Nearly every mood treatment we prescribe, from SSRIs to lithium, shifts the body’s internal clock
STUDY: Zürcher A et al, Pharmacopsychiatry 2026
STUDY TYPE: Review
FUNDING: Deutsche Forschungsgemeinschaft (German Research Foundation); Finnern Stiftung
Background
Problems with circadian rhythms contribute to bipolar and unipolar mood disorders. The brain’s internal 24-hour timekeeper is centered in the hypothalamus, which governs the timing of serotonin, dopamine, and cortisol release. This review pulls together the neurobiology of mood and the biology of circadian rhythm to make a case that many of the treatments we already use work partly by resetting that clock.
Summary
When the biological clock is advanced, sleep onset comes sooner. When it is delayed, sleep is delayed.
SSRIs advance the clock’s phase, while lithium and tricyclics delay it. Lithium increases the strength or amplitude of certain clock gene rhythms (like Per2).
Melatonin advances or delays the clock depending on whether it’s given in the morning (delays the clock) or afternoon/evening (advances it).
Evening chronotypes (“night owls”) tend to have worse depression, more suicidal thinking, and a weaker response to SSRIs. In bipolar disorder, the evening types have more depressive than manic episodes.
Light therapy treats both seasonal and non-seasonal depression in large, controlled trials.
A night of total sleep deprivation is one of the fastest antidepressant interventions available for Major Depressive Disorder, working in roughly half of patients within a day, though symptoms typically return after recovery sleep unless followed by a phase-advancing step like morning light.
Practice Implications
- Ask your depressed patients whether they run as morning or evening types, and pay attention to how medications affect that.
- Evening types benefit from melatonin 2-4 hours before sleep, blue light blocking glasses at night, and a dawn simulator in the morning to prevent oversleeping.
- Learn how to set the biological clock with Social Rhythm Therapy.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
