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Treatment-resistant schizophrenia (TRS) presents considerable challenges in contemporary psychiatric practice due to inadequate response to conventional antipsychotic treatments. Paliperidone, the primary active metabolite of risperidone, particularly in its long-acting injectable (LAI) form, has emerged as a promising option for TRS due to its consistent medication delivery, reducing symptom exacerbation and relapse associated with oral dosing fluctuations. This case report presents the clinical journey of a 42-year-old female diagnosed with schizophrenia at age 15. Despite numerous hospital admissions and trials of various oral and injectable antipsychotics, including clozapine and electroconvulsive therapy (ECT), her symptoms persisted. During her last admission, her condition showed minimal improvement despite extensive pharmacological interventions. Introducing paliperidone LAI while tapering off other antipsychotics led to significant improvements within four weeks. The patient exhibited reduced hallucinatory behaviour, delusions, and disorganized behaviour. Follow-up assessments confirmed sustained progress, with the patient showing increased engagement in daily activities and reduced irritability and suspiciousness. This case underscores the potential efficacy of paliperidone LAI in managing TRS. The patient's notable improvement highlights the importance of personalized treatment plans and continuous monitoring in complex psychiatric conditions. Its favourable safety and tolerability profile further supports its use as a long-term treatment option for TRS, potentially leading to enhanced patient compliance and overall quality of life. The significant symptomatic relief and functional improvement observed advocate for the consideration of paliperidone LAI as a promising therapeutic option for TRS, with the potential to be considered in the future among the first-line treatments for TRS.

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BACKGROUND: Antipsychotic and other psychotropic medication use is prevalent among community-dwelling older adults with dementia despite the potential for adverse effects. Two Centers for Medicare & Medicaid Services (CMS) initiatives, the National Partnership to Improve Dementia Care ("the Partnership") and the Five Star Quality Rating System for antipsychotic use reporting, have been successful in reducing antipsychotic use in nursing home residents. We assessed if these initiatives had a spillover effect in antipsychotic and other psychotropic medication use among community dwellers with dementia due to potential overlap in prescribers across settings. METHODS: Among community-dwelling older adults with dementia, we examined psychotropic medication class use (i.e., antipsychotics, antidepressants, anxiolytics, anticonvulsants/mood stabilizers, antidementia) in 2010-2017 Medicare fee-for-service claims using interrupted time series analyses across three periods ("Pre-Partnership": July 1, 2010 to March 31, 2012; "Post-Partnership": April 1, 2012 to January 31, 2015; "Five Star Quality Rating": February 1, 2015 to December 31, 2017). RESULTS: We included 1,289,401 community dwellers with dementia contributing 26,609,697 person-months. The mean age was 80 years, most were female (70%), approximately 80% were non-Hispanic Whites, 10% were non-Hispanic Blacks, and 5% were Hispanic ethnicity. Antipsychotic use was declining pre-Partnership (ß = -0.06, 95% CI: -0.08, -0.05) and post-Partnership (ß = -0.02, 95% CI: -0.02, -0.01). Post-Five Star Quality Rating, antipsychotic use remained stable with a nearly flat slope (ß = -0.01, 95% CI: -0.01, 0.00). Anticonvulsant and antidepressant use increased and anxiolytic and antidementia medication use decreased among community-dwelling older adults with dementia. CONCLUSIONS: These two CMS policies on antipsychotic use for nursing home residents were not associated with a spillover effect to community-dwelling older adults with dementia. Strategies to monitor the appropriateness of psychotropic medication use may be warranted for community-dwellers with dementia.

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Cognitive impairments are core features in individuals across the psychosis continuum and predict functional outcomes. Nevertheless, substantial variability in cognitive functioning within diagnostic groups, along with considerable overlap with healthy controls, hampers the translation of research findings into personalized treatment planning. Aligned with precision medicine, we employed a data driven machine learning method, self-organizing maps, to conduct transdiagnostic clustering based on cognitive functions in a sample comprising 228 healthy controls, 200 individuals at ultra-high risk for psychosis, and 98 antipsychotic-naïve patients with first-episode psychosis. The self-organizing maps revealed six clinically distinct cognitive profiles that significantly predicted baseline functional level and changes in functional level after one year. Cognitive flexibility in particular, as well as specific executive functions emerged as cardinal in differentiating the profiles. The application of self-organizing maps appears to be a promising approach to inform clinical decision-making based on individualized cognitive profiles, including patient allocation to different interventions. Moreover, this method has the potential to enable cross-diagnostic stratification in research trials, utilizing data-driven subgrouping informed by categories from underlying dimensions of cognition rather than from clinical diagnoses. Finally, the method enables cross-diagnostic profiling across other data modalities, such as brain networks or metabolic subtypes.

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BACKGROUND: In the United States, clozapine was first approved for treatment-resistant schizophrenia and then for suicidality in schizophrenia psychoses. Systematic reviews support clozapine's anti-suicidal effect, but the forensic literature stresses its lethality during overdoses. RESEARCH DESIGN AND METHODS: Clozapine reports to the international pharmacovigilance database (VigiBase) were analyzed for suicidal ideation, suicide attempts, intentional overdose, and completed suicides from introduction to 1 January 2024. VigiBase uses the information component (IC) as a disproportionality analysis. RESULTS: The clozapine ICs (range: other antipsychotics) were: 1) suicidal ideation IC = 0.570 with IC025 = 0.454 to IC975 = 0.680 (IC = 3.568 for aripiprazole and 1.729 for risperidone), 2) suicide attempt IC = 1.428 with IC025 = 1.323 to IC975 = 1.529 (IC = 4.150 for quetiapine and 2.968 for risperidone), 3) intentional overdose: IC = 0.995 with IC025 = 0.864 to IC975 = 1.120 (IC = 4.080 for quetiapine and 1.957 for aripiprazole), and 4) completed suicide IC = 1.133 with IC025 = 1.026 to IC975 = 1.235 (IC = 4.648 for quetiapine and 2.160 for risperidone). In summary, all clozapine ICs were significantly lower. We found 2391 clozapine-treated patients on the suicidality spectrum (627 cases with suicidal ideation, 752 with suicide attempt, 488 with intentional overdose, and 731 with completed suicide) but many were taking other antipsychotics. The most frequent reporting countries were the United States, the United Kingdom, and Croatia. CONCLUSION: This pharmacovigilance study, with all its inherent limitations, provides independent proof, not overlapping with prior literature, that clozapine may have specific strong anti-suicidal effects that do not appear to be present in other antipsychotics. Further VigiBase studies are needed to compare the lethality of an intentional overdose of clozapine (14.3%) with other antipsychotics.

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Schizophrenia (SCH) is a mental disorder that requires long-term antipsychotic treatment. SCH patients are thought to have an increased sensitivity to stress. The dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, observed in SCH, could include altered levels of glucocorticoids, glucocorticoid receptors (GRs), and associated proteins. The perinatal administration of phencyclidine (PCP) to rodents represents an animal model of SCH. This study investigated the effects of perinatal PCP exposure and subsequent haloperidol/clozapine treatment on corticosterone levels measured by ELISA and the expression of GR-related proteins (GR, pGR, HSP70, HSP90, FKBP51, and 11ß-Hydroxysteroid dehydrogenase-11ß-HSD) determined by Western blot, in different brain regions of adult rats. Six groups of male rats were treated on the 2nd, 6th, 9th, and 12th postnatal days (PN), with either PCP or saline. Subsequently, one saline and one PCP group received haloperidol/clozapine from PN day 35 to PN day 100. The results showed altered GR sensitivity in the rat brain after PCP exposure, which decreased after haloperidol/clozapine treatment. These findings highlight disturbances in the HPA axis in a PCP-induced model of SCH and the potential protective effects of antipsychotics. To the best of our knowledge, this is the first study to investigate the effects of antipsychotic drugs on the HPA axis in a PCP animal model of SCH.

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OBJECTIVE: The proportion of long-term care (LTC) residents being treated with antipsychotic medication is high, and these medications may exacerbate behavioral symptoms. We used propensity scores to investigate the effect of antipsychotic use on the worsening of behavioral symptoms among residents in LTC facilities. DESIGN: A retrospective study. SETTING AND PARTICIPANTS: Residents in LTC in 8 provinces and 1 territory in Canada, without severe aggressive behavior at baseline and reassessed at follow-up, between March 2000 and March 2022. METHODS: We used propensity score matching and weighting to balance baseline covariates and logistic regression to estimate the effect of antipsychotics on the worsening of behavioral symptoms in the original, matched, and weighted cohorts. The treatment variable was use of antipsychotic medication at baseline and the outcome was worsening of behavior at follow-up. RESULTS: A total of 494,215 participants were included (318,234 women and 175,981 men; mean age 82.8 years [SD 10.1; range 18-112]).130 558 (26.4%) used antipsychotics at baseline and 88,632 (17.9%) had worsening behavior in follow-up. In the matched cohort, there were 249,698 participants, and 124,849 were matched (1:1) in each treatment group. There was a significant association between antipsychotic use at baseline and worsening in behavior at follow-up in the adjusted regression models (OR 1.27 [95% CI 1.25-1.29], <0.0001) as well as in matched (OR 1.20 [95% CI 1.17-1.21], <0.0001) and weighted (OR 1.26 [95% CI 1.24-1.28], <0.0001) cohorts. CONCLUSIONS AND IMPLICATIONS: This study further evidence to support the cautious use of antipsychotics in LTC facilities. Future research in LTC facilities could include a more granular analyses of behavior change, including bidirectional analyses between different symptom severity classifications.

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OBJECTIVE: We present an evaluation of antipsychotic prescribing in an inpatient psychiatry ward in Hobart, Tasmania, to establish pattern of use, alignment with other psychiatric wards or centres and the recommendations in the Royal Australian and New Zealand College of Psychiatry Clinical Practice Guidelines, and to determine predictors of polypharmacy. METHODS: A descriptive cross-sectional survey design was used. Data from 118 patients discharged from the Royal Hobart Hospital (RHH) Mental Health Inpatient Unit between 01/02/2021 to 01/08/2021 were evaluated. RESULTS: Antipsychotic polypharmacy (APP) was observed in 40% of patients. When low doses of adjunctive ('PRN') use of olanzapine and quetiapine were excluded, the APP proportion was 35%. APP was predicted by age and by a schizophrenia diagnosis. Long-acting injections (LAIs) were used in 46% of the patients. The most common LAI was risperidone (52%). Average daily dose of antipsychotic at the time of discharge was 529 mg chlorpromazine (CPZ) equivalents. High dose antipsychotics (more than 1000 mg CPZ equivalents per day) was observed in 13% of the patients. CONCLUSIONS: The observed prescribing practice is consistent with other clinical settings. Antipsychotic prescribing practice should, however, continue to be monitored to ensure adherence to best practice guidelines.

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Background: Reducing the dose of psychosis drugs in a gradual hyperbolic manner may minimise withdrawal effects and risk of relapse. There is presently limited guidance on tapering decanoate-based long-acting injectable dopamine antagonists (LIDAs). Objectives: We aimed to apply hyperbolic principles of tapering to the decanoate-based LIDAs flupentixol, zuclopenthixol and haloperidol to develop withdrawal regimens. Design: We used in silico methodology to predict plasma drug levels and D2 occupancy for different LIDA regimens. Methods: Existing pharmacokinetic and receptor occupancy data from nuclear neuroimaging studies were used to power modelling. Abrupt discontinuation was examined as a potential strategy, and dose reduction was modelled with pre-defined constraints used in similar work of 10 (fast regimens), 5 (moderate) and 2.5 (slow) percentage points of D2 occupancy change per month. Results: Abrupt discontinuation of decanoate-based LIDAs leads to excessive change in D2 occupancy which violated our pre-defined constraints, potentially resulting in withdrawal symptoms and increased risk of relapse. Reduction of LIDA dose allowed hyperbolic reduction in plasma level consistent with imposed constraints on receptor occupancy reduction rate. For equivalent per-weekly LIDA dosing, more frequent administration allowed a more gradual reduction of D2 occupancy. However, switching to oral forms is required to continue hyperbolic tapering to full discontinuation; reduction to zero using only LIDA produces too large a reduction in D2 occupancy. Guidance for reduction and cessation of LIDAs according to slow, moderate and fast criteria is provided. Conclusion: Abrupt cessation of decanoate LIDAs is not consistent with gradual hyperbolic tapering, despite their longer half-lives compared with oral formulations. Reduction to the point of full discontinuation can only be achieved by switching to oral therapy to complete the taper. These results are limited by the in silico and theoretical nature of the study, and there is a need to confirm these findings through real-world observational and interventional studies.

Computer-based research on the best way to reduce the dose and eventually stop three depot antipsychotics What is the problem? Psychosis affects how someone experiences reality. Antipsychotics are used to treat psychosis. They work by blocking a chemical called dopamine. Stopping these too rapidly can cause psychosis to occur again. This might be because the dopamine block is removed suddenly. Sometimes antipsychotics are given by injection. Injections stay in the body for a longer time than tablets. The best way to reduce these injections is currently unknown. What did we do? We explored the best way to reduce and stop antipsychotic injections. We looked at three different types of psychosis injection. We used existing data to assess how these drugs affect the brain. We examined what would happen if an antipsychotic injection was suddenly stopped. We then evaluated the effect of reducing the dose gradually. What did we find? Stopping antipsychotic injections suddenly would lead to rapid changes at brain receptors. This might lead to symptoms of withdrawal and a high risk of psychosis recurring. Reducing the dose of injections leads to less change than stopping suddenly. Switching to a tablet allows for more control when reducing dose. Having injections more often also reduce the changes occurring between injections. We outline three different rates of dose reduction. What does this mean? Antipsychotic injections stay in the body longer than tablets. However, stopping injections suddenly may still not be safe. We recommend that people reduce the dose of their injection instead. We also recommend people switch to tablets or liquid before stopping. It should be noted that our research is computer-based. We would like to see our recommendations tested in the real world.

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Schizophrenia (SCZ) is a severe neuropsychiatric disorder characterized by cognitive, affective, and social dysfunction, resulting in hallucinations, delusions, emotional blunting, and disordered thinking. In recent years, proteomics has been increasingly influential in SCZ research. Glycosylation, a key post-translational modification, can alter neuronal stability and normal signaling in the nervous system by affecting protein folding, stability, and cellular signaling. Recent research evidence suggests that abnormal glycosylation patterns exist in different brain regions in autopsy samples from SCZ patients, and that there are significant differences in various glycosylation modification types and glycosylation modifying enzymes. Therefore, this review explores the mechanisms of aberrant modifications of N-glycosylation, O-glycosylation, glycosyltransferases, and polysialic acid in the brains of SCZ patients, emphasizing their roles in neurotransmitter receptor function, synaptic plasticity, and neural adhesion. Additionally, the effects of antipsychotic drugs on glycosylation processes and the potential for glycosylation-targeted therapies are discussed. By integrating these findings, this review aims to provide a comprehensive perspective to further understand the role of aberrant glycosylation modifications in the pathophysiology of SCZ.

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Treatment with antipsychotics (APs) for schizophrenia spectrum disorders (SSDs) is generally effective, however, a significant proportion does not respond favorably. Childhood trauma (CT) subtypes (physical, sexual, and emotional abuse, physical and emotional neglect) could influence treatment effectiveness; however, research is scarce. Heterogeneity in AP response could be explained by differentiating by CT subtype. The present study was based on the Bergen-Stavanger-Trondheim-Innsbruck (BeSt InTro) study. CTQ-SF assessed CT subtypes in SSDs (n = 98). CT subtypes were examined in relation to psychosis symptoms measured by PANSS during one year of treatment with APs, by means of linear mixed effects (LME) models. Results were significant for CT subtypes, where increased levels of sexual abuse and physical neglect were associated with increased mean levels of psychosis symptoms throughout the course of treatment from baseline to 52 weeks. AP effectiveness may thus be influenced by CT subtype in SSDs. The results support clinical guidelines recommending a focus on assessment and treatment of trauma in SSDs.

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Introduction: Qualitative research methods can be used to obtain a deeper understanding of patient experience by collecting information in the patients' own words about their encounters, perspectives, and feelings. In this study, patients with schizophrenia were interviewed to capture their voice and to complement the quantitative data typically obtained in clinical trials. Methods: Semi-structured exit interviews were conducted with 41 patients who completed or prematurely discontinued from a phase 3, open-label trial (NCT02873208). The interview guide included open-ended questions on current and prior disease burden, symptoms, quality of life, and treatment experiences. Steps taken to reduce interview stress and secure the validity of data included interviewer sensitivity training specific to mental health conditions and schizophrenia, use of in-person interviews whenever possible and use of videoconferencing for remote interviews to promote trust and comfort, and working closely with clinical site staff to identify patient eligibility and willingness to participate. Transcripts based on audio recordings were content coded and analyzed using thematic analysis; a post-hoc quantitative content analysis was conducted. Results: Patients reported that the symptoms of schizophrenia negatively impacted their work, relationships, self-esteem, emotional health, and daily activities. Most patients had positive experiences with medications that alleviated hallucinations, depression, and anxiety. However, side effects of medications were associated with negative impacts on physical, emotional, behavioral, and cognitive health. Lack of energy/drowsiness, weight gain, mood changes, and involuntary movements were the most common side effects reported with the use of antipsychotic medications. Patients reported unmet treatment needs related to better symptom control and to improved social and physical functioning. Conclusion: Collection of qualitative information within a schizophrenia clinical development process provides value and insights into patients' views on burden of illness, experiences with previous medications, and experiences following participation in a clinical trial and can inform design for future studies.

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Musical hallucinations (MH) represent a rare and complex auditory phenomenon where individuals perceive music without external stimuli. This case study explores auditory Charles Bonnet syndrome (ACBS) in a 51-year-old male with a history of bilateral sensorineural hearing loss. The patient reported hearing recognizable prayer chants, initially perceived as external sounds from a nearby temple. Over time, these hallucinations persisted and interfered with his daily activities, prompting medical consultation. Despite the absence of psychiatric illness, the patient was diagnosed with ACBS and treated with risperidone, an atypical antipsychotic. The intervention led to a significant reduction in the frequency and intensity of the hallucinations, alongside improved sleep and concentration. The patient also experienced a recurrence of symptoms upon discontinuation of the medication, highlighting the importance of adherence to treatment. This case underscores the need for awareness and understanding of non-psychotic auditory hallucinations in individuals with hearing impairments. The pathophysiology of MH is not fully understood but is believed to involve abnormal activity in the auditory associative cortices due to sensory deprivation. Treatment approaches often include both pharmacological and non-pharmacological strategies, such as optimizing hearing with aids and providing psychoeducation. This study contributes to the limited literature on ACBS and emphasizes the efficacy of antipsychotics in managing MH. Further research is essential to explore the underlying mechanisms and to develop comprehensive management plans for patients experiencing these distressing auditory phenomena. The findings advocate for a multidisciplinary approach to treatment, integrating audiological and psychiatric care to improve patient outcomes.

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OBJECTIVE: To evaluate the association between exposure to atypical antipsychotics during pregnancy and risk of miscarriage. MATERIAL AND METHODS: This nested case-control study used a large Japanese administrative database. Pregnancy onset and outcomes were estimated using previously reported algorithms, classifying cases as women becoming pregnant between 2013 and 2022 and ending in a miscarriage. Controls were randomly selected from the entire pregnancy cohort by risk-set sampling with replacement and were individually matched to the cases (3:1). The association between exposure to atypical antipsychotics and risk of miscarriage was assessed using conditional logistic regression adjusted for confounders. The association between benzodiazepine exposure and the risk of miscarriage was assessed as a positive control. RESULTS: In the cohort, 44,118 patients were matched with 132,317 controls. The mean ages (standard deviations) of the case and control groups were 33.3 (5.7) and 33.2 (5.5) years, respectively. The prevalence of atypical antipsychotics was 0.5% in both groups. Aripiprazole is an individual antipsychotic with the highest prescription prevalence. The adjusted odds ratios (aOR) for miscarriage were 0.966 (95% confidence interval [CI], 0.796-1.173) for atypical antipsychotics and 0.998 (0.784-1.269) for aripiprazole. A higher aOR (1.431, 95% CI 1.303-1.573) suggested an association with benzodiazepines. A sensitivity analysis that limited the population to women diagnosed with schizophrenia alone did not suggest an association between atypical antipsychotics and the risk of miscarriage. CONCLUSIONS: The results of this study do not suggest an association between exposure to atypical antipsychotics during pregnancy and the risk of miscarriage.

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Introduction: The primary objective of this study was to compare the incidence of antipsychotic use in those with venous thromboembolism (VTE) resulting in hospital admission. This study expands upon current knowledge regarding VTE risk and antipsychotic use and investigates potential risk factors and lab values that may precede antipsychotic-induced coagulopathy. Methods: This retrospective, case-control, chart review investigated patients admitted to an acute care hospital with either a VTE or non-VTE diagnosis. Primary outcome analysis compared the presence of an antipsychotic medication in patients who had a VTE versus those who did not. Secondary analysis included: 1) the duration, class, dose, frequency, and route of antipsychotic and 2) coagulation parameters, patient characteristics, and VTE risk factors. Results: Analysis included 400 participants with 200 participants in each group (VTE and non-VTE). Of the 51 patients who received an antipsychotic, 29 (56.9%) developed or presented with a VTE. However, there was no significant difference in VTE development between groups when controlled for antipsychotic use (OR 1.37, 95% CI 0.76-2.50, P-value=0.30). Conclusion: While primary study findings were not statistically significant, results support a weak association of exposure to antipsychotic(s) in VTE groups compared to control (non-VTE). Obesity significantly increased the odds of VTE whereas a history of type 2 diabetes significantly decreased the odds of VTE.

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Premature mortality in people living with a severe mental illness (SMI) is often attributed to multiple factors including the use of medicines such as antipsychotics. Second-generation antipsychotics (SGAs) are known to cause metabolic syndrome which can increase the risk of cardiovascular disease. Practice guidelines have recommended regular physical health monitoring, particularly of metabolic parameters, however, metabolic monitoring for people living with SMI using antipsychotics remains suboptimal. Therefore, highlighting the need for ongoing research. This scoping review aimed to provide an overview of current metabolic monitoring practices. We anticipate that this information will assist clinicians and policymakers and inform future research. The following databases were searched: MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO), the Cochrane Database of Systemic Reviews (Wiley), APA PsycInfo (Ovid) and Scopus (Elsevier Science Publishers). The target group was adults (aged ≥ 18) diagnosed with SMI (including bipolar disorder, major depressive disorder and psychotic disorders) and taking SGAs. In total, 44 studies from 14 countries were retrieved. Our findings highlighted that most studies conducted in hospitals did not report on metabolic monitoring practices. Additionally, the roles and responsibilities of healthcare professionals in metabolic monitoring for SMI were infrequently described and parameters such as waist circumference and BMI were often poorly monitored. The scoping review highlights that no streamlined approach towards metabolic monitoring currently exists. There is a need to stipulate and define the roles and responsibilities of all health professionals involved in metabolic monitoring in SMI to optimise care for these individuals. Moreover, there is a need for ongoing research, particularly in the community setting, to promote increased accessibility to metabolic monitoring for SMI.

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Purpose: Little is known about adherence to and discontinuation of newly initiated oral antipsychotics (OAPs) as well as associated factors among Medicare beneficiaries with schizophrenia. This study aimed to examine rates of OAP adherence and discontinuation and associated factors in a national sample of fee-for-service Medicare beneficiaries with schizophrenia. Patients and Methods: This retrospective study used 100% fee-for-service Medicare claims data to identify adult beneficiaries with schizophrenia, initiating a new OAP between 01/01/2017 and 12/31/2019 (index date = date of new OAP prescription). Outcomes included adherence and discontinuation. Factors associated with adherence were assessed using logistic and linear regressions; Cox regressions were used to assess factors associated with discontinuation. Results: In our final sample of 46,452 Medicare beneficiaries with schizophrenia, 35.4% were adherent to their newly initiated OAP (mean [SD] PDC: 0.52 [0.37]) over 12 months after initiation. Most patients (79.4%) discontinued their new OAP (median [IQR] time to discontinuation: 3.6 (1.0, 9.9) months). Factors associated with lower odds of adherence included younger age (OR: 0.43; 95% CI: 0.40-0.47, p <0.001 for patients aged 18-35 relative to patients aged ≥65 years); non-White race (OR: 0.72; 95% CI: 0.69-0.75, p <0.001 relative to White patients); and evidence of prior schizophrenia-related hospitalization (OR: 0.80; 95% CI: 0.77-0.83, p <0.001 relative to patients without evidence of prior schizophrenia-related hospitalization). Similar associations were observed for discontinuation outcomes. Twice-daily dosing frequency was also associated with lower odds of adherence (odds ratio [OR]: 0.93; 95% CI: 0.89-0.97, p = 0.0014) and higher hazard of discontinuation (hazard ratio [HR]: 1.03; 95% CI: 1.00-1.05, p = 0.0244) relative to once-daily dosing frequency. Conclusion: We found high rates of non-adherence and discontinuation among Medicare beneficiaries initiated on currently available OAPs. We also identified risk factors that contribute to increased odds of medication non-adherence. By identifying at-risk patient populations, targeted interventions can be initiated to facilitate treatment continuity.

Plain Language Summary: Although half of patients with schizophrenia are covered by Medicare, little is known about how consistently they take their antipsychotic medications, which is a crucial part of successful treatment. We found that only 1/3 of Medicare beneficiaries consistently took their medications and nearly 80% discontinued treatment, often shortly after starting it. Younger patients, non-White patients, and patients who had to take pills multiple times per day were less likely to consistently take their medications.

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Neuroleptic malignant syndrome (NMS) is a rare life-threatening condition associated with the use of antipsychotic medications. This case report describes a male patient in his early 30s who presented with fever, breathlessness, and lower limb weakness, ultimately diagnosed with NMS despite the absence of muscular rigidity. On examination, he was febrile, tachycardic, and tachypneic with an oxygen saturation of 88% and elevated blood pressure. On auscultation diffuse crepitations in both lungs were revealed. Neurological assessment indicated motor strength of 3/5 in both lower limbs, without rigidity, sensory loss, or cerebellar signs. It was noted that he was on irregular atypical antipsychotic medication for the past one year. Laboratory investigations revealed leukocytosis, elevated transaminases, dyselectrolytemia, elevated creatine phosphokinase (CPK), and serum creatinine. NMS was not initially considered due to the lack of muscular rigidity. However, the patient later developed autonomic dysregulation manifestations, such as paralytic ileus. Once organic causes were excluded, NMS was diagnosed. Supportive therapy included 23 cycles of hemodialysis and colonic decompression for pseudo-obstruction. He was treated with intravenous fluids and dopamine receptor agonist medications. NMS usually presents with fever, muscular rigidity, altered mental status, and autonomic instability; yet, the absence of muscular rigidity in this patient is a distinctive and unusual feature.

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Introduction: There is no consensus on the optimal antipsychotic for acute agitation. Whereas haloperidol is frequently used and has proven efficacy, second generation antipsychotics show similar efficacy and improved safety and tolerability. This study aimed to determine the effectiveness of short-acting intramuscular (IM) haloperidol versus other IM antipsychotics for acute agitation in adults admitted to an inpatient psychiatry unit. Methods: This was a retrospective medical record review of patients who received 1 or more doses of a short-acting IM antipsychotic, including chlorpromazine, haloperidol, olanzapine, or ziprasidone. The primary endpoint was the need for subsequent IM antipsychotic(s) or physical restraint within 2 hours of the initial IM antipsychotic. Secondary endpoints assessed outcomes at 24 hours and adverse events. Results: One hundred six patients were included. Four patients in the haloperidol group and 0 patients in the other antipsychotic group received an additional IM antipsychotic or required physical restraints within 2 hours (5.3% versus 0%, p = .319). More patients in the other antipsychotic group required an additional dose of IM antipsychotic within 24 hours compared with the haloperidol group (p = .0096). More adverse events were seen in patients who received haloperidol. Discussion: Haloperidol was used more frequently than other short-acting IM antipsychotics. Whereas the effectiveness at 2 hours was not significantly different between groups, patients who received haloperidol were more likely to experience adverse events and were more often subjected to polypharmacy with benzodiazepines and/or diphenhydramine. This study further supports the use of olanzapine and ziprasidone for acute agitation in patients hospitalized in inpatient psychiatry.