Is treatment-resistant depression real?

Perspectives and practical handling

How is Depression Defined? When does a depressed mood turn into illness? And which possibilities of classification besides the ICD 10 help the family doctor to correctly classify depressive symptoms or to track down the cause of depression in the case of physical complaints? In addition to these practical aspects, this article is intended to encourage reflection on the concept of "depression".

Guidelines and standardized recommendations should not be discussed in this article. While guidelines are essentially based on statistical statements about groups, which are based on the highest possible quality study results in the sense of evidence-based medicine, in this article we want to undertake an individualized consideration of patients with a depressive problem, as typically occurs in the general practitioner's practice [14, 30].

Classification and diagnostics

Depressive disorders are among the most common occasions for advice and illnesses in general medical care [4]. For most patients with depression, general practitioners are the first point of contact [18]. A didactic aid for the basic differential diagnostic classification of depressive states is the triad shown in Fig. 1, which has proven particularly useful in depressed patients with comorbid physical symptoms, as can often be found in general practice [3]. The following must be distinguished from depressive illnesses in the narrower sense:
  • The grief reaction: It is a normal human and healthy way of reacting to successfully processing and coping with losses. For this purpose z. B. also include the loss of physical integrity in the event of illness. Grief should not be pathologized in order not to hinder the coping process [24].
  • Symptoms that are phenomenologically similar to depression, but reflect an underlying organ disease. Examples include weakness, loss of appetite and lack of drive (fatigue) in cancer and multiple sclerosis, or fear, agitation and sleep disorders in hyperthyroidism. Here it is important to recognize and treat the underlying disease, then the psychological symptoms will usually also remit [12].

Furthermore, there is also an overlap between grief reactions and depression (e.g. in the case of pathological grief in the sense of an adjustment disorder) or between physical illnesses and depression, e.g. For example, a cancer patient may have manifest depression in addition to fatigue [12].

In addition to this pragmatic differential diagnostic classification, what we currently understand by depression "in the narrower sense", depending on the zeitgeist, is of considerable relevance in general medical practice [7]. When are we ready to regard mental impairment as an illness? With regard to mental illnesses, three different basic conceptions can be named paradigmatically [36].

The nominal definition:

According to the current classification system (ICD-10), diseases become "disorders". A diagnosis is made here on the basis of descriptive psychopathological and progression criteria. The following criteria apply to depressive episodes F32 and F33 [13]:

Main symptoms:

  • Gloomy mood
  • Loss of interest, joylessness
  • Reduced drive, increased fatigue

Additional symptoms:

  • Decreased focus and attention
  • Decreased self-esteem and self-confidence
  • Feelings of guilt and feelings of worthlessness
  • Negative and pessimistic future prospects
  • Thoughts of suicide, self-harm or suicidal behavior
  • sleep disorders
  • Decreased appetite

Symptoms must have been present for at least 14 days to diagnose a depressive episode, unless they are unusually severe or rapid.

For a mild depressive episode, at least two of the three main symptoms and at least two of the seven additional symptoms must be present. For a moderate episode, at least two of three main symptoms and at least three of the other additional symptoms must be present, and for a major depressive episode there must be all three main symptoms and at least four additional symptoms.

Objectivity and supra-individual validity are sought. The diagnosis is made in a context-free manner, i.e. not related to biography and life situation [13].

The real definition:

This can be contrasted with a real definition of illness, according to which a disease actually exists, as it were as an objective, scientific "thing". After this, the patient "has" a depression, just as he can, for example, have an objectively diagnosable gastric ulcer or a "runny nose".

The biographical-individual conception of illness:

In the biographical-individual recording of mental illnesses, mental disorders are primarily an expression of an individually understandable biographical undesirable development. The subjectively individual has priority over general concepts.

Although the nominal definition is the "objectively valid" one and all therapeutic studies and epidemiological information on depression are essentially based on it, it is of little help in the doctor's office to refer exclusively to this. Ultimately, the three basic views mentioned above overlap both with the doctor and with the patient and his relatives, without this always being reflected on. However, it is precisely this reflection that seems necessary to us in order to be able to offer the patient an appropriate treatment. In the following, we want to illustrate this using practical examples.

To this end, we first divide the different constellations of depression perception on the part of patients and doctors into three groups.

Group 1: Patients who consider themselves depressed.

The 46-year-old Ms. S. is referred to a psychiatric specialist by the family doctor because of the significant tendency towards chronicity of a first-time depressive episode. She reports pronounced anger and sadness, joylessness, insomnia and lack of drive as well as thoughts of being tired of life, but is clearly distanced from suicidality. After evaluating the self-reported PHQ-D ("Patient Health Questionnaire", German version: Löwe et al. [32]) and a health questionnaire, the patient met the criteria for a moderate depressive episode. In psychiatric exploration, on the other hand, the well-groomed and eloquently reporting patient appears primarily angry and emotionally unstable. The symptoms have existed for about four years and since the separation from the severely disabled husband, with whom she only disputes in court through lawyers, whereby it is about maintenance payments and the care of their children. She has not been working for almost a year and an attempt to return to work based on the Hamburg model has already failed. She broke off behavior therapy because she did not get along with the therapist, and the antidepressant medication she was taking (already the second preparation) did not help her. She would now like to go to a day clinic and that we should support her with an application for a severe disability, which she also submitted because she had been advised to "beat her husband with his own weapons".

With this patient, the impression soon arises that the diagnosis "depression" also has an important function for the patient quite independently of its objective justification (nominal definition). As early as the first consultation, the patient presented the symptoms of depression according to ICD 10. It is clear that she is not doing well and that she suffers from complaints such as brooding, joylessness, inner restlessness and insomnia. However, a considerable secondary gain in disease can also be assumed. Ms. S. herself mentions several times that she wants to "upgrade" against her ex-husband. To do this, she herself uses the diagnosis according to a real definition, as if she had an objective disease. With this she wants to achieve a severe disability and thus compete with her ex-husband.


Here, in addition to its nominal definition, depression is also understood according to a real definition, as a context-independent, objective, scientific disease. But depression is also wanted and needed by the patient as an illness in a socio-political protective function, such as justification of inability to work, receipt of sick pay, possibly EU pension and even severe disability. The current form of reporting suits this patient: "More and more people are suffering from depression" or "One in five people will develop depression in the course of their life" [33]. In this context, it is interesting to see the development of pensions due to reduced earning capacity over the past decade. In the diagnoses leading to retirement, the increase in mental disorders - with depression being the most common - almost completely corresponds to the decrease in diseases of the musculoskeletal system [1].

Group 2: Patients who do not consider themselves depressed.

The 54-year-old Ms. H. was first referred to a neurologist by her family doctor because she had been suffering from migraine attacks for three to four years. She reports that she can no longer calm down, often brooding, experiencing herself as fundamentally inadequate, suffering from fear of the future, no longer relaxing and unable to enjoy anything, and sleeping very poorly. The patient looks worn out, the affect is markedly changed; it seems downgraded, agitated, but there is no suicidality: "You shouldn't do that to your parents and children." The patient is strongly performance-oriented, she has not yet been absent from work and in recent years has taken care of her seriously ill son, who is now no longer vitally endangered, at home. Although she has agreed to be referred for specialist psychiatric treatment, she initially rejects the idea of ​​suffering from depression.

An antidepressant treatment attempt approved by her after several months failed after just taking one tablet. The patient attributed an extremely agonizing inner restlessness and physical discomfort to the tablet. Only after a kind of cathartic discussion with colleagues and superiors on the job, who conveyed to her that she was depressed and therefore less efficient, and encouraged her to seek treatment and to support her, did Ms. H. speak of her depressed state . Until then, she had firmly believed that she was rejected at work and wanted to get rid of her as quickly as possible because of her reduced performance.


Despite a partially successful destigmatization of mental illnesses, there are not a few patients who see their suffering in their very personal biographical and lifeworld context and who cannot reconcile it with their self-concept to objectify this in a psychiatric diagnosis [14]: These patients let themselves treatment is also not possible or only with great difficulty [21]. Here, the criteria for a depressive episode are met according to the nominal definition; if context factors are of subordinate importance with regard to the extent of the disorder, one could perhaps even speak of the presence of an endogenous-looking depression (real definition). However, the patient herself persists in a biographical, individual view of the disease and runs the risk of not receiving an efficient antidepressant treatment from this perspective.

Group 3: Patients in whom neither the doctor nor the patient (initially) considers the possibility of depression.

Depression can be masked by physical complaints or not be considered because of a predominant somatic disease that requires treatment. The rate of depression doubles in diabetes mellitus, high blood pressure, CHD and myocardial infarction and triples in terminal kidney failure, COPD and cerebrovascular diseases [15]. It is currently assumed that depression is not only to be understood as a consequence of the severe physical illness, but that there is a complex, interacting set of conditions that lead to somatic illness and depressive disorder. In addition, epidemiological studies show that depressed patients have an increased risk of somatic diseases [6, 20, 42] and that untreated depression worsens the course of the somatic disease

The second part of the article in issue 11 of The general practitioner will use case vignettes to specifically address the symptoms of depressive disorders in the general practitioner's practice, discuss pitfalls in the diagnostic process and provide pragmatic recommendations for the treatment of depressive disorders.

1. Abholz H, Schmacke N (2014) Patients with sadness and depression - prevalence, therapy and care in the family doctor's practice. In: Klauber NJ et al. (Ed.) Supply report 2013/2014, focus: Depression. Schattauer, Stuttgart
2. Archer J, Bower P, Gilbody S, et al. (2012) Collaborative care for depression and anxiety problems. Cochrane Database Syst Rev 2012, 10: CD006525. doi: 10.1002 / 14651858.CD006525.pub2.
3. Arolt V, Rothermundt M (2003) Depressive disorder in the physically ill. Neurologist 74: 1033-1054
4. Medical Center for Quality in Medicine (ÄZQ) (2003) Guideline clearing report "Depression". ezq series of publications Volume 12. Verlag videel OHG, Niebüll
5. Balint M (2010) The doctor, his patient and the disease. 11th edition, Klett-Cotta, Stuttgart
6. Builder H et al. (2004) Mental disorders in patients with musculoskeletal and cardiovascular diseases compared to the general population. Z Klin Psychother 33 (1): 33-41
7. Blazer DG (2005) The Age of Melancholy: "Major Depression" and its Social Origins. Routledge, New York
8. Bschor T, Baethge C (2010) No evidence for switching the antidepressant: systematic review and meta-analysis of RCTs of a common therapeutic strategy. Acta Psychiatr Scand 121: 174-179
9. Bschor T, Bauer M, Mazda A (2014) Chronic and therapy-resistant depression - diagnostics and step therapy. Dtsch Arztebl Int 2014; 111 (45): 766-776
10. German Society for General Medicine and Family Medicine (DEGAM) (2012) Fatigue. DEGAM guideline No. 2. Omikron publishing, Düsseldorf,
11. German Society for Psychiatry, Psychotherapy, Psychosomatics and Neurology (DGPPN) et al (2010) National Care Guideline - Unipolar Depression. S3 Practice guidelines in psychiatry & psychotherapy. Springer, Berlin - Heidelberg
12. Diefenbacher A et al (2015) Consultation and liaison services for mental disorders. In: Berger M (Ed.) Mental Illnesses. Clinic and Therapy. 5th edition, Elsevier, Munich
13. Dilling H, Mombour W, Schmidt MH (2014) International Classification of Psychiatric Disorders. ICD-10 Chapter V (F) Clinical Diagnostic Guidelines. 9th edition, Huber, Bern
14. Dowrick C (2004) Beyond Depression - A New Approach to Understanding and Management. Oxford University Press, New York
15. Egede LE (2007) Major depression in individuals with chronic medical disorders: prevalence, correlates and association with health resource utilization, lost productivity and functional disability. Gen Hosp Psychiatry 29: 409-416
16. Ekers D, Murphy R, Archer J et al. (2013) Nurse-delivered collaborative care for depression and long-term physical conditions: A systematic review and meta-analysis. J Affect Disord 2013; 149 (1-3): 14-22
17. Fava GA, Offdiani E (2011) The mechanisms of tolerance in antidepressant action. Prog Neuropsychopharmacol Biol Psychiatry 35: 1593-1602
18. Gensichen J, Peitz M (2006) Treatment potential in general medical care. In: Stoppe G, Bramesfeld A, Schwartz FW (Ed.) Widespread Disease Depression? Inventory and perspectives. Springer, Berlin - Heidelberg - New York
19. Götze P, Papenhausen R (1988) Psychodynamic aspects of psychopharmacological therapy resistance. In: Burchard JM (Ed.) Therapy ability through psychopharmacological treatment. Munich Scientific Publications, Munich
20. Goldberg D (2010) The detection and treatment of depression in the physically ill. World Psychiatry 9: 16-20
21. Härter M et al. (2006) Improving quality of care for depression: the German Action Program for the implementation of evidence-based guidelines. Int J Qual Health Care 18 (2): 113-119
22. Hegerl U (2013) Should mild depression be treated exclusively with psychotherapy? Cons. Neurologist 84: 388-389
23. Hibbeler B (2012) Prevention: "Recipe for exercise" presented. Dtsch Arztebl 109 (4): A-126 / B-118 / C-118
24. Horwitz A, Wakefield J (2007) The Loss of Sadness. How Psychiatry Transformed Normal Sorrow into Depressive Disorder. Oxford University Press, New York
25. Kirsch I (2014) Review Article - Antidepressants and the Placebo Effect. Z Psychol 222 (3): 128-134
26. Kühlein T et al. (2010) Quaternary Prevention - A Task for General Practitioners. Primary Care 10: 350-354.
27. Kühlein T et al.(2013) Patient-Oriented Medicine - The Art of Omission. Dtsch Arztebl 110 (48): A 2312-2314
28. Langbehn K (2014) It can affect anyone. The Tagesspiegel v. November 13, 2014,
29. Lehmann D, Burian R, Barrett B, Diefenbacher A (2011) Cooperation between consulting psychiatrists and general practitioners - a longitudinal study. In: Stoppe G (Ed.) The care of mentally ill elderly people. Volume 3, Deutscher Ärzte-Verlag, Cologne
30. Leiß O (2015) No l’art pour l’art, but for the benefit of the patient. Deut Arztebl 112 (4): A-130 / B-114 / C-110
31. Löllgen H (2014) Physical activity: The great therapy deficit. Deut Arztebl 111 (29/30): 1296
32. Löwe B et al (2002) PHQ-D. Health questionnaire for patients. Manual full version and short form. Authorized German version of the "Prime MD Patient Health Questionnaire (PHQ)". 2nd edition, Pfizer GmbH, Karlsruhe
33. Melchior H et al. (2014) Health fact check. Regional differences in the diagnosis and treatment of depression. Bertelsmann Stiftung, https://depression. Faktencheck_depression_studie.pdf
34. Moncrieff J, Kirsch I (2005) Efficacy of antidepressants in adults. BMJ 331: 155-159
35. Pigott HE et al (2010) Efficacy and Effectiveness of antidepressant: current status of research. Psychother Psychosome 79: 267-279
36. Sass H, Hoff P (2002) Descriptive psychopathological assessment. In: Möller HJ, Laux G, Kapfhammer HP (eds.) Psychiatry and psychotherapy. 2nd edition, Springer, Berlin - Heidelberg - New York
37. Schauenburg H, Bschor T (2013) Should mild depression be treated exclusively with psychotherapy? Per. Neurologist 84: 386-387
38. Schwabe U, Paffrath D (2014) Drug Prescription Report 2014: Current data, costs, trends and comments. Springer, Berlin - Heidelberg - New York
39. Shorter E (2009) Before Prozac. The Troubled History of Mood Disorders in Psychiatry. Oxford University Press, New York
40. Sielk M, Abholz HH (2005) Why do general practitioners refer to other patients as depressed than psychiatrists do? Z General Med 81: 486-490
41. Simon GE et al. (1999) An international study of the relation between somatic symptoms and depression. N Engl J Med 341 (18) 1329-1335
42. Tiemeier H et al. (2004) Relationship between atherosclerosis and late-life depression: the Rotterdam Study. Arch Gen Psychiatry 61 (4): 369-376
43. Von Uexküll T, Wesiack W (1997) Theory of the diagnostic process. In: Adler RH et al. (Ed.) Psychosomatic Medicine. 5th edition, Urban & Schwarzenberg, Munich - Vienna - Baltimor
44. Wancata J et al. (2013) Recognizing Psychiatric Disorders Earlier - Possibilities and Limits. In: Stelzig M, Rathner M, Klaushofer R (eds.) The consequences of not diagnosing mental illnesses. Jan Sramek Verlag, Vienna
45. Whooley MA, Avins AL, Miranda J, Browner WS (1997) Case-finding instruments for depression. Two questions are as good as many. J Gen Intern Med 12 (7): 439-445

Prof. Dr. med. Albert Diefenbacher
Department of Psychiatry and Psychosomatics, Evangelical Hospital Queen Elisabeth Herzberge gGmbH

Conflicts of Interest: The authors have not declared any.

More articles on similar topics