What Is Endogenous Depression?

As the scientific community learns more about mental disorders and how to treat them, diagnostic and treatment criteria change. 

You won’t find endogenous depression in the most recent edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) because the term and concepts are somewhat outdated. However, this doesn’t necessarily mean everyone has stopped using the term.

If you or a loved one was diagnosed with endogenous depression in the past, you might wonder what this shift in understanding means for you. Let’s unpack it together.

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Endogenous depression: a focus on the cause

In the late 1920s and early 1930s, psychiatrists began debating whether all forms of depression could be grouped together as a single disorder. They also posited whether there was a difference between psychotic or endogenous depression and neurotic or reactive depression.¹

World War II dampened the debate, but it surfaced again in the 1960s and 1970s. The dualistic view emerged triumphant and shaped the understanding of depression in the following decades. 

At this point in our little history lesson, you might feel more confused than when we started. Don’t worry; you’re not alone. The terminology is confusing and has evolved over time. 

The terms psychotic and endogenous depression are no longer understood as they were in the 1930s. Over time, scientists ungrouped psychotic depression and endogenous depression. Psychotic depression took on the definition of severe depression accompanied by delusions and hallucinations. 

The term endogenous depression initially described the “cause” of the depression. More recently, endogenous depression or melancholia refers to a subtype of depressive symptoms related to an inability to experience pleasure (anhedonia). Researchers have used reactive depression interchangeably with exogenous depression. 

Let’s keep it simple here and stick to the terms “endogenous” and “exogenous” depression. 

What is the difference between endogenous and exogenous depression?

In the endogenous/exogenous paradigm, the cause of depression is either internal biological factors (endogenous) or external factors (exogenic). 

Endogenous depression appears seemingly without reason as a result of a “chemical imbalance,” while exogenous depression is a response to environmental factors. Whether or not a perceived stressor preceded the depressive episode was the basis of the diagnosis. 

This model has no interplay between biological, social, and psychological factors. As such, the theory was that patients with endogenous depression should take antidepressants to correct their brain chemistry, while patients with exogenous depression should undergo psychotherapy.

When scientists conceived the model, the idea that life events could alter fundamental biochemistry seemed far-fetched.   

What diagnosis has replaced endogenous depression?

Doctors who might previously have diagnosed you with endogenous depression would now most likely diagnose you with major depressive disorder (MDD). 

The current understanding of depression acknowledges the cause as a complex interplay of biological, physiological, psychological, and social factors. The current edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) takes an approach to depression that doesn’t differentiate subtypes of depression. 

What are the symptoms of a major depressive episode?

According to the DSM-5-TR, you need to experience five or more symptoms of depression within two weeks for a clinical diagnosis of a major depressive episode. At least one of these symptoms needs to be either a depressed mood or loss of interest or pleasure in activities that you previously found enjoyable. 

The secondary symptoms are:

  • Appetite or weight changes

  • Sleep difficulties (too much or too little sleep)

  • Psychomotor agitation (purposeless and restless movements) or retardation (difficulty starting or completing daily tasks)

  • Fatigue or loss of energy

  • Diminished ability to think or concentrate

  • Feelings of worthlessness or excessive guilt

  • Suicidality (persistent thoughts about death or hurting yourself)

To establish the severity of your depression — mild, moderate, or severe — your healthcare provider will likely use a depression rating scale such as the Hamilton Depression Rating Scale. 

What are the risk factors for major depressive disorder?

A risk factor increases your chances of developing a particular condition. If you have many risk factors, you are more likely to develop the illness. The risk factors for depression are wide-ranging, and you can modify some but not others. The risk factors for depression include:

  • Genetic predisposition

  • Chronic stress

  • Stressful life events such as the loss of a loved one, job, or divorce

  • History of trauma — physical, emotional, or sexual — especially during childhood

  • Being female (females are twice as likely to experience depression than males)

  • An unhealthy diet high in processed foods and sugar

  • Certain prescription medications, such as corticosteroids and beta-blockers

  • Use of alcohol, nicotine, and recreational drugs

  • Head injuries

  • Neurodegenerative diseases, such as Alzheimer’s or Parkinson’s

  • Living with chronic pain

  • Certain medical conditions, such as diabetes, cardiovascular disease, or hypertension

  • Other mental illnesses, such as anxiety or personality disorders

  • A lack of social support

  • Excessive screen time

How is major depressive disorder treated?

There is no one-size-fits-all treatment for major depressive disorder. Because the causes of depression are varied, complex, and interconnected, treatments that work for one person might not work for another. 

While most cases of major depressive disorder are treatable, there are, unfortunately, individuals who develop treatment-resistant depression (TRD). This condition does not respond well to any of the existing treatment options. 

For the most part, doctors treat the major depressive disorder with medication, psychotherapy, or a combination of the two. In some treatment-resistant cases, they may also use neuro-stimulation treatments such as electroconvulsive therapy and vagus nerve stimulation. 


Antidepressant medications change the availability of certain neurotransmitters (chemicals that carry messages between brain cells) in the brain. Among other things, serotonin, dopamine, and norepinephrine affect mood, appetite, sleep, energy levels, motivation, and attention.²

The most common antidepressants are:

  • Selective serotonin reuptake inhibitors (SSRIs)

  • Serotonin-norepinephrine reuptake inhibitors (SNRIs) 

  • Norepinephrine-dopamine reuptake inhibitors (NDRIs)

Older classes of antidepressants known as tricyclics and monoamine oxidase inhibitors (MAOIs) are associated with more side effects. Doctors sometimes still prescribe them if newer antidepressants are ineffective. 

Pharmaceutical companies are also developing new antidepressants that may be more effective than existing therapies. For example, research has found that esketamine in nasal spray form rapidly relieves depressive symptoms in people with treatment-resistant depression.³

Antidepressants take time to work. You may need to take an antidepressant for four to eight weeks before you see an improvement in your symptoms. As your body adjusts, some antidepressants might cause unpleasant side effects such as headaches, nausea, and vomiting. 

For this reason, your doctor may start you on a low dose and gradually increase the dose according to your tolerance. It is important to take the medication as directed and not stop it abruptly if you feel it isn’t working. If one class of antidepressants isn’t working, your doctor may prescribe a different one.


When you have depression, you can get caught up in unhelpful thinking and behavior patterns that reinforce your symptoms. Psychotherapy can help you identify and change these patterns.

One of the most regularly used therapies for people with depression is cognitive behavior therapy (CBT). Instead of focusing on the past, cognitive behavioral therapy focuses on the present and how you can change current patterns of thinking and behavior. 

A therapist will help you recognize distortions in your thinking and teach you problem-solving skills to better cope with difficult situations. Cognitive behavior therapy aims to equip you with the knowledge and skills necessary to recognize and change unhelpful thinking and behaviors. 

Neuro-stimulation therapies

Neuro-stimulation therapies typically take place in hospital settings, making them less accessible than antidepressant medications and psychotherapy. 

However, in people with treatment-resistant depression, research has shown electroconvulsive therapy (ECT) to be very effective, with 30% of patients going into remission after six ECT sessions.⁴

During ECT, you’ll be under anesthetic, and the technician passes small electric currents through your brain, triggering a seizure that changes brain chemistry. Side effects can include disorientation, impaired learning, and retrograde amnesia (memory loss). While this sounds terrifying, the side effects of ECT usually resolve after a short period. 

How can I better manage my depression? 

While doctors can treat depression, they can’t cure it, and many people experience recurrent depressive episodes. This can lead to a sense of helplessness, but that doesn’t mean you are helpless.

In addition to following your prescribed treatment regimen, you can make lifestyle changes to manage your depression better. These include:

  • Reconnect with nature: Spending time in nature can boost your mood.⁵

  • Regular physical activity: Exercise releases endorphins, making you feel good.

  • Meditation and mindfulness: Even a few minutes of meditation a day can help. 

  • Get enough sleep: Sleep is essential for mental well-being. 

  • Watch your diet: Opt for a diet high in fruits, vegetables, whole grains, and fish.

  • Social connection: Spending time with loved ones can improve your resilience.

How can I get help? 

Depression is one of the leading causes of disability globally because it interferes with daily functioning. For some people, having depression means being unable to work or maintain relationships. 

For others, it can be life-threatening; depression significantly increases your risk of suicide. Globally, almost a million people commit suicide every year, and a far greater number (approximately 20 million people) attempt to take their lives but do not succeed.⁶

If you suspect you have depression, make an appointment to see your healthcare provider as soon as possible. You can also seek help via one of these sources:

  • Suicide & Crisis Lifeline: Call or text 988 for confidential support

  • Crisis Text Line: Text “hello” to 741741 to connect with a crisis counselor who can provide you with support and helpful information

  • Veterans Crisis Line: Call 1-800-273-TALK, and press 1, or text 838255

The lowdown

Depression is no longer defined as being endogenous (internal cause) or exogenous (external cause). The medical community now considers the terms and model to be outdated. 

Currently, scientists believe depression results from a complex interplay between biological, physiological, psychological, and social factors. What would previously have been diagnosed as endogenous depression is now diagnosed as a major depressive disorder. Medical professionals treat it with medication, psychotherapy, neurostimulation therapy, or a combination.

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