Citations

Importance There is a need for greater recognition of clinical psychopharmacology endpoints, including instances where specific psychotropic medications may become unnecessary, redundant, contradictory, or otherwise inappropriate and therefore merit deprescribing. Objective To address circumstances warranting psychotropic medication deprescribing. Evidence Review The American Society of Clinical Psychopharmacology convened a panel of 45 international psychopharmacology experts who developed and completed a multiround Delphi survey and conducted a focused literature review between January and May of 2025, in order to identify areas of consensus or disagreement on key aspects of the deprescribing of psychotropic medications. These included collaborative risk-benefit assessments with patients; pharmacokinetic and pharmacodynamic factors; pharmacogenomics; distinguishing redundant or conflictual from complementary mechanisms of action; managing adverse effects; assuring medication adherence; drug tolerance or tachyphylaxis; medication misuse; and the psychological context and ramifications of deprescribing. Findings Consensus was achieved on 44 of 50 final Delphi statements (88%). Panelists unanimously agreed that components of a pharmacotherapy regimen should undergo periodic review to ensure that treatments target relevant symptoms and have favorable risk-benefit ratios. Key points of consensus were that deprescribing: (1) should not occur without first assessing medication adherence; (2) merits consideration if less than partial therapeutic response is apparent, or if treatment goals have been reached and relapse prevention is not a long-term objective; (3) involves psychological ramifications that warrant attention; (4) should be followed by close clinical monitoring; and (5) risk-benefit decisions should ideally involve active patient participation within a shared decision-making model. Conclusions and Relevance Through this Consensus Statement, the Task Force identified circumstances in which the selective elimination of certain psychotropic medications may be clinically indicated. Empirical trials are needed to assess the implementation of deprescribing protocols and gauge their safe, effective, and acceptable outcomes.

In this 5-year follow-up from the CheckMate 743 study in patients with unresectable pleural mesothelioma (PM), we evaluated updated efficacy and safety outcomes and biomarkers and performed treatment-switching analyses with first-line nivolumab plus ipilimumab versus chemotherapy. With a median follow-up of 66.8 months, nivolumab plus ipilimumab demonstrated continued overall survival (OS) benefit versus chemotherapy in all randomly assigned patients (5-year OS rates, 14% v 6%; hazard ratio [HR], 0.74 [95% CI, 0.62 to 0.88]); similar benefit was observed regardless of tumor histology. Of biomarker-evaluable patients treated with nivolumab plus ipilimumab (n = 242), high baseline monocytic myeloid-derived suppressor cell (M-MDSC) levels correlated with worse OS versus low M-MDSC levels (HR, 1.25 [95% CI, 1.09 to 1.43]). After adjusting for 24% of patients in the chemotherapy arm who received subsequent immunotherapy, nivolumab plus ipilimumab demonstrated continued OS benefit versus chemotherapy (HR, 0.64 [95% CI, 0.53 to 0.78]). No new safety signals were observed. These results demonstrate long-term, durable clinical benefit with nivolumab plus ipilimumab versus chemotherapy, which continued to be preserved even after treatment-switching adjustment in the chemotherapy arm. Exploratory analyses suggested greater benefit with nivolumab plus ipilimumab in the low M-MDSC subgroup. These results further support first-line nivolumab plus ipilimumab as standard of care for unresectable PM.

Background/Objectives: Diagnostic evaluation and management of nontraumatic osteonecrosis of the femoral head (ONFH) vary substantially. This systematic review was conducted to inform development of the Association Research Circulation Osseous (ARCO) clinical practice guideline for diagnosis and treatment of ARCO stages I to III ONFH. Methods: We searched MEDLINE, EMBASE, Web of Science, SCOPUS, Global Index Medicus, and the Cochrane Library for studies evaluating imaging modalities and treatments for adult ONFH. We assessed risk of bias using the QUADAS-2, the ROB-2, and the ROBINS-I tools; conducted meta-analyses using random-effects regression; and evaluated certainty of evidence using GRADE methodology. Results: Among 36 included studies, 18 addressed diagnostic test accuracy and 18 addressed comparative effectiveness of treatments. Magnetic resonance imaging (MRI) demonstrated the highest pooled sensitivity (0.91; 95% confidence interval (CI), 0.87 to 0.94) and specificity (0.96; 95% CI, 0.87 to 0.99) for ONFH diagnosis. Bone marrow edema and grade 2+ joint effusion on MRI differentiated symptomatic versus asymptomatic disease. Computed tomography and MRI better detected subchondral fractures than plain radiography. Very low-grade evidence suggested lower rates of femoral head collapse with core decompression plus bone marrow concentrate compared with core decompression alone (pooled relative risk [RR], 0.55; 95% CI, 0.36 to 0.83), and with vascularized versus non-vascularized bone grafting (RR, 0.35; 95% CI, 0.14 to 0.84) over a ≤5-year follow-up. Based on three non-comparative case series, osteotomies might have a lower risk of collapse over a 10- to 20-year follow-up, but this needs to be evaluated in future comparative research. Inconsistent outcome reporting hindered treatment outcome pooling. There were no comparative studies that evaluated observation only versus intervention in asymptomatic disease or strategies for monitoring treatment response. Conclusions: Evidence supporting optimal imaging modalities and early joint-preserving interventions remains limited and predominantly observational, underscoring the need for high-quality comparative studies with consistently defined core outcomes to guide clinical decision-making.