Evidence-Based Research
The Science Behind Our Treatments
At Crestline Health & Wellness, every treatment we offer is grounded in current medical research.
This page highlights a selection of peer-reviewed studies and systematic reviews supporting the use of:
- Ketamine infusion therapy for depression, suicidality, PTSD, OCD, and chronic pain
- Transcranial magnetic stimulation (TMS) and EXOMind’s ExoTMS™ technology for depression and other mental health conditions
Ketamine for Depression & Treatment-Resistant Depression (TRD)
- Taming the Ketamine Tiger
Domino EF. Taming the Ketamine Tiger. Anesthesiology. 2010;113(3):678-686.
A reflective historical review of ketamine’s evolution from anesthetic to therapeutic agent, exploring pharmacology, safety, and emerging psychiatric uses. - Ketamine in Multiple Treatment-Resistant Depressed Inpatients
Vestring S et al. Ketamine in multiple treatment-resistant depressed inpatients: A naturalistic cohort study. Journal of Affective Disorders. 2024.
A real-world cohort study evaluating IV ketamine in inpatients with multiple treatment-resistant depression, providing preliminary evidence that ketamine can significantly reduce depressive symptoms even in highly refractory cases. - Antidepressant effects of IV ketamine (landmark Yale/2000 trial)
Berman RM et al. Antidepressant effects of ketamine in depressed patients. Biological Psychiatry. 2000.
Single sub-anesthetic IV ketamine infusion produced rapid (within 72 hours) and robust reductions in depressive symptoms vs placebo in patients with major depression. - Dose-ranging IV ketamine in TRD (active placebo-controlled)
Fava M et al. Double-blind, placebo-controlled, dose-ranging trial of IV ketamine in treatment-resistant depression. Journal of Affective Disorders. 2018/2020.
Compared multiple ketamine doses vs active placebo in adults with TRD; sub-anesthetic doses produced significant rapid antidepressant effects.
Bahji A et al. Efficacy and safety of racemic ketamine and esketamine for depression: A meta-analysis of randomized controlled trials. Journal of Affective Disorders. 2022.
Concludes that ketamine and esketamine are effective, safe, and acceptable treatments for individuals with depression, including bipolar depression and TRD.
Yavi M et al. Ketamine treatment for depression: a review. Neurological Sciences. 2022.
Summarizes early and recent trials showing rapid-onset antidepressant effects (often within one day) in both MDD and bipolar depression, with effects lasting several days.
Alnefeesi Y et al. Real-world effectiveness of ketamine in treatment-resistant depression. Journal of Psychiatric Research. 2022.
Naturalistic sample showing that ketamine retains significant antidepressant effectiveness outside of highly controlled research settings.
Nikolin S et al. & related 2025 review: Ketamine for unipolar depression: A systematic review of randomized controlled trials. Australian & New Zealand Journal of Psychiatry. 2025.
Concludes that ketamine significantly reduces depressive symptoms and suicidal ideation within hours, especially in treatment-resistant cases.
Ketamine & Suicidal Ideation
- Rapid reduction of suicidal thoughts (single IV infusion)
Wilkinson ST et al. The effect of a single dose of IV ketamine on suicidal ideation in treatment-resistant depression. Depression and Anxiety. 2017.
Single IV ketamine significantly reduced suicidal thoughts within one day, with benefits lasting up to one week. - Large RCT in severe suicidal ideation
Abbar M et al. Ketamine for the acute treatment of severe suicidal ideation. BMJ. 2022.
Randomized controlled trial showing ketamine is a fast-acting and effective treatment for suicidal ideation in severe depression.
Grunebaum MF et al. Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolam-controlled randomized clinical trial. American Journal of Psychiatry. 2018.
Adjunctive ketamine led to greater reduction in suicidal ideation within 24 hours compared with active placebo.
Pan Y et al. Suicidal ideation following ketamine prescription in routine care. Translational Psychiatry. 2024.
Real-world evidence that ketamine has sustained benefits in reducing suicidal ideation among adults with recurrent MDD.
Chen-Li DCJ et al. Effect of intravenous ketamine on suicidality in adults with depression: Real-world evidence. Psychiatry Research. 2025.
Finds ketamine helpful for suicidal ideation in naturalistic clinical practice with outcomes comparable to trial data.
Ketamine for PTSD, OCD & Other Psychiatric Conditions
- RCT: Ketamine for chronic PTSD
Feder A et al. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry. 2014.
Cross-over trial showing ketamine produced significant, clinically meaningful reductions in PTSD symptoms compared with midazolam. - Repeated ketamine infusions for PTSD
Feder A et al. A randomized controlled trial of repeated ketamine infusions in PTSD. American Journal of Psychiatry. 2021.
Provides evidence that multiple ketamine infusions can further reduce PTSD symptom severity.
Almeida TM et al. Effectiveness of ketamine for the treatment of post-traumatic stress disorder. Journal of Clinical Medicine. 2024.
Suggests ketamine is a promising option for PTSD, especially when combined with psychotherapy.
Bandeira ID et al. Ketamine in the treatment of obsessive-compulsive disorder: A systematic review. CNS Spectrums. 2022.
Review of nine studies (including randomized trials) showing potential for rapid symptom reduction and good tolerability, while noting that evidence is still emerging.
Rodriguez CI et al. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder. American Journal of Psychiatry. 2013.
IV ketamine produced rapid, short-term reductions in OCD symptoms in treatment-refractory patients.
Ketamine for Chronic Neuropathic Pain & CRPS
- Ketamine infusions for CRPS – clinical efficacy
Koffler SP et al. Neurocognitive effects of 5-day anesthetic ketamine for complex regional pain syndrome. Journal of Anxiety Disorders. 2007.
Five-day ketamine infusion therapy significantly reduced CRPS pain with acceptable cognitive effects. - Meta-analysis: Ketamine infusion in CRPS
Zhao J et al. Effect of ketamine infusion in the treatment of complex regional pain syndrome: a systematic review and meta-analysis. Pain Physician. 2018.
Suggests IV ketamine provides clinically meaningful short-term pain relief (up to 3 months) in CRPS, while calling for more standardized trials.
Lii TR et al. Ketamine for complex regional pain syndrome: A narrative review. Anesthesiology Clinics. 2023.
Summarizes existing trials and notes that sub-anesthetic IV ketamine can provide long-lasting but not permanent pain relief.
University of Illinois Chicago Drug Information Group. What guidelines are available about ketamine use in the management of complex regional pain syndrome? FAQ, 2025.
Reviews current evidence and guideline positions on ketamine infusions as an investigational but promising CRPS treatment.
TMS & EXOMind for Depression and Related Conditions
EXOMind uses ExoTMS™, an advanced form of repetitive transcranial magnetic stimulation (rTMS). The device itself is newer, but it is built on a large body of rTMS research for depression and other conditions.
- Pivotal multisite RCT of rTMS in MDD (basis for FDA clearance)
O’Reardon JP et al. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: A multisite randomized controlled trial. Biological Psychiatry. 2007.
Large RCT showing left prefrontal rTMS significantly improved depressive symptoms versus sham, with good tolerability—key evidence supporting FDA clearance. - rTMS monotherapy for depression
George MS et al. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: A sham-controlled randomized trial. Archives of General Psychiatry / JAMA Psychiatry. 2010.
Demonstrated clinically meaningful antidepressant effects of daily left-DLPFC rTMS as monotherapy compared with sham.
Vida RG et al. Efficacy of rTMS adjunctive therapy for MDD after two antidepressant treatment failures: Meta-analysis of randomized sham-controlled trials. BMC Psychiatry. 2023.
Confirms that high-frequency left-sided rTMS is effective for patients with TRD who have failed multiple medications.
Kar SK. Effectiveness of rTMS for MDD, schizophrenia, and OCD: An umbrella meta-analysis. The Primary Care Companion for CNS Disorders. 2023.
Summarizes multiple meta-analyses and supports rTMS as an effective, safe treatment for major depression and selected other conditions.
Noda Y et al. Repetitive transcranial magnetic stimulation as maintenance treatment compared with lithium in preventing relapse of TRD. JAMA Network Open. 2025.
Found rTMS comparable to lithium in preventing relapse, with fewer adverse events in the rTMS group.
Carmi L et al. Efficacy and safety of deep transcranial magnetic stimulation for obsessive-compulsive disorder: A multicenter randomized trial. American Journal of Psychiatry. 2019.
High-frequency dTMS over medial prefrontal cortex/anterior cingulate significantly improved OCD symptoms vs sham in treatment-resistant patients.
Kar SK & co-authors; Fitzsimmons SMDD et al.; Perera MPN et al. 2022–2023.
Multiple meta-analyses show rTMS and dTMS targeting DLPFC or SMA significantly reduce OCD symptoms compared with sham.
Edinoff AN et al. Transcranial magnetic stimulation for post-traumatic stress disorder. Frontiers in Psychiatry. 2022.
Reviews RCTs showing rTMS reduces PTSD symptoms, particularly with left-DLPFC high-frequency protocols.
Wang YX et al. Effects of rTMS on PTSD: Meta-analysis. Journal of Affective Disorders. 2025.
Concludes rTMS is an effective, non-invasive treatment for PTSD, with dose-response effects related to session number.
- ExoTMS™ Technology – Novel TMS Advancement
Dees M, Halaas Y, McCoy J. ExoTMSTM Technology: A Novel Breakthrough in Transcranial Magnetic Stimulation for Enhancing Mental Well-Being. Journal of Psychiatry & Psychiatric Disorders. 2025.
Describes the next-generation ExoTMS™ platform used in EXOMind systems, demonstrating improved comfort, precision, and clinical outcomes compared to conventional rTMS devices. - ExoTMS™ for Binge Eating – Symptom Reduction Study
Pánek D, Donchev TS. ExoTMS transcranial magnetic stimulation for the reduction of binge eating symptoms. Psychiatry and Clinical Neurosciences Reports. 2025;4(3):e70200.
Evaluates a novel ExoTMS™-based TMS device in adults with binge eating symptoms, showing substantial reductions in binge severity and high treatment comfort, supporting ExoTMS™ as a safe and effective neuromodulation option.
A Note from Crestline Health & Wellness
Evidence matters. So does how you feel when you walk through our door.
At Crestline Health and Wellness, we combine rigorous, up-to-date research with deeply compassionate care. If you have questions about any of these studies or how they apply to your situation, we’re always happy to talk through them with you in plain language.
We’re here to help. MAKE AN APPOINTMENT
COMPASSIONATE CARE
Located in the heart of Mountain Brook, we serve individuals throughout Central Alabama seeking relief from depression, anxiety, chronic pain, weight concerns, burnout, and more. Our clinic blends medical expertise with deeply personalized, patient-first care to help you feel better, function better, and live better.
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