Exercise + Ibuprofen for Bipolar Depression

Overseen By Jonathan Savitz

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Laureate Institute for Brain Research, Inc.

Must not be taking: Immune-modulating, NSAIDs, Heart-modulating, others

Disqualifiers: Schizophrenia, Cardiac disease, Substance use, others

Compensation: Varies

Number of Visits: 4

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how exercise and ibuprofen might reduce depression symptoms in people with bipolar disorder. Researchers are testing whether exercise alone has antidepressant effects and if taking ibuprofen (an over-the-counter pain reliever) before exercise alters these effects. Participants will alternate between biking and resting, with and without ibuprofen, to observe how each combination affects mood and brain activity. Suitable candidates for this study are those with bipolar disorder currently experiencing depression and who are comfortable with physical activity. As a Phase 1 and Phase 2 trial, this research aims to understand the treatment's mechanism and measure its effectiveness in a smaller group, offering participants a chance to contribute to early-stage treatment development.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking certain medications like those with significant interactions with ibuprofen, immune-modulating medications, or regular NSAIDs more than 3 times a week.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies have found that exercise, such as riding a stationary bike, is well-tolerated by people with severe mental illness. Most participants reported satisfaction with the activity, indicating it was safe and acceptable. This suggests exercise is generally safe for those with bipolar depression.

Research shows mixed results for using ibuprofen, a common pain reliever, in treating depression. While it is usually well-tolerated, its effects on depression are inconsistent. Some studies suggest it might help, while others do not find a clear benefit. Although ibuprofen is safe for most people, more research is needed to understand its impact on depression. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial exploring exercise combined with ibuprofen as a treatment for bipolar depression because it offers a potentially quicker and more accessible approach than traditional medications like mood stabilizers and antipsychotics. Exercise is known to boost mood and improve overall mental health, while ibuprofen, a common anti-inflammatory, might help by reducing inflammation linked to depression. This combination could provide an immediate mood lift and a novel way to manage symptoms without the side effects often associated with standard psychiatric medications.

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

Research has shown that exercise can greatly alleviate depression symptoms. A review of several studies found that exercise significantly reduced these symptoms. Specifically, a study on bipolar depression found that aerobic exercise effectively lessened depressive symptoms.

Regarding ibuprofen, research suggests that anti-inflammatory drugs like it might help treat depression. Reviews of multiple studies indicate these drugs can have strong antidepressant effects, although some studies have shown mixed results.

This trial will explore different combinations of treatments. One group of participants will engage in exercise combined with ibuprofen, while another group will receive exercise with a placebo. Additionally, some participants will receive ibuprofen alone, and others will receive a placebo alone. This approach aims to determine if combining exercise and ibuprofen might effectively reduce depression symptoms in people with bipolar disorder. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 with bipolar depression, a BMI of 18.5-35, and who are stable on medication or deemed appropriate to participate. They must be able to undergo behavioral testing, MRI scans, and blood draws. Exclusions include severe substance abuse, complex psychiatric medication regimens, significant heart conditions or unstable medical issues, pregnancy or breastfeeding without contraception use, metal in the body that affects MRI safety, suicidal tendencies recently or certain medications like NSAIDs.

Inclusion Criteria

You have provided a signed and dated consent form.

My depression is severe, scoring over 11 on the QIDS.

I am currently experiencing a major depressive episode.

Exclusion Criteria

Clinically significant abnormality on EKG

You smoke a lot or smoke heavily according to the Fagerstrom scale.

I have or had heart disease, irregular heartbeats, or underwent a procedure to correct heart rhythm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Experimental Sessions

Participants complete four experimental sessions, two with an exercise challenge and two with a resting control condition, receiving either ibuprofen or placebo.

4 sessions

4 visits (in-person)

Follow-up

Participants are monitored for neural and psychological effects post-intervention

2 hours post each session

What Are the Treatments Tested in This Trial?

Interventions

• Acute Exercise
• Ibuprofen

Trial Overview The study tests if acute exercise can alleviate symptoms of bipolar depression by comparing four sessions: two involving exercise and two rest periods. Before these activities participants take either ibuprofen (800mg) or placebo to see if blocking inflammation affects the benefits of exercise on mood and brain function.

How Is the Trial Designed?

Group I: Session 1 Experimental Treatment 2 Interventions

Exercise (30 min on bicycle ergometer at 60% peak power output) and a single oral dose 800mg of ibuprofen

Group II: Session 3 Active Control 2 Interventions

30 minutes rest (sitting in chair) and a single oral dose 800mg of ibuprofen

Group III: Session 2 Active Control 2 Interventions

Exercise (30 min on bicycle ergometer at 60% peak power output) and matching placebo

Group IV: Session 4 Placebo Group 2 Interventions

30 minutes rest (sitting in chair) and matching placebo

Who Is Running the Clinical Trial?

Laureate Institute for Brain Research, Inc.

Lead Sponsor

Trials

53

Recruited

5,400+

Published Research Related to This Trial

A study involving 25 individuals with Bipolar Disorder highlighted that exercise can play a significant role in mood regulation, but it also has potential risks, indicating it can be a 'double-edged sword' for those with the condition.

Participants noted that exercise helps bring structure to their lives, suggesting that incorporating physical activity could be beneficial in managing Bipolar Disorder, but more research is needed to understand the nuances of this relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

'It's a double edged sword': a qualitative analysis of the experiences of exercise amongst people with Bipolar Disorder. Wright, K., Armstrong, T., Taylor, A., et al.[2018]

This study will evaluate the efficacy of exercise as a treatment for bipolar disorder in 100 patients aged 20-65, comparing an exercise intervention with a placebo stretching intervention over a 6-week period.

The research aims to provide comprehensive evidence on the effectiveness of exercise by assessing various clinical, biological, and genetic markers, potentially establishing exercise as a beneficial treatment for bipolar depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Exercise on Functional Recovery in Patients with Bipolar Depression: A Study Protocol for a Randomized Controlled Trial. Hamada, F., Hori, H., Iida, H., et al.[2023]

Structured individualized physical exercise can significantly alleviate affective and cognitive difficulties in individuals with bipolar disorder (BD), suggesting it may improve overall mental health.

Exercise is proposed to positively influence neurobiological systems related to metabolism, inflammation, and cellular health, potentially leading to better psychiatric and physical outcomes for those with BD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise and bipolar disorder: a review of neurobiological mediators. Alsuwaidan, MT., Kucyi, A., Law, CW., et al.[2021]

Aerobic exercise, particularly high-intensity interval training (HIIT), may significantly help in managing symptoms of bipolar disorder (BD) by improving cardiorespiratory fitness (VO2max) and potentially stabilizing mood.

The review suggests that exercise can influence the pathophysiology of BD through mechanisms like monoaminergic action and neurotrophin release, indicating that physical activity could be a valuable adjunct to traditional treatments for BD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise is medicine: a new perspective for health promotion in bipolar disorder. Sá Filho, AS., Cheniaux, E., de Paula, CC., et al.[2021]

Adolescents with bipolar disorder (BD) showed significantly lower exercise tolerance and cardiorespiratory fitness compared to healthy controls, indicating a potential barrier to engaging in physical activity.

While exercise preference did not differ significantly between groups, lower exercise preference in youth with BD was linked to lower fitness levels and higher perceived exertion, suggesting that improving fitness may enhance their willingness to exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise preference and tolerance in youth with bipolar disorder. Shickh, R., Mio, M., Khoubaeva, D., et al.[2023]

Patients with bipolar disorder often experience suboptimal outcomes with medication alone, and adding exercise could significantly enhance both short-term and long-term results.

Exercise may improve mood and functioning in bipolar disorder by increasing brain-derived neurotrophic factor (BDNF), which promotes neurogenesis and reduces stress on the body, suggesting a need for further clinical trials to explore this adjunct treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise treatment for bipolar disorder: potential mechanisms of action mediated through increased neurogenesis and decreased allostatic load. Sylvia, LG., Ametrano, RM., Nierenberg, AA.[2010]

Participation in a long-distance ski race was linked to a significantly lower risk of being diagnosed with bipolar disorder, with a hazard ratio of 0.48 over a follow-up period of up to 21 years, based on a study of nearly 200,000 skiers and matched non-skiers.

While a physically active lifestyle generally reduces the risk of bipolar disorder, higher performance in women (indicated by faster race finishing times) was associated with an increased risk, suggesting that exercise intensity may have different effects based on sex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A physically active lifestyle is associated with lower long-term incidence of bipolar disorder in a population-based, large-scale study. Svensson, M., Erhardt, S., Hållmarker, U., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12497790/

Exercise interventions for depressive, manic, and anxiety ... Meta-analysis demonstrated that exercise significantly improved depressive symptoms (SMD =-0.63, 95%CI: -1.11 to -0.14, P=0.01) and anxiety ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9705266/

Effect of online aerobic exercise training in patients with ... The main hypothesis of this trial is that aerobic exercise is an effective therapy to improve depressive symptoms among bipolar depression ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2772598724000199

A feasibility study of high intensity interval training ... High intensity interval training (HIIT) may improve cardiometabolic risk and mental wellbeing for people with SMI. This study explores the acceptability and ...

4. journalbipolardisorders.springeropen.com journalbipolardisorders.springeropen.com/articles/10.1186/s40345-023-00294-8

Structured physical exercise for bipolar depression: an open ... This pilot, open-label, single-arm study in patients diagnosed with BD demonstrated a robust improvement in depressive symptoms (MADRS) at 12 ...

5. pilotfeasibilitystudies.biomedcentral.com pilotfeasibilitystudies.biomedcentral.com/articles/10.1186/s40814-021-00937-6

Study protocol for a pilot high-intensity interval training ... This protocol describes a feasibility study for a high-intensity interval training (HIIT) intervention among inpatients with SMI, to improve their physical and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31883740/

High Intensity Interval training (HIIT) for people with severe ... HIIT appears as feasible as MCT, with few safety concerns. Following HIIT, there was a moderate improvement in CRF and depression. There was no difference ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178119317718

High Intensity Interval training (HIIT) for people with severe ... HIIT appears as feasible as MCT, with few safety concerns. Following HIIT, there was a moderate improvement in CRF and depression. There was no difference ...