Ketamine for Chronic Lower Back Pain and Depression

Overseen By Victoria D Powell, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Disqualifiers: Psychotic disorders, Uncontrolled hypertension, Cardiac condition, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 18

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a pilot study to evaluate the feasibility, acceptability, and safety of ketamine infusions followed by a brief behavioral intervention in Veterans with chronic low back pain and depression.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it requires no changes in your pain or depression medication regimen for 4 weeks before starting. This suggests you should continue your current medications without changes.

Is ketamine generally safe for humans when used for chronic pain and depression?

Ketamine has been used for chronic pain and depression, and while it can cause side effects like changes in mood, heart rate, and perception, its safety profile is better at lower doses used for these conditions. However, there is limited long-term safety data, and more research is needed to fully understand its safety with repeated use. ^{1 2 3 4 5}

How does the drug ketamine differ from other treatments for chronic lower back pain and depression?

Ketamine is unique because it works on different brain receptors than typical painkillers and antidepressants, offering pain relief and mood improvement, especially when other treatments have failed. It can be administered in various ways, including epidurally, and has a lower risk of causing breathing problems compared to opioids. ^{1 5 6 7 8}

What data supports the effectiveness of the drug ketamine for chronic lower back pain and depression?

Research shows that ketamine can be effective in reducing chronic pain and has antidepressant effects, especially in cases where other treatments have failed. It has been used successfully for various chronic pain conditions, including cancer-related pain, and can reduce the need for opioids, which are strong painkillers. ^{1 5 9 10 11}

Who Is on the Research Team?

Victoria D Powell, MD

Principal Investigator

VA Ann Arbor Healthcare System, Ann Arbor, MI

Are You a Good Fit for This Trial?

This trial is for veterans who have long-term lower back pain paired with depression. It's a pilot study, which means it's an early test to see if the approach works well and is safe.

Inclusion Criteria

I am a veteran with chronic low back pain, it interferes with my daily life, and I feel significantly depressed.

I haven't been hospitalized for 3 days or more in the last month.

My pain or depression medication has been the same for the last 4 weeks.

Exclusion Criteria

I have high pressure in my brain, aneurysm, or high eye pressure.

I cannot participate because I do not speak English.

Inability or unwillingness to provide written informed consent (e.g. current delirium)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Pilot Phase

Open-label single-arm pilot of ketamine infusions followed by a brief behavioral intervention in a small sample of Veterans

8-10 days

7 visits

Randomized Controlled Trial Phase

Single-blind, two-arm pilot feasibility randomized controlled trial to assess feasibility benchmarks and collect outcome data

1 month

9 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

2 visits (1 month and 3 month follow-up)

What Are the Treatments Tested in This Trial?

Interventions

• Brief narrative intervention
• Ketamine hydrochloride

Trial Overview The study tests ketamine infusions (a type of medication that can affect mood and pain) followed by a short counseling session. The goal is to see if this combo helps more than usual care or just talking about one's life story.

How Is the Trial Designed?

Group I: Open label, single arm pilot Experimental Treatment 2 Interventions

Initial phase: A small open-label, single arm pilot study (n=5) will be conducted to develop and assess initial feasibility of study procedures and obtain participant feedback through semi-structured exit interviews. All participants in this open-label single arm pilot will receive the intervention (ketamine infusions followed by the brief behavioral intervention). There will be no control condition, randomization, or blinding.

Group II: Intervention + Minimally Enhanced Usual Care Experimental Treatment 3 Interventions

Second phase: Intervention arm of a single-blind, two-arm, pilot feasibility randomized controlled trial (RCT) (n=44, 22 per arm) which will (a) assess feasibility benchmarks and (b) collect outcome data that will be used to calculate sample size to power a larger RCT. Minimally Enhanced Usual Care will consist of educational reading materials regarding chronic back pain and depression.

Group III: Minimally Enhanced Usual Care Only Active Control 2 Interventions

Second phase: Control arm of a single-blind, two-arm, pilot feasibility randomized controlled trial (RCT) (n=44, 22 per arm) which will (a) assess feasibility benchmarks and (b) collect outcome data that will be used to calculate sample size to power a larger RCT. Minimally Enhanced Usual Care will consist of educational reading materials regarding chronic back pain and depression.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

Ketamine has been found to be an effective treatment for chronic pain conditions, including cancer-related neuropathic pain, and can help reduce the need for opioids by counteracting opioid-induced hyperalgesia.

At sub-anesthetic doses, ketamine demonstrates a significantly improved safety profile and fewer adverse events compared to its use as an anesthetic, making it a promising option for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine Use for Cancer and Chronic Pain Management. Culp, C., Kim, HK., Abdi, S.[2021]

A meta-analysis of 12 studies involving 88 patients indicates that Ketamine significantly reduces neuropathic pain compared to placebo, although the effects are typically short-lived after administration.

Ketamine has shown promise as an alternative to opioids for chronic pain management, with some studies reporting positive long-term outcomes, but further research with larger sample sizes is needed to confirm its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ketamine for treatment of chronic pain: meta-analysis]. Wiedemann, B.[2019]

In a study of 329 patients with treatment-refractory chronic pain, repeated ketamine administration significantly reduced pain intensity and improved mental and physical health over one year, with a notable effect size of -0.52.

The study found that depression, rather than the dose of ketamine, was the key factor mediating pain relief, suggesting that ketamine's effectiveness in reducing pain is primarily linked to its ability to alleviate depressive symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Initial Depressive State and Pain Relief With Ketamine in Patients With Chronic Refractory Pain. Voute, M., Lambert, C., Pereira, B., et al.[2023]

Ketamine hydrochloride has shown rapid and significant antidepressant effects in patients with treatment-resistant mood and anxiety disorders, although the studies supporting this have small sample sizes and limited long-term data.

While ketamine may offer benefits for some patients, there are important safety concerns and limitations in the existing research that must be considered when using it as an off-label treatment for psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. Sanacora, G., Frye, MA., McDonald, W., et al.[2022]

This systematic review analyzed 60 studies on the safety of ketamine for treating depression, revealing that acute doses of ketamine led to more frequent side effects, including psychiatric and cardiovascular issues, compared to placebo.

There is a notable lack of data on the long-term safety and effects of repeated ketamine dosing, highlighting the need for large-scale clinical trials to better understand its safety profile over extended use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side-effects associated with ketamine use in depression: a systematic review. Short, B., Fong, J., Galvez, V., et al.[2019]

In a study involving 7 patients with severe pain, epidural administration of 4 mg ketamine resulted in pain relief for all participants, with effects lasting from 30 minutes to over 6 hours.

Ketamine's use in this context showed no adverse side effects or neurological damage, and it presents a safer alternative to opioids, as it is unlikely to cause respiratory depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidural ketamine. A preliminary report. Mankowitz, E., Brock-Utne, JG., Cosnett, JE., et al.[2014]

In a study of 120 patients undergoing tumor resection, administering 2 or 3 escalating doses of intramuscular ketamine before surgery significantly reduced postoperative pain scores and decreased morphine consumption by about 35% compared to placebo.

The results indicate that repeated subanesthetic doses of ketamine can effectively enhance pain relief after surgery, although a single dose did not show the same benefits, and some patients experienced brief dizziness after the higher dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated and escalating preoperative subanesthetic doses of ketamine for postoperative pain control in patients undergoing tumor resection: a randomized, placebo-controlled, double-blind trial. Rakhman, E., Shmain, D., White, I., et al.[2013]

Ketamine shows moderate to weak evidence for efficacy in managing chronic pain, with level II evidence supporting its use for conditions like fibromyalgia and ischemic pain, while also being considered a 'third line' option when standard treatments fail.

For specific pain conditions such as phantom limb pain and postherpetic neuralgia, ketamine has demonstrated substantial pain relief, indicating its potential as an effective treatment in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine in chronic pain management: an evidence-based review. Hocking, G., Cousins, MJ.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Efficacy of outpatient ketamine infusions in refractory chronic pain syndromes: a 5-year retrospective analysis. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Ketamine Use for Cancer and Chronic Pain Management. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

[Ketamine for treatment of chronic pain: meta-analysis]. [2019]

4. China pubmed.ncbi.nlm.nih.gov

The use of ketamine in a palliative-supportive care unit: a retrospective analysis. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Assessment of Initial Depressive State and Pain Relief With Ketamine in Patients With Chronic Refractory Pain. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. [2022]

7. France pubmed.ncbi.nlm.nih.gov

[Ketamine and chronic pain: A narrative review of its efficacy and its adverse events]. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Side-effects associated with ketamine use in depression: a systematic review. [2019]

9. South Africa pubmed.ncbi.nlm.nih.gov

Epidural ketamine. A preliminary report. [2014]

10. United States pubmed.ncbi.nlm.nih.gov

Repeated and escalating preoperative subanesthetic doses of ketamine for postoperative pain control in patients undergoing tumor resection: a randomized, placebo-controlled, double-blind trial. [2013]

11. United States pubmed.ncbi.nlm.nih.gov

Ketamine in chronic pain management: an evidence-based review. [2022]