Major depressive disorder: what it is, symptoms, treatment, prognosis

What is major depressive disorder?

Major depressive disorder (BDR) - in contrast to the usual depression, by which almost any bad or depressed, melancholy mood is meant, major depressive disorder is a complex of symptoms. The disease is diagnosed when a person is constantly in a bad or depressed mood, anhedonia or a decrease in interest in pleasant activities, feelings of guilt or worthlessness, lack of energy, poor concentration, changes in appetite, psychomotor retardation or agitation, sleep disturbances, or suicidal thoughts. According to the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5), a person must have five of the above symptoms, one of which must be depressive mood or anhedonia causing social or occupational disorders, in order to diagnose MDD. A history of manic or hypomanic episodes must be ruled out to make a diagnosis of MDD. Children and adolescents with MDD can be irritable.

Causes and risk factors

The cause of major depressive disorder is thought to be multifactorial, including biological, genetic, environmental, and psychosocial factors. Previously, it was thought that MDD occurs mainly due to disturbances in neurotransmitters, especially serotonin, norepinephrine, and dopamine. This is evidenced by the use of various antidepressants such as selective receptor inhibitors serotonin, serotonin-norepinephrine receptor inhibitors, dopamine-norepinephrine receptor inhibitors, in treatment depression. People with suicidal thoughts have been found to have low levels of serotonin metabolites. However, recent theories show that this is primarily due to more complex neuroregulatory systems and neural circuits, causing secondary disturbances in neurotransmitter systems.

It has been found that GABA, an inhibitory neurotransmitter, as well as glutamate and glycine, which are major excitatory neurotransmitters, also play a role in the etiology of depression. Depressed patients have been found to have lower levels of GABA in plasma, cerebrospinal fluid, and brain. GABA is believed to exert its antidepressant effect by inhibiting the ascending monoamine pathways, including the mesocortical and mesolimbic systems. Medicines that antagonize NMDA receptors have antidepressant properties. Thyroid and growth hormone disorders are also implicated in the etiology of mood disorders. Multiple adverse childhood experiences and trauma are associated with the development of depression later in life.

Severe early stress can lead to dramatic changes in neuroendocrine and behavioral responses, which can cause structural changes in the cerebral cortex, which in the future will lead to severe depression. Structural and functional imaging of the brains of people with depression showed increased hyperintensity in the subcortical regions and decreased metabolism in the anterior part of the brain on the left, respectively. Studies of families, adoptions, and twins have shown a role for genes in susceptibility to depression. Genetic studies show a very high percentage of concordance in twins with MDD, especially monozygotic twins. Life events and personal qualities also play an important role. Learned helplessness theory links the onset of depression to the experience of uncontrollable events. According to cognitive theory, depression occurs as a result of cognitive biases in people who are depressed.

Epidemiology

Major depressive disorder is a very common mental disorder. Its lifetime prevalence is 5 to 17 percent, with an average of 12 percent. The prevalence rate in women is almost double that of men. This difference is thought to be related to hormonal differences, effects during childbirth, various psychosocial stressors in men and women, and learned helplessness behaviors. Although the average age at onset is around 40, recent research suggests trends towards an increase in morbidity among the younger population due to the use of alcohol and other drugs.

MDD is more common in people without close interpersonal relationships, divorced, separated, or widowed. No differences were found in the prevalence of MDD among races and socioeconomic status. People with MDD often have comorbidities such as substance use disorders, panic disorder, social anxiety disorder and obsessive compulsive disorder. The presence of these comorbid disorders in people diagnosed with MDD increases the risk of suicide. Among the elderly, depression is common among those with the aforementioned comorbidities. Depression is more common in rural areas than in cities.

Diagnostics

Major depressive disorder is a clinical diagnosis; the disorder is generally diagnosed based on the patient's medical history and mental status examination. The clinical interview should include medical history, family history, social and substance use history, and symptoms. Additional information from the patient's family / friends is a very important part of the psychiatric assessment.

A complete physical examination, including a neurologic examination, is required. It is important to rule out any underlying medical / organic causes of the depressive disorder. A complete medical history and family medical and psychiatric history should be taken. Mental health screening plays an important role in the diagnosis and assessment of major depressive disorder.

Despite the lack of objective tests to diagnose depression, routine laboratory work including complete blood count with differential, complex metabolic panel, thyroid-stimulating hormone analysis, free T4, vitamin D, urinalysis and toxicology screening are done to rule out organic or medical causes of depression.

Most hospitals typically use the Hamilton Depression Rating Scale (HDRS), which is a clinician-defined scale for assessing depression, to assess depression. The original HDRS uses 21 points for symptoms of depression, but the score is based on the first 17 points only.

- Differential diagnosis.

In assessing MDD, it is important to rule out depressive disorder caused by another disorder, depressive disorder caused by psychoactive substances / drugs, dysthymia, cyclothymia, bereavement, adjustment disorder with depressed mood, bipolar disorder, schizoaffective disorder, schizophrenia, anxiety disorders, and eating disorders for the appropriate treatment. Depressive symptoms can be secondary to the following reasons:

• Neurological causes such as impaired cerebral circulation, multiple sclerosis, subdural hematoma, epilepsy, Parkinson's disease, Alzheimer's disease.
• Endocrinopathies such as diabetes, thyroid disease, adrenal glands.
• Metabolic disorders such as hypercalcemia, hyponatremia.
• Drug / Substance Abuse: steroids, antihypertensives, anticonvulsants, antibiotics, sedatives, hypnotics, alcohol, withdrawal of stimulants.
• Nutrient deficiencies such as vitamin D, B12, B6 deficiencies, iron or folate deficiencies.
• Infectious diseases such as HIV and syphilis.
• Malignant neoplasms.

Treatment

Major depressive disorder can be managed with a variety of treatments, including pharmacological, psychotherapeutic, interventional, and lifestyle changes. Initial treatment for MDD includes medication and / or psychotherapy. Combination treatments that include both medication and psychotherapy have proven to be more effective than either of these treatments alone. Electroconvulsive therapy has proven to be more effective than any other form of treatment for severe depression.

The approved drugs for the treatment of MDD are as follows: All antidepressants are equally effective but differ in their side effect profiles.

• Selective serotonin reuptake inhibitors (SSRI) include fluoxetine, sertraline, citalopram, escitalopram, paroxetine, and fluvoxamine. They are usually the first line of treatment and the most commonly prescribed antidepressant.
• Serotonin and norepinephrine reuptake inhibitors (IOZSN) include venlafaxine, duloxetine, desvenlafaxine, levomilnacipran, and milnacipran. They are often used in depressed patients with comorbid psychiatric disorders.
• Serotonin modulators are trazodone, vilazodone, and vortioxetine.
• Atypical antidepressants include bupropion and mirtazapine. They are often prescribed as monotherapy or enhancers when patients develop sexual side effects from SSRIs or SNRIs.
• Tricyclic antidepressants (TCAs) Are amitriptyline, imipramine, clomipramine, doxepin, nortriptyline and desipramine.
• Available monoamine oxidase inhibitors (MAOIs) are tranylcypromine, phenelzine, selegiline and isocarboxazid. MAOIs and TCAs are usually not used due to the high incidence of side effects and mortality from overdose.
• Other medications include mood stabilizers, antipsychotics, which can be added to enhance the antidepressant effect.

Psychotherapy:

• Cognitive behavioral therapy;
• Interpersonal therapy.

Electroconvulsive therapy (ECT):

• Acute suicidal behavior;
• Severe depression during pregnancy;
• Refusal to eat / drink;
• Catatonia;
• Severe psychosis.

Transcranial magnetic stimulation (TMS):

• FDA approved for the treatment of refractory / refractory depression; for patients who have not passed at least one drug trial.

Vagus nerve stimulation (VNS therapy):

• FDA approved as a long-term adjunctive treatment for persistent depression; for patients who have not completed at least 4 drug trials.

Esquetamin:

• Nasal spray for use in combination with oral antidepressants for treatment-resistant depression; for patients who have not been helped by other antidepressants.

Forecast

Untreated depressive episodes in major depressive disorder can last from 6 to 12 months. About two-thirds of people with MDD think about suicide, and 10 to 15 percent commit suicide. MDD - chronic relapsing disease; the relapse rate is about 50% after the first episode, 70% after the second episode, and 90% after the third episode. About 5-10 percent of patients with MDD eventually develop bipolar disorder. The prognosis of MDD is favorable for patients with mild episodes, no psychotic symptoms, better adherence to treatment, a strong support system, and good premorbid functioning. The prognosis is poor in the presence of concomitant mental disorder, personality disorder, multiple hospitalizations, and advanced age of onset.

Complications

Major depressive disorder is one of the leading causes of disability worldwide. The disease not only causes serious functional disorders, but also negatively affects interpersonal relationships, reducing the quality of life. Individuals with MDD are at high risk of developing comorbid anxiety and substance use disorders, further increasing their risk of suicide. Depression can worsen comorbid conditions such as diabetes, hypertension, chronic obstructive pulmonary disease and coronary heart disease.