What is a Major Depressive Episode?


A major depressive episode (MDE) is a period characterised by the symptoms of major depressive disorder.

Sufferers primarily have a depressed mood for two weeks or more, and a loss of interest or pleasure in everyday activities, accompanied by other symptoms such as feelings of emptiness, hopelessness, anxiety, worthlessness, guilt and irritability, changes in appetite, problems concentrating, remembering details or making decisions, and thoughts of suicide. Insomnia or hypersomnia, aches, pains, or digestive problems that are resistant to treatment may also be present. The description has been formalized in psychiatric diagnostic criteria such as the DSM-5 and ICD-10.

Biological, psychological, and social factors are believed to be involved in the cause of depression, although it is still not well understood. Factors like socioeconomic status, life experience, and personality tendencies play a role in the development of depression and may represent increases in risk for developing a MDE. There are many theories as to how depression occurs. One interpretation is that neurotransmitters in the brain are out of balance, and this results in feelings of worthlessness and despair. Magnetic resonance imaging shows that brains of people who have depression look different than the brains of people not exhibiting signs of depression. A family history of depression increases the chance of being diagnosed.

Emotional pain and economic costs are associated with depression. In the United States and Canada, the costs associated with major depression are comparable to those related to heart disease, diabetes, and back problems and are greater than the costs of hypertension. According to the Nordic Journal of Psychiatry, there is a direct correlation between major depressive episode and unemployment.

Treatments for a major depressive episode include psychotherapy and antidepressants, although in more serious cases, hospitalization or intensive outpatient treatment may be required.

Signs and Symptoms

The criteria below are based on the formal DSM-V criteria for a major depressive episode. A diagnosis of major depressive episode requires that the patient has experienced five or more of the symptoms below, and one of the symptoms must be either depressed mood or loss of interest or pleasure (although both are frequently present). These symptoms must be present for at least 2 weeks and represent a change from the patient’s normal behaviour.

Depressed Mood and Loss of Interest (Anhedonia)

Either depressed mood or a loss of interest or pleasure must be present for the diagnosis of a MDE. Depressed mood is the most common symptom seen in major depressive episodes. Interest or pleasure in everyday activities can be decreased; this is referred to as anhedonia. These feelings must be present on an everyday basis for two weeks or longer to meet DSM-V criteria for a MDE. In addition, the person may experience one or more of the following emotions: sadness, emptiness, hopelessness, indifference, anxiety, tearfulness, pessimism, emotional numbness, or irritability. In children and adolescents, a depressed mood often appears more irritable in nature. There may be a loss of interest in or desire for sex, or other activities once found to be pleasant. Friends and family of the depressed person may notice that they have withdrawn from friends, or neglected or quit doing activities that were once a source of enjoyment.


Nearly every day, the person may sleep excessively, known as hypersomnia, or not enough, known as insomnia. Insomnia is the most common type of sleep disturbance for people who are clinically depressed. Symptoms of insomnia include trouble falling asleep, trouble staying asleep, or waking up too early in the morning. Hypersomnia is a less common type of sleep disturbance. It may include sleeping for prolonged periods at night or increased sleeping during the daytime. The sleep may not be restful, and the person may feel sluggish despite many hours of sleep, which may amplify their depressive symptoms and interfere with other aspects of their lives. Hypersomnia is often associated with an atypical depression, as well as seasonal affective disorder.

Feelings of Guilt or Worthlessness

Depressed people may have feelings of guilt that go beyond a normal level or are delusional. These feelings of guilt and/or worthlessness are excessive and inappropriate. MDE’s are notable for a significant, often unrealistic, drop in self-esteem. The guilt and worthlessness experienced in a MDE can range from subtle feelings of guilt to frank delusions or to shame and humiliation. Additionally, self-loathing is common in clinical depression, and can lead to a downward spiral when combined with other symptoms.

Loss of Energy

Persons going through a MDE often have a general lack of energy, as well as fatigue and tiredness, nearly every day for at least 2 weeks. A person may feel tired without having engaged in any physical activity, and day-to-day tasks become increasingly difficult. Job tasks or housework become very tiring, and the patient finds that their work begins to suffer.

Decreased Concentration

Nearly every day, the person may be indecisive or have trouble thinking or concentrating. These issues cause significant difficulty in functioning for those involved in intellectually demanding activities, such as school and work, especially in difficult fields. Depressed people often describe a slowing of thought, inability to concentrate and make decisions, and being easily distracted. In the elderly, the decreased concentration caused by a MDE may present as deficits in memory. This is referred to as pseudodementia and often goes away with treatment. Decreased concentration may be reported by the patient or observed by others.

Change in Eating, Appetite, or Weight

In a major depressive episode, appetite is most often decreased, although a small percentage of people experience an increase in appetite. A person experiencing a depressive episode may have a marked loss or gain of weight (5% of their body weight in one month). A decrease in appetite may result in weight loss that is unintentional or when a person is not dieting. Some people experience an increase in appetite and may gain significant amounts of weight. They may crave certain types of food, such as sweets or carbohydrates. In children, failure to make expected weight gains may be counted towards this criteria. Overeating is often associated with atypical depression.

Motor Activity

Nearly every day, others may see that the person’s activity level is not normal. People suffering from depression may be overly active (psychomotor agitation) or be very lethargic (psychomotor retardation). Psychomotor agitation is marked by an increase in body activity which may result in restlessness, an inability to sit still, pacing, hand wringing, or fidgeting with clothes or objects. Psychomotor retardation results in a decrease in body activity or thinking. In this case, a depressed person may demonstrate a slowing of thinking, speaking, or body movement. They may speak more softly or say less than usual. To meet diagnostic criteria, changes in motor activity must be so abnormal that it can be observed by others. Personal reports of feeling restless or feeling slow do not count towards the diagnostic criteria.

Thoughts of Death and Suicide

A person going through a MDE may have repeated thoughts about death (other than the fear of dying) or suicide (with or without a plan), or may have made a suicide attempt. The frequency and intensity of thoughts about suicide can range from believing that friends and family would be better off if one were dead, to frequent thoughts about committing suicide (generally related to wishing to stop the emotional pain), to detailed plans about how the suicide would be carried out. Those who are more severely suicidal may have made specific plans and decided upon a day and location for the suicide attempt.

Comorbid Disorders

MDE’s may show comorbidity (association) with other physical and mental health problems. About 20-25% of individuals with a chronic general medical condition will develop major depression. Common comorbid disorders include: eating disorders, substance-related disorders, panic disorder, and obsessive-compulsive disorder. Up to 25% of people who experience a major depressive episode have a pre-existing dysthymic disorder.

Some persons who have a fatal illness or are at the end of their life may experience depression, although this is not universal.


The cause of a MDE is not well understood. However, the mechanism is believed to be a combination of biological, psychological, and social factors. A MDE can often follow an acute stress in someone’s life. Evidence suggests that psychosocial stressors play a larger role in the first 1-2 depressive episodes, while having less influence in later episodes. People who experience a major depressive episode often have other mental health issues.

Other risk factors for a depressive episode include:

  • Family history of a mood disorder;
  • Recent negative life events;
  • Personality (insecure, worried, stress-sensitive, obsessive, unassertive, dependent);
  • Early childhood trauma;
  • Postpartum; and
  • Lack of interpersonal relationships.

One gene by itself has not been linked to depression. Studies show that depression can be passed down in families, but this is believed to be due to a combined effect of genetic and environmental factors. Other medical conditions, like hypothyroidism for example, may cause someone to experience similar symptoms as a MDE, however this would be considered a mood disorder due to a general medical condition, according to the DSM-V.



The two main symptoms in a major depressive episode are a depressed mood or a loss of interest or pleasure. From the list below, one bold symptom and four other symptoms must be present for a diagnosis of MDE. These symptoms must be present for at least 2 weeks and must be causing significant distress or impairment in functioning.

  • Depressed mood.
  • Loss of interest or pleasure.
  • Change in appetite.
  • Change in sleep.
  • Change in body activity (psychomotor changes).
  • Loss of energy.
  • Feelings of worthlessness and excessive or inappropriate guilt.
  • Indecisiveness or a decrease in concentration.
  • Suicidal ideation.

To diagnose a major depressive episode, a trained healthcare provider must make sure that:

  • The symptoms do not meet the criteria for a mixed episode.
  • The symptoms must cause considerable distress or impair functioning at work, in social settings or in other important areas in order to qualify as an episode.
  • The symptoms are not due to the direct physiological effects of a substance (e.g. abuse of a drug or medication) or a general medical condition (e.g. hypothyroidism).


No labs are diagnostic of a depressive episode. But some labs can help rule out general medical conditions that may mimic the symptoms of a depressive episode. Healthcare providers may order some routine blood work, including routine blood chemistry, CBC with differential, thyroid function studies, and Vitamin B12 levels, before making a diagnosis.

Differential Diagnosis

There are other mental health disorders or medical conditions to consider before diagnosing a MDE:

  • Bipolar disorder.
  • Cyclothymic disorder.
  • Disruptive mood dysregulation disorder.
  • Persistent depressive disorder.
  • Anxiety disorder (Generalised anxiety, PTSD, obsessive compulsive disorder).
  • Substance abuse or Substance Use Disorder.
  • Personality disorder with depressive symptoms.
  • Adjustment disorder.
  • Depression due to a general medical condition.
  • Premenstrual dysphoric disorder.


Healthcare providers may screen patients in the general population for depression using a screening tool, such as the Patient Healthcare Questionnaire-2 (PHQ-2). If the PHQ-2 screening is positive for depression, a provider may then administer the PHQ-9. The Geriatric Depression Scale is a screening tool that can be used in the elderly population.


Depression is a treatable illness. Treatments for a MDE may be provided by mental health specialists (i.e. psychologist, psychiatrists, social workers, counsellors, etc.), mental health centres or organisations, hospitals, outpatient clinics, social service agencies, private clinics, peer support groups, clergy, and employee assistance programmes. The treatment plan could include psychotherapy alone, antidepressant medications alone, or a combination of medication and psychotherapy.

For major depressive episodes of severe intensity (multiple symptoms, minimal mood reactivity, severe functional impairment), combined psychotherapy and antidepressant medications are more effective than psychotherapy alone. Meta-analyses suggest that the combination of psychotherapy and antidepressant medications is more effective in treating mild and moderate forms of depression as well, compared to either type of treatment alone. Patients with severe symptoms may require outpatient treatment or hospitalisation.

The treatment of a major depressive episode can be split into 3 phases:

  • Acute phase: the goal of this phase is to resolve the current major depressive episode.
  • Continuation: this phase continues the same treatment from the acute phase for 4-8 months after the depressive episode has resolved and the goal is to prevent relapse.
  • Maintenance: this phase is not necessary for every patient but is often used for patients who have experienced 2-3 or more MDE’s.
    • Treatment may be maintained indefinitely to prevent the occurrence and severity of future episodes.


Psychotherapy, also known as talk therapy, counselling, or psychosocial therapy, is characterised by a patient talking about their condition and mental health issues with a trained therapist. Different types of psychotherapy are used as a treatment for depression. These include cognitive behavioural therapy, interpersonal therapy, dialectical behaviour therapy, acceptance and commitment therapy, and mindfulness techniques. Evidence shows that cognitive behavioural therapy can be as effective as medication in the treatment of a MDE.

Psychotherapy may be the first treatment used for mild to moderate depression, especially when psychosocial stressors are playing a large role. Psychotherapy alone may not be as effective for more severe forms of depression.

Some of the main forms of psychotherapies used for treatment of a major depressive episode along with what makes them unique are included below:

  • Cognitive psychotherapy: focus on patterns of thinking.
  • Interpersonal psychotherapy: focus on relationships, losses, and conflict resolution.
  • Problem-solving psychotherapy: focus on situations and strategies for problem-solving.
  • Psychodynamic psychotherapy: focus on defence mechanisms and coping strategies.


Medications used to treat depression include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), norepinephrine-dopamine reuptake inhibitors (NDRIs), tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), and atypical antidepressants such as mirtazapine, which do not fit neatly into any of the other categories. Different antidepressants work better for different individuals. It is often necessary to try several before finding one that works best for a specific patient. Some people may find it necessary to combine medications, which could mean two antidepressants or an antipsychotic medication in addition to an antidepressant. If a person’s close relative has responded well to a certain medication, that treatment will likely work well for him or her. Antidepressant medications are effective in the acute, continuation, and maintenance phases of treatment, as described above.

The treatment benefits of antidepressant medications are often not seen until 1-2 weeks into treatment, with maximum benefits being reached around 4-6 weeks. Most healthcare providers will monitor patients more closely during the acute phase of treatment and continue to monitor at longer intervals in the continuation and maintenance phases.

Sometimes, people stop taking antidepressant medications due to side effects, although side effects often become less severe over time. Suddenly stopping treatment or missing several doses may cause withdrawal-like symptoms. Some studies have shown that antidepressants may increase short-term suicidal thoughts or actions, especially in children, adolescents, and young adults. However, antidepressants are more likely to reduce a person’s risk of suicide in the long run.

Below are listed the main classes of antidepressant medications, some of the most common drugs in each category, and their major side effects:

  • Selective serotonin reuptake inhibitors (citalopram, escitalopram, paroxetine, fluoxetine, sertraline): major side effects include nausea, diarrhoea, and sexual dysfunction.
  • Serotonin and norepinephrine reuptake inhibitors (duloxetine, venlafaxine, desvenlafaxine): major side effects include nausea, diarrhoea, increased heart rate, increased blood pressure, and tremor.
  • Tricyclic antidepressants (amitryptiline, desipramine, doxepin, imipramine, nortriptyline): major side effects include sedation, low blood pressure when moving from sitting to standing (orthostatic hypotension), tremor, and heart issues like conduction delays or arrhythmias.
  • Monoamine oxidase inhibitors (isocarboxazid, phenelzine, selegiline): major side effects include high blood pressure (emergency) if eaten with foods rich in tyramine (e.g. cheeses, some meats, and home-brewed beer), sedation, tremor, and orthostatic hypotension.

Alternative Treatments

There are several treatment options that exist for people who have experienced several episodes of major depression or have not responded to several treatments.

Electroconvulsive therapy is a treatment in which a generalised seizure is induced by means of electrical current. The mechanism of action of the treatment is not clearly understood but has been show to be most effective in the most severely depressed patients. For this reason, electroconvulsive therapy is preferred for the most severe forms of depression or depression that has not responded to other treatments, known as refractory depression.

Vagus nerve stimulation is another alternative treatment that has been proven to be effective in the treatment of depression, especially people that have been resistant to four or more treatments. Some of the unique benefits of vagus nerve stimulation include improved neurocognitive function and a sustained clinical response.

Transcranial magnetic stimulation is also an alternative treatment for a major depressive episode. It is a non-invasive treatment that is easily tolerated and shows an antidepressant effect, especially in more typical depression and younger adults.


If left untreated, a typical MDE may last for several months. About 20% of these episodes can last two years or more. About half of depressive episodes end spontaneously. However, even after the MDE is over, 20% to 30% of patients have residual symptoms, which can be distressing and associated with disability. 50% of people will have another major depressive episode after the first. However, the risk of relapse is decreased by taking antidepressant medications for more than 6 months.

Symptoms completely improve in six to eight weeks in 60%-70% of patients. The combination of therapy and antidepressant medications has been shown to improve resolution of symptoms and outcomes of treatment.

Suicide is the 8th leading cause of death in the United States. The risk of suicide is increased during a MDE. However, the risk is even more elevated during the first two phases of treatment. There are several factors associated with an increased risk of suicide, listed below:

  • Greater than 45 years of age;
  • Male;
  • History of suicide attempt or self-injurious behaviours;
  • Family history of suicide or mental illness;
  • Recent severe loss;
  • Poor health;
  • Detailed plan;
  • Inability to accept help;
  • Lack of social support
  • Psychotic features (auditory or visual hallucinations, disorganisation of speech, behaviour, or thought);
  • Alcohol or drug use or comorbid psychiatric disorder; and/or
  • Severe depression.


Estimates of the numbers of people suffering from MDE’s and major depressive disorder (MDD) vary significantly. Overall, 13-20% of people will experience significant depressive symptoms at some point in their life. The overall prevalence of MDD is slightly lower ranging from 3.7-6.7% of people. In their lifetime, 20% to 25% of women, and 7% to 12% of men will suffer a MDE. The peak period of development is between the ages of 25 and 44 years. Onset of major depressive episodes or MDD often occurs to people in their mid-20s, and less often to those over 65. The prevalence of depressive symptoms in the elderly is around 1-2%. Elderly persons in nursing homes may have increased rates, up to 15-25%. African-Americans have higher rates of depressive symptoms compared to other races. Prepubescent girls are affected at a slightly higher rate than prepubescent boys.

In a National Institute of Mental Health study, researchers found that more than 40% of people with post-traumatic stress disorder suffered from depression four months after the traumatic event they experienced.

Women who have recently given birth may be at increased risk for having a major depressive episode. This is referred to as postpartum depression and is a different health condition than the baby blues, a low mood that resolves within 10 days after delivery.

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