Rarely diagnosed and treated despite momentous implications

Comorbidity rates of depression and diabetes are high and pathophysiological mechanisms influence each other. Impairment of diabetes self-management is a key factor here. Validated and feasible screening instruments exist, but are rarely used in clinical practice.

According to epidemiological data, the prevalence of depressive disorders in type 2 diabetes is twice as high worldwide than in the general population [1]. The incidence of depression is three times higher in individuals with type 2 diabetes than the general average [2,3]. According to expert estimates, about two-thirds of all diabetes patients with comorbid depression remain undiagnosed [7].

“Diabetes Distress” and Depressive Disorders.

Diabetes-related depressive disorders have a negative impact on disease progression and quality of life and are associated with increased rates of morbidity and mortality [2]. The direct and indirect economic effects are substantial [5,6]. With regard to diabetes as a primary disease, stress in connection with the regularly required insulin measurement and substitution, as well as fear of hyperglycemia and late consequences of the disease are among the depressogenic influencing factors. In technical jargon, this is subsumed under the term “diabetes distress” [8]. Leading symptoms of a clinically manifest major depressive episode are persistent and severe impairment of mood or interests; other possible symptoms include sleep disturbances, loss of appetite, impaired concentration, agitation [9,10]. According to DSM-5, the diagnostic criteria for major depressive disorder are one of each of the leading symptoms and at least four of the following symptoms: Feelings of worthlessness, guilt, exhaustion or lack of energy, difficulty concentrating, suicidality, weight loss or weight gain (at least 5% change), psychomotor slowing or agitation, increased need for sleep, or insomnia over a period of at least two weeks [10]. A distinction is made between first episode, recurrent episode, and chronic depression [10]. In terms of severity, there are mild, moderate, or severe forms with or without psychotic symptoms [10].

Complicated interaction structure

People with diabetes are significantly more likely to suffer from depressive disorders; conversely, depressives have a higher risk of developing diabetes. The bidirectional relationships are complex (Fig. 1). Data from a meta-analysis show that individuals with depressive symptoms have a 37% increased risk of developing type 2 diabetes [14]. According to an Australian study published in Nature 2018, approximately one-third of type 2 diabetes sufferers experience depressive symptoms or “diabetes distress,” and decreased compliance with smoking cessation, diet, exercise, and glucose monitoring was found in this patient population (confounding factors were statistically controlled) [15]. A poorly adjusted glucose value resp. Hypoglycemia is associated with depressive symptom severity (confounding factors were statistically controlled) [13].

In addition to lifestyle factors, altered stress metabolism (e.g., increased cortisol levels) with negative effects on insulin metabolism (insulin resistance), is another possible pathomechanism. The hypothesis of a dysregulation of the hypothalamic-pituitary-adrenal axis as a central factor regarding diabetes and comorbid depression was confirmed according to a secondary analysis published in 2017 [16]. Other possible influencing factors include side effects of antidiabetic medication [17].

Screening and therapy: guideline-based recommendations

Regardless of the causes, experts recommend screening for depressive symptoms in people with diabetes and seeking treatment if necessary ( see box).

The S3 guidelines of the German Society for Psychiatry and Psychotherapy, Psychosomatics and Neurology (DGPPN) recommend the same approach to psychopharmacological treatment as for non-diabetic patients with depression [7]. According to a Cochrane Review by Baumeister et al. psychotherapeutic interventions led to a reduction in depressive symptomatology and both psychotherapy and antidepressant medication resulted in a significantly higher remission rate than standard therapy/basic care [20].

In terms of pharmacotherapy, selective serotonin reuptake inhibitors (SSRIs) are considered the first choice drug class [7]. In contrast to tricyclic antidepressants, which often lead to weight gain, SSRIs facilitate weight loss and thus promote improvement in glycemic metabolism [7]. However, potential risks of unfavorable interaction effects are also pointed out, which should be considered in the context of polypharmacy and regarding cardiovascular factors [7].

Evidence-based treatment options

A secondary analysis by Markowitz provides efficacy evidence for psychotherapy, with positive effects of cognitive behavioral therapy on comorbid depressive symptomatology in particular [21]. It is a goal-oriented form of therapy that is intended to contribute to symptom reduction by changing patterns of thinking, behavior, and emotional responses [22]. There are studies on depression in which relapse rates were lower after cognitive behavioral therapy than after antidepressant pharmacotherapy [23]. Among the effective factors is a possible mood elevation on the one hand, and an increase in insulin sensitivity at the cellular level on the other.

An innovative approach to treating comorbid depression is online-based cognitive-behavioral therapy. According to a pilot study published in 2017, it is an effective, low-threshold and low-cost method [24]. The online program included 6 sessions of cognitive-behavioral therapy over a 10-week period and was superior in a comparison with standard therapy in the outcome parameter diabetes-related burden (PAID) and proved equal in terms of Target HbA1c [24].

Non-drug and pharmacological methods can also be used in combination. Exercise (e.g., walking) has been shown to have depression-relieving effects [25]. That a combination of cognitive behavioral therapy and exercise has positive effects on depression- and diabetes-related outcome parameters was demonstrated in a single-arm study (n=50) by de Groot et al [26]. The program included ten sessions of manualized cognitive behavioral therapy, as well as 12 consecutive weekly aerobic exercise sessions and six other exercise sessions with an average aerobic activity of 193 minutes per week (range: 76-478 minutes) [26]. Follow-up measurements were performed three months after baseline, showing a remission rate of 63% (p<0.001) regarding depressive symptoms.

Literature:

1. Roy T, Lloyd CE: Epidemiology of depression and diabetes: a systematic review. J Affect Disord 2012; 142(Suppl): S8-S21.
2. Guérin E, et al: Intervention Strategies for Prevention of Comorbid Depression Among Individuals With Type 2 Diabetes: A Scoping Review. Front Public Health 2019; 7: 35. doi: 10.3389/fpubh.2019.00035. eCollection 2019.
3. Andreoulakis E, et al: Depression in diabetes mellitus: a comprehensive review. Hippokratia 2012; 16: 205-214.
4. Semenkovich K, et al: Depression in type 2 diabetes mellitus: prevalence, impact, and treatment. Drugs 2015; 75: 577-587. doi: 10.1007/s40265-015-0347-4
5. Egede LE, et al: Trends in costs of depression in adults with diabetes in the United States: medical expenditure panel survey, 2004-2011. J Gener Intern Med 2016; 31: 615-622. doi: 10.1007/s11606-016-3650-1
6. OECD: Making Mental Health Count: The Social and Economic Costs of Neglecting Mental Health Care. OECD Health Policy Studies. Paris: OECD Publishing; 2014. doi: http://dx.doi.org/10.1787/9789264208445-en.
7. German Society for Psychiatry and Psychotherapy, Psychosomatics and Neurology (DGPPN): S3-Leitlinie/Nationale VersorgungsLeitlinie. Unipolar depression. Long version. 2nd edition, version 1 November 2015 AWMF Register No.: nvl 005, www.leitlinien.de/mdb/downloads/nvl/depression/archiv/depression-2aufl-vers1-lang.pdf
8. Esbitt SA, Tanenbaum ML, Gonzalez JS: Disentangling clinical depression from diabetes-specific distress: making sense of the mess we’ve made. In: Lloyd CE, Pouwer F, Hermanns N, editors. Screening for Depression and Other Psychological Problems in Diabetes: A Practical Guide. London: Springer (2013): 27-46.
9. APA (American Psychiatric Association): Diagnostic and Statistical Manual of Mental Disorders (DSM-5). 5th edition. Arlington, VA (2013): 947.
10. APA (American Psychiatric Association): Task Force. Diagnostic and statistical manual of mental disorders DSM-5. Fifth edition 2013.
11. Gonzalez JS, et al: Distress and type 2 diabetes-treatment adherence: A mediating role for perceived control. Health Psychol 2015; 34(5): 505-513. doi: 10.1037/hea0000131. Epub 2014 Aug 11. https://www.ncbi.nlm.nih.gov/pubmed/25110840
12. PAID: Questionnaire: Problem Areas in Diabetes Care, www.diabetes-psychologie.de/downloads/PAID_Fragebogen.pdf
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HAUSARZT PRAXIS 2019; 14(6): 41-42