Depression in Type 2 Diabetes Mellitus: Prevalence, Impact, and Treatment

Clinically significant depression is present in one of every four people with type 2 diabetes mellitus (T2DM). Depression increases the risk of the development of T2DM and the subsequent risks of hyperglycemia, insulin resistance, and micro- and macrovascular complications. Conversely, a diagnosis of T2DM increases the risk of incident depression and can contribute to a more severe course of depression. This linkage reflects a shared etiology consisting of complex bidirectional interactions among multiple variables, a process that may include autonomic and neurohormonal dysregulation, weight gain, inflammation, and hippocampal structural alterations. Two recent meta-analyses of randomized controlled depression treatment trials in patients with T2DM concluded that psychotherapy and antidepressant medication (ADM) were each moderately effective for depression and that cognitive behavior therapy (CBT) had beneficial effects on glycemic control. However, the number of studies (and patients exposed to randomized treatment) included in these analyses is extremely small and limits the certainty of conclusions that can be drawn from the data. Ultimately, there is no escaping the paucity of the evidence base and the need for additional controlled trials that specifically address depression management in T2DM. Future trials should determine both the effects of treatment and the change in depression during treatment on measures of mood, glycemic control, and medical outcome.

[1]  R. Carney,et al.  Effects of Nortriptyline on Depression and Glycemic Control in Diabetes: Results of a Double-blind, Placebo-controlled Trial , 1997, Psychosomatic medicine.

[2]  Martin L. Lee,et al.  Effect of Pharmacological Treatment of Depression on A1C and Quality of Life in Low-Income Hispanics and African Americans With Diabetes , 2009, Diabetes Care.

[3]  Janet B W Williams,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[4]  Wayne Katon,et al.  Relationship of depression and diabetes self-care, medication adherence, and preventive care. , 2004, Diabetes care.

[5]  C. Andrade,et al.  Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications , 2010, Mens Sana Monographs.

[6]  Martin L. Lee,et al.  The Effect of Pharmacologic Treatment of Depression on Glycated Hemoglobin and Quality of Life in Low Income Hispanics and African Americans with Diabetes: A Randomized, Double Blind, Placebo Controlled Trial Running Title - Pharmacological Treatment of Depression , 2009 .

[7]  M. Thase,et al.  The efficacy profile of vilazodone, a novel antidepressant for the treatment of major depressive disorder , 2012, Current medical research and opinion.

[8]  I. Kirsch,et al.  Efficacy of antidepressants in adults , 2005, BMJ : British Medical Journal.

[9]  S. Suissa,et al.  Long-term use of antidepressants for depressive disorders and the risk of diabetes mellitus. , 2009, The American journal of psychiatry.

[10]  L. Delahanty,et al.  Validity of Medication Adherence Self-Reports in Adults With Type 2 Diabetes , 2013, Diabetes Care.

[11]  B. Anderson,et al.  Depressive Symptoms and Quality of Life in Adolescents With Type 2 Diabetes , 2011, Diabetes Care.

[12]  Blair T. Johnson,et al.  Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration , 2008, PLoS medicine.

[13]  C. Nemeroff,et al.  Hypercortisolemia and hippocampal changes in depression , 1993, Psychiatry Research.

[14]  R. Durai,et al.  Antidepressant drugs 'work', but they are not clinically effective. , 2008 .

[15]  K. Freedland,et al.  The prevalence of comorbid depression in adults with diabetes: a meta-analysis. , 2001, Diabetes care.

[16]  Jeffrey S. Gonzalez,et al.  A review of treating depression in diabetes: emerging findings. , 2011, Psychosomatics.

[17]  M. E. Bernard,et al.  What Is Rational-Emotive Therapy (RET)? , 1985 .

[18]  M. Olfson,et al.  National trends in second-generation antipsychotic augmentation for nonpsychotic depression. , 2014, The Journal of clinical psychiatry.

[19]  I. Kirsch Review: benefits of antidepressants over placebo limited except in very severe depression , 2010, Evidence Based Mental Health.

[20]  J. Ballenger Atypical Antipsychotic Augmentation in Major Depressive Disorder: A Meta-Analysis of Placebo-Controlled Randomized Trials , 2011 .

[21]  E. Geringer Affective Disorders and Diabetes Mellitus , 1990 .

[22]  K. Freedland,et al.  Cognitive Behavior Therapy for Depression in Type 2 Diabetes Mellitus , 1998, Annals of Internal Medicine.

[23]  Harold Alan Pincus,et al.  National trends in the outpatient treatment of depression. , 2002, JAMA.

[24]  K. Freedland,et al.  Predicting response to cognitive behavior therapy of depression in type 2 diabetes. , 1998, General hospital psychiatry.

[25]  R. Carney,et al.  Cognitive Behavior Therapy, Relaxation Training, and Tricyclic Antidepressant Medication in the Treatment of Depression , 1995, Psychological reports.

[26]  Gerhard Andersson,et al.  Adding psychotherapy to pharmacotherapy in the treatment of depressive disorders in adults: a meta-analysis. , 2009, The Journal of clinical psychiatry.

[27]  S. Stahl Comprar Stahl's Essential Psychopharmacology. Neuroscientific Basis and Practical Applications | Stephen M. Stahl | 9780521857024 | Cambridge University Press , 2008 .

[28]  I. Lucki,et al.  Effects of diabetes on hippocampal neurogenesis: Links to cognition and depression , 2013, Neuroscience & Biobehavioral Reviews.

[29]  Theo Stijnen,et al.  Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. , 2010, Archives of general psychiatry.

[30]  R. Carney,et al.  Depression and Poor Glycemic Control , 2000 .

[31]  Risk factors for heart disease and stroke among diabetic persons, by disability status. , 2005, Journal of diabetes and its complications.

[32]  Ali H Mokdad,et al.  The association of depression and anxiety with obesity and unhealthy behaviors among community-dwelling US adults. , 2008, General hospital psychiatry.

[33]  K. Freedland,et al.  Cognitive behavior therapy for depression in type 2 diabetes mellitus. A randomized, controlled trial. , 1998, Annals of internal medicine.

[34]  Mark Olfson,et al.  Proportion of antidepressants prescribed without a psychiatric diagnosis is growing. , 2011, Health affairs.

[35]  Meena Kumari,et al.  Prospective study of social and other risk factors for incidence of type 2 diabetes in the Whitehall II study. , 2004, Archives of internal medicine.

[36]  R. Sapolsky,et al.  The role of the hippocampus in feedback regulation of the hypothalamic-pituitary-adrenocortical axis. , 1991, Endocrine reviews.

[37]  F. Wolf Standards of Medical Care in Diabetes—2014 , 2013, Diabetes Care.

[38]  J. Feighner,et al.  Diagnostic criteria for use in psychiatric research. , 1972, Archives of general psychiatry.

[39]  S. Hollon,et al.  A review of empirically supported psychological therapies for mood disorders in adults , 2010, Depression and anxiety.

[40]  Thomas Hagen,et al.  Hippocampal volume reduction and HPA-system activity in major depression. , 2007, Journal of psychiatric research.

[41]  Richard W Grant,et al.  Depression, Self-Care, and Medication Adherence in Type 2 Diabetes , 2007, Diabetes Care.

[42]  R. Holman,et al.  Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study , 2000, BMJ : British Medical Journal.

[43]  Michael W Kattan,et al.  Meta-analysis: Its strengths and limitations. , 2008, Cleveland Clinic journal of medicine.

[44]  L. Egede,et al.  Depression and all-cause and coronary heart disease mortality among adults with and without diabetes. , 2005, Diabetes care.

[45]  A. Convit,et al.  A blunted cortisol awakening response and hippocampal atrophy in type 2 diabetes mellitus , 2009, Psychoneuroendocrinology.

[46]  N. Clark,et al.  Standards of Medical Care in Diabetes: Response to Power , 2006 .

[47]  R. DeRubeis,et al.  Effect of cognitive therapy with antidepressant medications vs antidepressants alone on the rate of recovery in major depressive disorder: a randomized clinical trial. , 2014, JAMA psychiatry.

[48]  J. Eriksson,et al.  Quality of life and metabolic status in mildly depressed women with type 2 diabetes treated with paroxetine: A single-blind randomised placebo controlled trial , 2003, BMC family practice.

[49]  R. Carney,et al.  The Depression Interview and Structured Hamilton (DISH): Rationale, Development, Characteristics, and Clinical Validity , 2002, Psychosomatic medicine.

[50]  R. Carney,et al.  Depression and Coronary Heart Disease in Women With Diabetes , 2003, Psychosomatic medicine.

[51]  O. Franco,et al.  Bidirectional association between depression and type 2 diabetes mellitus in women. , 2010, Archives of internal medicine.

[52]  K. Khunti,et al.  The prevalence of co‐morbid depression in adults with Type 2 diabetes: a systematic review and meta‐analysis , 2006, Diabetic medicine : a journal of the British Diabetic Association.

[53]  S. Hollon,et al.  Specificity of depressotypic cognitions in clinical depression. , 1986, Journal of abnormal psychology.

[54]  S. Kennedy,et al.  The effect of antidepressants on glucose homeostasis and insulin sensitivity: synthesis and mechanisms , 2006, Expert opinion on drug safety.

[55]  D. Ford,et al.  Depression and Risk for Onset of Type II Diabetes: A prospective population-based study , 1996, Diabetes Care.

[56]  Irl B Hirsch,et al.  The relationship of depressive symptoms to symptom reporting, self-care and glucose control in diabetes. , 2003, General hospital psychiatry.

[57]  H. Anisman,et al.  Central ghrelin signaling mediates the metabolic response of C57BL/6 male mice to chronic social defeat stress. , 2013, Endocrinology.

[58]  J. Meigs,et al.  Correlates of health-related quality of life in type 2 diabetes , 2006, Diabetologia.

[59]  M. Ezzati,et al.  National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants , 2011, The Lancet.

[60]  A. Ellis,et al.  Handbook of Rational-Emotive Therapy , 1986 .

[61]  J. Eriksson,et al.  Quality of life and metabolic status in mildly depressed patients with type 2 diabetes treated with paroxetine: A double-blind randomised placebo controlled 6-month trial , 2007 .

[62]  F. Pouwer,et al.  Type 2 diabetes mellitus as a risk factor for the onset of depression: a systematic review and meta-analysis , 2010, Diabetologia.

[63]  J. Chan,et al.  Erratum to "Effect of interventions for major depressive disorder and significant depressive symptoms in patients with diabetes mellitus : A systematic review and meta-analysis" [General Hospital Psychiatry 32 (2010) 380-395] , 2010 .

[64]  F. Pouwer,et al.  Depression and Type 2 Diabetes Over the Lifespan: A Meta-Analysis , 2009, Diabetes Care.

[65]  伸二 鍵本 おさえておきたい 糖尿病の海外文献 ●文献●Depression and advanced complications of diabetes: a prospective cohort study. うつと糖尿病進行合併症:前向きコホート研究 , 2010 .

[66]  Stafford L. Lightman,et al.  The HPA axis in major depression: classical theories and new developments , 2008, Trends in Neurosciences.

[67]  P. de Jonge,et al.  Depressive disorder and incident diabetes mellitus: the effect of characteristics of depression. , 2010, The American journal of psychiatry.

[68]  J. Manson,et al.  Use of antidepressant medication and risk of type 2 diabetes: results from three cohorts of US adults , 2011, Diabetologia.

[69]  Nicky J Welton,et al.  Evidence Synthesis for Decision Making in Healthcare , 2012 .

[70]  M. Hernandez-Tejada,et al.  Effect of comorbid depression on quality of life in adults with Type 2 diabetes , 2013, Expert review of pharmacoeconomics & outcomes research.

[71]  H. Baumeister,et al.  Psychological and pharmacological interventions for depression in patients with diabetes mellitus and depression. , 2012, The Cochrane database of systematic reviews.

[72]  S. Weyerer,et al.  Psychiatric disorders and diabetes--results from a community study. , 1989, Journal of psychosomatic research.

[73]  J. Manson,et al.  Depressive symptoms and risk of type 2 diabetes in women. , 2004, Diabetes care.

[74]  K. Freedland,et al.  Association of Depression and Diabetes Complications: A Meta-Analysis , 2001, Psychosomatic medicine.

[75]  S. Norris,et al.  Depressive symptoms and mortality among persons with and without diabetes. , 2005, American journal of epidemiology.

[76]  Philippe Moulin,et al.  Associations Between Anxiety, Depression, and the Metabolic Syndrome , 2007, Biological Psychiatry.

[77]  R. Carney,et al.  Depression and the Reporting of Diabetes Symptoms , 1989, International journal of psychiatry in medicine.

[78]  P. Areán,et al.  Patients With Type 2 Diabetes at Risk for Major Depressive Disorder Over Time , 2011, The Annals of Family Medicine.

[79]  Heleen Riper,et al.  Web-Based Depression Treatment for Type 1 and Type 2 Diabetic Patients , 2011, Diabetes Care.

[80]  A. Malla,et al.  Recurrent Subthreshold Depression in Type 2 Diabetes: An Important Risk Factor for Poor Health Outcomes , 2014, Diabetes Care.

[81]  Olga V. Demler,et al.  The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). , 2003, JAMA.

[82]  W. Katon,et al.  Depression and incident diabetic retinopathy: a prospective cohort study. , 2011, General hospital psychiatry.

[83]  S. Newman,et al.  History of depression increases risk of type 2 diabetes in younger adults. , 2005, Diabetes care.

[84]  A. Beck,et al.  Psychometric properties of the Beck Depression Inventory: Twenty-five years of evaluation , 1988 .

[85]  I. Kirsch Antidepressant drugs 'work', but they are not clinically effective. , 2008, British journal of hospital medicine.

[86]  M. Olfson,et al.  National patterns in antidepressant medication treatment. , 2009, Archives of general psychiatry.

[87]  I. Kirsch,et al.  The Emperor's New Drugs: An Analysis of Antidepressant Medication Data Submitted to the U.S. Food and Drug Administration , 2002 .

[88]  G. Andersson,et al.  The contribution of active medication to combined treatments of psychotherapy and pharmacotherapy for adult depression: a meta‐analysis , 2009, Acta psychiatrica Scandinavica.

[89]  Q. Gu,et al.  Antidepressant use in persons aged 12 and over: United States, 2005-2008. , 2011, NCHS data brief.

[90]  P. Lustman,et al.  Fluoxetine for Depression in Diabetes , 2000 .

[91]  Jason S. Snyder,et al.  Adult hippocampal neurogenesis buffers stress responses and depressive behavior , 2011, Nature.

[92]  K. Matthews,et al.  Depressive Symptoms, Insulin Resistance, and Risk of Diabetes in Women at Midlife , 2004 .

[93]  S. Bandinelli,et al.  Hypercortisolemic depression is associated with the metabolic syndrome in late-life , 2007, Psychoneuroendocrinology.

[94]  W. Polonsky,et al.  Assessing psychosocial distress in diabetes: development of the diabetes distress scale. , 2005, Diabetes care.

[95]  D. Kupfer,et al.  National Depressive and Manic-Depressive Association consensus statement on the use of placebo in clinical trials of mood disorders. , 2002, Archives of general psychiatry.

[96]  M. Hamon,et al.  Repeated social defeat-induced depression-like behavioral and biological alterations in rats: involvement of cholecystokinin , 2008, Molecular Psychiatry.

[97]  B. Lebowitz,et al.  Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. , 2006, The American journal of psychiatry.

[98]  Evette Ludman,et al.  The association of comorbid depression with mortality in patients with type 2 diabetes. , 2005, Diabetes care.

[99]  I. Heuser,et al.  Major depression and impaired glucose tolerance , 2000, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[100]  Nicky J Welton,et al.  Evidence Synthesis for Decision Making in Healthcare: Welton/Evidence Synthesis for Decision Making in Healthcare , 2012 .

[101]  E. Nestler,et al.  A Novel Role of the WNT-Dishevelled-GSK3β Signaling Cascade in the Mouse Nucleus Accumbens in a Social Defeat Model of Depression , 2011, The Journal of Neuroscience.