Revisiting Depression — Dopamine-Serotonin Balance Gains Attention for Treatment-Resistant Depression

Dr. Joseph Mercola - Take Control of Your Health

Briana Mercola

Health & Fitness, Health, Alternative Health

4.6 • 1.5K Ratings

🗓️ 10 November 2025

⏱️ 7 minutes

🔗️ Recording | iTunes | RSS

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Summary

A major clinical trial in The Lancet Psychiatry found that boosting dopamine with pramipexole improved symptoms in treatment-resistant depression. This challenges the long-dominant serotonin deficiency theory
Supporting those findings, another study showed that agomelatine, a serotonin-blocking drug, consistently reduced anxiety and depression in multiple placebo-controlled trials
Research shows polyunsaturated and monounsaturated fats (PUFs and MUFs) directly trigger platelet aggregation and serotonin release, while saturated fats do not, linking modern diets to serotonin excess
Studies confirm that combinations of unsaturated fats amplify serotonin release even at sub-threshold levels, making everyday dietary choices especially relevant to serotonin-driven health risks and mood instability
Increasing GABA helps your body break down serotonin, restoring calm, better sleep, and mood stability without SSRI side effects, making it a safer alternative for addressing depression and anxiety

Transcript

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0:00.0	If your depression hasn't improved despite multiple medications,
0:03.5	could you be dealing with too much serotonin rather than too little?
0:07.5	Welcome to Dr. Mercola's cellular wisdom.
0:10.8	Stay informed with quick, easy-to-listen summaries of our latest articles,
0:14.7	perfect for when you're on the go.
0:16.2	No reading required.
0:17.5	Subscribe for free at Mercola.com for the latest health insights.
0:20.9	Hello. And welcome to Dr. Mercola's cellular wisdom. I'm Ethan Foster, and today we're looking at a different model for treatment-resistant depression.
0:30.6	Restoring balance between serotonin and dopamine instead of pushing serotonin higher.
0:35.6	I'm Alara Sky. We'll walk through new clinical evidence
0:39.3	on a dopamine boosting therapy, why blocking certain serotonin receptors can calm stress, how everyday
0:45.4	dietary fats can raise serotonin activity, and why supporting GABA may offer a practical path
0:51.4	without typical SSRI side effects. A major trial published in the Lancet Psychiatry followed people with long-standing,
0:59.0	treatment-resistant depression, who stayed on their usual care while adding
1:03.0	either Pramipexol or a placebo for 48 weeks.
1:08.0	Pramipixel increases dopamine signaling, and by week 12, participants on the drug
1:12.6	showed clear symptom improvements that persisted across the study. That kind of durability is uncommon
1:18.7	in this group. Side effects mattered, though. About one in five stopped Pramipixel because of issues
1:24.8	like nausea, dizziness, or sleep disturbance. For those who continued,
1:30.3	the gains in mood and function were meaningful, and the overall signal suggests that lifting dopamine,
1:36.0	while offsetting serotonin's dominance, can help when standard strategies don't.
1:41.2	There's converging evidence from another angle. Agamelotin blocks the five H.T2C serotonin
	...

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