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Cureus Jan 2024Background Major depressive disorder (MDD) has many facets including mixed or atypical depression that requires personalized care to improve treatment-related outcomes....
Background Major depressive disorder (MDD) has many facets including mixed or atypical depression that requires personalized care to improve treatment-related outcomes. Second-generation antipsychotics (SGAs) offer complementary mechanisms for clinical roles in difficult-to-treat depression and treatment-resistant depression cases. Aim/objective To further delineate a consensus on the clinical positioning of SGAs for MDD, mixed, or atypical depression, a Knowledge Attitude Perception (KAP)-mediated Delphi Statement was planned. Material/methods A literature review for the definition, diagnosis, and management of MDD, mixed, and atypical depression as treatment-resistant depression (TRD) or difficult-to-treat depression (DTD) was conducted by a steering committee of academic and clinical experts (n=6) while developing a validated KAP questionnaire. Scientific statements as clinical recommendations were evolved using the Delphi methodology before building a clinical expert consensus with an online survey (n=24). Results Twenty-four psychiatrists highlighted DTD to offer a multidimensional approach to assess treatment strategies involving selective serotonin reuptake inhibitors (SSRIs) or SGAs, while ensuring symptom, functional, and quality of life (QoL) domain improvement for improved outcomes and remission rates. MDD cases with anxiety, anhedonia, comorbidities, and risk traits require personalized care with early induction of SGAs for severe cases or symptom persisters with functional impairment. Early augmentation with SGAs including aripiprazole or cariprazine can provide a favorable risk-benefit profile for clinical cases of MDD with or without the antecedent of mixed depression or personality disorder. Conclusion The literature review and KAP responses emphasize the importance of early identification for personalized care strategies with SGAs for DTD. Large-scale real-world evidence needs to evolve with due recognition of different phenotypes as TRD or DTD with partial or functional impairment to understand the impact of appropriate treatment pathways with SGAs.
PubMed: 38406088
DOI: 10.7759/cureus.52878 -
Cureus Jan 2024Stiff-person syndrome (SPS) is an uncommon autoimmune neurological disorder marked by painful muscle stiffness, muscle spasms, and limb weakness. Neurological symptoms...
Stiff-person syndrome (SPS) is an uncommon autoimmune neurological disorder marked by painful muscle stiffness, muscle spasms, and limb weakness. Neurological symptoms in SPS can mimic a psychogenic movement disorder in which symptoms are triggered by sudden movement and emotional distress, which might delay proper treatment. However, psychiatric symptoms are far less common, and there is limited understanding regarding the co-occurrence of psychiatric conditions. Psychiatric symptoms include nonspecific anxiety, agoraphobia, and depression, which can be triggered by sudden movement, noise, or emotional stress. This case report dives into the psychiatric manifestations seen in a patient with SPS. The case report focuses on a 42-year-old female with SPS, migraines, systemic lupus erythematosus, Sjogren's syndrome, and a psychiatric history of anorexia, depression, and anxiety. Her unique presentation underscored the necessity for a multidisciplinary approach to psychiatric care. The patient was evaluated and managed during her admission to the psychiatric unit for unspecified psychosis. Her course included a complicated medical evaluation for cardiovascular and neurologic symptoms and comprehensive psychiatric management. She manifested resistance to specific psychiatric medications and care strategies. She had atypical presentations, like sensory symptoms and left-sided chest pain. She exhibited paranoia and psychosis, which were managed with a combination of pharmacologic treatments, including aripiprazole. Psychotic symptoms were resolved upon discharge, with an emphasis on strict outpatient follow-up. This case report enhances our understanding of the clinical nuances associated with SPS and its intersection with psychiatric symptoms. The objective of this case report is to detail the diagnostic and therapeutic complexities of managing psychosis in a patient with SPS, along with a pre-existing complex medical and psychiatric profile, and to contribute to a deeper understanding of SPS and associated psychiatric conditions and more effective management strategies.
PubMed: 38406022
DOI: 10.7759/cureus.52930 -
BioRxiv : the Preprint Server For... Feb 2024Invasive fungal infections (IFIs) impose an enormous clinical, social, and economic burden on humankind. For many IFIs, ≥ 30% of patients fail therapy with existing...
Invasive fungal infections (IFIs) impose an enormous clinical, social, and economic burden on humankind. For many IFIs, ≥ 30% of patients fail therapy with existing antifungal drugs, including the widely used azole class. We previously identified a collection of 13 approved medications that antagonize azole activity. While gain-of-function mutants resulting in antifungal resistance are often associated with reduced fitness and virulence, it is currently unknown how exposure to azole antagonistic drugs impact physiology, fitness, or virulence. In this study, we examined how exposure to azole antagonists affected phenotype and capacity to cause disease. We discovered that most of the azole antagonists had little impact on fungal growth, morphology, stress tolerance, or gene transcription. However, aripiprazole had a modest impact on hyphal growth and increased cell wall chitin content. It also worsened the outcome of disseminated infections in mice at human equivalent concentrations. This effect was abrogated in immunosuppressed mice, indicating an additional impact of aripiprazole on host immunity. Collectively, these data provide proof-of-principle that unanticipated drug-fungus interactions have the potential to influence the incidence and outcomes of invasive fungal disease.
PubMed: 38405954
DOI: 10.1101/2024.02.13.580133 -
Pharmaceuticals (Basel, Switzerland) Jan 2024Pharmacological treatment for psychiatric disorders has shown to only be effective in about one-third of patients, as it is associated with frequent treatment failure,...
Pharmacological treatment for psychiatric disorders has shown to only be effective in about one-third of patients, as it is associated with frequent treatment failure, often because of side effects, and a long process of trial-and-error pharmacotherapy until an effective and tolerable treatment is found. This notion emphasizes the urgency for a personalized medicine approach in psychiatry. This prospective patient- and rater-blinded, randomized, controlled study will investigate the effect of dose-adjustment of antidepressants and or antipsychotics and according to the latest state-of-the-art international dosing recommendations for and metabolizer status in patients with mood, anxiety, and psychotic disorders. A total sample of N = 2500 will be recruited at nine sites in seven countries (expected drop-out rate of 30%). Patients will be randomized to a pharmacogenetic group or a dosing-as-usual group and treated over a 24-week period with four study visits. The primary outcome is personal recovery using the Recovery Assessment Scale as assessed by the patient (RAS-DS), with secondary outcomes including clinical effects (response or symptomatic remission), side effects, general well-being, digital phenotyping, and psychosocial functioning. This is, to our knowledge, the first international, multi-center, non-industry-sponsored randomized controlled trial (RCT) that may provide insights into the effectiveness and utility of implementing pharmacogenetic-guided treatment of psychiatric disorders, and as such, results will be incorporated in already available dosing guidelines.
PubMed: 38399366
DOI: 10.3390/ph17020151 -
Psychiatry Research Apr 2024A significant heterogeneity prevails in antipsychotics (APs) safety monitoring recommendations. Youths are deemed more vulnerable to cardiometabolic side effects. We...
A significant heterogeneity prevails in antipsychotics (APs) safety monitoring recommendations. Youths are deemed more vulnerable to cardiometabolic side effects. We aimed to assess age-dependent reporting of cardiac and metabolic disorders in youths, relying on the WHO safety database (VigiBase®). VigiBase® was queried for all reports of cardiac, glucose, lipid and nutritional disorders involving APs. Patients <18 years were classified as pediatric population. Disproportionality analyses relied on the Information Component (IC): the positivity of the lower end of its 95 % confidence interval was required to suspect a signal. We yielded 4,672 pediatric reports. In disproportionality analysis, nutritional disorders were leading in youths (IC 3.9 [3.9-4.0]). Among healthcare professionals' reports, stronger signals were detected in youths than in adults. Children had the greatest signal with nutritional disorders (IC 4.7 [4.6-4.8]). In adolescents, aripiprazole was ascribed to non-alcoholic steatohepatitis (NASH). Our findings, based on real-world data, support the hypothesis of a greater propensity for nutritional disorders in youths, despite limitations of pharmacovigilance studies. We suggest specific safety profiles, such as aripiprazole and NASH. Pending more answers from population-based studies, a careful anamnesis should seek for risk factors before AP initiation. A cautious monitoring is warranted to allow earlier identification of side effects.
Topics: Adult; Humans; Child; Adolescent; Antipsychotic Agents; Aripiprazole; Non-alcoholic Fatty Liver Disease; World Health Organization; Nutrition Disorders
PubMed: 38387164
DOI: 10.1016/j.psychres.2024.115786 -
Frontiers in Pharmacology 2023Autism spectrum disorder (ASD) may affect family and social life profoundly. Although there is no selective pharmacotherapy for ASD, the Food and Drug Administration... (Review)
Review
Autism spectrum disorder (ASD) may affect family and social life profoundly. Although there is no selective pharmacotherapy for ASD, the Food and Drug Administration (FDA) has recommended risperidone/aripiprazole to treat the associated symptoms of ASD, such as agitation/irritability. Strong associations of some pharmacokinetic/pharmacodynamic gene variants, e.g., and , with risperidone-induced hyperprolactinemia have been found in children with ASD, but such strong genetic associations have not been found directly for aripiprazole in ASD. In addition to pharmacogenomic (PGx) factors, drug-drug interactions (DDIs) and possibly cumulative effects of DDIs and PGx may affect the safety or effectiveness of risperidone/aripiprazole, which should be assessed in future clinical studies in children with ASD. Reimbursement, knowledge, and education of healthcare professionals are the key obstacles preventing the successful implementation of ASD pharmacogenomics into routine clinical practice. The preparation of national and international PGx-based dosing guidelines for risperidone/aripiprazole based on robust evidence may advance precision medicine for ASD.
PubMed: 38375208
DOI: 10.3389/fphar.2023.1285967 -
Cureus Jan 2024Acute laryngeal dystonia (ALD) is a rare side effect of antipsychotic medications, but it is a life-threatening condition. We are introducing the case of a 49-year-old...
Acute laryngeal dystonia (ALD) is a rare side effect of antipsychotic medications, but it is a life-threatening condition. We are introducing the case of a 49-year-old Saudi single male, who has been known to have schizophrenia for the last 20 years. He developed three attacks of acute laryngeal dystonia owing to different antipsychotic medications. The first was because of haloperidol on a dose of 20 mg a day. After being treated for dystonia and stabilized physically, the patient received oral aripiprazole at a dose of 10 mg a day. Unfortunately, he developed acute laryngeal dystonia, and treatment had to be discontinued. The third attack of dystonia was two months later because of the use of olanzapine in a dose of only 5 mg/day. The patient was finally stabilized on quetiapine with no more side effects. This case highlights the importance of careful monitoring of patients who are receiving antipsychotic medications, even newer ones, to avoid, or treat, such a rare but serious side effect early.
PubMed: 38344557
DOI: 10.7759/cureus.52001 -
Healthcare (Basel, Switzerland) Jan 2024This narrative review explores the efficacy and tolerability of third-generation antipsychotics (TGAs)-aripiprazole, cariprazine, brexpiprazole, and lurasidone-for the... (Review)
Review
This narrative review explores the efficacy and tolerability of third-generation antipsychotics (TGAs)-aripiprazole, cariprazine, brexpiprazole, and lurasidone-for the management of substance-induced psychosis (SIP). SIP is a psychiatric condition triggered by substance misuse or withdrawal, characterized by unique features distinct from those of primary psychotic disorders. These distinctive features include a heightened prevalence of positive symptoms, such as hallucinations and delusions, in addition to a spectrum of mood and cognitive disturbances. This review comprehensively investigates various substances, such as cannabinoids, cocaine, amphetamines, and LSD, which exhibit a greater propensity for inducing psychosis. TGAs exhibit substantial promise in addressing both psychotic symptoms and issues related to substance misuse. This review elucidates the distinctive pharmacological properties of each TGA, their intricate interactions with neurotransmitters, and their potential utility in the treatment of SIP. We advocate for further research to delineate the long-term effects of TGAs in this context and underscore the necessity for adopting an integrated approach that combines pharmacological and psychological interventions. Our findings underscore the intricate and multifaceted nature of treating SIP, highlighting the potential role of TGAs within therapeutic strategies.
PubMed: 38338224
DOI: 10.3390/healthcare12030339 -
Cureus Jan 2024Antipsychotics are considered a gold standard treatment for schizophrenia. However, there is considerable variation in antipsychotic medication choice. Factors...
Antipsychotics are considered a gold standard treatment for schizophrenia. However, there is considerable variation in antipsychotic medication choice. Factors considered involved include symptomatology, prior response, and adverse reactions. This case report presents a 38-year-old male patient with schizophrenia in acute psychosis refractory to several antipsychotics. Hypotheses for the mechanism of action of antipsychotics and psychopharmacology are discussed, and treatment resistance is defined. The patient's psychiatric, medical, and social history and past antipsychotic medications are reviewed. Afterward, the rationale for initiating perphenazine is discussed, and the patient's improvement with this medication is examined. Current literature on perphenazine's efficacy is also reviewed and discussed alongside its limitations.
PubMed: 38313962
DOI: 10.7759/cureus.51593 -
Journal of Affective Disorders Apr 2024We conducted a one-year, retrospective, mirror-image study to investigate the clinical effectiveness and safety of aripiprazole once monthly (AOM) in patients with...
BACKGROUND
We conducted a one-year, retrospective, mirror-image study to investigate the clinical effectiveness and safety of aripiprazole once monthly (AOM) in patients with bipolar disorder (BD). We compared pre-treatment conditions with outcomes after 12 months of AOM treatment.
METHODS
Seventy-five bipolar patients were recruited from 12 hospitals in Korea. We included 75 patients with BD who had received at least three AOM treatments from September 2019 to September 2022 and had accessible electronic medical record (EMRs) for the year before and after the baseline visit.
RESULTS
The overall number of mood episodes significantly decreased from a mean of 1.5 ± 1.2 episodes pre-AOM to 0.5 ± 1.2 episodes post-AOM. Manic episodes significantly decreased from 0.8 ± 0.8 episodes pre-AOM to 0.2 ± 0.5 episodes post-AOM, and depressive episodes significantly decreased from 0.5 ± 0.8 episodes pre-AOM to 0.2 ± 0.6 episodes post-AOM (p = 0.017). Moreover, the number of psychiatric medications and pills and the proportion of patients treated with complex polypharmacy were significantly decreased post-AOM.
LIMITATIONS
The small sample size was insufficient to fully represent the entire population of individuals with BD, and potential selection bias was introduced due to only including subjects who received AOM three or more times.
CONCLUSION
The results of this study suggest that AOM can reduce mood episode relapse and may be clinically beneficial in the treatment of BD patients, potentially reducing issues associated with polypharmacy in some individuals.
Topics: Humans; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Recurrence; Retrospective Studies
PubMed: 38302064
DOI: 10.1016/j.jad.2024.01.257