• FOR PROVIDERS

Michigan Progressive Health is dedicated to providing the best ketamine experience possible for your patient.  As a founding board member and current Vice President of the American Society of Ketamine Physicians, Psychotherapists and Practitioners (ASKP), Dr. Megan Oxley is up to date on the most current practice of ketamine therapy for mood disorders and pain conditions.  An emergency physician by training, Dr. Oxley is highly experienced in both administration of IV ketamine and psychiatric diagnoses and crisis. Having performed over 3,000 infusions, Dr. Oxley is well versed on ketamine effects both medically and psychiatrically.

The entire staff at MPH is trained to treat our patients with the utmost respect and compassion and our goal is to work with you to help your patient get well.

Feel free to reach out to Dr. Oxley via phone or email, or fill out the new patient referral form below.


View Our New HIPPA

HIPAA Release of Information


Please Fill Out Our

New Patient Referral Form

SCIENTIFIC ARTICLES

The Cause of Depression is Life Events and Not Brain Chemistry

Moncrieff, J, et al. “The serotonin theory of depression: a systematic umbrella review of the evidence”. Mol Psychiatry (2022).

https://www.nature.com/articles/s41380-022-01661-0

SUMMARY: “[There is] no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations.” A large meta study reviewing research that covered some 6500 individuals found no relationship between serotonin expression and depression, and an additional review of genetic markers for serotonin expression covering 158,000 people found no association between serotonin and depression. A lead co-author of the study, in an interview about this study, stated “Low mood is a response to people’s lives and cannot be boiled down to a simple chemical equation.” (1) University College London. “No evidence that depression is caused by low serotonin levels, finds comprehensive review.” ScienceDaily. ScienceDaily, 20 July 2022. <www.sciencedaily.com/releases/2022/07/220720080145.htm>.

Ketamine and Depression / Suicidal Ideation

1) Oliver PA, et al. “Clinical Effectiveness of Intravenous Racemic Ketamine Infusions in a Large Community Sample of Patients With Treatment-Resistant Depression, Suicidal Ideation, and Generalized Anxiety Symptoms: A Retrospective Chart Review”. Journal of Clinical Psychiatry. 2022 Nov/Dec; 83:6.

https://www.psychiatrist.com/jcp/depression/clinical-effectiveness-intravenous-racemic-ketamine-treatment-resistant-depression-suicidal-ideation-generalized-anxiety-symptoms/

SUMMARY: A review of a community ketamine clinic found the treatment to be “excellent” for Depression and suicidal ideation, and demonstrated significant effectiveness for Generalized Anxiety. Among responders, after 6 infusions 50% of clients had achieved a clinically significant response (50% reduction in symptoms) and 20% had complete remission of Depression. Response rate increased with the number of infusions; with 10 infusions 72% of clients had at least a 50% decrease in symptoms, and 38% were in complete remission from depression. If clients saw a significant response within 10 infusions, the researchers found enough clients went on to full remission that further infusions were warranted. Additionally after 6 infusions, 50% of clients no longer had suicidal ideation, with continued improvement in suicidal ideation up to 15 infusions, at which point 85% of clients no longer had any suicidal ideation. Anxiety was also impacted by the treatment, with an average reduction of 30%. Clients with a history of psychosis and suicide planning trended towards higher response rates. The authors suggest ketamine could be a good alternative for ECT with its significant risk of long term side effects, as clinical ketamine has no long-term side effects.

2) Mcinnes, L and Q, et al.  “A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings”. Journal of Affective Disorders. 2022.

https://pubmed.ncbi.nlm.nih.gov/35027209/

SUMMARY: Real world ketamine clinics are achieving significant and sustained improvements for clients with depression. The study looked at 537 clients at 178 clinics administering ketamine for depression. After an initiation series the median reduction in depression scores was 52%, an effectiveness of up to 5x that of conventional antidepressants (1). 53% of clients reduced their depression score by half or more, and 28.9% had their depression enter full remission. The durability of antidepressant effects were 60% at 8 weeks after infusions. 73% of clients with suicidal thoughts experienced a decrease in suicidal thinking, with 42% experiencing no suicidal thinking after infusions. The study suggests more severe depression responds slightly better to treatment, while 8% of clients have their depression get worse. Clients received an average of 2.6 maintenance infusions after their initial series, with an average of 46 days to first maintenance dose. Clients who responded to ketamine treatment received a higher number of maintenance infusions with a longer time to first maintenance dose. (1) Hengartner MP, Plöderl M. “Statistically Significant Antidepressant-Placebo Differences on Subjective Symptom-Rating Scales Do Not Prove That the Drugs Work: Effect Size and Method Bias Matter!” Front Psychiatry. 2018 Oct 17;9:517.

3) Murrough, Perez, et al. “Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression” Biological Psychiatry 2013 Aug 15; 74(4): 250–256.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725185/

SUMMARY: In this article, there were 24 patients treated with six IV infusions of ketamine (.5mg/kg) over 12 days. The overall response rate was 71% as defined as a reduction in the MADRS scale by greater than 50%. The median time to relapse after the last ketamine infusion was 18 days. 25% were symptom free at 90 days, 75% of patients had symptoms free days between 11-27 days. Side effects were reported to be a mild significant increase in dissociative symptoms. One patient had to discontinue therapy due to an increase in blood pressure that did not respond to medications (highest BP 180/115).

4) Shiroma, Johns et al. “Augmentation of response and remission to serial intravenous subanesthetic ketamine in treatment resistant depression” Journal of Affective Disorders. 2014 Feb;155:123-9.

http://www.jad-journal.com/article/S0165-0327%2813%2900778-7/abstract

SUMMARY: In this article, there were 14 patients treated with six IV infusions during a 12 day period. 12 subjects finished all six infusions with 92% response rate and 66% went into remission. 5 out of 11 responders remained in “response status” during the next 28 days. For the 6 out of 11 responders that relapsed, the mean time was 16 days. Response was defined as ≥50% improvement in baseline MADRS score and remission was defined as MADRS score ≤9. No subject experienced severe dissociative symptoms or hemodynamic changes that required stopping the infusions.

5) Sanacora, Frye, McDonald, et al. “A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders” JAMA Psychiatry. April 2017;74(4):399-405.

http://jamanetwork.com/journals/jamapsychiatry/fullarticle/2605202

SUMMARY: This review and consensus statement provides a general overview of the data on the use of ketamine for the treatment of mood disorders and highlights the limitations of the existing knowledge. The suggestions provided are intended to facilitate clinical decision making and encourage an evidence-based approach to using ketamine in the treatment of psychiatric disorders considering the limited information that is currently available. This article provides information on potentially important issues related

6) Calabrese, L. Titrated Serial Ketamine Infusions Stop Outpatient Suicidality and Avert ER Visits and Hospitalizations. Int J Psychiatr Res. 2019; 2(6): 1-12

https://www.scivisionpub.com/pdfs/titrated-serial-ketamine-infusions-stop-outpatient-suicidality-and-avert-er-visits-and-hospitalizations-918.pdf

SUMMARY: This community based clinic found 79% of clients achieving substantial reduction in their suicidality, and 59% with complete remission of their suicidal ideation. Clients were able to achieve remission with an average of 4.1 infusions. These results were obtained with a population that was severely depressed with a significant history of mental health challenges; 80% had failed at least 4 anti-depressants, and 53% had a previous mental health hospitalization.

Ketamine and Anxiety

Whittaker E, et al. ”Systematic review and meta-analysis of randomized controlled trials of ketamine in the treatment of refractory anxiety spectrum disorders”. Therapeutic Advances in Psychopharmacology. January 2021.

https://journals.sagepub.com/doi/full/10.1177/20451253211056743#bibr22-20451253211056743

SUMMARY: The first “meta-study” summarizing studies of ketamine treatment for anxiety disorders concludes it may be a “safe and broadly effective” treatment, but requires more study based on limited available research. The studies reviewed show that for General Anxiety Disorder and Social Anxiety Disorder, ketamine can cause immediate anxiety relief, on average up to 50% reduction, that fades over time. Maintenance or weekly treatments can increase and sustain relief leading to improvements in work and social functioning.

Ketamine and PTSD

1) Feder, P., et al. “Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial.” JAMA Psychiatry. 2014 Jun;71(6):681-8.

http://archpsyc.jamanetwork.com/article.aspx?articleid=1860851

SUMMARY: In this double blind, placebo-controlled cross over study, a single dose of Ketamine (.5mg/kg over 40 minutes) was compared to midazolam. Authors note a significant immediate reduction in the CAPS score and frequently this reduction was maintained for over 2 weeks. The only side effects noted were transient dissociative symptoms, none of which required stopping the infusion.

2) Bentley S, et al. “Response to intravenous racemic ketamine after switch from intranasal (S)-ketamine on symptoms of treatment-resistant depression and post-traumatic stress disorder in Veterans: A retrospective case series.” Pharmacotherapy. 2022;42:272–279.

https://pubmed.ncbi.nlm.nih.gov/35122282/

SUMMARY: Ketamine can be an effective treatment for PTSD; in a study of veterans with treatment resistant depression and PTSD undergoing ketamine treatment, clinically significant improvements were seen for both depression and PTSD symptoms. For this study, veterans received intranasal ketamine first and were moved to ketamine infusions based on lack of desired response; infusions were shown to be more impactful than intranasal. Veterans achieved clinically significant results during their initiation series of 6 infusions for both depression and PTSD. Whereas depression scores leveled off after the initiation series, PTSD improvements continued during booster administration. PTSD has 4 clusters of symptoms: 1) re-experiencing 2) avoidance 3) mood and cognition and 4) hyperarousal. All PTSD symptom clusters responded to treatment except avoidance.

Ketamine and Substance Use
Jones JL,et al. “Efficacy of Ketamine in the Treatment of Substance Use Disorders: A Systematic Review”. Front Psychiatry. 2018 Jul 24;9:277.
SUMMARY: A review of seven studies on Ketamine and Substance Use Disorders found that Ketamine may be an effective intervention to increase abstinence. The studies reviewed on ketamine infusion’s impact on alcohol and opioid use found increased abstinence rates, for as long as up to 2 years after a single infusion. The studies on ketamine impact on cocaine use found increased abstinence as well as improvements in craving and motivation. The authors conclude the state of the research as promising and deserving of more studies.

Ketamine and Psychotherapy:

Drozdz SJ, et al. “Ketamine Assisted Psychotherapy: A Systematic Narrative Review of the Literature”. J Pain Res. 2022 Jun 15;15:1691-1706.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207256/

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.

https://www.tandfonline.com/doi/full/10.1080/02791072.2019.1587556

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.

https://pubmed.ncbi.nlm.nih.gov/34186531/

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.

Ketamine and Chronic or Complex Pain
1) Patil S, Anitescu M. “Efficacy of outpatient ketamine infusions in refractory chronic pain syndromes: a 5-year retrospective analysis. Pain Medicine. 2012 Feb;13(2):263-9.

http://painmedicine.oxfordjournals.org/content/13/2/263.long

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 ten point 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.

2) Correll, Maleki et al. “Subanesthetic ketamine infusion therapy: a retrospective analysis of a novel therapeutic approach to complex regional pain syndrome.” Pain Medicine. 2004 Sep;5(3):263-75.

http://painmedicine.oxfordjournals.org/content/painmedicine/5/3/263.full.pdf

SUMMARY: This article reviewed 33 cases of patients with CRPS that were treated with Ketamine infusion. The patients received a prolonged low dose infusion of ketamine, on average 10-20mg/hr over 2-4 days. 76% of patients experienced complete pain relief after the first course of treatment. Pain relief lasted at least three months for most patients. Adding a second course of treatment allowed over 50% to be pain free for over a year. One patient had to discontinue additional treatments after the first infusion after developing elevated liver enzymes. These did normalize after treatment was stopped.

Oral and At Home Ketamine

1) Hull, TD, et al. “At-home, sublingual ketamine telehealth is a safe and effective treatment for moderate to severe anxiety and depression: Findings from a large, prospective, open-label effectiveness trial”. Journal of Affective Disorders. Volume 314, 1 October 2022, Pages 59-67

https://pubmed.ncbi.nlm.nih.gov/35809678/

SUMMARY: At home ketamine use with psychosocial support and professional monitoring can be an effective treatment for anxiety and depression. A sample of 1247 clients using at home ketamine found that after 4 weekly sessions 63% achieved significant relief for depression and anxiety (50% reduction in MDD and GAD scores), and 32% found complete remission for depression and 31% for anxiety. An important caveat to these results is that this study excluded anyone exhibiting active suicidal thoughts, substance use disorder, history of or active symptoms of psychosis, active mania, or history of severe and unresolved trauma. The average starting depression and anxiety scores were moderate to moderately severe. Three types of client response emerged from their data: “Improvement” clients (79%) had lower scores and quickly responded, “Delayed” clients (9%) had higher scores and responded after 2 weeks, and “Chronic” clients (11%) had higher scores and higher suicidality and did not significantly respond to treatment.

2) Arabzadeh, S. et al. “Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial”. Journal of Affective Disorders. 2018 Aug 1;235:236-241

https://www.ncbi.nlm.nih.gov/pubmed/29660637

SUMMARY:  In this study 81 patients were randomized to two groups.  150mg of sertraline plus 50mg of daily oral ketamine and 150mg of sertraline and placebo.  The oral ketamine cohort had a statistically significant mood improvement (85.4%) as compared to the placebo group (42.5%) as measured by HADRS at 2,4 and 6 weeks.  For both groups, side effects were mild and the frequency was the same between groups. No patients developed abuse of dependence to ketamine.

3) Hartberg, J et al.  “Impact of oral ketamine augmentation on hospital admissions in treatment-resistant depression and PTSD: a retrospective study.”  Psychopharmacology. 2018 Feb;235(2):393-398

https://www.ncbi.nlm.nih.gov/pubmed/29151192

SUMMARY:  In this study, 37 patients with Treatment Resistant Depression (15 of whom had PTSD as their primary diagnosis) were given oral ketamine twice a week.  Doses started at .5mg/kg orally and were titrated to effect. After initiation of ketamine therapy, the participants had a 70% reduction in hospital admissions.  The average dose was ultimately 2.0mg/kg twice a week. There was no evidence of tolerance and in fact there was typically a decrease in the amount of ketamine needed over time. No serious adverse events were recorded among patients. The most common side effects were light-headedness, sedation and mild dissociative effects.

Ketamine infusions are more effective than Intranasal Ketamine

Bahji A, et al. “Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis”. J Affect Disord. 2021;278:542-555.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704936/

SUMMARY: A large meta study of 24 trials including 1877 participants found that ketamine infusions are more effective than intranasal ketamine; ketamine infusions had more than double the response rate, a 50% reduction in symptoms and more than double the remission rate, a full relief of depression (RR = 3.01 vs. RR = 1.38 and RR = 3.70 vs. RR = 1.47, respectively).

Ketamine for Pediatric Clients

1) Dwyer JB, et al. “Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial.” Am J Psychiatry. 2021 Apr 1;178(4):352-362. doi: 10.1176/appi.ajp.2020.20010018. Epub 2021 Mar 3. PMID: 33653121.

https://pubmed.ncbi.nlm.nih.gov/33653121/

SUMMARY: Ketamine can be an effective, fast acting depression intervention for adolescents. A randomized controlled study on 17 adolescents with MDD receiving a single infusion of either ketamine or midazolam, an active placebo. Clients who received ketamine had a 76% response rate, compared to 35% for the placebo, and these improvements appeared to be sustained at a 2 week follow-up.

2) Cullen, CR, et al. “Intravenous Ketamine for Adolescents with Treatment-Resistant Depression: An Open-Label Study”. Journal of Child and Adolescent Psychopharmacology. Sep 2018. 437-444. http://doi.org/10.1089/cap.2018.0030

https://www.liebertpub.com/doi/10.1089/cap.2018.0030

SUMMARY: A ketamine infusion initiation series can be an effective intervention for Treatment Resistant Depression in adolescents. Thirteen participants received 6 infusions over 2 weeks, and 38% achieved a clinically significant response in their depression symptoms. For those who responded, 60% maintained their response at 6 weeks while 40% had experienced relapse.

Maintenance Ketamine

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.

https://www.sciencedirect.com/science/article/abs/pii/S2215036622003170?dgcid=author

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.

MICHIGAN PROGRESSIVE HEALTH
PROVIDER EDUCATIONAL PROGRAM

Dr. Oxley and the staff at MPH are committed to not only providing the most up to date treatment with ketamine, but also training other providers to ensure the most safe and therapeutic treatment is available to patients. As such, Dr. Oxley has created two training programs for providers:

How to add oral or intranasal ketamine to an existing psychiatric practice:

  • This program consists of a two hour one-on-one lecture with Dr. Oxley which can take place in person or via on-line video chat as well as two follow up phone calls and one year of consultation service.
  • Participants will have access to the key articles supporting ketamine therapy for treatment of mood disorders, GAD and OCD.
  • This program will review the risks, benefits and alternatives of oral ketamine for mood disorders, GAD and chronic pain conditions. Dosing strategies, office observation and long term follow up will be discussed.
  • Participants will receive copies of our patient consent form for oral ketamine administration and home use agreement.

How to provide IV ketamine infusions for mood disorders and chronic pain:

  • This program consists of three days on-site clinical education at the MPH clinic. We have four infusion rooms as well as a group therapy room and perform 8-14 infusions a day.  We have a therapist on staff two days a week and have group patient meetings weekly.  The prospective provider can also bring one staff member with them for the clinical education.
  • Along with clinical education, the provider will have access to the 20 most important published research papers on ketamine reviewing: Standards of Care, Dosing Protocols, Mechanism of Action, Long Term Studies, Oral Ketamine, Ketamine Assisted Psychotherapy, Ketamine for Pediatrics as well as Ketamine for Chronic Pain.
  • Lastly, the participant will receive paper and electronic copies of our dosing protocols and all the forms needed to establish a ketamine clinic. These forms consist of consents per condition, patient information sheets, discharge instructions, necessary registration forms, medication logs, procedure sheets and others.

Please email Dr. Oxley directly at droxley@michiganprogressivehealth.com for further information.  You can also call our office at 248-291-7709 and ask to speak to our office manager, Ryan.