Major depressive disorder

The modern concept of depression is similar to the older concept of melancholy . The concept of melancholy originates from “black bile”, one of the “four temperaments” described by Hippocrates .

In the Middle Ages , however, many of the scientific creations of ancient physicians were lost, and a major depressive disorder was long regarded as an " obsession with the Devil ." The appropriate treatment was offered: rites of exorcism, fasting or fasting , prayers . Patients with severe depressive agitation ( agitation ) were proposed to bind, beat. During the Inquisition, depressed patients with self-incriminating ideas were fertile material for the Inquisitors ^[5] . The revival of the approach to depression as a disease that requires medical intervention and treatment, and not rites of exorcism, began only in the late Middle Ages , in the era of the beginning of the Renaissance and the growth of interest in antiquity and its achievements. The first classification of psychoses was invented by Felix Shater (1537-1614), where depression appears under the term Melancholia in the class Mentis alienatio - a group of psychoses in the literal sense of the word ^[5] .

Table of diagnostic codes for major depressive disorder in the modern classifier DSM-5 : ^[3]

For diagnosis of major depressive disorder, at least 5 of the following criteria must be present: ^[3]

1. Depressive mood ;
2. Insomnia or hypersomnia ;
3. Significant weight loss in the absence of a diet or weight gain, or a decrease or increase in appetite ;
4. Significantly reduced interest or loss of pleasure in all or almost all of the activity;
5. Decreased ability to concentrate, think , or indecision;
6. Psychomotor agitation or delayed motor and mental activity;
7. Feeling of worthlessness or excessive guilt ;
8. Fatigue or loss of energy;
9. Periodic thoughts of death , repeated suicidal thoughts without a specific plan, or suicide attempts , or a specific plan for committing suicide.

Symptoms should be present most of the day, almost every day ^[3] . Symptoms can be noted both by the patient himself and by other people (they can notice, for example, the patient’s crying or lethargy of speech and movements) ^[3] . The greatest severity of symptoms can be observed in the morning or in the evening, depending on the course of the disease. At least one of the symptoms should relate to a decreased mood, or to a loss of interest or pleasure ^[3] . For diagnosis, the symptoms must cause clinically significant disorders in the professional, social, or other important areas ^[3] . To diagnose major depressive disorder, the duration of the disorder should be at least 2 weeks ^[3] .

In 20-30% of patients in remission, residual depressive symptoms (primarily asthenic and somatovegetative) are observed, which can persist for a long time without adequate maintenance therapy (months or even years) ^[6] .

Depressive patients systematically distort their perception of events, finding in them confirmation of ideas about their worthlessness, negative views on the surrounding reality and their future. Such characteristic distortions of thinking as randomness of conclusions, “all or nothing” thinking, excessive generalization, selective abstraction and exaggeration can take place.

Severe depression without psychotic manifestations (F32.2) is characterized by a predominance of either melancholy or apathy, psychomotor retardation, and suicidal tendencies are possible. Significantly disrupted social functioning. For severe depression with psychotic manifestations (F32.3) - delusions of guilt, illness, motor lethargy (up to a stupor) or anxiety (agitation) ^[6] .

Screening tests reveal patients with depression much better than specially trained medical personnel. Studies in the United States, as well as in low- and middle-income countries, have shown that volunteers and support staff (nurses, social workers) can be trained to screen for depression (as well as other mental disorders) using small questionnaires. In particular, the United States raises the question of introducing screening for depression in the standard of care, however, when conducting such a screening, several questions arise at once - what criteria should be used when screening for depression, how should screening be done, who should be screened, and when. You can offer annual screening to all adults who come to the doctor - but the number of patients can then significantly exceed the possibilities of medical intervention. An alternative approach is screening in high-risk groups (mothers of newborns, people with sleep disorders, chronic diseases, severe social stress factors or medically unexplained somatic complaints) ^[7] .

Over the years, several depressive disorder screening tools have been developed. These tools include self-assessment tests such as the Zanga Scale for Depression Self-Assessment ^[8] , Beck Depression Scale ^[9] , PHQ-9 Questionnaire ^[10], and Major Depression Questionnaire . ^[eleven]

In 2012, transcriptome biomarkers specific for adolescents with major depressive disorder were found in blood cells ^[12] . In addition, a partially overlapping set of biomarkers has been found to distinguish cases where major depressive disorder is combined with anxiety disorder . In the event that these results are confirmed in wider studies, in addition to a new approach to the diagnosis of major depressive disorder, this may lead to the development of individualized approaches to treatment.

A variety of major depressive disorder is resistant depression , in which, during two consecutive courses (3-4 weeks) of antidepressant treatment, there is a lack or insufficiency of the clinical effect ^{[13] [14]} . The causes of resistant depression may vary ^[14] :

• Primary , or true , resistance (very rare, due to biological and clinical factors);
• Secondary , or relative , resistance (due to the phenomenon of adaptation to psychopharmacotherapy);
• Pseudoresistance (due to improper pharmacotherapy, is very common);
• Intolerance (intolerance to prescribed drugs).

• Antidepressants with a predominantly stimulating effect ( fluoxetine , venlafaxine , bupropion , milnacipran , clomipramine , imipramine ) are used to treat patients with depression, accompanied by lethargy, hypersomnia , apathy and longing.
• Antidepressants of predominantly sedative effects ( paroxetine , mirtazapine , amitriptyline, mianserin ) are indicated for anxiety depression, unaccountable anxiety, poor sleep, and gloomy irritability.

If the antidepressant is selected incorrectly, without taking into account the predominance of a stimulating or sedative component in its action, taking the drug can lead to a worsening of the condition: when prescribing a stimulating antidepressant, it can aggravate anxiety and increase suicidal tendencies; when prescribing a sedative drug - to the development of psychomotor inhibition (lethargy, drowsiness) and a decrease in concentration ^[15] .

In a 2009 meta-analysis comparing 12 new-generation antidepressants, mirtazapine , escitalopram , venlafaxine and sertraline were found to be significantly superior to others with major depression ^[16] .

If the antidepressant used is ineffective, you should first try to find out the possible causes of resistance. Such reasons may include an insufficient dose or duration of antidepressant medication; underestimation of factors contributing to the chronicity of the condition (for example, comorbidity with other mental disorders or with somatic or neurological pathology; adverse life circumstances; metabolic disorders affecting the concentration of an antidepressant in the blood; a genetic predisposition to a particular reaction to an antidepressant, etc.); lack of control over compliance with the treatment regimen ^[14] .

In almost 50% of cases, resistant depression is accompanied by latent somatic pathology , psychological and personality factors play an important role in their development. Therefore, only psychopharmacological methods of overcoming resistance without a complex effect on the somatic sphere, influencing the socio-psychological situation and intensive psychotherapeutic correction can hardly be fully effective and lead to stable remission ^[17] .

If the above measures have not led to sufficient antidepressant efficacy, a change of drug is used by another antidepressant (usually a different pharmacological group). The third step in case of inefficiency of the second may be the appointment of combination therapy with antidepressants of various groups ^[14] . In particular, a combined intake of bupropion , mirtazapine and one of the SSRI drugs, such as fluoxetine , escitalopram , paroxetine , sertraline ; or bupropion , mirtazapine and one of the antidepressants of the SSRI group, venlafaxine , milnacipran or duloxetine .

There is one small study showing that a combination of two antidepressants (for example, mirtazapine with fluoxetine , venlafaxine or bupropion ) can increase the number of remissions by about half compared with single drug therapy ^[18] .

A potentiation strategy ^[14] (that is, adding another substance that is not in itself used as a specific drug to treat depression but can increase the response to an antidepressant taken can also be effective in resistant depression). There are a huge number of drugs that can be used for potentiation, but most of them do not have the necessary level of evidence for their use. The highest degree of evidence is observed for lithium salts , lamotrigine , quetiapine , some antiepileptic drugs , triiodothyronine , melatonin , testosterone , clonazepam , scopolamine and buspirone ; they are potentiators of the first line. Nevertheless, drugs with a low level of evidence may also find use in resistant depression in the case of ineffectiveness of potentiating agents of the first line ^[19] .

In the treatment of therapeutically resistant depression, electroconvulsive therapy can also be used. Today, new treatments for these conditions, such as transcranial magnetic stimulation , are being intensively explored. In the treatment of the most refractory forms of depression, invasive psychosurgical techniques can be used, for example, vagus nerve stimulation, deep brain stimulation, cingulotomy , amygdalotomy, anterior capsulotomy.

In 2013, The Lancet magazine published the results of a study showing that in patients who did not benefit from antidepressant treatment, cognitive-behavioral therapy , used in addition to therapy with these drugs, can reduce symptoms of depression and help improve patients' quality of life. ^[twenty]

According to sociological studies, at least 16% of the population experienced conditions that meet the diagnostic criteria for major depressive disorder at least once in a lifetime. However, less than half of people who have experienced these conditions have sought or are seeking medical and / or psychological help and received an official diagnosis. Often, patients try to keep silent about the symptoms of depression. Many are afraid of prescribing antidepressants and their side effects; some believe that controlling emotions is their own business, not the care of a doctor; there are also concerns that the mention of a case of depression will fall into the medical record and somehow become known to the employer; finally, some are afraid to be referred for treatment by a psychiatrist . This suggests that therapists should use screening tools, including brief questionnaires, in cases not excluding depression ^[21] .

Major depressive disorder is today one of the main causes of temporary disability in the United States and other developed countries.

Major depressive disorder is also more common among the population of large cities and megacities compared with the population of small cities, towns and villages, more often among the population of developed countries than backward and developing ones. Probably, this difference is largely due to better diagnostics, a higher level of medicine and healthcare and a greater awareness of the population of developed countries and especially large cities about what depression is, and, as a result, more frequent visits to doctors. But the crowding and overpopulation of large cities, a faster pace of life, a higher level of social requirements and more stress , apparently also play a role in the greater prevalence of major depression in developed countries and in large cities.

Major depressive disorder also occurs with increased frequency among people who are often stressed - for example, unemployed , people with a poor socio-economic situation (low paid, without their own housing), people working in hard, boring, monotonous, unloved or uninteresting work, at work associated with an increased amount of stress and psychological overload (such as top managers). Often (but not always) a major depressive disorder develops after a mental trauma - for example, loss of work, bankruptcy, serious illness or death of a loved one or loved one, divorce, moving to a new place with the loss of all previous social connections , etc. But often it develops by itself, without any apparent reason, or from insignificant, at first glance, stress.

An increased incidence of clinical depression occurs in patients with or with migraines ^{[22] [23]} . Several scientific studies have shown statistical correlations between some pesticides and agricultural depression ^{[24] [25] [26] [27] [28] [29]} . In 2018, the relationship between depression and sleep disorders was established - molecular genetic pathways were found that are involved in the development of both major depressive disorder and insomnia ^[30] .

An important role in the development of major depressive disorder in adolescents and adults is played by the conditions in which this person grew and developed in childhood. Показано, что у лиц, подвергавшихся жестокому обращению в детстве , подростковом или юношеском возрасте (физическому насилию: дёргание, шлепки , пощёчины , побои , сексуальное совращение, изнасилование — или (и) психологическому насилию : ругань, придирки со стороны родителя (родителей), явные или завуалированные вербальные или поведенческие провокации со стороны родителя (родителей) или другого взрослого (взрослых) по отношению к ребёнку или подростку с целью вызвать у него чувство вины , стыда , собственной неполноценности, никчёмности), во взрослом возрасте наблюдается запрограммированность на стрессовые и депрессивные реакции, постоянное ожидание чего-то плохого; повышен по сравнению с нормой «фоновый» уровень стрессового гормона кортизола и наблюдается более резкий подъём уровня кортизола при даже незначительном стрессе, чем в норме, и чем у людей, подвергавшихся стрессам и плохому обращению уже взрослыми и сформировавшимися. У этих людей частота возникновения «большой депрессии» более чем в 3 раза превышает среднюю частоту в популяции в целом. И наоборот — среди больных с большим депрессивным расстройством повышена доля лиц, подвергавшихся той или иной форме насилия , унижения или плохого обращения в детстве, подростковом или юношеском возрасте ^[31] . Также с повышенной частотой «большая депрессия» развивается у лиц, у которых родственники (особенно ближайшие) страдали или страдают такими аффективными расстройствами , как биполярное аффективное расстройство , шизоаффективное расстройство и некоторыми другими психическими заболеваниями. Это указывает на важную роль наследственной, генетической предрасположенности в развитии большой депрессии и на возможное наличие общих механизмов развития целого ряда психических расстройств, имеющих в своём составе аффективный компонент.

Рядом приверженцев так называемой психоаналитической теории в своё время полностью отрицалось значение наследственной предрасположенности, генетических и биохимических факторов в развитии большого депрессивного расстройства. Сторонники психоаналитической теории происхождения депрессий придавали основное значение детским и подростковым психотравмам, импринтингу , запрограммированности на стресс. В то же время рядом так называемых биологических психиатров полностью отрицалось значение детских психотравм для возникновения и развития «большой депрессии» у взрослого индивида. Основное значение в биологической теории депрессий придавалось генетическим нарушениям и биохимическим дефектам, а также текущему или недавно воздействовавшему стрессу как провоцирующему фактору.

В настоящее время принято считать, что истина лежит посередине: в развитии любых депрессий в разной пропорции участвуют и наследственно-генетические факторы, создающие предрасположенность к депрессиям, пониженную устойчивость к стрессам, и импринтинг в детстве (также создающий предрасположенность, запрограммированность на стрессовые и депрессивные реакции), и текущий хронический или недавно воздействовавший острый стресс как провокатор депрессии. Неправильно отрицать или недооценивать значение любого из этих факторов и сводить сложный, многофакторный патогенетический механизм, приводящий к развитию депрессий, к воздействию лишь одного из факторов.

• Антидепрессанты
• Малая депрессия
• Депрессивное поведение у животных

• A. S. Tiganov , A. V. Snezhnevsky , D. D. Orlovskaya et al. Psychiatry Manual in 2 volumes / Ed. Academician of the RAMS A.S. Tiganov. - M .: " Medicine ", 1999. - T. 1. - 712 p. - ISBN 5-225-02676-1 .

In the Brockhaus-Efron Encyclopedic Dictionary

• Melancholy // Brockhaus and Efron Encyclopedic Dictionary : in 86 volumes (82 volumes and 4 additional). - SPb. , 1890-1907.
• Taedium vitae // Brockhaus and Efron Encyclopedic Dictionary : in 86 volumes (82 volumes and 4 additional). - SPb. , 1890-1907.

• The criteria for major depression (neopr.) . according to DSM-IV . Date of treatment March 2, 2012. Archived May 12, 2012.
• Clinical Depression Site Date of treatment March 2, 2012. Archived May 12, 2012.