Best Medications for Major Depressive Disorder (MDD): SSRIs, SNRIs, and More

Major Depressive Disorder (MDD) is one of the most common mental health conditions—and one of the most treatable. Whether you’re newly diagnosed or seeking a better treatment fit, understanding your medication options is a key step in recovery.

At Dignity Brain Health, we provide personalized, evidence-based psychiatric medication management through telehealth in Massachusetts, New Hampshire, and Florida, with a special focus on Boston-area communities like Brookline, Cambridge, Newton, Somerville, and Back Bay.

Let’s break down the most effective medications for MDD, what to expect when starting treatment, and how to get help—online and on your terms.

What Is Major Depressive Disorder (MDD)?

MDD is more than feeling sad or tired. It's a serious clinical condition characterized by:

  • Persistent low mood or hopelessness

  • Loss of interest in activities once enjoyed

  • Sleep disturbances or appetite changes

  • Difficulty concentrating or making decisions

  • Feelings of worthlessness or guilt

According to the National Institute of Mental Health (NIMH), over 21 million U.S. adults experienced major depression in 2021 alone.

How Medication Helps

Psychiatric medications target brain chemistry to help relieve the symptoms of depression. They may:

  • Improve mood, energy, and focus

  • Reduce negative thinking

  • Improve sleep and appetite

  • Restore function in daily life

At Dignity Brain Health, our experienced providers—including mental health nurse practitioners—create customized treatment plans, with or without therapy, depending on your needs.

Most Effective Medications for Depression

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs are often the first-line treatment for MDD due to their proven efficacy and relatively low side effect profile.

Common SSRIs:

  • Sertraline (Zoloft)

  • Fluoxetine (Prozac)

  • Escitalopram (Lexapro)

  • Citalopram (Celexa)

SSRIs work by increasing the amount of serotonin available in the brain, a neurotransmitter that regulates mood and emotion.

📖 Scientific Evidence:
Cipriani et al. (2018) analyzed 522 trials and found SSRIs among the most effective and tolerable treatments for major depression.

“SSRIs showed favorable efficacy and acceptability compared with placebo.”
(Cipriani et al., 2018)

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs work on both serotonin and norepinephrine and are often used if SSRIs aren’t fully effective—especially in patients with fatigue or chronic pain.

Common SNRIs:

  • Venlafaxine (Effexor XR)

  • Duloxetine (Cymbalta)

📖 Scientific Evidence:
Thase et al. (2005) found that SNRIs offer higher remission rates for certain patients, especially those with physical symptoms alongside depression.

Atypical Antidepressants

These medications act on other neurotransmitters and are used when SSRIs/SNRIs cause side effects or don’t provide enough relief.

Common Atypicals:

  • Bupropion (Wellbutrin) – stimulating, good for low motivation or sexual side effects

  • Mirtazapine (Remeron) – sedating, ideal for insomnia or appetite issues

📖 Scientific Evidence:
Papakostas et al. (2006) found bupropion to be equally effective as SSRIs, with fewer sexual side effects, making it a strong alternative option.

Tricyclic Antidepressants (TCAs)

TCAs are older antidepressants sometimes used in treatment-resistant depression or when other medications fail.

Examples:

  • Amitriptyline

  • Nortriptyline (Pamelor)

While effective, TCAs tend to have more side effects, including dry mouth, dizziness, and weight gain.

📖 Scientific Evidence:
Anderson (2000) reported TCAs as effective in severe depression, though they are less tolerated compared to newer medications.

Augmentation and Advanced Options

Some patients may benefit from add-on treatments, especially in treatment-resistant cases:

  • Atypical antipsychotics (e.g., aripiprazole/Abilify)

  • Esketamine nasal spray (Spravato)

  • Genetic testing to match you with the right medication (learn more here)

What to Expect When Starting Medication

How Long Do Antidepressants Take to Work?

Most medications begin working within 2–4 weeks, with full benefits at 6–8 weeks. It’s important to stay consistent and keep your follow-up appointments.

Common Side Effects

Side effects usually improve over time and may include:

  • Nausea or upset stomach

  • Fatigue or insomnia

  • Sexual side effects

  • Headache

  • Dry mouth

If side effects are severe or persistent, your provider may adjust your dosage or recommend a different medication.

Monitoring and Check-Ins

We provide ongoing virtual follow-ups to monitor:

  • Effectiveness of medication

  • Side effects or mood changes

  • Dose adjustments or switching strategies

Your plan is reviewed regularly to ensure the best possible outcome.

Frequently Asked Questions

Can I get antidepressants online in Massachusetts?

Yes. At Dignity Brain Health, we offer HIPAA-compliant online psychiatric care across the Commonwealth—including Cambridge, Brookline, Newton, Somerville, and Back Bay.

Do I need therapy to get medication?

Not necessarily. While therapy can be very helpful, we also support medication-only treatment based on your preference and symptoms.

Will antidepressants change my personality?

The goal is to help you feel more like yourself—not less. Many patients report feeling more motivated, hopeful, and emotionally balanced.

Local Mental Health Resources in Massachusetts

We encourage you to explore these valuable supports:

  • NAMI Massachusetts – Peer-led support and education

  • Massachusetts Department of Mental Health – Public mental health services

  • McLean Hospital – Leading psychiatric hospital affiliated with Harvard Medical School

  • Samaritans Boston – 24/7 emotional support and crisis help

How Dignity Brain Health Can Support You

  • 🌐 Tele‑psychiatry Medication Management: Accessible from anywhere in MA, including Brookline, Cambridge, Newton, Somerville, Back Bay, as well as New Hampshire (NH), and Florida (FL).

  • 👩‍⚕️ Certified psychiatric clinicians tailor meds, monitor progress, and adjust as needed.

  • 🧬 Genetic testing services to help select effective medications faster.

  • 📅 Flexible online scheduling —start your onboarding process here.

👉 Start your your online psychiatric medication consultation process now

Learn more:
Medication Management in Massachusetts
Our Team & Approach

🔍 References (APA Format)

Anderson, I. M. (2000). Selective serotonin reuptake inhibitors versus tricyclic antidepressants: A meta-analysis of efficacy and tolerability. Journal of Affective Disorders, 58(1), 19–36. https://doi.org/10.1016/S0165-0327(99)00092-0

Cipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., ... & Geddes, J. R. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis. The Lancet, 391(10128), 1357–1366. https://doi.org/10.1016/S0140-6736(17)32802-7

Papakostas, G. I., Thase, M. E., Fava, M., Nelson, J. C., & Shelton, R. C. (2006). A meta-analysis of clinical trials comparing bupropion with selective serotonin reuptake inhibitors for the treatment of major depressive disorder. Biological Psychiatry, 59(7), 636–642. https://doi.org/10.1016/j.biopsych.2005.08.022

Thase, M. E., Entsuah, A. R., & Rudolph, R. L. (2005). Remission rates during treatment with venlafaxine or SSRIs. British Journal of Psychiatry, 187(4), 342–347. https://doi.org/10.1192/bjp.187.4.342

Kristina BelarminoDignity Brain Health