Cross-sectional and longitudinal analyses were carried out to assess the relationship between dementia patient suffering, caregiver depression, and antidepressant medication use in 1222 dementia patients and their caregivers. We assessed the prevalence of 2 types of patient suffering, emotional and existential distress, and examined their independent associations with caregiver depression and antidepressant medication use when controlling for sociodemographic characteristics of caregivers and patients, cognitive and physical disability of the patient, the frequency of patient memory problems and disruptive behaviors, and the amount of time spent caring for the patient. Multiple linear regression models showed that both aspects of perceived patient suffering independently contribute to caregiver depression (emotional distress: beta=1.24; P<0.001; existential distress: beta=0.66; P<0.01) whereas only existential suffering contributes to antidepressant medication use: odds ratio=1.25 95% confidence interval, 1.10-1.42; P<0.01. In longitudinal analyses, increases in both types of suffering were associated with increases in caregiver depression (emotional distress: beta=1.02; P<0.01; existential distress: beta=0.64; P<0.01). This is the first study to show in a large sample that perceived patient suffering independently contributes to family caregiver depression and medication use. Medical treatment of patients that maintain or improve memory but do not address suffering may have little impact on the caregiver. Alzheimer disease patient suffering should be systematically assessed and treated by clinicians.