Major depressive disorder can have symptoms that are physical, mental and emotional, including:¹

• Lasting feelings of sadness, anxiety or emptiness/numbness.

• Loss of interest in activities. 

• Appetite and weight changes.

• Changes in sleep patterns.

• Slowing of physical activity, speech and thinking. 

• Agitation, increased restlessness and irritability.

• Decreased energy, feeling tired or "slowed down" almost every day.

• Ongoing feelings of worthlessness and/or feelings of undue guilt.

• Trouble concentrating or making decisions.

• Repeating thoughts of death or suicide, wishing to die or attempting suicide.

If you are experiencing suicidal thoughts or thoughts of harming yourself, please seek emergency medical services (ER); call 911; or call 988, the Suicide and Crisis Lifeline.

The Beck Depression Inventory (BDI) is a tool for self-reporting depression symptoms and characteristics.² It includes 21-item inventory that measures characteristic attitudes and symptoms of depression. Participants are asked to rate each item on a scale of four choices ranging from absence of symptom to an intense level.³

One depressive episode from major depressive disorder can last six to 12 months if left untreated. Major depressive disorder is a chronic condition that is highly likely to return in people with one episode. The risk of a recurring episode increases with each episode. The risk for repeat episodes increases 50% after one episode, 70% after second episode and 90% after a third episode.⁴

Fatigue or tiredness is one of the most prominent symptoms of major depressive disorder. Most patients diagnosed with major depressive disorder report fatigue as a symptom. It is also the second most prominent residual symptom after a major depressive episode.⁵

Major depressive disorder is one of the leading causes of disability worldwide. Left untreated, major depressive disorder can cause functional impairment, complicate relationships and increase risk of other conditions like anxiety disorders, substance use disorders, diabetes, hypertension, chronic obstructive pulmonary disease and coronary artery disease.⁶

Sometimes debilitating depression is recognized with other names like crippling, severe or overwhelming depression. Any depression that affects your ability to function could be classified as a disability.⁷

Persistent depressive disorder is a newer term in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) for a condition previously called chronic major depression or dysthymia. A person can meet the diagnostic criteria for both major depressive disorder and persistent depressive disorder. The main factor that sets major depressive disorder apart from persistent depressive disorder is the presence of a depressed mood for at least two years with no absence of symptoms for more than two months. To qualify as major depressive disorder, there also must be a presence of at least two of the following symptoms:⁸

1. Poor appetite or overeating.

2. Insomnia or hypersomnia.

3. Low energy/fatigue.

4. Low self-esteem.

5. Poor concentration/decision making.

6. Hopelessness.

The neurotransmitters most associated with major depressive disorder are dopamine, norepinephrine and serotonin.⁹ 

Major depressive disorder with psychotic features is when depression symptoms are accompanied by hallucinations, delusions or both. Nearly 18.5% of people with major depressive disorder will experience psychotic features.¹⁰

If you are experiencing hallucinations, delusions, suicidal thoughts or thoughts of self-harm, please seek medical attention immediately, or call 911 or the crisis hotline at 988.

1. John Hopkins

2. American Psychological Association

3. ScienceDirect

4. National Library of Medicine

5. National Library of Medicine

6. National Library of Medicine

7. PsychCentral

8. National Library of Medicine

9. National Library of Medicine

10. National Library of Medicine

Medication can be part of your treatment plan for major depressive disorder. Commonly prescribed medications include:

• Selective serotonin reuptake inhibitors (SSRIs): Fluoxetine (Prozac®), paroxetine (Paxil®), sertraline (Zoloft®), citalopram (Celexa®) and escitalopram (Lexapro®).

• Serotonin and norepinephrine reuptake inhibitors (SNRIs): Duloxetine (Cymbalta®), venlafaxine ER (Effexor XR®), desvenlafaxine (Pristiq®) and levomilnacipran (Fetzima®).

• Atypical antidepressants: Bupropion (Wellbutrin®), trazodone (Desyrel®), mirtazapine (Remeron®), vortioxetine (Trintellix®) and vilazodone (Viibryd®).

• Tricyclic antidepressants: Imipramine, nortriptyline (Pamelor®), amitriptyline (Elavil®), doxepin and desipramine (Norpramin®).

One of the newest FDA-approved medications for major depressive disorder is gepirone hydrochloride extended-release tablets, brand name EXXUA. This drug is the first oral selective 5HT1A receptor agonist approved by the FDA to treat major depressive disorder. It has been shown in clinical trials to be effective at treating mood and depression symptoms without the sexual side effects that often accompany other antidepressants. The drug should be available for prescription in 2024.¹² 

RedBox Rx does not offer EXXUA at this time. 

There are currently no FDA-approved medications available over the counter for major depressive disorder.¹³ 

You can get major depressive disorder medication from a licensed medical provider or doctor. You can visit in-person or you can get online medication for major depressive disorder with a telehealth provider like RedBox Rx. Start an online consult to see if medication is right for you.

11. Cleveland Clinic

12. Psychiatric Times

13. FDA