Double-edged sword of antipsychotic therapy: Navigating the intersection of psychiatric recovery, endoplasmic reticulum stress, and cardiovascular survival

Table 1 Relationship between antipsychotic drug prescriptions and mortality rates

Study metric	No antipsychotic use	Any antipsychotics	Clozapine
All-cause mortality (aHR)	1.00 (reference)	0.48	0.39
Cardiovascular mortality (aHR)	1.00 (reference)	0.62	0.55
Suicide mortality (aHR)	1.00 (reference)	0.52	0.21
20-year cumulative mortality (%)	46.2	25.7	15.6

Adjusted hazard ratios are based on the Finnish nationwide cohort[38]. A lower ratio indicates a higher protective effect compared to non-use. aHR: Adjusted hazard ratios.

Table 2 Clinical evaluation checklist: Integrated metabolic-psychiatric care

Domain	Assessment item	Status/metric	Clinical action if red flag
Psychiatric stability	PANSS score/clinical impression	Stable vs fluctuating	Do not switch meds if stable; prioritize adjuncts over switching
Psychiatric stability	Suicide risk assessment	Low vs high	If high, prioritize clozapine/Lithium regardless of metabolic risk
Metabolic markers	HbA1c/fasting glucose	< 5.7% (target)	If elevated, consider metformin or GLP-1 RA early
Metabolic markers	Triglyceride/HDL ratio	Target < 3.0	Consider statins or ERS-mitigating nutraceuticals
Anthropometrics	BMI and waist circumference	BMI < 25/waist < 102 cm (male)	7% weight gain from baseline triggers intervention
Lifestyle habits	Smoking status	Yes/no	Provide nicotine replacement or varenicline immediately
Lifestyle habits	Physical activity (steps/day)	Target > 7000	Referral to “exercise as medicine” psychiatric programs
Pharmacology	Medication load	Monotherapy vs polypharmacy	Reduce polypharmacy; calculate chlorpromazine equivalents 600 mg or less

This checklist is designed for clinicians to use at 3-month intervals to ensure that neither metabolic health nor psychiatric stability is being sacrificed. PANSS: Positive and Negative Syndrome Scale; HbA1c: Glycated hemoglobin; HDL: High-density lipoprotein; BIM: Body mass index; GLP-1 RA: Glucagon-like peptide 1 receptor agonist; ERS: Endoplasmic reticulum stress.