Psychiatry

Profound cognitive impairment and dementia-range scores are the norm in severe, treatment-resistant schizophrenia

Among 155 continuously hospitalized patients with severe, extremely treatment-resistant schizophrenia, 98.7% scored below the MoCA cutoff for mild cognitive impairment. Nearly half scored in the severe dementia range, yet their item-level profile differed from Alzheimer, frontotemporal, and Lewy body dementias. The cognitive pattern closely matched that of community-dwelling individuals with schizophrenia, suggesting a schizophrenia-specific dementia phenotype. No Mendelian dementia variants were detected, and APOE4 frequency was lower than in Alzheimer and Lewy body dementia cohorts. Cognitive impairment was not explained by medications, vascular risk, institutionalization, premorbid intellectual disability, or poor effort, implying an intrinsic disease process. Clinicians should frame long-term prognosis in SETRS around very high likelihood of profound cognitive and functional decline. 1

Mortality differs by antipsychotic in Alzheimer’s disease, favoring aripiprazole and quetiapine

In 17,004 patients with incident Alzheimer’s disease starting aripiprazole, risperidone, quetiapine, or olanzapine, all-cause mortality varied substantially by agent. Aripiprazole was associated with lower mortality than olanzapine and quetiapine after adjustment and propensity matching. Quetiapine showed lower mortality than olanzapine and risperidone. In patients using type 2 diabetes medications, aripiprazole remained protective versus quetiapine and risperidone. These data support preferring aripiprazole or quetiapine when antipsychotics are unavoidable, especially in Alzheimer’s disease patients with diabetes. 2

ADHD medications coincide with, but may not cause, elevated suicidal behavior

Among 830,352 ADHD patients aged 9–64 using stimulants, atomoxetine, or alpha-2 agonists, suicidal behavior peaked in the two months before treatment initiation. This pretreatment spike was particularly marked for atomoxetine and alpha-2 agonists, consistent with initiation during clinical deterioration. Compared with off-treatment periods excluding pretreatment, suicidal behavior odds during treatment were modestly higher for all three medication classes. Within-individual comparisons reduce confounding by indication but cannot exclude residual time-varying confounding. Clinically, starting or changing ADHD medication should prompt intensified suicide-risk monitoring, not automatic avoidance of pharmacotherapy. 3

Two-variable BIOERES model predicts 5-year treatment resistance after first-episode schizophrenia

In 44 first-episode schizophrenia-spectrum patients followed for five years, 29.5% developed treatment-resistant schizophrenia by TRRIP and clozapine criteria. Lower baseline CSF lactate dehydrogenase levels were independently associated with later treatment resistance in adjusted logistic models. A model combining CSF LDH with early antipsychotic response achieved an AUC of 0.86, outperforming LDH alone. This simple BIOERES model could, if validated, identify high-risk patients early for faster clozapine consideration or trial referral. The findings highlight central bioenergetic dysfunction and early treatment response as promising stratification targets. 4