The Chronobiological–Adherence Axis: Evaluating the Impact of Circadian Disruption on Psychotropic Medication Regimen Compliance

Psychotropic non-adherence affects between two-fifths and three-fifths of patients with schizophrenia-spectrum, major depressive, and bipolar disorders, yet circadian disruption, among the most prevalent features of these illnesses, has rarely been examined as one of its determinants. This narrative review develops the construct of a chronobiological–adherence axis: the bidirectional pathway through which circadian desynchrony erodes, and circadian stabilisation supports, adherence to psychotropic regimens. Integrating molecular-clock biology, chronopharmacology, adherence epidemiology, and intervention research, it identifies five convergent mechanisms: time-of-day-dependent drug handling, rhythmic drug targets, destabilisation of the daily routines that scaffold dose-taking, symptom- and insight-mediated dropout, and treatment-emergent sleep disruption. Poor sleep quality, persistent sleep disturbance, and excessive daytime sleepiness are associated with poorer adherence, while evening chronotype and circadian phase markers predict weaker antidepressant response. Chronotherapeutic strategies, including dosing-time optimisation, bright light, melatonergic agents, wake therapy, interpersonal and social rhythm therapy, and cognitive behavioural therapy for insomnia, improve circadian parameters, but their effects on adherence are seldom measured. Circadian disruption should be treated as a modifiable determinant of non-adherence; adherence assessment should capture circadian status and dose timing; and chronotherapeutic interventions should be tested against objective adherence endpoints.