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Supported by multiple clinical trials and systematic reviews

Depression (Major Depressive Disorder)

Depression (Major Depressive Disorder, MDD) is a common, potentially severe mood disorder marked by persistent low mood and/or loss of interest or pleasure, along with changes in sleep, appetite, energy, concentration, and thoughts of worthlessness or suicide. In Western medicine, MDD is diagnosed using DSM-5 criteria: at least five of nine symptoms present for two weeks or more, causing distress or impairment, with one being depressed mood or anhedonia, and not better explained by substances, a medical condition, or bipolar disorder. Severity ranges from mild to severe and may include specifiers (e.g., melancholic, peripartum, seasonal). Effective care is guided by symptom severity, patient preference, medical comorbidities, and past treatment response. Western approaches are highly evidence-based. Psychotherapies such as cognitive behavioral therapy (CBT), behavioral activation (BA), and interpersonal therapy (IPT) have strong support, particularly for mild to moderate depression; BA can be as effective as CBT and is often more scalable. First-line medications include selective serotonin reuptake inhibitors (SSRIs) like sertraline and escitalopram due to favorable tolerability; serotonin–norepinephrine reuptake inhibitors (SNRIs) are also common. Alternatives such as bupropion or mirtazapine can be chosen based on symptom profile (e.g., low energy or insomnia). In treatment-resistant depression (often defined after at least two adequate medication trials), evidence-based options include augmentation strategies (e.g., lithium or certain atypical antipsychotics), electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), and ketamine/esketamine. A stepped-care model is widely endorsed: start with low-intensity interventions for mild cases, step up to combined psychotherapy and pharmacotherapy as needed, and use somatic treatments for resistant or severe illness—always with ongoing symptom monitoring (e.g., PHQ-9) and safety checks. In “e

Mental health Updated February 19, 2026

This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication regimen.

Western Medicine

Diagnosis

DSM-5 MDD: Five or more symptoms during the same 2-week period, representing a change from previous functioning, with at least one being depressed mood or loss of interest/pleasure. Other symptoms include significant weight/appetite change, sleep disturbance, psychomotor changes, fatigue, feelings of worthlessness/excessive guilt, diminished concentration/indecisiveness, and recurrent thoughts of death or suicidal ideation/behavior. Symptoms cause clinically significant distress/impairment, are not attributable to a substance/medical condition, and there is no history of manic or hypomanic episodes (unless substance/medically induced).

Treatments

  • Stepped-care model (guided self-help/low-intensity therapy for mild cases; psychotherapy and/or antidepressants for moderate; combined/augmented strategies and somatic treatments for severe or resistant cases)
  • Psychotherapies: CBT, Behavioral Activation (BA), Interpersonal Therapy (IPT), Problem-Solving Therapy
  • First-line pharmacotherapy: SSRIs (sertraline, escitalopram)
  • Alternative/next-line antidepressants: SNRIs (venlafaxine, duloxetine), bupropion, mirtazapine, vortioxetine
  • Augmentation for partial/nonresponse: lithium; atypical antipsychotics (e.g., aripiprazole, quetiapine XR); thyroid hormone (selected cases)
  • Somatic treatments for treatment-resistant depression: ECT, rTMS
  • Rapid-acting options for resistant cases: ketamine (IV) and intranasal esketamine (Spravato) with monitoring
  • Collaborative care models in primary care; measurement-based care (e.g., PHQ-9 tracking)
  • Lifestyle supports: sleep regularity, structured exercise, substance-use reduction; management of comorbidities

Medications

  • SSRIs: sertraline, escitalopram, fluoxetine, citalopram, paroxetine
  • SNRIs: venlafaxine, desvenlafaxine, duloxetine, levomilnacipran
  • Atypical antidepressants: bupropion, mirtazapine, vortioxetine, vilazodone
  • Augmentation: lithium; aripiprazole, quetiapine XR, brexpiprazole; liothyronine (selected)
  • Somatic/rapid-acting: ketamine (IV), intranasal esketamine (Spravato)

Limitations

Up to one-third of patients have inadequate response to first-line treatment; residual symptoms and relapse are common. Antidepressants can cause side effects (e.g., GI upset, sexual dysfunction, sleep changes) and may increase suicidal thoughts in some adolescents/young adults early in treatment. ECT requires anesthesia and may cause transient cognitive effects; rTMS and ketamine/esketamine require specialized access and monitoring. Adherence, cost, and availability can limit outcomes.

Evidence: Strong Evidence

Sources

  • American Psychiatric Association. Practice Guideline for the Treatment of Patients With Major Depressive Disorder (2020 update).
  • NICE Guideline NG222: Depression in adults: treatment and management (2022/2023).
  • Rush AJ et al. STAR*D trial: Am J Psychiatry. 2006;163:1905-1917.
  • Richards DA et al. Behavioral activation vs CBT: Lancet. 2016;388:871-880.
  • UK ECT Review Group. Lancet. 2003;361:799-808.
  • O’Reardon JP et al. rTMS for MDD: Biol Psychiatry. 2007;62:1208-1216.
  • Daly EJ et al. Esketamine in TRD: JAMA Psychiatry. 2018;75:139-148.

Eastern & Traditional Medicine

Traditional Chinese Medicine (TCM)

Frames depression as disharmony among organ systems and qi. Common patterns include liver qi stagnation (mood lability, irritability, chest/abdominal distension), heart blood deficiency (insomnia, palpitations, anxiety), and kidney yang deficiency (low energy, coldness, demoralization). Treatment aims to move liver qi, nourish heart blood/spirit (shen), and tonify kidney to restore balance.

Techniques

  • Acupuncture (e.g., points chosen for pattern such as LR3, PC6, HT7, DU20)
  • Chinese herbal formulas individualized to pattern (e.g., Xiao Yao San, Chai Hu Shu Gan San, Gan Mai Da Zao Tang)
  • Qigong/taiji, diet and lifestyle guidance
Licensed acupuncturist (L.Ac.)/Oriental medicine practitioner TCM herbalist Integrative physician trained in TCM
Evidence: Emerging Research

Acupuncture (focused)

Adjunctive acupuncture may reduce depressive symptoms and can be combined with usual care. Evidence suggests modest benefits versus usual care; comparative efficacy versus sham varies across trials.

Techniques

  • Manual acupuncture
  • Electroacupuncture
  • Course-based treatment (e.g., 1–3 sessions/week for several weeks)
Licensed acupuncturist (L.Ac.) Medical acupuncturist (physician)
Evidence: Moderate Evidence

Herbal medicine – St. John’s Wort (Hypericum perforatum)

For mild to moderate depression, standardized Hypericum extracts perform better than placebo and comparably to SSRIs in many European trials, with fewer adverse effects. However, it induces CYP3A4 and P-glycoprotein, causing numerous drug interactions.

Techniques

  • Standardized extract under clinician supervision
  • Avoid combination with serotonergic antidepressants and interacting drugs
Integrative/primary care physician Naturopathic doctor (ND) Clinical herbalist Pharmacist for interaction screening
Evidence: Strong Evidence

Ayurveda

Depression is viewed as imbalance among doshas (often kapha/tamas with vata involvement). Care includes satvavajaya (mind-based therapy), diet/lifestyle (dinacharya), meditation/pranayama, and selected herbs. Evidence for specific herbs in depression is emerging; stronger data exist for anxiety/stress overlap.

Techniques

  • Herbal formulations such as Brahmi (Bacopa monnieri) for cognition/mood support
  • Withania somnifera (Ashwagandha) for stress/anxiety with secondary mood benefits
  • Abhyanga (oil massage), routine regularization, meditation/pranayama, yoga
Ayurvedic practitioner (BAMS/AYP) Integrative physician ND
Evidence: Emerging Research

Sources

  • Smith CA et al. Acupuncture for depression. Cochrane Database Syst Rev. 2018;CD004046.
  • NCCIH. Traditional Chinese Medicine: An Introduction (overview).
  • Linde K et al. St John’s wort for major depression. Cochrane Database Syst Rev. 2008;CD000448 (and updates).
  • NCCIH. St. John’s Wort and Depression (fact sheet).
  • Ng QX et al. Withania somnifera for anxiety/stress: Systematic review. Medicine (Baltimore). 2020;99:e21731.
  • Stough C et al. Bacopa monnieri and cognition/mood: Hum Psychopharmacol. 2001;16:345-351.

Integrative Perspective

A pragmatic integrative plan pairs evidence-based psychotherapy (CBT, BA, or IPT) with selected complementary options for symptom relief and self-regulation. For mild to moderate depression, combining therapy with acupuncture, structured yoga (asana plus breathwork), or, where appropriate, St. John’s Wort or saffron may improve outcomes and acceptability. For moderate to severe or treatment-resistant depression, prioritize guideline-concordant care (optimized antidepressants, augmentation, ECT/rTMS, or esketamine) and layer mind-body practices for coping and functional gains. Use measurement-based care (e.g., PHQ-9) to track response. Safety is paramount: Do not combine St. John’s Wort with SSRIs/SNRIs, MAOIs, or other serotonergic agents due to serotonin syndrome risk; it can also reduce effectiveness of oral contraceptives and interact with anticoagulants (e.g., warfarin), transplant drugs (e.g., cyclosporine), HIV medications, and others—pharmacist review is essential. SAMe may precipitate mania in bipolar disorder; screen for bipolarity before any antidepressant strategy. Coordination among prescribers and complementary practitioners helps avoid interactions and ensures consistent monitoring. Severe depression, suicidality, psychotic features, or marked functional decline require prompt professional treatment and close follow-up. If there is imminent risk of self-harm, contact emergency services or local crisis lines immediately.

Sources

  1. American Psychiatric Association. Practice Guideline for the Treatment of Patients With Major Depressive Disorder (2020 update).
  2. NICE Guideline NG222: Depression in adults: treatment and management (2022/2023).
  3. Rush AJ et al. STAR*D: Am J Psychiatry. 2006;163:1905-1917.
  4. Richards DA et al. Behavioral activation vs CBT: Lancet. 2016;388:871-880.
  5. UK ECT Review Group. Lancet. 2003;361:799-808.
  6. O’Reardon JP et al. rTMS for MDD: Biol Psychiatry. 2007;62:1208-1216.
  7. Daly EJ et al. Esketamine in TRD: JAMA Psychiatry. 2018;75:139-148.
  8. Linde K et al. St John’s Wort for major depression. Cochrane Database Syst Rev. 2008;CD000448 (and updates).
  9. Smith CA et al. Acupuncture for depression. Cochrane Database Syst Rev. 2018;CD004046.
  10. Cramer H et al. Yoga for depression: J Affect Disord. 2013;150:1059-1069; and Depress Anxiety. 2017;34:846-857.
  11. Lopresti AL, Drummond PD. Saffron for depression: J Integr Med. 2014;12:197-204.
  12. Papakostas GI et al. SAMe augmentation RCT: Am J Psychiatry. 2010;167:942-948.
  13. NCCIH. St. John’s Wort and Depression (accessed 2026).

Health Disclaimer

This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication regimen.