse. Sublingual (SL) asenapine is absorbed transmucosally, bypassing gut absorption, making it a viable consideration. We report on three patients, one with short bowel syndrome, one with viral gastritis, and one with aortic dissection who were trialed on SL asenapine for agitation after failing alternative antipsychotics. Two of these patients had an extensive history of psychiatric admissions for bipolar disorder and substance-induced psychosis. All three patients had significant reductions in agitation within 1-5 days, with no reported adverse effects. However, benefit of SL asenapine was hindered in two of these patients as they began inappropriately swallowing the medication, reducing bioavailability to nil. Clinicians should consider the use of SL asenapine for medically complex agitated patients where gastric absorption is questionable. There is an urgent need for guidelines on this matter, as well as more, alternative dosage forms for various medications that may help with agitation in this population.

New-Onset Prolonged Psychosis Following Synthetic Cannabinoid Use in an Older Patient: A Case Report.

Synthetic cannabinoids (SCs), a class of new psychoactive substances (NPS) commonly known as "spice," has rapidly gained popularity and become the most ubiquitous NPS on the illegitimate drug market. SCs, unlike natural cannabis (NC), are not controlled by international drug conventions, posing a significant risk to public health. These substances are easily accessible, relatively inexpensive, and challenging to detect in routine drug screenings. The existing literature provides strong evidence of an association between NC use and psychosis, but there is significantly less data on SC psychosis. We present a clinical case report of a 51-year-old African American female with no known psychiatric history who was admitted to the inpatient psychiatric unit after reported paranoia and altered mental status for the preceding six days. During hospitalization, she exhibited disorganization, persecutory delusions, extreme agitation, and bizarre behaviors that included the concealment of a set of stolen keys in her vagina, necessitating an ethics consult. After consideration of differentials, the patient was diagnosed with substance-induced psychotic disorder secondary to SC. The patient was stabilized on 3 mg Risperidone at bedtime. After 16-day hospitalization, she reached her baseline and later revealed that she had recently smoked SC for the first time. The primary goal of this case is to highlight the sequelae of SC-associated psychosis. A SC-associated psychosis could drastically vary from NC and is often undetectable on a typical UDS, which may result in a lifelong primary psychotic disorder misdiagnosis.

Manic episode following psilocybin use in a man with bipolar II disorder: a case report.

There has been an increase in research on the topic of psychedelic substances and their effects as treatment options in neuropsychiatric conditions. Psilocybin is a psychedelic drug that has recently garnered increased interest as an effective treatment modality for treatment-resistant depression, depression associated with terminal conditions, certain substance use disorders, and obsessive-compulsive disorder. However, sparse data exist as to the effects that psilocybin might have on patients at risk for mania, in large part secondary to the exclusion of this patient population from studies due to the concern for inducing mania or worsening illness course. We describe a case of a 21-year-old male with a recent diagnosis of bipolar II disorder who developed a manic episode following the ingestion of psilocybin in the form of hallucinogenic mushrooms. Given the incidence of depression in those with bipolar disorder, impulsivity, and a tendency to abuse substances associated with the illness, further research is needed into the risks of psilocybin and other psychedelic use in those with bipolar disorder.

Antipsychotics and obsessive-compulsive disorder/obsessive-compulsive symptoms: A pharmacovigilance study of the FDA adverse event reporting system.

OBJECTIVE: Antipsychotics have conflicting data with respect to obsessive-compulsive disorder/symptoms (OCD/OCS), with some reporting causality and some reporting treatment benefits. This pharmacovigilance study aimed to investigate reporting of OCD/OCS in association with the use of antipsychotics in comparison to one another, as well as treatment failure using data derived from the FDA Adverse Event Reporting System (FAERS). METHODS: Data from January 1st, 2010 to December 31st, 2020 on suspected adverse drug reactions (ADRs) including OCD/OCS was obtained. The information component (IC) was used to determine a disproportionality signal, and reporting odds ratio (ROR) calculations were performed via intra-class analyses to discern differences between the evaluated antipsychotics. RESULTS: A total of 1454 OCD/OCS cases were utilized in IC and ROR calculations and 385,972 suspected ADRs were used as non-cases. A significant disproportionality signal was seen with all second generation antipsychotics. Relative to other antipsychotics, only aripiprazole had a significant ROR of 23.87 (95% CI: 21.01-27.13; p < 0.0001). The ROR for antipsychotic treatment failure in those with OCD/OCS was highest with aripiprazole, and lowest with risperidone and quetiapine. Sensitivity analyses were largely in favor of the primary findings. Our analysis appears to implicate the 5-HT1A receptor or an imbalance between this receptor and the D2 -receptor in antipsychotic treatment-emergent OCD/OCS. CONCLUSIONS: In contrast to prior reports noting clozapine as the antipsychotic most commonly associated with de novo or exacerbated OCD/OCS, this pharmacovigilance study found aripiprazole was most frequently reported for this adverse effect. While these findings from FAERS offer a unique perspective on OCD/OCS with different antipsychotic agents, due to the inherent limitations of pharmacovigilance studies they should ideally be validated through alternative prospective research studies involving direct comparisons of antipsychotic agents.

Delta-8-THC association with psychosis: A case report with literature review.

Background: Cannabis (Δ9-THC) is the most commonly consumed illicit drug. The Agricultural Improvement Act of 2018 removed hemp, a strain of Cannabis sativa, as a controlled substance. This law allowed the plant to be processed into its components, which contain <0.3% Δ9-THC. As a result, delta-8-tetrahydrocannabinol (Δ8-THC), a federally unregulated substance, grew in popularity in 2020. Δ8-THC is readily available in most gas stations or head shops and may be considered harmless by patients. However, an increasing number of patients admitted for psychiatric hospitalization report use, with limited literature on the effects. Case presentations: This case report describes three individual cases of patients who required admission to a university psychiatric hospital after the regular use solely of Δ8-THC. All three patients developed psychotic and paranoid symptoms concurrently with the use of Δ8-THC, with a severity exceeding their previous historical presentations. The presenting psychotic symptoms were also atypical for all three patients. New-onset violence and visual hallucinations were noted in two of the patients, one patient with no previous psychiatric history and one patient while on a therapeutic dose of his antipsychotic. In the third case, a new onset of bizarre, fixed delusions of puppies dissolving in the bathtub developed. Conclusion: This report adds to the limited body of evidence on Δ8-THC documenting a temporal association between Δ8-THC use and the development of psychotic symptoms. A strong body of research already correlates the continued use of Δ9-THC with psychosis, and Δ8-THC acts at the same CB1 and CB2 receptors as Δ9-THC. Therefore, it is hypothesized that Δ8-THC may have similar adverse psychiatric effects as Δ9-THC. These conclusions are not without speculation, due to the need for self or collateral-reporting of Δ8-THC use as urine drug screening cannot distinguish Δ8-THC from Δ9-THC, and the patients' symptoms could be explained by medication non-adherence and primary psychotic disorders. However, physicians should be encouraged to gather a specific history of Δ8-THC use and treat patients with Δ8-THC-related intoxication and symptoms.

Use of a Novel Standardized Administration Protocol Reduces Agitation Pro Re Nata (PRN) Medication Requirements: The Birmingham Agitation Management (BAM) Initiative.

BACKGROUND: Agitation management is a principal challenge on inpatient psychiatric units. Overreliance on common prescribing strategies of pro re nata (PRN) medication administration is problematic, given the tendencies to have overlapping or unclear indications. OBJECTIVE: Piloted project to determine whether a standardized protocol for agitation intervention may reduce PRN medication administration. METHODS: The Birmingham Agitation Management (BAM) interdisciplinary team uniquely connected the Brøset Violence Checklist (BVC) for assessment of agitation severity to a standardized PRN medication order set. Nurses on the piloted unit were trained on how to score the BVC and administer medications. Patients were assessed by the BVC every 4 hours and, based on their score, would receive no medication, low-dose benzodiazepine, high-dose benzodiazepine, or high-dose benzodiazepine plus antipsychotic. The primary end point compared the number of PRNs administered after novel protocol implementation with a retrospective cohort. Secondary measures included analysis of medication-related effects, seclusion, and physical restraint rates. RESULTS: 377 patients were included in the final analyses (184 pre-BAM, 193 BAM intervention group). No significant differences were seen in patient characteristics between groups. The total number of PRNs administered decreased by 42.5%, with both the mean and median number of administrations decreasing significantly (95% confidence interval [CI] = [1.68-5.75]; P < 0.001). A trend was noted between the number of PRNs administered and seclusion rates, but did not reach statistical significance (95% CI = [-7.28 to 60.31]; P = 0.124). CONCLUSIONS: In seemingly the first initiative of its kind, we found that a standardized agitation management protocol can help decrease the total number of PRN administrations for agitation without worsening of restraint rates and may possibly reduce the risk of adverse effects. These results require validation in specific, larger populations.

Paliperidone-Associated Sialorrhea: A Case Report With Review of Current Literature.

PURPOSE/BACKGROUND: Antipsychotic-associated sialorrhea is a problematic adverse effect with potentially negative consequences on quality of life and medication adherence. While clozapine is the antipsychotic that is most associated with sialorrhea, there have been published reports of other second-generation antipsychotics associated with sialorrhea, including aripiprazole, olanzapine, quetiapine, and risperidone. Although drooling is mentioned within the package insert for paliperidone, to date there have been minimal published reports in which paliperidone is implicated as the offending agent. METHODS/PROCEDURES: Here, we present a case of sialorrhea in a 56-year-old man with schizoaffective disorder who had a supratherapeutic paliperidone level after both oral and intramuscular paliperidone use. FINDINGS/RESULTS: Paliperidone was ultimately cross tapered to aripiprazole, and the patient was given atropine drops and benztropine with resolution of the sialorrhea. We provide a review of the literature regarding the other available reports of paliperidone-associated sialorrhea, possible mechanisms behind pathophysiology, as well as reports from the World Health Organization and Food and Drug Administration adverse event reporting systems. IMPLICATIONS/CONCLUSIONS: Clinicians should be aware of the potential for paliperidone and other nonclozapine second-generation antipsychotics to be associated with sialorrhea, especially given the increased frequency of their use for a variety of psychiatric disorders.

Psychotropic-Induced Priapism in a Treatment-Refractory Patient: A Case Report.

PURPOSE: A case report of multiple episodes of priapism associated with the use of 4 different psychotropic medications. SUMMARY: A 34-year-old African American male with treatment-refractory schizoaffective disorder suffered priapism on 6 separate occasions. His medical history is relatively unremarkable, with the exception of possible undiagnosed thalassemia. All incidences were potentially attributable to psychotropic medications, with chlorpromazine, risperidone, trazodone, and quetiapine being the most likely culprits. The onset of priapism ranged from hours after a single injection of chlorpromazine, to years after multiple injections of risperidone, with nothing to indicate a medication dose or duration relationship to priapism. While on clozapine, fluphenazine, haloperidol, lurasidone, and olanzapine at varying times, the patient did not appear to develop priapism. The commonality of high-affinity alpha-1 antagonism with these psychotropics may be to blame. No pharmacokinetic or pharmacodynamic interactions were noted, which would have produced elevations in the levels of these psychotropics, nor was the patient on any phosphodiesterase type 5 (PDE-5) inhibitors or antihypertensives known to cause priapism. Depending on the offending agent, the Naranjo et al's Adverse-Reaction Probability Scale scores ranged from 5 to 8 (probable). CONCLUSION: A man suffered from multiple episodes of priapism attributed to psychotropic medications. This is not the first case to describe this effect, but will give clinicians a timeline of events and medications that did and did not appear to elicit priapism in a patient with treatment-refractory schizoaffective disorder. Knowledge of which psychotropic medications may be more likely to induce priapism is crucial to preventing long-term penile damage.

A case report of acute hypothermia during initial inpatient clozapine titration with review of current literature on clozapine-induced temperature dysregulations.

BACKGROUND: Here we describe a unique case of clozapine-associated hypothermia during initial titration of this medication in an acute inpatient psychiatry setting. Only a handful of cases on this topic have been published. We discuss possible pharmacologic mechanisms supporting or refuting the propensity of clozapine to induce hypothermia, as well as risk factors for clozapine-induced hypothermia, and a comparison to clozapine-induced hyperthermia. CASE PRESENTATION: A 70 year-old African American female with treatment-refractory schizoaffective disorder developed hypothermia with a nadir temperature of 89 °F (31.7 °C) after 7 days on clozapine, on a total dose of 50 mg twice daily. Accompanying symptoms included bradycardia, hypotension, QTc prolongation, tachypnea, hypoxemia, and an absence of shivering. The patient was transferred to the ICU, and rewarmed within 10 h with the discontinuation of her clozapine, ziprasidone, and carvedilol. Broad spectrum antibiotics were initiated, but discontinued shortly after, as the patient had no leukocytosis, and blood cultures were negative. DISCUSSION: While hypoglycemia, hypothyroidism, sepsis, and stroke were effectively ruled out, alternative drug-disease (including chronic kidney disease), and drug-drug interactions were considered possible contributing features. Benzodiazepines, valproic acid, ziprasidone, and the numerous antihypertensive agents the patient was taking were considered as either primary or compounding factors for hypothermia. After exclusion or inclusion of these alternative causes, we calculated a score of 4 (possible) for clozapine-induced hypothermia on the Naranjo Scale. CONCLUSIONS: Clozapine-induced hypothermia may occur more commonly than clinicians believe. Practitioners should be cognizant of this potentially fatal phenomenon, and monitor for temperature dysregulations while on clozapine, especially during initial titration, in those with multiple comorbid factors, and on additional medications that may contribute to hypothermia.