Depression Recovery Protocol (Non-SSRI)

Rule out medical causes: Thyroid (TSH, free T3/T4 - even subclinical hypothyroid causes depression), vitamin B12/folate (deficiency causes depression), vitamin D (low D strongly associated), anemia (iron, B12), testosterone (low T in men causes depression), chronic inflammation (CRP), sleep apnea, chronic pain, medications (beta-blockers, benzos, corticosteroids can cause depression)

SAMe: 400-1600mg daily on empty stomach (S-adenosylmethionine - methylation, neurotransmitter synthesis. Multiple RCTs show efficacy equal to SSRIs, faster onset. Start 400mg, increase to 800-1600mg divided doses) - can trigger mania in bipolar (screen first)

Methylfolate: 7.5-15mg daily (L-methylfolate - active form, especially if MTHFR mutation. Enhances antidepressant response, effective as monotherapy in some. Deplin is pharmaceutical version 7.5-15mg)

Omega-3: 2-3g EPA/DHA daily (higher EPA:DHA ratio, e.g., 2:1. Multiple meta-analyses show antidepressant effect. EPA 1000-2000mg + DHA 500-1000mg)

Vitamin D: Optimize 60-80 ng/ml (low D associated with depression, supplementation improves mood - 5000+ IU daily)

St. John's Wort: 900mg daily (300mg 3x/day standardized to 0.3% hypericin - multiple RCTs show efficacy for mild-moderate depression, equal to SSRIs. But drug interactions - avoid with most medications)

Saffron: 30mg daily (stigma extract - RCTs show antidepressant effects equal to SSRIs, well-tolerated, no side effects. Emerging evidence)

Rhodiola rosea: 340-680mg daily (adaptogenic, antidepressant effects, reduces fatigue, improves stress resilience)

Ashwagandha: KSM-66 600mg 2x/day (reduces cortisol, anxiety, improves mood and energy)

5-HTP: 100-300mg daily (serotonin precursor - converts to serotonin. Take with B6 and green tea extract to prevent peripheral serotonin. Alternatively L-tryptophan 500-3000mg) - don't combine with SSRIs (serotonin syndrome risk)

Vitamin B-complex: Methylated forms (B6, B12, folate for neurotransmitter synthesis and methylation. Many depressed patients have MTHFR polymorphisms impairing folate metabolism)

Zinc: 30-50mg daily (low zinc associated with depression, especially treatment-resistant. Enhances antidepressant response)

Magnesium: 400-800mg (low magnesium associated with depression, NMDA modulation. Glycinate or threonate forms)

Probiotics: Psychobiotics (Lactobacillus helveticus R0052 + Bifidobacterium longum R0175 studied for depression - gut-brain axis. 25 billion CFU daily)

Creatine: 5-10g daily (brain energy, may augment antidepressants, emerging evidence for treatment-resistant depression)

Inositol: 12-18g daily (second messenger signaling, studied in depression and anxiety - high dose needed, well-tolerated)

Exercise: 150+ min/week aerobic exercise (proven antidepressant effect comparable to SSRIs in mild-moderate depression - Blumenthal studies. Resistance training also helps)

Light therapy: 10,000 lux light box 30 min each morning (proven for seasonal affective disorder, also helps non-seasonal depression. Critical for winter depression)

Sleep optimization: Address insomnia (CBT-I, sleep hygiene, melatonin 1-3mg if needed), consistent sleep schedule, 7-9 hours (sleep deprivation worsens depression, but also symptom of depression)

Mediterranean diet: Anti-inflammatory diet associated with lower depression risk (SMILES trial - diet intervention reduced depression)

Psychotherapy: CBT most evidence-based (cognitive-behavioral therapy - changes thought patterns, behavior activation), IPT (interpersonal therapy), ACT (Acceptance and Commitment Therapy). Therapy + lifestyle often as effective as medications for mild-moderate

TMS: Transcranial magnetic stimulation (FDA-approved for treatment-resistant depression, non-invasive brain stimulation, 4-6 week daily treatment course, 50%+ response rate)

Ketamine: IV ketamine or intranasal esketamine (Spravato) for treatment-resistant depression (rapid antidepressant effects within hours, 70% response rate, requires medical setting, series of 6 infusions or twice-weekly intranasal)

Acupuncture: Some evidence for depression (comparable to SSRIs in some trials)

Mind-body: Meditation, yoga (reduce stress, improve mood), MBSR (Mindfulness-Based Stress Reduction)

Social connection: Loneliness is major depression risk - reconnect with friends, support groups, therapy groups, volunteering

Avoid: Alcohol (depressant, worsens depression despite temporary relief), excessive caffeine (anxiety, sleep disruption), isolation (worsens depression), rumination (therapy addresses)

Taper SSRIs if using: Work with prescriber - slow taper (10-25% dose reduction every 2-4 weeks), add natural support, monitor closely (withdrawal and relapse risks)