Evidence-Based Treatment for Depression

Overview

Depression is highly treatable. Approximately 80-90% of people with depression eventually respond well to treatment. The most effective approaches include psychotherapy, medication, or a combination of both.

Treatment choice depends on severity, prior treatment history, patient preference, and availability of resources. Mild depression often responds to psychotherapy alone, while moderate-to-severe depression typically benefits from combined therapy and medication.

Psychotherapy

Evidence-based psychotherapies show large effect sizes comparable to medication for mild-to-moderate depression, with benefits that persist after treatment ends.

• First-Line

  Cognitive Behavioral Therapy (CBT)

  CBT identifies and modifies negative thought patterns and maladaptive behaviors. Structured, goal-oriented, typically 12-16 sessions. Meta-analyses show 50-60% response rates with lasting benefits.

  Core components: Cognitive restructuring, behavioral activation, problem-solving, relapse prevention.

• First-Line

  Interpersonal Therapy (IPT)

  Focuses on improving interpersonal relationships and communication. Particularly effective for depression triggered by life transitions, grief, role disputes, or social isolation. Typically 12-16 sessions.

  Targets: Grief, role transitions, role disputes, interpersonal deficits.

• Evidence-Based

  Behavioral Activation (BA)

  Increases engagement in rewarding activities to counter avoidance and withdrawal. Simpler than CBT, shown to be equally effective for depression. 8-12 sessions.

  Focus: Activity scheduling, values-based action, reducing avoidance behaviors.

• Adjunctive

  Mindfulness-Based Cognitive Therapy (MBCT)

  Combines mindfulness meditation with CBT principles. Particularly effective for preventing relapse in recurrent depression. 8-week group program.

  Relapse reduction: 43% reduction in relapse risk for those with 3+ prior episodes.

Antidepressant Medications

Medications are most effective for moderate-to-severe depression. Typically take 4-6 weeks for full therapeutic effect. All medication decisions should be made with a prescribing physician.

First-Line Medications

Second-Line & Atypical Antidepressants

• Bupropion (Wellbutrin) — Dopamine/norepinephrine reuptake inhibitor. Lower risk of sexual side effects and weight gain. Contraindicated in seizure disorders.
• Mirtazapine (Remeron) — Sedating, increases appetite. Useful for depression with insomnia and weight loss.
• Trazodone — Often used off-label for insomnia comorbid with depression.

Emerging & Advanced Treatments

For treatment-resistant depression (failure to respond to 2+ adequate medication trials), several advanced options show promise.

• FDA-Approved

  Transcranial Magnetic Stimulation (TMS)

  Non-invasive brain stimulation using magnetic pulses. FDA-approved for treatment-resistant depression. Daily sessions for 4-6 weeks. Response rates 50-60% in treatment-resistant patients.

  Advantages: Non-invasive, no anesthesia, few side effects (mild headache, scalp discomfort).

• FDA-Approved

  Electroconvulsive Therapy (ECT)

  Most effective treatment for severe, treatment-resistant, or psychotic depression. 80-90% response rate. Requires anesthesia. Modern ECT has minimal side effects; main concern is temporary memory disruption.

  Indications: Severe depression, psychotic features, acute suicide risk, catatonia.

• FDA-Approved (Nasal Spray)

  Esketamine (Spravato)

  Nasal spray ketamine derivative for treatment-resistant depression. Administered in clinical setting with monitoring. Rapid onset (hours to days vs weeks). Requires Risk Evaluation and Mitigation Strategy (REMS) program.

  Mechanism: NMDA receptor antagonist. Different from traditional antidepressants.

• Investigational

  Psilocybin-Assisted Therapy

  FDA Breakthrough Therapy designation for treatment-resistant depression. Phase 3 clinical trials showing promising results. Not yet approved for clinical use outside of research settings.

Lifestyle & Adjunctive Interventions

While not sufficient as sole treatment for moderate-to-severe depression, lifestyle changes enhance other treatments and prevent relapse:

• Exercise — 150 minutes/week of moderate aerobic activity shows antidepressant effects comparable to medication for mild depression.
• Sleep hygiene — Consistent sleep schedule, limiting screens before bed, creating optimal sleep environment.
• Social connection — Maintaining relationships, joining support groups, volunteering.
• Nutrition — Mediterranean diet patterns associated with reduced depression risk.
• Light therapy — 10,000 lux light box for 30 minutes daily. Particularly effective for seasonal affective disorder.

Treatment Selection