Cognitive Training + Ketamine for Depression

Recruiting at 2 trial locations

Overseen By Rebecca B Price, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Pittsburgh

Must be taking: Ketamine

Disqualifiers: Psychosis, Mania, Dementia, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

In a sample of patients already receiving ketamine treatment as part of their clinical care, this project seeks to test whether we can enhance and/or extend ketamine's rapid effects by introducing helpful information delivered by a computer-based cognitive training protocol. This work could ultimately lead to the ability to treat depression more efficiently and with broader dissemination by rapidly priming the brain for helpful forms of learning.

Will I have to stop taking my current medications?

The trial requires that you keep a stable schedule of your current psychiatric medications during the ketamine treatment phase and for 4 weeks after. Minor changes to medications taken as needed (PRN) and timing are allowed.

Is the combination of cognitive training and ketamine safe for treating depression?

Ketamine has been shown to have a generally good safety profile at low single doses for depression, but there is limited data on its long-term safety and effects with repeated use. Some side effects like psychiatric and cardiovascular issues have been reported, and more research is needed to fully understand the safety of combining ketamine with cognitive training. ^{1 2 3 4 5}

How does the treatment of Cognitive Training + Ketamine for Depression differ from other treatments for depression?

This treatment is unique because it combines cognitive training, which aims to improve mental processes like memory and attention, with ketamine, a drug known for its rapid antidepressant effects. Ketamine is administered intravenously at a low dose, which has been shown to quickly reduce depressive symptoms and may also enhance cognitive function, making it different from traditional antidepressants that take longer to work. ^{1 2 6 7 8}

What data supports the effectiveness of the treatment Cognitive Training + Ketamine for Depression?

Research shows that computerized cognitive training (CCT) can improve mood and cognitive function in people with depression. Studies have found that CCT is effective in enhancing cognitive performance and mood, making it a promising treatment for depression. ^{9 10 11 12 13}

Who Is on the Research Team?

Rebecca B Price, PhD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for individuals already receiving ketamine treatment for depression. It aims to see if adding a computer-based cognitive training can improve the effects of ketamine.

Inclusion Criteria

Be willing and able to provide names and contact information for at least 1 additional emergency contact in the patient's proximal geographic area (in addition to the ketamine treatment team at the enrolling site)

Score ≥20 on the Montgomery-Asberg Depression Rating Scale (MADRS)

I have been diagnosed with a specific type of depression or bipolar disorder.

Exclusion Criteria

Presence of current/acute psychosis, mania, moderate-severe substance/alcohol use disorder, or dementia, or a diagnosis of developmental disorder with significant language and/or intellectual impairment (e.g., autism spectrum disorder)

Current/acute suicide risk with intent to act, defined as CSSRS past-week ideation score ≥ 4

Mini-Mental State Exam (MMSE) < 24

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive ketamine treatment as part of their clinical care, with cognitive training introduced to enhance effects

Up to 12 weeks

Post-CT Assessment

Assessment of cognitive training effects approximately 5 days post-infusion

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, with various outcome measures tracked

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Cognitive Training

Trial Overview The study is testing whether a special computer program called 'Cognitive Training' can make ketamine treatment more effective for depression, compared to a fake version of the program known as 'Sham Training'.

How Is the Trial Designed?

Group I: Cognitive Training Experimental Treatment 1 Intervention

Web-based cognitive training

Group II: Sham Training Placebo Group 1 Intervention

Web-based sham training

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

This study aims to systematically review and analyze the efficacy of computerized cognitive training (CCT) in improving cognitive performance in adults with depression, focusing on randomized controlled trials.

The research will explore how CCT affects not only cognitive outcomes but also mood and daily functioning, making it the first comprehensive analysis of its kind in this specific clinical population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computerized cognitive training in people with depression: a protocol for a systematic review and meta-analysis. Lampit, A., Launder, NH., Minkov, R., et al.[2022]

Computerized cognitive training (CCT) using Brain HQ showed significant cognitive improvements in psychiatric rehabilitation clients, with an average increase of 4.4 points in BACS t-scores after about 17 days of training.

Higher engagement in training (measured by levels completed per day) was positively correlated with cognitive gains, suggesting that monitoring engagement can help identify patients who may need additional support to benefit from CCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Training engagement, baseline cognitive functioning, and cognitive gains with computerized cognitive training: A cross-diagnostic study. Harvey, PD., Balzer, AM., Kotwicki, RJ.[2020]

In a study involving 46 young adults with mild depressive symptoms, executive functioning and processing speed (EF/PS)-focused computerized cognitive training (CCT) led to greater improvements in those specific cognitive areas compared to verbal ability-focused CCT.

Both types of CCT resulted in significant improvements in mood and everyday functioning, but the EF/PS group achieved similar mood benefits with only half the training time, suggesting that the content of CCT may not be as crucial as the engagement in the training itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computerized cognitive training in young adults with depressive symptoms: Effects on mood, cognition, and everyday functioning. Motter, JN., Grinberg, A., Lieberman, DH., et al.[2019]

Ketamine has been shown to provide rapid antidepressant effects within 24 hours, making it a potential option for patients with treatment-resistant depression, although its long-term efficacy remains unclear.

The safety profile of low doses of ketamine is generally good, but there is insufficient data on the effects of repeated higher doses, highlighting the need for further research on its long-term use in treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine and depression: a narrative review. Corriger, A., Pickering, G.[2020]

Ketamine and esketamine demonstrate rapid antidepressant effects, with improvements in clinical response observed within 40 minutes to 1 week for ketamine and 2 hours to 4 weeks for esketamine, along with reductions in depression scores and suicidality.

Despite their effectiveness, the long-term safety and efficacy of ketamine and esketamine remain uncertain, and the overall quality of the studies reviewed was critically low, highlighting the need for more rigorous research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses. Lima, TM., Visacri, MB., Aguiar, PM.[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]

A systematic review of 6 clinical trials with 340 patients indicates that electroconvulsive therapy (ECT) is more effective than ketamine for reducing depression severity, with a significant pooled effect size of -0.69.

Both treatments have distinct safety profiles, with ketamine associated with fewer headaches and muscle pain, while ECT has lower risks for visual disturbances and dissociative symptoms, suggesting that treatment choice should be tailored to individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ketamine vs Electroconvulsive Therapy Among Patients With Major Depressive Episode: A Systematic Review and Meta-analysis. Rhee, TG., Shim, SR., Forester, BP., et al.[2023]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

[Computer assisted cognitive training advances mood and psychological wellbeing - a comparison to paper pencil training relating to neuropsychological parameters, mood and cognitions]. [2011]

2. England pubmed.ncbi.nlm.nih.gov

Computerized cognitive training in people with depression: a protocol for a systematic review and meta-analysis. [2022]

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

Training engagement, baseline cognitive functioning, and cognitive gains with computerized cognitive training: A cross-diagnostic study. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Computerized cognitive training in young adults with depressive symptoms: Effects on mood, cognition, and everyday functioning. [2019]

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

A Systematic Review and Meta-Analysis of Cognitive Training in Adults with Major Depressive Disorder. [2022]

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

The Effects of Ketamine on Cognition in Treatment-Resistant Depression: A Systematic Review and Priority Avenues for Future Research. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Ketamine and depression: a narrative review. [2020]

8. Germany pubmed.ncbi.nlm.nih.gov

Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Is ketamine an appropriate alternative to ECT for patients with treatment resistant depression? A systematic review. [2021]

10. England pubmed.ncbi.nlm.nih.gov

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

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

Efficacy and Safety of Ketamine vs Electroconvulsive Therapy Among Patients With Major Depressive Episode: A Systematic Review and Meta-analysis. [2023]

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

KETAMINE FOR TREATMENT-RESISTANT UNIPOLAR AND BIPOLAR MAJOR DEPRESSION: CRITICAL REVIEW AND IMPLICATIONS FOR CLINICAL PRACTICE. [2018]

13. Ireland pubmed.ncbi.nlm.nih.gov

The effect of intravenous ketamine on cognitive functions in adults with treatment-resistant major depressive or bipolar disorders: Results from the Canadian rapid treatment center of excellence (CRTCE). [2021]