Depression Isn’t Treatment-Resistant.

It’s Multi-Factorial

The evidence suggests that individualized, multimodal treatment plans may be more effective than medication-only approaches for many patients. This newsletter examines evidence-based approaches to treating depression, particularly for those who haven't found relief through medication alone. While antidepressants show modest average effects, many non-pharmaceutical interventions demonstrate comparable or superior outcomes. Exercise shows particularly robust effects, and combining multiple approaches—including therapy, sleep interventions, dietary changes, and mind-body practices—offers meaningful lasting symptom reduction.

Quick Takes

Holiday Blues Are Real, But the Suicide Spike Isn't
Many people experience worsening depression symptoms during the holidays, but the common belief about increased suicides in late December is a myth. Research shows the seasonal pattern involves higher suicidal behavior in spring, possibly linked to seasonal affective disorder.

Antidepressants Work About as Well as Placebo for Many
If you've tried medication without success, you're not alone. Large analyses show that for most people, antidepressants produce only modest improvements over placebo—with effect sizes (0.3-0.4) falling well short of what most people would notice (0.8). Individual responses vary widely.

Exercise Rivals or Beats Medication
A 2023 meta-analysis found exercise produced a large effect size of about 0.95 for reducing depressive symptoms—more than double the effect of antidepressants. Both aerobic exercise and strength training showed substantial benefits.

Sleep Problems Aren't Just a Symptom—They're a Target
Treating insomnia with cognitive behavioral therapy (CBT-I) can double depression response rates, from about 17% to 32%, beyond the improvements in sleep alone. Addressing sleep disturbances directly is an efficient way to improve mood.

Combining Approaches Works Best
Studies using integrated programs that address cognitive, behavioral, physical, mindfulness, and lifestyle factors together show roughly two-thirds of patients improving—similar to coordinated care models where professionals systematically track patient progress across multiple interventions.

Favorite Finds

The Healing Depression Project
This is a most exciting approach, a residential program that incorporates interventions from functional medicine, including therapeutic ketogenic nutrition and mindfulness practices. They have generous scholarships and are enrolling now for March.

My other links are to individual tools that people can put together themselves. However, from the Deep Dive you will see that support and guidance appear to at least double success rates. 

EFT (Emotional Freedom Technique)
Tapping-based intervention showing large effect sizes for depression

HeartMath
Heart rate variability biofeedback training for mood regulation

Tai Chi
Gentle movement practice with evidence for depression reduction. From research publications, tai chi for brain health includes cognition and mood benefits.

CBT-I Apps
Digital tools for cognitive behavioral therapy for insomnia. Direct work with a knowledgeable therapist may be preferable, but apps also have research support.

Deep Dive: What Actually Works for Depression

Click on link if you want to read all the details and see the references. I believe the Favorite Find I mentioned (The Healing Depression Project) offers a similar type of multi-modal intervention, in addition to a therapeutic diet and functional medicine expertise.

References

At Deep Dive link above.