The SSRI citalopram increases the sensitivity of the human circadian system to light in an acute dose
Disturbances of the circadian system are common in depression. Though they typically subside when depression is treated with antidepressants, the mechanism by which this occurs is unknown. Despite being the most commonly prescribed class of antidepressants, the effect of selective serotonin reuptake inhibitors (SSRIs) on the human circadian clock is not well understood.
To examine the effect of the SSRI citalopram (30 mg) on the sensitivity of the human circadian system to light.
This study used a double-blind, placebo-controlled, within-subjects, crossover design. Participants completed two melatonin suppression assessments in room level light (~ 100 lx), taking either a single dose of citalopram 30 mg or a placebo at the beginning of each light exposure. Melatonin suppression was calculated by comparing placebo and citalopram light exposure conditions to a dim light baseline.
A 47% increase in melatonin suppression was observed after administration of an acute dose of citalopram, with all participants showing more suppression after citalopram administration (large effect, d = 1.54). Further, melatonin onset occurred later under normal room light with citalopram compared to placebo.
Increased sensitivity of the circadian system to light could assist in explaining some of the inter-individual variability in antidepressant treatment responses, as it is likely to assist in recovery in some patients, while causing further disruption for others.
KeywordsLight sensitivity Circadian rhythms Depression Antidepressants Melatonin suppression Light at night Sleep
We would like to thank Mr. Michael Cummins, Mr. Arnold Moss and Mr. Frank Suss of the Monash University Campus Pharmacy for their assistance in coordinating this trial, in particular Mr. Michael Cummins for performing and maintaining the randomisation and blinding. We would like to additionally thank and acknowledge Dr. Hamni Sahi for her assistance conducting medical screening of participants for the study. Lastly, we would like to acknowledge the contribution of the staff and students of the Monash University Sleep and Circadian Medicine Laboratory for their assistance in running the project.
EM McGlashan receives financial support from the Australian Government through a Research Training Program (RTP) Scholarship. P Vidafar receives a PhD scholarship from the National Health and Medicine Research Council (NHMRC), via the Neurosleep Centre for Research Excellence (CRE).
Compliance with ethical standards
Conflicts of interest
EM McGlashan, P Vidafar, LS Nandam, DR Mansfield and SW Cain report no conflicts of interest. SMW Rajaratnam reports no conflicts or funding in direct relation to this work, but that he has served as a consultant through his institution to Vanda Pharmaceuticals, Philips Respironics, EdanSafe, The Australian Workers’ Union, National Transport Commission, Transport Accident Commission, New South Wales Department of Education and Communities, and has through his institution received research grants and/or unrestricted educational grants from Vanda Pharmaceuticals, Shell, Teva Pharmaceuticals, Rio Tinto, Seeing Machines, Takeda Pharmaceuticals North America, Philips Lighting, Philips Respironics, Cephalon, and ResMed Foundation, and reimbursements for conference travel expenses from Vanda Pharmaceuticals. His institution has received equipment donations or other support from OptalertTM, Compumedics, and Tyco Healthcare. He has served as an expert witness and/or consultant to shift work organisations. SMW Rajaratnam also serves as a Program Leader in the Cooperative Research Centre for Alertness, Safety and Productivity.
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