Cognitive Training + Ketamine for Depression

Enrolling by invitation 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether combining cognitive training with ketamine can improve and extend ketamine's effects in treating depression. Participants will receive either actual cognitive training or a sham (placebo-like) version to compare outcomes. It targets individuals already receiving ketamine treatment, who have resistant depression, and are willing to maintain stable psychiatric medication schedules. The goal is to determine if adding cognitive exercises can help people feel better more quickly and for longer periods. As an unphased trial, this study allows participants to contribute to innovative research that could enhance depression treatment strategies.

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.

What prior data suggests that this cognitive training protocol is safe for patients with depression?

Research shows that computerized cognitive training (CCT) is safe for people with depression. Studies have found that CCT can maintain or even improve thinking skills in various groups, including those with depression. Reports of major side effects are absent. In fact, CCT might also lift mood and enhance overall brain function. Therefore, prospective participants in a CCT trial can feel confident that it is generally well-tolerated and considered safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the combination of cognitive training and ketamine for treating depression because it offers a novel approach compared to traditional treatments like antidepressant medications and psychotherapy. Unlike standard medications that can take weeks to show effects, ketamine has the potential to provide rapid relief from depressive symptoms. Additionally, cognitive training is a web-based technique designed to enhance mental functions, which might amplify the benefits of ketamine, offering a unique dual-action approach. This combination aims to target both the chemical and cognitive aspects of depression, potentially leading to more effective and faster results for patients.

What evidence suggests that this trial's treatments could be effective for depression?

Research has shown that computerized cognitive training (CCT) effectively improves thinking skills and daily life in people with depression. Studies have found that CCT helps with mood and overall thinking abilities, including understanding and reasoning. This training enhances focus, planning, decision-making, and overall quality of life. In this trial, some participants will receive CCT, while others will receive sham training. Combined with ketamine treatment, CCT might enhance and prolong ketamine's quick effects on depression. This combination could help the brain process helpful information better, potentially making depression treatment more effective. ^{1 4 5 6 7}

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

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8740357/

Computerized cognitive training in people with depression Computerized cognitive training (CCT) is a safe and efficacious strategy to maintain or enhance cognitive performance in a range of clinical populations.

2. sciencedirect.com sciencedirect.com/science/article/pii/S266691532400091X

The effectiveness of cognitive training in people ... The findings suggest that integrating cognitive training could enhance daily functioning and cognitive performance among psychiatric patients with depressive ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10827875/

Effect of computerized cognitive training on mood ... Our findings support the previous literature that CCT is useful in improving mood symptoms among older adults with depression and demonstrate ...

4. medrxiv.org medrxiv.org/content/10.1101/2021.03.23.21254003.full

Computerized Cognitive Training in People with Depression Outcomes The primary outcome was change from baseline to post-intervention in overall cognition. Secondary outcomes were depressive symptoms, ...

5. jmir.org jmir.org/2025/1/e73140

The Effectiveness of Computerized Cognitive Training in ... We conclude that CCT can significantly enhance general cognitive function, attention, executive function, and quality of life in PSCI patients.

6. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1287822/full

Effect of computerized cognitive training on mood ... This trial provides preliminary evidence of CCT improving mood, cognition, and BDNF level in LLD. With our populations ageing rapidly, LLD being ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11590405/

Efficacy and safety of Neurocognitive Adaptive Training for ... This randomized, open-label study examined the therapeutic effects of Neurocognitive Adaptive Training for Depression (NCAT-D) combined with selective ...