The Science Behind What we do
At Luvita, we believe that good healthcare for treatment-resistant conditions comes from experienced providers, science-backed treatment options, and close collaboration between medical experts.
Treatment of mental health conditions and chronic pain symptoms is a field that goes back hundreds, or even thousands, of years. As our understanding has deepened, we have come closer to uncovering effective and rapid ways of relieving these harmful symptoms.
Our providers use time-tested, evidence-based, tried-and-true treatment options at the forefront of the mental health revolution. To learn more about these science-backed options, we’ve gathered resources from respected academic institutions.
A large body of research has shown that measurement-based care (MBC) can improve clinical outcomes and provide a number of benefits to both providers and patients in mental health care. See the following whitepaper from Osmind to learn more information on MBC and a review of the relevant scientific literature.
Murrough, J. W., Perez, A. M., Pillemer, S., Stern, J., Parides, M. K., aan het Rot, M., Collins, K. A., Mathew, S. J., Charney, D. S., & Iosifescu, D. V. (2013). Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biological Psychiatry, 74(4), 250–256. https://doi.org/10.1016/j.biopsych.2012.06.022
SUMMARY: Participants with TRD (n = 24) underwent a washout of antidepressant medication followed by a series of up to six IV infusions of ketamine (.5 mg/kg) administered open-label three times weekly over a 12-day period. Participants meeting response criteria were monitored for relapse for up to 83 days from the last infusion. The overall response rate at study end was 70.8%. There was a large mean decrease in Montgomery-Åsberg Depression Rating Scale score at 2 hours after the first ketamine infusion (18.9 ± 6.6, p < .001), and this decrease was largely sustained for the duration of the infusion period. Response at study end was strongly predicted by response at 4 hours (94% sensitive, 71% specific). Conclusions: Ketamine was associated with a rapid antidepressant effect in TRD that was predictive of a sustained effect. Future controlled studies will be required to identify strategies to maintain an antidepressant response among patients who benefit from a course of ketamine.
Shiroma, P. R., Johns, B., Kuskowski, M., Wels, J., Thuras, P., Albott, C. S., & Lim, K. O. (2014). Augmentation of response and remission to serial intravenous subanesthetic ketamine in treatment resistant depression. Journal of Affective Disorders, 155, 123–129. https://doi.org/10.1016/j.jad.2013.10.036
SUMMARY: Fourteen subjects were enrolled. Out of twelve subjects who completed all six infusions, eleven (91.6%) achieved response criterion while eight (66.6%) remitted. After the first infusion, only three and one out of twelve subjects responded and remitted, respectively. Four achieved response and six remitted after 3 or more infusions. Five out of eleven subjects remain in response status throughout the 4 weeks of follow-up. The mean time for six subjects who relapsed was 16 days. Conclusions: Safety and efficacy of repeated ketamine infusions were attained without medication-free state in patients with TRD. Repeated infusions achieved superior antidepressant outcomes as compared to a single infusion with different trajectories of response and remission. Future studies are needed to elucidate neural circuits involved in treatment response to ketamine.
Albott, C. S., Lim, K. O., Forbes, M. K., Erbes, C., Tye, S. J., Grabowski, J. G., Thuras, P., Batres-y-Carr, T. M., Wels, J., & Shiroma, P. R. (2018). Efficacy, safety, and durability of repeated ketamine infusions for comorbid posttraumatic stress disorder and treatment-resistant depression. The Journal of Clinical Psychiatry, 79(3). https://doi.org/10.4088/jcp.17m11634
SUMMARY: The remission rate for PTSD was 80.0%, and the response rate for TRD was 93.3%. Participants in remission from PTSD after the infusion series (n = 12) had a median time to relapse of 41 days. Similarly, participants whose depression symptoms responded to the infusion series (n = 14) had a median time to relapse of 20 days. Repeated ketamine infusions were associated with transient increases in dissociative symptoms. No participant reported worsening of PTSD symptoms over the study duration. Conclusions: This study, the first open-label study of repeated ketamine infusions in a comorbid population, found rapid and sustained improvement in PTSD and depression symptoms. This report suggests that repeated ketamine treatments are safe and may represent an efficacious treatment for individuals with comorbid PTSD and TRD.
Feder, A., Costi, S., Rutter, S. B., Collins, A. B., Govindarajulu, U., Jha, M. K., Horn, S. R., Kautz, M., Corniquel, M., Collins, K. A., Bevilacqua, L., Glasgow, A. M., Brallier, J., Pietrzak, R. H., Murrough, J. W., & Charney, D. S. (2021). A randomized controlled trial of repeated ketamine administration for chronic posttraumatic stress disorder. American Journal of Psychiatry, 178(2), 193–202. https://doi.org/10.1176/appi.ajp.2020.20050596
SUMMARY: Individuals with chronic PTSD (N=30) were randomly assigned (1:1) to receive six infusions of ketamine or midazolam (psychoactive placebo control) over 2 consecutive weeks. The ketamine group showed a significantly greater improvement in CAPS-5 and MADRS total scores than the midazolam group from baseline to week 2. At week 2, the mean CAPS-5 total score was 11.88 points (SE=3.96) lower in the ketamine group than in the midazolam group (d=1.13, 95% CI=”0.36,” 1.91). Sixty-seven percent of participants in the ketamine group were treatment responders, compared with 20% in the midazolam group. Conclusions: This randomized controlled trial provides the first evidence of efficacy of repeated ketamine infusions in reducing symptom severity in individuals with chronic PTSD. Further studies are warranted to understand ketamine’s full potential as a treatment for chronic PTSD.
Feder, A., Parides, M. K., Murrough, J. W., Perez, A. M., Morgan, J. E., Saxena, S., Kirkwood, K., aan het Rot, M., Lapidus, K. A., Wan, L.-B., Iosifescu, D., & Charney, D. S. (2014). Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder. JAMA Psychiatry, 71(6), 681. https://doi.org/10.1001/jamapsychiatry.2014.62
SUMMARY: Proof-of-concept, randomized, double-blind, crossover trial comparing ketamine with an active placebo control, midazolam, conducted at a single site (Icahn School of Medicine at Mount Sinai, New York, New York). Forty-one patients with chronic PTSD related to a range of trauma exposures were recruited via advertisements. Ketamine infusion was associated with significant and rapid reduction in PTSD symptom severity, compared with midazolam, when assessed 24 hours after infusion (mean difference in Impact of Event Scale-Revised score, 12.7 [95% CI, 2.5-22.8]; P = .02). Greater reduction of PTSD symptoms following treatment with ketamine was evident in both crossover and first-period analyses, and remained significant after adjusting for baseline and 24-hour depressive symptom severity. Ketamine was also associated with reduction in comorbid depressive symptoms and with improvement in overall clinical presentation. Ketamine was generally well tolerated without clinically significant persistent dissociative symptoms.
Glue, P., Neehoff, S. M., Medlicott, N. J., Gray, A., Kibby, G., & McNaughton, N. (2018). Safety and efficacy of maintenance ketamine treatment in patients with treatment-refractory generalised anxiety and social anxiety disorders. Journal of Psychopharmacology, 32(6), 663–667. https://doi.org/10.1177/0269881118762073
SUMMARY: There were 10 women (50%) and 10 men (50%); 15 patients (75%) met criteria for GAD and 18 (90%) for SAD. One hour after dosing, Fear Questionnaire ratings decreased by ~50%, as did Hamilton Anxiety ratings. Clinician Administered Dissociative States Scale mean scores declined over time, from 20 points at week 1 to 8.8 points at week 14. Compared with pre-dose values, mean systolic and diastolic blood pressure increased by ~10 mm Hg at 30 min. The most common adverse events were nausea, dizziness and blurred vision. Of the 20 patients, 18 reported improved social functioning and/or work functioning during maintenance treatment. Conclusions: Weekly ketamine dosing was safe and well tolerated, and post-dose dissociative symptoms tended to reduce after repeated dosing. Patients reported marked improvements in functionality and in their personal lives. Maintenance ketamine may be a therapeutic alternative for patients with treatment refractory GAD/SAD.
Jones, J. L., Mateus, C. F., Malcolm, R. J., Brady, K. T., & Back, S. E. (2018). Efficacy of ketamine in the treatment of Substance Use Disorders: A systematic review. Frontiers in Psychiatry, 9. https://doi.org/10.3389/fpsyt.2018.00277
SUMMARY: In this systematic review of all available studies from 1997 to 2018, seven completed studies were identified. Two studies focused on alcohol use disorder, two focused on cocaine use disorder, and three focused on opioid use disorder. Both cocaine studies found improvements in craving, motivation, and decreased cocaine use rates, although studies were limited by small sample sizes, a homogeneous population and short follow-up. Studies of alcohol and opioid use disorders found improvement in abstinence rates in the ketamine group, with significant between-group effects noted for up to two years following a single infusion, although these were not placebo-controlled trials. These results suggest that ketamine may facilitate abstinence across multiple substances of abuse and warrants broader investigation in addiction treatment. We conclude with an overview of the six ongoing studies of ketamine in the treatment of alcohol, cocaine, cannabis, and opioid use disorders and discuss future directions in this emerging area of research.
Patil, S., & Anitescu, M. (2012). Efficacy of outpatient ketamine infusions in refractory chronic pain syndromes: A 5-year retrospective analysis. Pain Medicine, 13(2), 263–269. https://doi.org/10.1111/j.1526-4637.2011.01241.x
Correll, G. E., Maleki, J., Gracely, E. J., Muir, J. J., & Harbut, R. E. (2004). Subanesthetic ketamine infusion therapy: A retrospective analysis of a novel therapeutic approach to complex regional pain syndrome. Pain Medicine, 5(3), 263–275. https://doi.org/10.1111/j.1526-4637.2004.04043.x
SUMMARY: A total of 33 patients with diagnoses of CRPS who had undergone ketamine treatment at least once were identified. Due to relapse, 12 of 33 patients received a second course of therapy, and two of 33 patients received a third. The degree of relief obtained following the initial course of therapy was impressive (N=33); there was complete pain relief in 25 (76%), partial relief in six (18%), and no relief in two (6%) patients. The degree of relief obtained following repeat therapy (N=12) appeared even better, as all 12 patients who received second courses of treatment experienced complete relief of their CRPS pain. The duration of relief was also impressive, as was the difference between the duration of relief obtained after the first and after the second courses of therapy. In this respect, following the first course of therapy, 54% of 33 individuals remained pain free for >/=3 months and 31% remained pain free for >/=6 months. After the second infusion, 58% of 12 patients experienced relief for >/=1 year, while almost 33% remained pain free for >3 years. The most frequent side effect observed in patients receiving this treatment was a feeling of inebriation. Hallucinations occurred in six patients. Less frequent side effects also included complaints of lightheadedness, dizziness, and nausea. In four patients, an alteration in hepatic enzyme profile was noted; the infusion was terminated and the abnormality resolved thereafter. Conclusion: This retrospective review suggests that limited subanesthetic inpatient infusions of ketamine may offer a promising therapeutic option in the treatment of appropriately selected patients with intractable CRPS. More study is needed to further establish the safety and efficacy of this novel approach.
Kiefer, R.-T., Rohr, P., Ploppa, A., Dieterich, H.-J., Grothusen, J., Koffler, S., Altemeyer, K.-H., Unertl, K., & Schwartzman, R. J. (2008). Efficacy of ketamine in anesthetic dosage for the treatment of refractory complex regional pain syndrome: An open-label phase II study. Pain Medicine, 9(8), 1173–1201. https://doi.org/10.1111/j.1526-4637.2007.00402.x
SUMMARY: In this article 20 patients with CRPS received ketamine for 5 days and achieved significant pain relief at the 1, 3, and 6 month mark. At 1 month, all 20 patients had complete remission, at 3 months, 17 patients continued pain-free, and at 6 months, 16 patients were still pain-free. For the few that relapse did occur, their pain was still significantly better than before.
Patil, S., & Anitescu, M. (2012). Efficacy of outpatient ketamine infusions in refractory chronic pain syndromes: A 5-year retrospective analysis. Pain Medicine, 13(2), 263–269. https://doi.org/10.1111/j.1526-4637.2011.01241.x
SUMMARY: This article reviewed 49 patients receiving outpatient ketamine infusions for various pain syndrome – 18 with CRPS. For patients with CRPS, the average reduction in the pain score on a scale was 7.2. For the other pain conditions, the average reduction in the pain score was 5.1. Average pain relief was at least three weeks.
Bahji, A., Vazquez, G. H., & Zarate, C. A. (2021). Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis. Journal of Affective Disorders, 278, 542–555. https://doi.org/10.1016/j.jad.2020.09.071
SUMMARY: This study is a systematic review and meta-analysis of 24 trials of a combined 1877 patients with depression. Conclusion: Intravenous ketamine appears to be more efficacious than intranasal esketamine for the treatment of depression.
Drozdz SJ, et al. “Ketamine Assisted Psychotherapy: A Systematic Narrative Review of the Literature”. J Pain Res. 2022 Jun 15;15:1691-1706.
SUMMARY: Ketamine Assisted Psychotherapy (KAP) can improve and prolong reductions in pain, anxiety, depression and substance use. This “meta-study” reviewed 17 articles covering 603 patients with a variety of conditions integrating psychotherapy before, during or after ketamine medicine sessions. Positive results were found for clients with Major Depressive Disorder (MDD), Obsessive-Compulsive Disorder (OCD), Post-Traumatic Stress Disorder (PTSD), Substance Use Disorders (SUD), mixed diagnosis clients and chronic pain. Overall, the authors found that “higher-doses of ketamine, more frequent KAP sessions, and longer durations of psychotherapy increase the efficacy and durability of improvements within patients with a range of disorders.
Dore J., et al. “Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy”. Journal of Psychoactive Drugs. 2019.
SUMMARY: Ketamine in combination with psychotherapy can be an effective treatment for depression and anxiety. A large study of 235 clients across three clinics that integrate psychotherapy before, during, and after ketamine sessions found significant improvements. Clients had a variety of conditions including Depression, PTSD, co-occurring Substance Use Disorders, Bipolar I and II depressive phases, OCD, and psychological coping difficulties with physical or life-threatening illness. The study found that clients had more success in treatment if they began with more severe symptoms, had developmental trauma (cPTSD), or were older. The number of sessions varied widely (1-25), and those who engaged in more sessions found higher benefits. The paper describes the qualities of ketamine’s unique “non-ordinary state” of consciousness in depth and its utility for the therapeutic process.
Wilkinson, ST, et al. “Cognitive Behavioral Therapy to Sustain the Antidepressant Effects of Ketamine in Treatment-Resistant Depression: A Randomized Clinical Trial”. Psychother Psychosom 2021;90:318–327.
SUMMARY: Clients who engage in Cognitive Behavioral Therapy (CBT) after an initiation series of six infusions are more likely to sustain their symptom relief than those who do not. Clients whose symptoms responded to the infusion series engaged in CBT therapy for 2x a week for 2 weeks and then weekly for 15 more weeks. Clients who engaged in CBT had better outcomes at week 17 than those who did not engage in CBT, with a moderate to large effect size.
Smith Apple-doorn SY, et al. “Maintenance ketamine treatment for depression: a systematic review of efficacy, safety, and tolerability.” Lancet Psychiatry. 2022; 9: 907–21.
SUMMARY: The first major review (meta-study) of research on maintenance ketamine, covering 45 articles with a total of 1495 patients. The review analyzed clients who had achieved initial remission from depression from an initiation series of ketamine going on to receive maintenance treatment. Studies included a diverse range of treatment with varying routes of administration (infusions, oral, etc), and varying frequency (from daily to every three months). They found rates of clients sustaining remission from depression ranged from 21%-100% at 6 months and up to 1 year. The authors found the initial results of maintenance ketamine promising; many of these results were found with clients with treatment resistant depression and even those with non-treatment resistant depression have a 23% relapse rate with conventional treatment. The authors also found the safety profile of maintenance ketamine similar to short term treatment, with serious adverse events being very uncommon.
