Exploring Holistic Treatments as Antidepressant Alternatives

Sleep and Mental Health: Why Sleep Care Is Foundational Sleep is essential for emotional regulation, cognitive function, and neuroplasticity. Disrupted sleep, especially insomnia, is not just a symptom but a risk factor and potential driver for mood and anxiety disorders, including depression. Insomnia can impair brain plasticity, over-activate the stress system (including cortisol dysregulation), and promote neuroinflammation, all of which contribute to psychiatric symptoms and vulnerability to mental illness. 1 2 3 4 Chronic insomnia is associated with increased risk of new-onset depression and can worsen the course of existing psychiatric conditions. 5 6 7 4 Treating Insomnia Improves Mental Health Improving sleep quality leads to measurable improvements in mental health. Meta-analyses and randomized controlled trials show that interventions targeting sleep — especially cognitive behavioral therapy for insomnia (CBT-I) — not only improve sleep but also reduce symptoms of depression, anxiety, and stress, and enhance overall psychological well-being. 8 9 10 11 There is a dose-response relationship: greater improvements in sleep yield greater improvements in mental health. 9 Treating insomnia can also prevent the onset of depression and improve outcomes in those with comorbid mood disorders. 6 11 Sleep, Hormones, and Mood Sleep physiology is tightly linked to hormone regulation. Sleep loss and insomnia can disrupt the hypothalamic-pituitary-adrenal (HPA) axis, leading to abnormal cortisol rhythms, and may affect reproductive hormones such as progesterone, which in turn can influence mood and sleep quality. 12 Evaluating and addressing hormonal imbalances can be an important part of a comprehensive sleep and mental health assessment. What a Thorough Sleep Consultation Covers A thorough sleep consultation — including review of sleep habits, medication effects, and hormone status — can identify modifiable contributors to insomnia and psychiatric symptoms. Medication review is crucial, as many drugs can worsen sleep or interact with mood. Addressing sleep hygiene, optimizing medications, and evaluating hormone levels (such as cortisol and progesterone) can all support better sleep and, by extension, better mental health. 12 7 Bottom Line Prioritizing sleep health is a powerful, evidence-based strategy for healing the mind and preventing psychiatric illness. Comprehensive sleep consultations, hormone evaluation, and medication review are key services that can help patients achieve restorative sleep and improved mood. 1 5 2 12 6 9 7 10 3 11 4 At Unchained Wellness, we take an integrative approach to restoring balance — addressing the underlying hormonal, nutritional, and psychological factors that influence sleep and emotional well-being. Schedule a consultation today to begin your personalized path toward deeper rest, improved focus, and renewed vitality.  References Sleep, Insomnia and Mental Health — Palagini L, Hertenstein E, Riemann D, Nissen C. Journal of Sleep Research. 2022;31(4):e13628. https://doi.org/10.1111/jsr.13628 The Key Role of Insomnia and Sleep Loss in the Dysregulation of Multiple Systems Involved in Mood Disorders — Palagini L, Bastien CH, Marazziti D, Ellis JG, Riemann D. Journal of Sleep Research. 2019;28(6):e12841. https://doi.org/10.1111/jsr.12841 Sleep Markers in Psychiatry: Do Insomnia and Disturbed Sleep Play as Markers of Disrupted Neuroplasticity in Mood Disorders? — Palagini L, Geoffroy PA, Riemann D. Current Medicinal Chemistry. 2022;29(35):5595-5605. https://doi.org/10.2174/0929867328666211214164907 Sleep, Insomnia, and Depression — Riemann D, Krone LB, Wulff K, Nissen C. Neuropsychopharmacology. 2020;45(1):74-89. https://doi.org/10.1038/s41386-019-0411-y Insomnia Disorder: State of the Science and Challenges for the Future — Riemann D, Benz F, Dressle RJ, et al. Journal of Sleep Research. 2022;31(4):e13604. https://doi.org/10.1111/jsr.13604 Recent Advances in Sleep and Depression — Mirchandaney R, Asarnow LD, Kaplan KA. Current Opinion in Psychiatry. 2023;36(1):34-40. https://doi.org/10.1097/YCO.0000000000000837 Insomnia Disorder — Winkelman JW. New England Journal of Medicine. 2015;373(15):1437-1444. https://doi.org/10.1056/NEJMcp1412740 Emotional Processing Following Digital CBT-I in People With Depressive Symptoms: RCT — Tamm S, Tse KYK, Hellier J, et al. JAMA Network Open. 2025;8(2):e2461502. https://doi.org/10.1001/jamanetworkopen.2024.61502 Improving Sleep Quality Leads to Better Mental Health: Meta-analysis of RCTs — Scott AJ, Webb TL, Martyn-St James M, Rowse G, Weich S. Sleep Medicine Reviews. 2021;60:101556. https://doi.org/10.1016/j.smrv.2021.101556 Effect of Digital CBT-I on Health and Well-being: RCT — Espie CA, Emsley R, Kyle SD, et al. JAMA Psychiatry. 2019;76(1):21-30. https://doi.org/10.1001/jamapsychiatry.2018.2745 Sleep Disturbance and Psychiatric Disorders — Freeman D, Sheaves B, Waite F, Harvey AG, Harrison PJ. The Lancet Psychiatry. 2020;7(7):628-637. https://doi.org/10.1016/S2215-0366(20)30136-X Sleep Physiology, Pathophysiology, and Sleep Hygiene — Baranwal N, Yu PK, Siegel NS. Progress in Cardiovascular Diseases. 2023;77:59-69. https://doi.org/10.1016/j.pcad.2023.02.005

Why Antidepressants Aren’t Always Enough — The Rise of Integrative Psychiatry Many patients with major depressive disorder and fatigue do not achieve remission with standard antidepressant therapy alone. Integrative psychiatry combines medication, hormone therapy, nutrition, intravenous therapies, IV supplementation, red light therapy, Spravato (esketamine), and transcranial magnetic stimulation (TMS) to address these unmet needs. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 Medication and Hormone Therapy Conventional antidepressants remain foundational, but many patients require additional strategies. Hormonal interventions targeting the HPA, HPT, and HPG axes—including estrogen, progesterone derivatives, and testosterone—may benefit select individuals, especially when endocrine dysfunction is present. 1 6 10 11 Nutrition and IV Supplementation Nutritional optimization and IV therapies, such as ketamine, can be considered for documented deficiencies or as adjuncts in treatment-resistant cases. IV ketamine has demonstrated rapid antidepressant effects, while micronutrient supplementation remains investigational. 7 8 12 Red Light Therapy (Photobiomodulation) Transcranial and systemic photobiomodulation using red or near-infrared light is a non-invasive neuromodulation technique with emerging evidence for efficacy in moderate-grade depression. Optimal protocols are still being defined, but the therapy is well tolerated. 2 3 4 5 9 13 Spravato (Esketamine) Spravato is an FDA-approved intranasal formulation of esketamine indicated for adults with treatment-resistant depression and for depressive symptoms with acute suicidal ideation or behavior, always in conjunction with an oral antidepressant. 14 19 21 27 Clinical trials show rapid symptom improvement, often within hours, and a favorable sexual side effect profile compared to SSRIs/SNRIs. 19 21 Dosing for TRD typically starts at 56 mg or 84 mg twice weekly for 4 weeks, then transitions to weekly or biweekly maintenance. 21 Administration requires in-clinic monitoring due to transient dissociative symptoms and blood pressure changes. Transcranial Magnetic Stimulation (TMS) TMS is a non-invasive brain stimulation technique approved for treatment-resistant depression. High-frequency repetitive TMS to the dorsolateral prefrontal cortex yields response rates of 25–37% and remission rates of 17–30% in TRD, with a number needed to treat of 6–8. 24 25 28 29 TMS is well tolerated, with minimal adverse effects, and can be considered early in the course of treatment-resistant depression. 15 22 23 24 25 26 28 29 Recent consensus guidelines endorse TMS as a safe and effective option, with newer protocols offering faster and potentially more robust results. 25 Summary Integrative psychiatry leverages a multidisciplinary toolkit—including medication, hormone therapy, nutrition, IV therapies, red light therapy, Spravato, and TMS—to optimize outcomes for patients with treatment-resistant depression and fatigue. This approach is supported by clinical guidelines and recent evidence, and offers a personalized, holistic framework for care. 15 24 25 27 28 29 If you’ve struggled to find full relief from antidepressants or feel persistently fatigued despite treatment, schedule a consultation with Unchained Wellness to explore a personalized, integrative care plan. Together, we can identify underlying contributors and design a treatment approach that restores balance—mind, body, and spirit.  References Hormonal Treatments for Major Depressive Disorder: State of the Art — Dwyer JB, Aftab A, Radhakrishnan R, et al. American Journal of Psychiatry. 2020;177(8):686-705. Photobiomodulation: Shining a Light on Depression — Wang L et al. Theranostics. 2025;15(2):362-383. Transcranial and Systemic Photobiomodulation for Major Depressive Disorder: A Systematic Review — Caldieraro MA, Cassano P. Journal of Affective Disorders. 2019;243:262-273. Photobiomodulation for Major Depressive Disorder — Vieira WF et al. Harvard Review of Psychiatry. 2023;31(3):124-141. Photobiomodulation Therapy in Mood Disorders — Montazeri K et al. Lasers in Medical Science. 2022;37(9):3343-3351. Translational Interdisciplinary Research on hCG’s Enhancement of Neuroendocrine Crosstalk — Gaspary JFP et al. Frontiers in Psychiatry. 2025;16:1537442. Comparative Efficacy of Ketamine, Esketamine, Aripiprazole, and Lithium in TRD — Terao I et al. Journal of Affective Disorders. 2024;346:49-56. Double-Blind, Placebo-Controlled, Dose-Ranging Trial of IV Ketamine — Fava M et al. Molecular Psychiatry. 2020;25(7):1592-1603. Photobiomodulation Improves Depression Symptoms — Ji Q et al. Frontiers in Psychiatry. 2023;14:1267415. Low-Dose Testosterone Augmentation for Antidepressant-Resistant Depression in Women — Dichtel LE et al. American Journal of Psychiatry. 2020;177(10):965-973. Promoting Good Mental Health Over the Menopause Transition — Brown L et al. The Lancet. 2024;403(10430):969-983. Effectiveness of Repeated IV Ketamine — McIntyre RS et al. Journal of Affective Disorders. 2020;274:903-910. Photobiomodulation: An Emerging Treatment Modality for Depression — Vieira WF et al. Psychiatric Clinics of North America. 2023;46(2):331-348. FDA Orange Book — U.S. Food and Drug Administration. Management of Major Depression: Guidelines From the VA/DoD — AAFP 2023. TMS and Ketamine: Implications for Combined Treatment — Dębowska W et al. Frontiers in Neuroscience. 2023;17:1267647. Treatment-Resistant Depression in Older Adults — Steffens DC. New England Journal of Medicine. 2024;390(7):630-639. Comparing Efficacy of Ketamine and TMS for TRD — Mikellides G et al. Frontiers in Psychiatry. 2021;12:784830. Spravato for Treatment-Resistant Depression: Efficacy and Sexual Side Effect Profile — Raza AA et al. Neuropsychiatric Disease and Treatment. 2025;21:2125-2140. Therapeutic Strategies for TRD — Goh KK et al. Current Pharmaceutical Design. 2020;26(2):244-252. Spravato Label Information — FDA. Updated Aug 2025. Comparative Effectiveness Research Trial (ASCERTAIN-TRD) — Papakostas GI et al. Molecular Psychiatry. 2024;29(8):2287-2295. Recent Innovations in Non-Invasive Brain Stimulation — Piccoli E et al. International Review of Psychiatry. 2022;34(7-8):715-726. Treating Depression With rTMS: A Clinician’s Guide — Chen L et al. American Journal of Psychiatry. 2025;182(6):525-541. Consensus Review and Considerations on TMS to Treat Depression — Trapp NT et al. Clinical Neurophysiology. 2025;170:206-233. Management of Major Depressive Disorder (VA 2022) — Department of Veterans Affairs. Synthesizing the Evidence for Ketamine and Esketamine in TRD — McIntyre RS et al. *American Journal