This Month in Psychopharmacology

NEI Congress Scientific Poster Session

The 2024 NEI Congress Scientific Poster Session was held on Friday, November 8th and featured 126 posters covering the full spectrum of mental health research and clinical data. Among them, three particularly stood out for the quality of their data and contributions to the field. Presented below are the winners of the 2024 NEI Congress Young Investigator Poster Competition.


2024 NEI Congress Scientific Poster Session Winners


First Place
A Review of Olanzapine Post Delirium Sedation Syndrome (PDSS)
Ayyub Imtiaz, MD [1]; James Miller, MD [1]; Abidemi Onabadejo, MD [1]; Lauren Pengrin, DO [1]Affiliations: [1] - Saint Elizabeths Hospital - Department of Behavioral Health, Washington D.C.


Introduction: Schizophrenia is a chronic progressive neuropsychiatric condition that carries extensive morbidity for both patients and communities. Medication adherence is a key factor in optimizing positive outcomes in these patients. Long acting injectables (LAI) help with medication adherence. Olanzapine has an LAI option, Olanzapine pamoate. However, it is part of the Risk Evaluation and Mitigation Strategy (REMS) due to a black box warning of Post Delirium Sedation Syndrome (PDSS) after administration, which limits its use in practice. This review aims to synthesize the literature on PDSS to educate clinicians about PDSS.


Method: This summary review queried databases such as MEDLINE, EBSCO, PsycINFO, Scopus, and Google Scholar with keywords like “Olanzapine,” “long acting injectable,” “Olanzapine pamoate,” “Olanzapine LAI,” “post-injection delirium,” “post delirium sedation syndrome,” “PDSS,” and “olanzapine toxicity." Articles, theoretical reviews, and case reports were all utilized, with a focus on pathophysiology and treatment.


Results: Symptoms of PDSS emphasize sedation and delirium, but also include motor impairments (including speech, gait, coordination, extrapyramidal symptoms), cognitive impairments (confusion and disorientation), autonomic instability (fever, dizziness, hypertension), agitation, and seizures. Non-specific peripheral symptoms may precede more central signs as the medication crosses the blood-brain barrier. Symptoms start within 30 minutes to 3 hours of medication administration and usually resolve within 72 hours. Incidence is <0.1% of all injections, occurring in approximately 1.4% of patients. The risk is cumulative, with PDSS developing on average after the 21st injection. Two possible pathophysiological causes of PDSS include acute olanzapine toxicity, when medication leaks from the muscle into the bloodstream and/or prolonged anticholinergic exposure. Effective treatment in the literature has been intravenous physostigmine with additional oral rivastigmine afterwards if needed. Medications for neuroleptic malignant syndrome (NMS), like dantrolene or bromocriptine, have been added in cases with evidence of significant dopaminergic blockade.


Conclusion: PDSS is a potentially lethal but possibly overestimated side effect of Olanzapine pamoate. Care should be taken with injections to try and minimize leakage into the bloodstream. Moreover, it is pertinent for clinicians to remember the anticholinergic effects and how to manage them for effective and timely treatment. Potential for future research include the use of bedside imaging, like ultrasound, during injection to minimize vasculature damage as well as the use of use pro-cholinergic medications, like rivastigmine, as pretreatment prior to injection.

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Extended-Release Bupropion Hydrobromide for Treatment-Resistant Depression
Maxwell Zachary Price, BA: Hackensack Meridian School of Medicine, Nutley, New Jersey; Richard Louis Price, MD: Weill Cornell Medical College, New York, New York


Introduction: Treatment-Resistant Depression (TRD), defined as a failure of at least 2 oral antidepressants at adequate dose and duration in the current episode, is a common and often debilitating condition. Presently, there is only one FDA-approved oral TRD medication, fluoxetine-olanzapine, that carries potential sedation, cardiometabolic, extrapyramidal, and sexual side effects, and there is one approved adjunctive nasal spray, esketamine, that requires 2-hour in-office monitoring limiting its access. Extended-release (XL) bupropion hydrochloride (HCl) received FDA approval for Major Depressive Disorder (MDD) in 2003 and for Seasonal Affective Disorder (SAD) in 2006. Subsequently, XL bupropion hydrobromide (HBr) (Aplenzin®) received FDA approval in 2008 for both MDD and SAD following demonstration of pharmacokinetic bioequivalence to XL bupropion HCl. However, no human clinical efficacy trials of XL bupropion HBr have ever been completed and none comparing it to XL bupropion HCl. We wanted to compare equivalent FDA-approved dosing of XL bupropion HBr to generic XL bupropion HCl in adult patients with TRD.


Methods: We obtained informed consent from each patient prior to conducting a de-identified retrospective chart review of 30 adult outpatients with severe TRD (18 females, 12 males) who directly switched from their maximally tolerated dose of generic XL bupropion HCl, due to inadequate response with or without side effects, to an equivalent dose of XL bupropion HBr. Patient Health Questionnaire (PHQ-9) scales were administered by a blinded rater to measure antidepressant response.


Results: Patients had a mean age of 38.7 +/- 14.7 years, failed a mean of 4 +/- 2 antidepressants, and had a mean baseline PHQ-9 score of 20.9 +/- 4.3 prior to taking a mean XL bupropion HCl dose of 300 mg/day (range 150?450 mg/day) for a mean duration of 88.8 weeks (range 4?480 weeks). After 2 weeks on a mean XL bupropion HBr dose of 348 mg/day (range 174?522 mg/day), these patients demonstrated improvement in PHQ-9 scores from a mean of 15.3 +/- 5.3 on XL bupropion HCl to a mean of 6.4 +/- 5.0 on XL bupropion HBr (t = -8.63, p < 0.00001). The most commonly encountered side effects with generic XL bupropion HCl were insomnia (21 patients), anxiety (19 patients), and gastrointestinal upset (2 patients), which resolved on XL bupropion HBr except for residual insomnia (3 patients). 96.7% of patients (29 of 30) chose to continue on XL bupropion HBr rather than change back to generic XL bupropion HCl.


Conclusion: Adult patients suffering from TRD experience rapid and significant improvement in mood with greater tolerability when switching from generic XL bupropion HCl to an equivalent dose of XL bupropion HBr. A further double-blind study could enable the first FDA-approved oral TRD medication in nearly 2 decades.

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Flibanserin versus Bremelanotide: Comparing FDA Approved Drugs for Female Sexual Interest/Arousal Disorder
Keti Kutidze, MD1, Ayyub Imtiaz, MD2, Mamuka Khundadze, MD3, Ashwin Mathai, MD2 AFFILIATIONS: [1] - Phoenixville Hospital - Tower Health - Department of Psychiatry, Phoenixville, PA[, [2] - Saint Elizabeths Hospital - Department of Behavioral Health, Washington, D.C. [3] - David Tvildiani Medical University, Tbilisi, Georgia


Introduction: Female Sexual Interest/Arousal Disorder (FSIAD) is a new addition to DSM V, merging Hypoactive Sexual Desire Disorder and Female Sexual Arousal Disorder into one diagnosis. It is diagnosed after at least 6 months of significantly reduced sexual interest/arousal causing distress, and is not due to other mental disorders, severe relationship distress, other stressors, substance/medication effects, or medical conditions. It is thought that FSIAD is due to an imbalance in excitatory and inhibitory activities in the nervous system. FSIAD can contribute to the functional impairment in patients who have comorbid psychiatric conditions. This is also compounded by side effects of psychiatric medication like selective serotonin reuptake inhibitors (SSRIs). However, literature discussing FSIAD management is sparse. In this article, the authors compare the only FDA approved medications for FSIAD, flibanserin and bremelanotide.

Method: The authors conducted a narrative review on the usage of flibanserin and bremelanotide for FSIAD in the literature, as well as reviewing their FDA labels. Recurrent and differing themes between these medications regarding their use and side effects were extracted.


Results: Flibanserin is a serotonin 1A receptor agonist and serotonin 2A receptor antagonist that decreases serotonin but increases dopamine and norepinephrine levels in the prefrontal cortex, enhancing focus on sexual stimuli. It is taken daily and is safe to use with SSRIs. Flibanserin is contraindicated in patients with hepatic impairment and with moderate/strong CYP3A4 inhibitors. It has a black box warning of severe hypotension when consumed with alcohol. Common side effects include low blood pressure and sedation. Bremelanotide, an as-needed injection administered 45 minutes before sexual activity, acts as a melanocortin receptor agonist, enhancing dopamine and oxytocin release and affecting peripheral nerves in the clitoris and vagina. Common side effects include nausea, flushing, injection site reactions, headache, vomiting, and high blood pressure. Thus, it is contraindicated in patients with uncontrolled hypertension or known cardiovascular disease and is not recommended for those at high risk for cardiovascular issues. Bremelanotide should not be used with naltrexone due to decreased efficacy, and its interactions with SSRIs are not extensively studied.


Conclusion: Providers should consider FSIAD and its corresponding treatments in patients with existing residual sexual dysfunction that is causing significant interpersonal impairment. While there are 2 options available for prescription, clinicians should be aware of the differences and contraindications when making a selection.

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