5-HTP + Creatine for Depression

Overseen By Hailey Nielson, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Utah

Must be taking: SSRI, SNRI

Must not be taking: Antipsychotics, Mood stabilizers

Disqualifiers: Renal disease, Pulmonary disease, Cardiac disease, Seizure disorder, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

106 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the potential benefits of 5-hydroxytryptophan (5-HTP) and creatine as additional treatments for depression. Participants will receive either low or high doses of these supplements or a placebo to determine their effect on depression symptoms. The trial also examines how these treatments influence specific brain and blood markers associated with depression. It suits individuals with a current diagnosis of major depression who have been on certain antidepressants for at least eight weeks and live above 4,000 feet elevation. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings in depression treatment.

Will I have to stop taking my current medications?

The trial requires that you stay on an existing SSRI or SNRI medication for at least 8 weeks before joining. You cannot be on antipsychotics, mood stabilizers, or non-SSRI/SNRI antidepressants, except for bupropion or trazodone at specified doses.

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

Research has shown that using 5-hydroxytryptophan (5-HTP) and creatine together is safe and generally well-tolerated for treating depression. In an initial study, most participants responded well to the treatment, although two people left the study. Another study found that creatine alone was as safe as a placebo, meaning it didn't cause more side effects than a sugar pill. These results suggest that both 5-HTP and creatine could be safe options for people with depression, but more research is needed to confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using 5-HTP and creatine for depression because these treatments offer a fresh approach compared to traditional antidepressants. Most antidepressants, like SSRIs and SNRIs, work by altering serotonin levels over several weeks. However, 5-HTP is a serotonin precursor that could potentially boost serotonin levels more rapidly. Additionally, creatine is thought to support brain energy metabolism, which might enhance mood and cognitive function. This combination targets both neurotransmitter levels and brain energy pathways, potentially offering quicker and more comprehensive relief for depression.

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

This trial will evaluate the combination of 5-hydroxytryptophan (5-HTP) and creatine for treating depression. Studies have shown that this combination can be effective, especially for individuals whose depression did not improve with common medications like SSRIs (selective serotonin reuptake inhibitors) or SNRIs (serotonin-norepinephrine reuptake inhibitors). Creatine has also been noted to reduce symptoms of depression and boost brain energy, making it a promising option. While more research is needed, these findings suggest that using 5-HTP and creatine together could be a helpful treatment for depression. Participants in this trial will receive either a low dose or high dose of the combination, or a double placebo. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with major depressive disorder (MDD), currently on an SSRI or SNRI antidepressant for at least 8 weeks, and have a moderate to severe depression score. They must be right-handed and have lived above 4000 ft elevation for the past 12 weeks.

Inclusion Criteria

You are right-handed.

I have consistently taken an approved depression/anxiety medication for at least 8 weeks.

I have been diagnosed with major depressive disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either low dose 5-HTP and creatine, high dose 5-HTP and creatine, or double placebo for 8 weeks

8 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 5-HTP and Creatine

Trial Overview The study tests two doses of 5-HTP (100mg and 200mg twice daily) combined with two doses of creatine (5g and 10g daily) against a placebo over eight weeks. It aims to see if these supplements improve depression by measuring changes in brain chemistry and connectivity.

How Is the Trial Designed?

Group I: Low Dose 5-hydroxytryptophan and Creatine Monohydrate Experimental Treatment 3 Interventions

5-HTP 100mg PO BID plus creatine 5g PO Qday

Group II: High Dose 5-hydroxytryptophan and Creatine Monohydrate Experimental Treatment 2 Interventions

5-HTP 200mg PO BID plus creatine 10mg PO Qday

Group III: Double Placebo Placebo Group 1 Intervention

Creatine-matched placebo and 5-HTP-matched placebo

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Published Research Related to This Trial

5-hydroxytryptophan (5-HTP), a precursor to serotonin, shows potential antidepressant properties based on a review of studies, suggesting it may help in treating depression.

The use of 5-HTP in depressed patients is generally associated with relatively few adverse effects, making it a safer option compared to other treatments, although more trials are needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Hydroxytryptophan: a review of its antidepressant efficacy and adverse effects. Byerley, WF., Judd, LL., Reimherr, FW., et al.[2013]

5-hydroxytryptophan (5-HTP) may be effective in treating depression, as supported by preclinical and clinical evidence, particularly from double-blind, placebo-controlled trials.

While 5-HTP can enhance serotonin production, its safety profile raises concerns, particularly regarding risks of eosinophilia myalgia syndrome (EMS) and serotonin syndrome, which need to be carefully monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Turner, EH., Loftis, JM., Blackwell, AD.[2022]

In a Phase 2 open clinical trial involving 14 hospitalized depressed patients, a low dose of L-5-hydroxytryptophan (150 mg for seven days) resulted in a response in 50% of the participants, indicating potential antidepressant effects.

The study found that non-responders to L-5-HTP treatment had significantly lower levels of serotonin and its metabolites in their urine and plasma, suggesting that the effectiveness of L-5-HTP may be linked to the patients' baseline serotonin levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measurement of 5-hydroxyindole compounds during L-5-HTP treatment in depressed patients. Takahashi, S., Takahashi, R., Masumura, I., et al.[2019]

In a study of 15 women with major depressive disorder who did not respond to standard antidepressants, the combination of creatine monohydrate and 5-hydroxytryptophan (5-HTP) led to a significant reduction in depression symptoms, with Hamilton Depression Rating Scale scores dropping by 60%.

The treatment was well-tolerated, with no serious adverse events reported, suggesting that this augmentation strategy could be a safe option for women with treatment-resistant depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Open-Label Pilot Study of Combined Augmentation With Creatine Monohydrate and 5-Hydroxytryptophan for Selective Serotonin Reuptake Inhibitor- or Serotonin-Norepinephrine Reuptake Inhibitor-Resistant Depression in Adult Women. Kious, BM., Sabic, H., Sung, YH., et al.[2018]

In a Phase 2 open clinical trial involving 14 hospitalized depressed patients, a 150 mg oral dose of L-5-hydroxytryptophan (L-5-HTP) for seven days led to a response in 50% of the patients, indicating potential antidepressant effects.

The study found that non-responders to L-5-HTP treatment had significantly lower urinary and plasma levels of serotonin and its metabolites, suggesting that the effectiveness of L-5-HTP may be linked to the patients' baseline serotonin levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measurement of 5-hydroxyindole compounds during L-5-HTP treatment in depressed patients. Takahashi, S., Takahashi, R., Masumura, I., et al.[2013]

5-HTP (5-Hydroxytryptophan) shows strong therapeutic value in treating vital depressions, especially in patients with a deficiency in serotonin (5-HT), and may also have a prophylactic effect in this subgroup.

Combining 5-HTP with clomipramine can enhance treatment outcomes for therapy-resistant vital depressions, while studies on tryptophan have shown less consistent results, possibly due to differences in how patients' serotonin levels were considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serotonin precursors in the treatment of depression. van Praag, HM.[2013]

In a randomized double-blind study of 70 patients with their first depressive episode, l-5-hydroxytryptophan (l-5-HTP) demonstrated significant antidepressant effects comparable to fluoxetine over an 8-week treatment period.

Both l-5-HTP and fluoxetine showed similar reductions in depression severity as measured by the Hamilton Rating Scale for Depression, with positive responses observed in 73.33% of the l-5-HTP group and 80% of the fluoxetine group by the end of the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Jangid, P., Malik, P., Singh, P., et al.[2016]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04395183

NCT04395183 | 5-HTP and Creatine for Depression This is a three-armed clinical trial examining the effect of 5-hydroxytryptophan and creatine monohydrate as augmenting agents for the treatment of depression.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5578880/

An open-label pilot study of combined augmentation with ... Conclusions. Combination treatment with creatine and 5-HTP may represent an effective augmentation strategy for women with SSRI- or SNRI-resistant depression.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0924977X24007405

Efficacy and safety profile of oral creatine monohydrate in ... Creatine is as safe and well-tolerated as placebo in depressed participants at 8 weeks. •. Longer and adequately sized trials of creatine in depression are ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11567172/

Creatine Supplementation in Depression: A Review of ... Creatine supplementation reduces depressive symptoms, particularly when combined with selective serotonin reuptake inhibitors, and may improve brain energy ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05895747

5-HTP and Creatine for Depression R33 Phase | ... This is a three-armed clinical trial examining the effect of 5-hydroxytryptophan and creatine monohydrate as augmenting agents for the treatment of depression.