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

Trial Summary

What is the purpose of this trial?

This trial is testing if adding 5-HTP and creatine monohydrate to standard antidepressants can help people with depression who haven't responded to usual treatments. 5-HTP boosts serotonin, and creatine improves brain energy. The study will measure changes in brain activity and mood.

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.

What evidence supports the effectiveness of the drug 5-HTP and Creatine for treating depression?

Research suggests that combining 5-HTP and creatine with standard antidepressants may help women with depression who haven't responded to other treatments, as it could improve serotonin levels and brain energy. Additionally, studies show that 5-HTP alone has some effectiveness in reducing depressive symptoms, similar to other antidepressants. ^{1 2 3 4 5}

Is the combination of 5-HTP and Creatine safe for humans?

5-HTP has been studied for depression and is generally considered safe, but it can have side effects like serotonin syndrome (a potentially dangerous condition caused by too much serotonin) and eosinophilia myalgia syndrome (a rare condition causing muscle pain and high white blood cell counts). Creatine is commonly used as a supplement and is generally safe, but combining it with 5-HTP for depression is still being studied, so it's important to consult with a healthcare provider. ^{1 2 3 4 6}

How does the treatment of 5-HTP and creatine for depression differ from other treatments?

This treatment is unique because it combines 5-HTP, a serotonin precursor, with creatine, which may enhance brain energy, to potentially improve depression symptoms in women who do not respond to standard antidepressants. This combination aims to address both serotonin production and brain bioenergetics, offering a novel approach compared to traditional antidepressants. ^{1 2 3 5 7}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

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-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]

References

1. United States 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. [2018]

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

Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

Measurement of 5-hydroxyindole compounds during L-5-HTP treatment in depressed patients. [2013]

4. Japan pubmed.ncbi.nlm.nih.gov

Measurement of 5-hydroxyindole compounds during L-5-HTP treatment in depressed patients. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. [2016]

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

5-Hydroxytryptophan: a review of its antidepressant efficacy and adverse effects. [2013]

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

Serotonin precursors in the treatment of depression. [2013]