Expanding Integrative Horizons: Toward a Mechanistic Bridge Between Melatonin and Music Therapy in Radiotherapy-Induced Fatigue and Psychological Distress

Dear Editor,

We read with interest the article written by Sadeghi Yazdankhah et al, ¹ “Efficacy of Melatonin in Alleviating Radiotherapy-Induced Fatigue, Anxiety, and Depression in Breast Cancer Patients.” This triple-blinded randomized controlled trial was a significant clinical confirmation that melatonin is able to reduce fatigue and mood disturbances in women receiving radiotherapy. Yet, we propose to argue that the biological pathways by which melatonin achieves these effects are not limited to pharmacological regulation and include rhythmic, affective, and neuroendocrine regulations modulated non-pharmacologically—mainly by music therapy.

Melatonin and music have recently emerged as saccadic and autonomic synchronizers, respectively, based on the available evidence. They affect the HPA axis, modulate cortisol secretion, increase parasympathetic activity, and decrease levels of pro-inflammatory cytokines.^2,3 In this sense, the processes of music therapy are not just psychological or symbolic but also embodied, activating auditory, limbic, and endocrine systems which interact with those which melatonin affects. Therefore, this overlapping physiology means that music therapy might be a simultaneous—or cooperatively working synergistically with melatonin—approach to securing the same biopsychosocial results discovered in melatonin studies.

From an integrative oncology standpoint, the separation of pharmacological and creative arts therapies is becoming more arbitrary. Both are frames of reference for the daily timing of clock-regulated lipids—systems known to be disrupted by cancer and its therapies. They can also be conceived as chronotherapeutic cues which restore altered systems’ internal synchrony. The fatigue and psychological symptoms experienced during radiotherapy have been attributed in part to circadian disruption and neuroimmune dysregulation. Music therapy’s rhythmic entrainment mechanisms may be resynchronizing these temporal systems by modulating vagal function, reinstating coherence between physiological and affective rhythms. Such a chronobiological conceptualization might converge pharmacologic and expressive approaches, under common scientific terminology rather than divergent therapeutic lineages.

We further propose that the context of radiotherapy deserves to be more fully theorized. Patients are frequently exposed to a high-tech environment that encourages sensory deprivation and stress. For complex medical conditions, music therapy in such places isn’t just about relaxation—it perhaps recodes the sensory ecology of care. The individualizing of acoustical stimuli in exchange for common mechanical soundscapes changes the clinical milieu from depressor to rhythmic and calls out an emotional predictability which indirectly enhances the other effects, somatic and mental, of melatonin. This environmental re-modulation indicates that integrative oncology has neither to add further modalities, nor different categories of treatment, but to remake therapeutic settings.

Also, melatonin’s effect on sleep and oxidative stress can possibly interact with music-elicited dopaminergic and oxytocinergic pathways promoting resilience, immune surveillance, and mood regulation. ⁴ We thus advocate for investigations using mixed designs of randomized controlled trials on melatonin and music therapy, as part of structured sessions. Measures should incorporate multiple biomarkers—melatonin metabolites, heart-rate variability, cortisol, and inflammatory cytokines—and validated fatigue and distress instruments. These designs could test the hypothesized synergy empirically and lead the field toward precision-based integrative medicine.

At a policy level, national cancer programs and hospital administrators might consider employing certified music therapists as members of multidisciplinary oncology teams. This will not only enable non-pharmacological symptom management but also endorse meaning-centered coping and existential healing, two central dimensions often underemphasized in somatic-centric paradigms. By adopting integrative modes of practice for creative arts therapies we enable these to be integrated within evidence-based models and outgrow the model of “pharma plus adjunct” toward a genuinely transdisciplinary cancer care.

In conclusion, we postulate that melatonin and music therapy are not simply added-on modalities but mechanistically similar ones, the former acting through chronobiological pathways and the latter by way of affective-neuroendocrine channels. The next chapter of integrative oncology should be dedicated to elucidating these intersections in the laboratory and clinic. By conducting such cross-disciplinary investigations, we might learn that restoring rhythm—be it biochemical or musical—is key to the restoration of the quality and meaning of life in patients with cancer. ⁵

Gita Arisara, S.KM., M.KM.Department of Public Health, Faculty of Public Sciences, Sebelas April University, Sumedang, Jawa Barat, Indonesia Prof. Dr. dr. Oktia Woro Kasmini Handayani, M.Kes.Department of Public Health, Faculty of Medicine, Universitas Negeri Semarang, Semarang, Jawa Tengah, Indonesia Dini Afriani, S.ST., M.Kes.Department of Public Health, Faculty of Public Sciences, Sebelas April University, Sumedang, Jawa Barat, Indonesia Dominikus David Biondi Situmorang, S.Pd., M.Pd., M.Si., C.T., C.PS., C.BNLP., CFH.Psy.Department of Guidance and Counseling, Atma Jaya Catholic University of Indonesia, DKI Jakarta, Indonesia