Treating Narcissistic Disorders in General Psychiatry: Practical Application of Transference-Focused Psychotherapy Principles.

Patients with primary or co-occurring narcissistic disorders are seen routinely in general psychiatry settings. Contemporary trends in training and practice have impacted psychiatrists' skills and confidence in identifying and treating these disorders, which can range from relatively benign to high-acuity presentations. The goal of this article is to introduce key principles derived from transference-focused psychotherapy (TFP) for use by clinicians in general practice in their work with patients with narcissistic disorders, even when those clinicians do not routinely provide individual psychotherapy. Practical application of TFP principles in work with patients with narcissistic disorders in general psychiatry are proposed, including in diagnostic evaluation, family engagement, prescribing, and safety assessment and risk management calculus. Many psychiatrists whose practices are focused primarily on psychopharmacology, or a "medical model," may not appreciate fully the impact of pathological narcissism in their work. Clinicians who may benefit from familiarity with TFP principles in work with patients with narcissistic disorders include the approximately one-half of U.S. psychiatrists who do not offer psychotherapy in their practice.

Considerations for Opioid Use Disorder Treatment From Policy Makers' Experiences With COVID-19 Policy Flexibilities.

OBJECTIVE: This qualitative study aimed to examine how states implemented COVID-19 public health emergency-related federal policy flexibilities for opioid use disorder treatment from the perspective of state-level behavioral health policy makers. Recommendations are given for applying lessons learned to improve the long-term impact of these flexibilities on opioid use disorder treatment. METHODS: Eleven semistructured interviews were conducted with 13 stakeholders from six state governments, and transcripts were qualitatively coded. Data were analyzed by grouping findings according to state-, institution-, and provider-level barriers and facilitators and were then compared to identify overarching themes. RESULTS: Policy makers expressed positive opinions about the opioid use disorder treatment flexibilities and described benefits regarding treatment access, continuity of care, and quality of care. No interviewees reported evidence of increased adverse events associated with the relaxed medication protocols. Challenges to state-level implementation included gaps in the federal flexibilities, competing state policies, facility and provider liability concerns, and persistent systemic stigma. CONCLUSIONS: As the federal government considers permanent adoption of COVID-19-related flexibilities regarding opioid use disorder treatment policies, the lessons learned from this study are crucial to consider in order to avoid continuing challenges with policy implementation and to effectively remove opioid use disorder treatment barriers.

Practice Pearls for Stimulant Treatment of Attention-Deficit/Hyperactivity Disorder in Youth.

Over half of youth with attention-deficit/hyperactivity disorder (ADHD) have co-occurring psychiatric or medical conditions that present treatment challenges. Stimulants are the most effective pharmacologic treatment of ADHD for preschoolers to adults but questions about safety with co-occurring conditions frequently arise. In addition, stigma surrounding diagnosis and treatment can negatively impact care. This manuscript presents evidence-based practice pearls to guide treatment decisions for youth with ADHD and common coexisting psychiatric and medical conditions. Recommendations address specific stimulant adverse effects (i.e., anxiety, cardiac, growth, mania, psychosis) along with management strategies. Pearls were developed for the most common clinical questions, controversial topics, or therapeutic issues that may not be widely known. The goals of this manuscript are to: 1) provide a detailed resource for interprofessional teams regarding stimulant use in youth with ADHD, 2) improve therapeutic outcomes for youth with ADHD and co-occurring psychiatric and/or medical conditions through evidence-based recommendations, and 3) decrease stigma associated with stimulant use through education.

Trends in the nonmedical misuse of benzodiazepines and Z-hypnotics among school-aged adolescents (2016-2021): gender differences and related factors.

BACKGROUND: The misuse of psychotropic medication has increased during the past decade, especially among adolescents. The aim of our study was to describe the prevalence and patterns of the nonmedical use of benzodiazepines (BDZ) and Z-hypnotics among school-aged adolescents through the lens of sex. In addition, we sought to analyze the temporal evolution of the nonmedical use of these drugs during the period 2016-2021. METHODS: The temporal evolution of the nonmedical use of these drugs was analyzed based on survey data collected in 2016, 2018 and 2021, which includes the first years of the COVID-19 pandemic. To assess the possible effect of the COVID-19 pandemic, the year at survey was conducted was introduced as a categorical variable. We used data from the Spanish State Survey on Drug Use in Secondary Education, which covers drug use among students aged 14-18 years. Using multivariate logistic regression models, we estimated the independent effect of different variables (sociodemographic data, use of other psychoactive substances, risk perception and availability) on the nonmedical use of BDZ and Z-hypnotics. RESULTS: In total, survey data from 95,700 adolescents were included in our analysis. The nonmedical use of BDZ and Z-hypnotics increased among adolescents during the study period. The adjusted odds ratio (AOR) from 2016 to 2018 was 1.11 (95% CI 0.94-1.31) and from 2018 to 2021 the AOR was 1.26 (95% CI 1.08-1.46), using 2016 and 2018, respectively, as reference years. The nonmedical use of BDZ and Z-hypnotics was more likely in adolescent girls than boys (AOR = 2.11). The nonmedical use of prescription opioids (AOR = 3.44), novel psychoactive substances and other illicit psychoactive drugs (AOR = 4.10) were risk factors for the nonmedical use of BDZ and Z-hypnotics in both sexes. Use of cannabis (AOR = 1.38) was a predictor of nonmedical use in female adolescents only. CONCLUSIONS: This study shows that the trend of the nonmedical use of BDZ and Z-hypnotics among school-aged adolescents in Spain increased between 2016 and 2021. Among adolescents aged 14 to 18, the probability of nonmedical use of these psychoactive substances was twice as high for female adolescents as for male adolescents.

First 150 years of catatonia: Looking back at its complicated history and forward to the road ahead.

Karl Ludwig Kahlbaum (1828-1899) was the first to conceptualize and describe the main clinical features of a novel psychiatric illness, which he termed catatonia in his groundbreaking monograph published 150 years ago. Although Kahlbaum postulated catatonia as a separate disease entity characterized by psychomotor symptoms and a cyclical course, a close examination of his 26 cases reveals that most of them presented with motor symptom complexes or syndromes associated with various psychiatric and medical conditions. In his classification system, Kraepelin categorized catatonic motor symptoms that occur in combination with psychotic symptoms and typically have a poor prognosis within his dementia praecox (schizophrenia) disease entity. Because of the substantial influence of Kraepelin's classification, catatonia was predominantly perceived as a component of schizophrenia for most of the 20th century. However, with the advent of the psychopharmacotherapy era starting from the early 1950s, interest in catatonia in both clinical practice and research subsided until the early 2000s. The past two decades have witnessed a resurgence of interest in catatonia. The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition, marked a paradigmatic shift by acknowledging that catatonia can occur secondary to various psychiatric and medical conditions. The introduction of an independent diagnostic category termed "Catatonia Not Otherwise Specified" significantly stimulated research in this field. The authors briefly review the history and findings of recent catatonia research and highlight promising directions for future exploration.

Cheerfulness in the history of psychiatry.

In 1762, Louis-Antoine Marquis de Caraccioli (1719-1803), a prolific writer of the eighteenth century, dedicated a book to a psychological theme that medicine has forgotten: 'gaité' in French, which we will translate as 'cheerfulness'. At the beginning of the nineteenth century, this work inspired two doctoral theses in medicine, one defended in Montpellier, the other in Paris. In their texts, Louis Monferran (1785-?) and Vincent Rémi Giganon (1794-1857) explored the therapeutic benefits of the medical prescription of cheerfulness. In addition to lifestyle recommendations, they focused on the psychotropic substances available to them: alcohol, coca, hemp and opiates. In an original and novel way, Giganon introduced and recommended 'le gaz oxydule d'azote inspiré', or inhaled nitrous oxide gas.

Effects of Gabapentin on the Treatment of Behavioral Disorders in Dogs: A Retrospective Evaluation.

The use of gabapentin in treating dogs with behavioral disorders is not well described. To characterize behavioral effects of gabapentin, this study surveyed 50 owners whose dogs were prescribed gabapentin at a veterinary behavior-focused practice over a five-year period. Most owners (72%) reported that gabapentin was moderately or very effective at improving their dog's behavior. The majority of owners reported at least one side effect (70%), with sedation being the most common. Sedation was more likely to be seen at doses higher than 30 mg/kg. Specific dose ranges (mg/kg) did not correlate with any other reports of side effects nor effectiveness. Dogs with a diagnosis of conflict-related aggression were more likely to have owners report that gabapentin was effective at improving behavior compared to dogs with other behavioral diagnoses (p = 0.04), while dogs diagnosed with aggression secondary to high arousal were less likely to have owners report that gabapentin was effective (p = 0.01). Overall, reports of effect varied widely and, with the exception of sedation, did not correlate with specific mg/kg dose ranges. Results suggest that some dogs may be more sensitive or resistant to adverse and/or therapeutic effects than others and multiple dosage trials may be needed before finding the best fit.

On the Road to Individualizing Pharmacotherapy for Adolescents and Adults with Schizophrenia - Results from an Expert Consensus Following the Delphi Method.

Introduction: Schizophrenia is a severe mental illness that usually begins in late adolescence or early adulthood. Current pharmacological treatments, while acceptably effective for many patients, are rarely clinically tailored or individualized. The lack of sufficient etiopathological knowledge of the disease, together with overall comparable effect sizes for efficacy between available antipsychotics and the absence of clinically actionable biomarkers, has hindered the advance of individualized medicine in the treatment of schizophrenia. Nevertheless, some degree of stratification based on clinical markers could guide treatment choices and help clinicians move toward individualized psychiatry. To this end, a panel of experts met to formally discuss the current approach to individualized treatment in schizophrenia and to define how treatment individualization could help improve clinical outcomes. Methods: A task force of seven experts iteratively developed, evaluated, and refined questionnaire items, which were then evaluated using the Delphi method. Descriptive statistics were used to summarize and rank expert responses. Expert discussion, informed by the results of a scoping review on personalizing the pharmacologic treatment of adults and adolescents with schizophrenia, ultimately generated recommendations to guide individualized pharmacologic treatment in this population. Results: There was substantial agreement among the expert group members, resulting in the following recommendations: 1) individualization of treatment requires consideration of the patient's diagnosis, clinical presentation, comorbidities, previous treatment response, drug tolerability, adherence patterns, and social factors; 2) patient preferences should be considered in a shared decision-making approach; 3) identified barriers to personalized care that need to be overcome include the lack of actionable biomarkers and mechanistic similarities between available treatments, but digital tools should be increasingly used to enhance individualized treatment. Conclusion: Individualized care can help provide effective, tailored treatments based on an individual's clinical characteristics, disease trajectory, family and social environment, and goals and preferences.

Interactions between grapefruit juice and psychotropic medications: an update of the literature and an original case series.

INTRODUCTION: There is a large body of preclinical data implicating that grapefruit juice (GJ) inhibits many CYP 450 isoforms. The potential of GJ-to-drug is of high relevance to clinical psychiatry, because a wide range of psychotropic medicines undergo CYP 450 metabolism and P-gp transport. AREAS COVERED: Relevant data were identified by searching the electronic databases up to February 2024. This work constitutes a summary of preclinical and clinical data on GJ impact on CYP 450 metabolism, P-glycoprotein, and organic anion-transporting polypeptides (OATPs), with focus on studies that assessed GJ-to-psychotropic drug interactions. Additionally, an unpublished case series of nine patients is provided. EXPERT OPINION: The impact of GJ on CYP 3A4 appears to be the critical mechanism for the majority of GJ-to-psychopharmacotherapy interactions described in human studies or case reports. However, there are studies and cases of patients clearly showing that this is not the only route explaining the GJ effect, and at times, this particular is of no relevance and that other CYP 450 isoforms as well as drug transporting proteins might be involved. The risk of GJ-to-psychotropic drugs needs to be further evaluated in a 'real-world' setting and apply not only measures of pharmacokinetics but also treatment effectiveness and safety.

Chronic Behavioral and Neurochemical Effects of Four Novel N-Benzyl-2-phenylethylamine Derivatives Recently Identified as "Psychoactive" in Adult Zebrafish Screens.

Potently affecting human and animal brain and behavior, hallucinogenic drugs have recently emerged as potentially promising agents in psychopharmacotherapy. Complementing laboratory rodents, the zebrafish (Danio rerio) is a powerful model organism for screening neuroactive drugs, including hallucinogens. Here, we tested four novel N-benzyl-2-phenylethylamine (NBPEA) derivatives with 2,4- and 3,4-dimethoxy substitutions in the phenethylamine moiety and the -F, -Cl, and -OCF3 substitutions in the ortho position of the phenyl ring of the N-benzyl moiety (34H-NBF, 34H-NBCl, 24H-NBOMe(F), and 34H-NBOMe(F)), assessing their behavioral and neurochemical effects following chronic 14 day treatment in adult zebrafish. While the novel tank test behavioral data indicate anxiolytic-like effects of 24H-NBOMe(F) and 34H-NBOMe(F), neurochemical analyses reveal reduced brain norepinephrine by all four drugs, and (except 34H-NBCl) - reduced dopamine and serotonin levels. We also found reduced turnover rates for all three brain monoamines but unaltered levels of their respective metabolites. Collectively, these findings further our understanding of complex central behavioral and neurochemical effects of chronically administered novel NBPEAs and highlight the potential of zebrafish as a model for preclinical screening of small psychoactive molecules.

Implementation and Evaluation of Educational Workshops to Increase Primary Care Provider and Medical Student Comfort in Psychiatric Care.

OBJECTIVE: Mental health treatment is often initiated in primary care settings, but many primary care providers (PCPs), residents, and medical students report discomfort in managing psychiatric conditions. This study evaluated the effect of an educational workshop that featured an evidence-based psychopharmacology clinical decision support tool (CDST) on trainee confidence and willingness to treat psychiatric conditions. METHODS: Participants completed pre- and post-workshop surveys. Nine months after the workshop, a subset of trainees participated in a focus group. RESULTS: Of the participants, 62.5% of the obstetrics-gynecology (OB-GYN) resident physicians (10/16) and 100% of the medical students (18/18) completed both pre- and post-surveys. Following the workshop, OB-GYN resident physicians reported significantly improved confidence in treating psychiatric disorders (p < 0.001), sense of having psychiatric support tools (p < 0.001), and knowledge of treating psychiatric disorders (p = 0.021). Medical students reported significantly improved confidence in treating psychiatric disorders (p < 0.001), willingness to devise treatment plans for psychiatric disorders (p = 0.024), sense of having psychiatric support tools (p < 0.001), knowledge of treating psychiatric disorders (p < 0.001), and comfort in presenting a psychiatric treatment plan to an attending (p = 0.003). Most focus group participants (93.75%; 15/16) reported that they continued to use the CDST, and it increased their confidence in formulating psychiatric treatment plans. CONCLUSIONS: These findings suggest that educational workshops that introduce high-quality psychopharmacology CDSTs may be an effective method for improving provider comfort in treating psychiatric disorders.

From Consensus Statement to Pills to Pixels: New Innovations in Attention-Deficit/Hyperactivity Disorder Care.

Objectives: This review aims to present recent innovations and advancements in attention-deficit/hyperactivity disorder (ADHD) care, encompassing international consensus statement, new medication formulations, digital therapeutics, and neurostimulation devices. Methods: A comprehensive literature search of relevant articles published in the past five years was conducted, emphasizing the evidence base, efficacy, safety, and practical implications of these advancements. Results: The World Federation of ADHD Consensus Statement offers an updated diagnostic and treatment framework rooted in global scientific evidence. There are several newer ADHD medication formulations, including a nonstimulant (Viloxazine extended release) and the first transdermal amphetamine patch approved to treat ADHD. These options offer some unique benefits to personalize treatment based on symptom profile, lifestyle, preferences, and response. Digital tools offer additional means to restructure environments for individuals with ADHD, reducing impairment and reliance on others. In addition, digital therapeutics enhance access, affordability, personalization, and feasibility of ADHD care, complementing or augmenting existing interventions. Trigeminal nerve stimulation emerges as a well-tolerated nonpharmacological, device-based treatment for pediatric ADHD, with initial trials indicating effect sizes comparable to nonstimulant medications. Conclusions: These innovations in ADHD care represent clinically significant new treatment options and opportunities for personalized care. Health care professionals should integrate these developments into clinical practice, mindful of individual patient and family needs and preferences. Future research should assess long-term outcomes, cost-effectiveness, and acceptability of these innovations.

Case report: Avoiding intolerance to antipsychotics through a personalized treatment approach based on pharmacogenetics.

Introduction: The standard approach to treatment in psychiatry is known as "treatment as usual" (TAU), in which the same types of treatment are administered to a group of patients. TAU often requires numerous dose adjustments and medication changes due to ineffectiveness and/or the occurrence of adverse drug reactions (ADRs). This process is not only time-consuming but also costly. Antipsychotic medications are commonly used to treat various psychiatric disorders such as schizophrenia and mood disorders. Some of the inter-individual differences in efficacy and ADRs observed in psychopharmacotherapy can be explained by genetic variability in the pharmacokinetics and pharmacodynamics of antipsychotics. A better understanding of (in)efficacy and possible ADRs can be achieved by pharmacogenetic analysis of genes involved in the metabolism of antipsychotics. Most psychotropic drugs are metabolized by genetically variable CYP2D6, CYP1A2, CYP3A4, and CYP2C19 enzymes. To demonstrate the utility of pharmacogenetic testing for tailoring antipsychotic treatment, in this paper, we present the case of a patient in whom a pharmacogenetic approach remarkably altered an otherwise intolerant or ineffective conventional TAU with antipsychotics. Methods: In this case report, we present a 60-year-old patient with psychotic symptoms who suffered from severe extrapyramidal symptoms and a malignant neuroleptic syndrome during treatment with risperidone, fluphenazine, aripiprazole, brexpiprazole, and olanzapine. Therefore, we performed a pharmacogenetic analysis by genotyping common functional variants in genes involved in the pharmacokinetic pathways of prescribed antipsychotics, namely, CYP2D6, CYP3A4, CYP3A5, CYP1A2, ABCB1, and ABCG2. Treatment recommendations for drug-gene pairs were made according to available evidence-based pharmacogenetic recommendations from the Dutch Pharmacogenetics Working Group (DPWG) or Clinical Pharmacogenetics Implementation Consortium (CPIC). Results: Pharmacogenetic testing revealed a specific metabolic profile and pharmacokinetic phenotype of the patient, which in retrospect provided possible explanations for the observed ADRs. Based on the pharmacogenetic results, the choice of an effective and safe medication proved to be much easier. The psychotic symptoms disappeared after treatment, while the negative symptoms persisted to a lesser extent. Conclusion: With the case presented, we have shown that taking into account the pharmacogenetic characteristics of the patient can explain the response to antipsychotic treatment and associated side effects. In addition, pharmacogenetic testing enabled an informed choice of the most appropriate drug and optimal dose adjustment. This approach makes it possible to avoid or minimize potentially serious dose-related ADRs and treatment ineffectiveness. However, due to the complexity of psychopathology and the polypharmacy used in this field, it is of great importance to conduct further pharmacokinetic and pharmacogenetic studies to better assess gene-drug and gene-gene-drug interactions.

Exploring clozapine use in severe psychiatric symptoms associated with autism spectrum disorder: A scoping review.

BACKGROUND: Patients with autism spectrum disorder (ASD) may experience severe psychiatric symptoms, often unresponsive to conventional pharmacological therapies, highlighting the need for more effective alternatives. AIMS: This study aims to map and synthesize evidence on the use of clozapine as a therapeutic option for managing severe psychiatric symptomatology co-occurring with ASD. METHODS: We conducted a scoping review on multiple sources following the JBI guidelines. The search strategy was inclusive, targeting both peer-reviewed publications and gray literature presenting empirical data on the use of clozapine therapy for patients with ASD accompanied by comorbid psychiatric symptoms. Two independent evaluators performed the selection of studies, data extraction, and critical appraisal. RESULTS: The review included 46 studies, encompassing 122 ASD individuals who received clozapine therapy. The sources of evidence comprise 31 case reports, 8 case series, 6 retrospective observational studies, and 1 quasi-experimental prospective study. The tables present the findings along with a narrative summary. Clozapine treatment demonstrated benefits in four groups of severe and treatment-resistant psychiatric symptoms in ASD patients: disruptive behaviors, psychotic symptoms, catatonia, and mood symptoms. Although side effects were common, tolerability was generally satisfactory. However, severe adverse events, such as seizures, moderate neutropenia, and myocarditis, underscore the need for intensive clinical monitoring. CONCLUSIONS: While clozapine shows promise as a pharmacological intervention for severe psychopathologies in ASD, more rigorous clinical studies are required to elucidate its efficacy and safety in this population. The limited robustness of the evidence calls for caution, signaling an early research stage into this topic.

Interpersonal sensitivity and response to selective serotonin reuptake inhibitors in patients with acute major depressive disorder.

BACKGROUND: Patients with major depression often suffer from excessive interpersonal sensitivity, although it is not typically measured in antidepressant clinical trials. Preliminary evidence suggests selective serotonin reuptake inhibitors have the capacity to reduce interpersonal sensitivity. METHODS: This was a pooled analysis of data from 1709 patients in three randomized, double-blind, placebo-controlled trials of fluoxetine and paroxetine for acute major depressive disorder. Depressive symptoms were assessed with the Hamilton Depression Rating Scale. A factor from the Symptom Checklist was used to assess interpersonal sensitivity. Our outcome of interest was change from baseline scores at the last assessment (up to 8 or 12 weeks, depending on the trial). RESULTS: Both medications produced significantly greater reductions in interpersonal sensitivity relative to placebo. The effect of medication remained significant after controlling for depression improvement, which explained 18.5% of the variation in interpersonal sensitivity improvement among those treated with active medication. The effect of medication on depressive symptoms, relative to placebo, was not influenced by baseline interpersonal sensitivity. LIMITATIONS: The outcome measured interpersonal sensitivity over the last week, and the results do not necessarily reflect changes in long-standing, trait-like patterns of interpersonal sensitivity. Only two medications were studied. CONCLUSIONS: Selective serotonin reuptake inhibitors are effective at treating interpersonal sensitivity in acutely depressed patients. This appears to be a unique drug effect that is not only the result of depression improvement. Future clinical trials might benefit from assessing interpersonal sensitivity more routinely.

Clinician treatment choices for post-traumatic stress disorder: ambassadors survey of psychiatrists in 39 European countries.

BACKGROUND: Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians' treatment choices for post-traumatic stress disorder (PTSD). METHODS: The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) (n = 279), Southern Europe (SE) (n = 92), Northern Europe (NE) (n = 92), and Western Europe (WE) (N = 148). RESULTS: About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct "profiles" of clinicians. In Class 1 (N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 (N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 (N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 (N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines. CONCLUSIONS: Clinicians' decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.

Successful treatment of body integrity dysphoria with amputation: A case report.

Key Clinical Message: In select cases of body integrity identity disorder or body integrity dysphoria where noninvasive treatments prove ineffective and the patient's distress is substantial, elective amputation may serve as a viable and highly satisfying intervention, aligning the individual's physical self with their perceived identity. Abstract: This case report presents an illustration of body integrity identity disorder (BIID), wherein a 20 years old ambidextrous male experiencing profound distress over his left hand's fourth and fifth fingers sought elective amputation after noninvasive treatments proved unsuccessful. Despite ethical concerns and limited literature on BIID, the decision to proceed with elective surgery was based on the patient's sustained desire, potential risks of self-harm, and the distinct presentation involving two fingers rather than a complete limb. Following amputation, the patient experienced immediate relief, with nightmares ceasing, emotional distress subsiding, and improved functionality. This case highlights the potential efficacy and patient satisfaction associated with elective amputation in specific BIID presentations, shedding light on the unique challenges faced by affected individuals and emphasizing the importance of understanding, support, and inclusive healthcare practices.

Successful Clozapine Rechallenge After Clozapine-Induced Severe Anemia: A Case Report.

INTRODUCTION: Clozapine, a second-generation antipsychotic (SGA), is considered the gold standard medication to treat patients with treatment-resistant schizophrenia (TRS). Despite its efficacy, clozapine is associated with adverse effects, notably neutropenia and agranulocytosis. Other hematological adverse effects are less common. Severe anemia is a rare adverse effect seldom reported in the literature and is typically associated with pure red cell aplasia (PRCA). Nevertheless, the benefits of clozapine in managing TRS make rechallenge a reasonable option. CASE REPORT: We present the case of a 35-year-old man with TRS, resistant to previous antipsychotics, who experienced severe anemia during clozapine treatment. An investigation for clozapine-induced anemia revealed PRCA on myelogram. After discontinuing clozapine, the patient's hemoglobin levels recovered. Subsequent treatments with olanzapine, zuclopenthixol, and aripiprazole proved ineffective, leading us to consider a clozapine rechallenge. The rechallenge, monitored for 58 days, resulted in improved psychiatric symptoms and stable hemoglobin levels. The patient remained stable during 6 months of follow-up, with no hematological changes. DISCUSSION: PRCA is a very rare adverse effect of clozapine. The cause of drug-induced PRCA is still unknown; for clozapine, there are no studies. Rechallenge after a severe and rare adverse effect is a complex decision. This case is the first to report a successful clozapine rechallenge following severe anemia without other blood dyscrasias, emphasizing the imperative need for close monitoring during the rechallenge process. Further study is warranted to understand the predictive factors for a successful outcome in clozapine rechallenges.