Association between citalopram, escitalopram and QTc prolongation in a real-world geriatric setting.

BACKGROUND: Although the US Food and Drug Administration (FDA) recommended upper limits for citalopram dosing in older adults due to risk of corrected-QT (QTc) prolongation, which was adopted, and extended to escitalopram by Health Canada, the scientific basis is unclear. The objective of this study was to assess the relationship between citalopram/escitalopram dosages and QTc interval in a real-world geriatric setting. METHODS: We reviewed electronic health records at a university-affiliated geriatric health care center, over a 7-year period, to identify patients prescribed citalopram and escitalopram, who had an ECG within 90 days of initiation or dosage change. Linear regression analyses were conducted to assess the relationship between antidepressant dosage and QTc interval. RESULTS: 137 patients were identified (citalopram=97, escitalopram=40). No association was found between citalopram, escitalopram and QTc, in unadjusted or adjusted analyses. Among covariates, older age was significantly associated with QTc prolongation in the escitalopram group. LIMITATIONS: Limitations to the current study include its retrospective design and the small sample size. CONCLUSIONS: These data do not support the FDA or Health Canada's recommended maximum dosages of citalopram or escitalopram in the elderly. Therefore, for patients already on higher doses of these medications, the risk of QTc prolongation may not always outweigh the risk of dose lowering, such as relapse. Until larger prospective studies become available, the decision to comply or not with these federal agencies' recommendations should be weighed on an individual basis, taking into consideration all potential risk factors.

Can anxiety damage the brain?

PURPOSE OF REVIEW: Stress exacerbates mental illnesses such as depression but also appears to increase risk of dementia, suggesting a common mechanism for development of stress-induced affective and cognitive impairment. The purpose of this review is to address the question of whether anxiety 'damages' the brain, and to identify potential mechanisms for the link between stress and neuropsychiatric illness. RECENT FINDINGS: Anxiety disorders are associated with alterations in fear neurocircuitry such that 'bottom-up' processes in the amygdala which respond to threat are exaggerated, and regulation of these processes by the prefrontal cortex (PFC) and hippocampus is impaired. Chronic stress exposure similarly alters fear neurocircuitry by enhancing amygdalar functioning while causing structural degeneration in the PFC and hippocampus thereby inhibiting PFC/hippocampus control over the stress response. Pharmacological (e.g., antidepressant medications) and nonpharmacological interventions (cognitive-behavioral therapy, exercise) may reverse stress-induced damage in the brain. SUMMARY: Pathological anxiety and chronic stress lead to structural degeneration and impaired functioning of the hippocampus and the PFC, which may account for the increased risk of developing neuropsychiatric disorders, including depression and dementia. Longitudinal studies are needed to determine whether reversal of stress-induced brain changes by interventions such as cognitive-behavioral therapy can reduce risk of neuropsychiatric illness.