Frontotemporal dementia (FTD) and Lewy body dementia (LBD) are distinct neurodegenerative disorders that rarely co-occur. However, their overlapping features can obscure diagnosis and complicate management. We present the case of a 65-year-old man with a history of alcohol use disorder, diabetes, and blindness who developed acute behavioral changes, catatonia, and fluctuating mental status. He exhibited signs consistent with a behavioral variant FTD, including disinhibition, executive dysfunction, and hypersexuality, as well as features associated with LBD, including visual hallucinations, autonomic instability, and waxing-and-waning impairment in cognition. His hospital course was marked by episodic disorientation, variable language use, and persecutory delusions. Neuroimaging, cerebrospinal fluid analysis, and serial neuropsychological testing yielded mixed and inconclusive results, contributing to the diagnostic ambiguity. Treatment included lorazepam, which improved catatonic symptoms but was discontinued due to risk of delirium, and aripiprazole, which was tapered due to suspected neuroleptic sensitivity. The patient was ultimately discharged to memory care with a diagnosis of an unspecified dementia. This case underscores the challenges of diagnosing and managing patients with overlapping features of multiple neurodegenerative disorders. Recognizing points of overlap between syndromes like FTD and LBD is key to tailoring interventions and avoiding harm. Serial cognitive assessments, functional neuroimaging, and biomarker analysis may improve diagnostic accuracy, although these tools have limitations. A deeper understanding of the pathophysiology of overlapping dementia syndromes is crucial for improving diagnostic clarity and guiding treatment strategies.

In older adults, bipolar disorder (BD) frequently presents atypically, with manic symptoms manifesting as irritability or confusion rather than euphoria. Cognitive impairments, including mild cognitive impairment and dementia, can obscure or mimic bipolar symptoms, complicating accurate diagnosis. Depressive episodes tend to be more frequent and prolonged, increasing misdiagnosis risk as unipolar depression. Pharmacological management requires careful consideration of age-related pharmacokinetic and pharmacodynamic alterations. Mood stabilizers including lithium, valproate, and lamotrigine are commonly employed but necessitate vigilant monitoring for adverse effects and drug interactions. Atypical antipsychotics such as quetiapine and aripiprazole are generally preferred for their tolerability profiles, though comorbidity burden and polypharmacy substantially elevate risks of adverse drug reactions and interactions. Late-onset and early onset bipolar disorder in older adults (LOBD and EOBD) represent clinically relevant subgroups with differing diagnostic considerations. However, current evidence does not clearly support major differences in pharmacologic management. The purpose of this narrative review is to address this gap by comprehensively exploring the clinical presentations and diagnostic challenges in older-age BD (OABD) as well as the pharmacological treatment patterns worldwide. We also outlined clinically focused synthesis of special considerations and tailored approaches, and finally critically appraise the literature to determine future directions and research needs. Addressing the multifaceted diagnostic and pharmacotherapeutic challenges of OABD through dedicated age-specific clinical trials, comparative effectiveness studies, systematic evaluation of deprescribing strategies, and enhanced clinician awareness will be fundamental to improve outcomes for this understudied and expanding population.

Antipsychotic-induced decreased libido is a common clinical concern, yet drug-specific differences and their underlying neurobiological mechanisms remain poorly understood. We chronically exposed adult male zebrafish to risperidone (RIS), olanzapine (OLZ), quetiapine (QTP), or aripiprazole (ARP) to evaluate their effects on courtship behavior. Brain and testicular transcripts related to the hypothalamic-pituitary-gonadal (HPG) axis, kisspeptin, and monoamine receptors, along with systemic 11-ketotestosterone (11-KT) concentrations, were subsequently analyzed. RIS significantly decreased courtship duration, followed by a downward trend in the OLZ group, whereas QTP and ARP showed no detrimental effects. At the molecular level, RIS significantly reduced brain kiss2 and upregulated prl1 transcript levels. Conversely, the ARP group demonstrated a local transcriptional upregulation of neurosteroidogenic enzymes (cyp11c1 and hsd11b2) and downregulation of the inhibitory gnihr1 pathway in the brain, which may help preserve reproductive drive. Furthermore, RIS and OLZ groups showed significant transcriptional upregulation of central dopamine and serotonin receptors, reflecting marked monoaminergic alterations. These findings suggest that QTP and ARP have minimal impacts on libido, while RIS and OLZ carry a higher risk. This differential susceptibility is likely mediated by a complex interplay of kiss2 downregulation, prolactin elevation, altered local neurosteroidogenesis, and monoamine receptor transcript adjustments, rather than a uniform suppression of the peripheral HPG axis.

Neuropsychiatric symptoms including agitation, delirium, and psychosis are common in patients with primary or metastatic brain tumors and frequently necessitate antipsychotic treatment. Brain tumors create a hyperexcitable cortical environment characterized by glutamatergic excess, impaired inhibitory signaling, peritumoral edema, network disruption, and treatment-related neurotoxicity, all of which lower seizure threshold. Emerging data further implicates impaired astrocytic glutamate regulation, neuroligin-3-mediated neuron-glioma synaptic signaling, and IDH-mutant-associated oncometabolite accumulation as contributors to cortical instability. Neuropsychiatric symptoms often localize to frontal and temporal networks that are also highly epileptogenic, amplifying vulnerability. Brain tumor-related epilepsy further compounds this risk through recurrent seizures, interictal dysfunction, and antiseizure medication effects that contribute to cognitive and behavioral disturbance.

Olanzapine is a frequently used second-generation antipsychotic, often considered to have a favorable hematological safety profile than clozapine. We report a rare case of recurrent pancytopenia associated with olanzapine rechallenge in a 46-year-old woman with acute psychotic episode. She had previously responded well to olanzapine but developed moderate hematological decline, which resolved on discontinuation. During current psychotic episode, olanzapine was re-initiated, and serial blood counts suggested progressive pancytopenia, which was confirmed on peripheral smear. Alternative causes including nutritional deficiencies and autoimmune disorders were ruled out. Olanzapine was discontinued and replaced with aripiprazole, following which all three cell lines normalized subsequently. This case demonstrates a clear temporal challenge-dechallenge-rechallenge association, confirming olanzapine as the causative agent. Clinicians should maintain a high degree of suspicion for hematological adverse effects even with olanzapine, especially in patients with prior cytopenic episodes. In such patients, baseline and serial hematological monitoring is advised and rechallenge is contraindicated.

To improve medication adherence in Japanese patients with schizophrenia or bipolar I disorder, this population pharmacokinetic (popPK) modeling and simulation was conducted to support the regulatory submission of the two-injection start (TIS; two aripiprazole once-monthly long-acting injectable [LAI; 400 mg each] administered at different sites, along with a single oral dose of aripiprazole [6-15 mg]) regimen by comparing it with the original regimen (single LAI with 2-week concomitant oral dose of aripiprazole [6-15 mg]). Pharmacokinetic data from four Japanese clinical trials in patients with schizophrenia were used to externally validate and update a previously validated popPK model developed from seven non-Japanese trials in healthy subjects or in patients with schizophrenia/schizoaffective disorders. Simulations were conducted assuming two types of patients: with and without prior stabilization on oral aripiprazole. The dataset of 1123 participants (13,985 observations) from clinical trials, including 306 Japanese patients (5699 observations) from Japanese clinical trials, was used as the input in the popPK model. Simulations showed that the plasma concentration-time profiles of the original regimen and the TIS regimen were similar in the Japanese population. In addition, the currently available postmarketing safety data did not show any new safety concerns and/or an incremental safety risk with the TIS regimen compared with the original regimen. The aripiprazole TIS regimen provides a new option by reducing the oral aripiprazole administration period to a single day. This is expected to reduce the medication burden on patients and, consequently, reduce the burden on healthcare professionals and caregivers.