Current Diabetes Reports

, Volume 11, Issue 4, pp 275–284 | Cite as

Painful Diabetic Neuropathy is More than Pain Alone: Examining the Role of Anxiety and Depression as Mediators and Complicators

  • Rakesh Jain
  • Shailesh Jain
  • Charles L. Raison
  • Vladimir Maletic


A wealth of information exists regarding the plight of patients suffering with diabetic peripheral neuropathic pain (DPNP). Although physical pain is certainly a primary challenge in the management of this condition, disorders associated with emotional pain—especially depression and anxiety—also greatly complicate the clinician’s efforts to attain optimal outcomes for DPNP patients. This article reviews the high rate of comorbidity between DPNP and depression/anxiety with a focus on why this pattern of comorbidity exists and what can be done about it. To accomplish this, the many physiologic similarities between neuropathic pain and depression/anxiety are reviewed as a basis for better understanding how, and why, optimal treatment strategies use behavioral and pharmacologic modalities known to improve both physical pain and symptoms of depression and anxiety. We conclude by highlighting that screening, diagnosing, and optimally treating comorbid depression/anxiety not only improves quality of life, these but also positively impacts DPNP pain.


Diabetes mellitus Diabetic peripheral neuropathic pain (DPNP) Major depression Depressive symptoms Anxiety Prevalence Inflammation Peripheral nerves Central sensitization Kindling Serotonin reuptake inhibitors Serotonin-norepinephrine reuptake inhibitors Duloxetine Pregabalin α-2-δ ligands Tricyclic antidepressants Psychotherapy, Cognitive behavior l therapy Screening instruments 



Conflicts of interest: R. Jain: is on the advisory boards and speakers panels for Eli Lilly, Pfizer, Forest Pharmaceuticals, and Takeda Pharmaceutical Co.; S. Jain: none; C.L. Raison: none; V. Maletic: is on the advisory boards and speakers panels for Eli Lilly, Pfizer, Forest Pharmaceuticals, and Takeda Pharmaceutical Co.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Daly M. Diabetes and depression–a risky combination. Nurs N Z. 2010;16(2):14–5.PubMedGoogle Scholar
  2. 2.
    • Bair MJ et al. Prevalence of pain and association with quality of life, depression and glycaemic control in patients with diabetes. Diabet Med. 2010; 27(5):578–84. This article demonstrates the significant association between diabetes and pain.PubMedCrossRefGoogle Scholar
  3. 3.
    Kessler RC, McGonagle KA, Zhao S, Nelson CB. Lifetime and 12 month prevalence of DSM-III-R psychiatric disorders in the United States. Arch Gen Psychiatry. 1994;51:8–19.PubMedGoogle Scholar
  4. 4.
    Michaud CM, Murray CJ, Bloom BR. Burden of disease - implications for future research. JAMA. 2001;285(5):535–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Vehik K, Dabelea D. The changing epidemiology of type 1 diabetes: why is it going through the roof? Diabetes Metab Res Rev. 2010.Google Scholar
  6. 6.
    Farag YM, Gaballa MR. Diabesity: an overview of a rising epidemic. Nephrol Dial Transplant. 2011;26(1):28–35.PubMedCrossRefGoogle Scholar
  7. 7.
    • Li C et al. Diabetes and anxiety in US adults: findings from the 2006 behavioral risk factor surveillance system. Diabet Med. 2008; 25(7):878–81. This article articulates the issue of anxiety disorders in adults with diabetes.PubMedCrossRefGoogle Scholar
  8. 8.
    Collins MM, Corcoran P, Perry IJ. Anxiety and depression symptoms in patients with diabetes. Diabet Med. 2009;26(2):153–61.PubMedCrossRefGoogle Scholar
  9. 9.
    Gore M, Brandenburg N, Dukes E, Hoffman DL, Tai KS, Stacey B. Pain severity in diabetic peripheral neuropathy is associated with patient functioning, symptom levels of anxiety and depression, and sleep. J Pain Symptom Manage. 2005;30(4):374–85.PubMedCrossRefGoogle Scholar
  10. 10.
    de Groot M, Anderson R, Freedland KE, Clouse RE, Lustman PJ. Association of depressive and diabetic complications: a meta-analysis. Psychosom Med. 2001;63(4):619–30.PubMedGoogle Scholar
  11. 11.
    Waitzfelder B et al. Correlates of depression among people with diabetes: The Translating Research Into Action for Diabetes (TRIAD) study. Prim Care Diabetes. 2010;4(4):215–22.PubMedCrossRefGoogle Scholar
  12. 12.
    Pouwer F et al. Prevalence of comorbid depression is high in out-patients with Type 1 or Type 2 diabetes mellitus. Results from three out-patient clinics in the Netherlands. Diabet Med. 2010;27(2):217–24.PubMedCrossRefGoogle Scholar
  13. 13.
    Yoshida S et al. Neuropathy is associated with depression independently of health-related quality of life in Japanese patients with diabetes. Psychiatry Clin Neurosci. 2009;63(1):65–72.PubMedCrossRefGoogle Scholar
  14. 14.
    Sulaiman N, Handam A, Tamim H, Mahmood DA, Young D, The prevalence and coorelates of depression and anxiety in a sampe of diabetic patients in Sharjah, United Arab Emirates. BMC Fam Pract. 2010; 11.Google Scholar
  15. 15.
    Raval A, Dhanaraj E, Bhansali A, Grover S, Tiwari P. Prevalence and determinants of depression in type 2 diabetes patients in a tertiary care centre. Indian J Med Res. 2010;132:195–200.PubMedGoogle Scholar
  16. 16.
    Wagner JA, Tennen H, Osborn CY. Lifetime depression and diabetes self-management in women with Type 2 diabetes: a case-control study. Diabet Med. 2010;27(6):713–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Katon WJ et al. The relationship between changes in depression symptoms and changes in health risk behaviors in patients with diabetes. Int J Geriatr Psychiatry. 2010;25(5):466–75.PubMedCrossRefGoogle Scholar
  18. 18.
    Rubin RR et al. Cardiovascular disease risk factors, depression symptoms and antidepressant medicine use in the Look AHEAD (Action for Health in Diabetes) clinical trial of weight loss in diabetes. Diabetologia. 2010;53(8):1581–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Ahola AJ et al. Depression is associated with the metabolic syndrome among patients with type 1 diabetes. Ann Med. 2010;42(7):495–501.PubMedCrossRefGoogle Scholar
  20. 20.
    Raval A et al. Prevalence & determinants of depression in type 2 diabetes patients in a tertiary care centre. Indian J Med Res. 2010;132:195–200.PubMedGoogle Scholar
  21. 21.
    Herzer M, Hood KK. Anxiety symptoms in adolescents with type 1 diabetes: association with blood glucose monitoring and glycemic control. J Pediatr Psychol. 2010;35(4):415–25.PubMedCrossRefGoogle Scholar
  22. 22.
    Le TK, Able SL, Lage MJ. Resource use among patients with diabetes, diabetic neuropathy, or diabetes with depression. Cost Eff Resour Alloc. 2006;4:18.PubMedCrossRefGoogle Scholar
  23. 23.
    Boulanger L, Zhao Y, Bao Y, Russell MW. A retrospective study on the impact of comorbid depression or anxiety on healthcare resource use and costs among diabetic neuropathy patients. BMC Health serv Res. 2009; 9(111).Google Scholar
  24. 24.
    Lin EH et al. Depression and advanced complications of diabetes: a prospective cohort study. Diabetes Care. 2010;33(2):264–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Ali S et al. The association between depression and health-related quality of life in people with type 2 diabetes: a systematic literature review. Diabetes Metab Res Rev. 2010;26(2):75–89.PubMedCrossRefGoogle Scholar
  26. 26.
    •• Pouwer F, Kupper N, Adriaanse MC. Does emotional stress cause type 2 diabetes mellitus? A review from the European Depression in Diabetes (EDID) Research Consortium. Discov Med. 2010; 9(45):112–8. This thought-provoking article asks an important question: does stress act as a catalyst for the development of type 2 diabetes (and presumably its complications) in a prospective fashion? PubMedGoogle Scholar
  27. 27.
    • Pan A et al. Bidirectional association between depression and type 2 diabetes mellitus in women. Arch Intern Med. 2010; 170(21):1884–91. This article offers a well-reasoned look at the data on the bi-irectional nature of diabetes and depression.PubMedCrossRefGoogle Scholar
  28. 28.
    Atlantis E et al. Diabetes incidence associated with depression and antidepressants in the Melbourne Longitudinal Studies on Healthy Ageing (MELSHA). Int J Geriatr Psychiatry. 2010;25(7):688–96.PubMedCrossRefGoogle Scholar
  29. 29.
    Nouwen A et al. Type 2 diabetes mellitus as a risk factor for the onset of depression: a systematic review and meta-analysis. Diabetologia. 2010;53(12):2480–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Vinik AI et al. Diabetic neuropathy in older adults. Clin Geriatr Med. 2008;24(3):407–35. v.PubMedCrossRefGoogle Scholar
  31. 31.
    Costigan M, Scholz J, Woolf CJ. Neuropathic pain: a maladaptive response of the nervous system to damage. Annual Review of Neuroscience. 2009;32(1):1–32.PubMedCrossRefGoogle Scholar
  32. 32.
    • Doupis J et al. Microvascular reactivity and inflammatory cytokines in painful and painless peripheral diabetic neuropathy. J Clin Endocrinol Metab. 2009; 94(6):2157–63. This is an excellent review of the issue of inflammatory cytokines in DPNP.PubMedCrossRefGoogle Scholar
  33. 33.
    Scholz J, Woolf CJ. Can we conquer pain? Nat Neurosci. 2002;5(Suppl):1062–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci. 2007;10(11):1361–8.PubMedCrossRefGoogle Scholar
  35. 35.
    • Maletic V, Raison CL. Neurobiology of depression, fibromyalgia and neuropathic pain. Front Biosci. 2009; 14:5291–338. This article offers a comprehensive review of the shared neurobiology of pain and depression.PubMedCrossRefGoogle Scholar
  36. 36.
    Baron R. Mechanisms of disease: neuropathic pain–a clinical perspective. Nat Clin Pract Neurol. 2006;2(2):95–106.PubMedCrossRefGoogle Scholar
  37. 37.
    Marx J. Pain research. Prolonging the agony. Science. 2004;305(5682):326–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Moalem G, Tracey DJ. Immune and inflammatory mechanisms in neuropathic pain. Brain Res Rev. 2006;51(2):240–64.PubMedCrossRefGoogle Scholar
  39. 39.
    Ji RR et al. Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci. 2003;26(12):696–705.PubMedCrossRefGoogle Scholar
  40. 40.
    Ren K, Dubner R. Neuron-glia crosstalk gets serious: role in pain hypersensitivity. Curr Opin Anaesthesiol. 2008;21(5):570–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Yunus MB. Role of central sensitization in symptoms beyond muscle pain, and the evaluation of a patient with widespread pain. Best Pract Res Clin Rheumatol. 2007;21(3):481–97.PubMedCrossRefGoogle Scholar
  42. 42.
    Woolf CJ, Mannion RJ. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet. 1999;353(9168):1959–64.PubMedCrossRefGoogle Scholar
  43. 43.
    Kendler KS, Thornton LM, Gardner CO. Stressful life events and previous episodes in the etiology of major depression in women: an evaluation of the “kindling” hypothesis. Am J Psychiatry. 2000;157(8):1243–51.PubMedCrossRefGoogle Scholar
  44. 44.
    Post RM. Kindling and sensitization as models for affective episode recurrence, cyclicity, and tolerance phenomena. Neurosci Biobehav Rev. 2007;31(6):858–73.PubMedCrossRefGoogle Scholar
  45. 45.
    Miller L. Neurosensitization: A model for persistent disability in chronic pain, depression, and posttraumatic stress disorder following injury. NeuroRehabilitation. 2000;14(1):25–32.PubMedGoogle Scholar
  46. 46.
    Dadabhoy D et al. Biology and therapy of fibromyalgia. Evidence-based biomarkers for fibromyalgia syndrome. Arthritis Res Ther. 2008;10(4):211.PubMedCrossRefGoogle Scholar
  47. 47.
    Tracey I, Mantyh PW. The cerebral signature for pain perception and its modulation. Neuron. 2007;55(3):377–91.PubMedCrossRefGoogle Scholar
  48. 48.
    Blackburn-Munro G, Blackburn-Munro RE. Chronic pain, chronic stress and depression: coincidence or consequence? J Neuroendocrinol. 2001;13(12):1009–23.PubMedCrossRefGoogle Scholar
  49. 49.
    Schweinhardt P et al. Investigation into the neural correlates of emotional augmentation of clinical pain. Neuroimage. 2008;40(2):759–66.PubMedCrossRefGoogle Scholar
  50. 50.
    Borsook D et al. Neuroimaging revolutionizes therapeutic approaches to chronic pain. Mol Pain. 2007;3:25.PubMedCrossRefGoogle Scholar
  51. 51.
    Zhuo M. Cortical excitation and chronic pain. Trends Neurosci. 2008;31(4):199–207.PubMedCrossRefGoogle Scholar
  52. 52.
    Apkarian AV et al. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005;9(4):463–84.PubMedCrossRefGoogle Scholar
  53. 53.
    Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27(1):24–31.PubMedCrossRefGoogle Scholar
  54. 54.
    Neugebauer V et al. The amygdala and persistent pain. Neuroscientist. 2004;10(3):221–34.PubMedCrossRefGoogle Scholar
  55. 55.
    Apkarian AV et al. Chronic back pain is associated with decreased prefrontal and thalamic gray matter density. J Neurosci. 2004;24(46):10410–5.PubMedCrossRefGoogle Scholar
  56. 56.
    Sorensen L et al. Differences in metabolites in pain-processing brain regions in patients with diabetes and painful neuropathy. Diabetes Care. 2008;31(5):980–1.PubMedCrossRefGoogle Scholar
  57. 57.
    Cauda F et al. Altered resting state in diabetic neuropathic pain. PLoS ONE. 2009;4(2):e4542.PubMedCrossRefGoogle Scholar
  58. 58.
    Cauda F et al. Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in diabetic neuropathic pain. BMC Neurosci. 2009;10:138.PubMedCrossRefGoogle Scholar
  59. 59.
    Frodl T et al. Effect of hippocampal and amygdala volumes on clinical outcomes in major depression: a 3-year prospective magnetic resonance imaging study. J Psychiatry Neurosci. 2008;33(5):423–30.PubMedGoogle Scholar
  60. 60.
    Matthews SC et al. Decreased functional coupling of the amygdala and supragenual cingulate is related to increased depression in unmedicated individuals with current major depressive disorder. J Affect Disord. 2008;111(1):13–20.PubMedCrossRefGoogle Scholar
  61. 61.
    Baliki MN et al. Chronic pain and the emotional brain: specific brain activity associated with spontaneous fluctuations of intensity of chronic back pain. J Neurosci. 2006;26(47):12165–73.PubMedCrossRefGoogle Scholar
  62. 62.
    Goncalves L et al. Neuropathic pain is associated with depressive behaviour and induces neuroplasticity in the amygdala of the rat. Exp Neurol. 2008;213(1):48–56.PubMedCrossRefGoogle Scholar
  63. 63.
    Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res. 2002;53(4):865–71.PubMedCrossRefGoogle Scholar
  64. 64.
    Strouse TB. The relationship between cytokines and pain/depression: a review and current status. Curr Pain Headache Rep. 2007;11(2):98–103.PubMedCrossRefGoogle Scholar
  65. 65.
    Rajkowska G, Miguel-Hidalgo JJ. Gliogenesis and glial pathology in depression. CNS Neurol Disord Drug Targets. 2007;6(3):219–33.PubMedCrossRefGoogle Scholar
  66. 66.
    Pav M et al. Neurobiological aspects of depressive disorder and antidepressant treatment: role of glia. Physiol Res. 2008;57(2):151–64.PubMedGoogle Scholar
  67. 67.
    McNally L, Bhagwagar Z, Hannestad J. Inflammation, glutamate, and glia in depression: a literature review. CNS Spectr. 2008;13(6):501–10.PubMedGoogle Scholar
  68. 68.
    Tsuda M, Inoue K, Salter MW. Neuropathic pain and spinal microglia: a big problem from molecules in “small” glia. Trends Neurosci. 2005;28(2):101–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Zieglgansberger W, Berthele A, Tolle TR. Understanding neuropathic pain. CNS Spectr. 2005;10(4):298–308.PubMedGoogle Scholar
  70. 70.
    Chapman CR, Tuckett RP, Song CW. Pain and stress in a systems perspective: reciprocal neural, endocrine, and immune interactions. J Pain. 2008;9(2):122–45.PubMedCrossRefGoogle Scholar
  71. 71.
    Wieseler-Frank J, Maier SF, Watkins LR. Immune-to-brain communication dynamically modulates pain: physiological and pathological consequences. Brain Behav Immun. 2005;19(2):104–11.PubMedCrossRefGoogle Scholar
  72. 72.
    Acee AM. Detecting and managing depression in type II diabetes: PHQ-9 is the answer! Medsurg Nurs. 2010;19(1):32–8.PubMedGoogle Scholar
  73. 73.
    van Steenbergen-Weijenburg KM et al. Validation of the PHQ-9 as a screening instrument for depression in diabetes patients in specialized outpatient clinics. BMC Health Serv Res. 2010;10:235.PubMedCrossRefGoogle Scholar
  74. 74.
    Brennan C et al. The hospital anxiety and depression scale: a diagnostic meta-analysis of case-finding ability. J Psychosom Res. 2010;69(4):371–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Lloyd CE, Dyer PH, Barnett AH. Prevalence of symptoms of depression and anxiety in a diabetes clinic population. Diabet Med. 2000;17(3):198–202.PubMedCrossRefGoogle Scholar
  76. 76.
    Spitzer RL et al. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166(10):1092–7.PubMedCrossRefGoogle Scholar
  77. 77.
    Lowe B et al. Validation and standardization of the Generalized Anxiety Disorder Screener (GAD-7) in the general population. Med Care. 2008;46(3):266–74.PubMedCrossRefGoogle Scholar
  78. 78.
    • Reddy P et al. Identification of depression in diabetes: the efficacy of PHQ-9 and HADS-D. Br J Gen Pract. 2010; 60(575):239–45. This article offers a fair balanced review of the benefits and potential pitfalls of using PHQ-9 and HADS-D in DPNP patients.CrossRefGoogle Scholar
  79. 79.
    Gonzalez JS, Esbitt SA. Depression and treatment nonadherence in type 2 diabetes: assessment issues and an integrative treatment approach. Epidemiol Psichiatr Soc. 2010;19(2):110–5.PubMedGoogle Scholar
  80. 80.
    Fortmann AL et al. Support for disease management, depression, self-care, and clinical indicators among Hispanics with type 2 diabetes in San Diego County, United States of America. Rev Panam Salud Publica. 2010;28(3):230–4.PubMedCrossRefGoogle Scholar
  81. 81.
    Echeverry D et al. Effect of pharmacological treatment of depression on A1C and quality of life in low-income Hispanics and African Americans with diabetes: a randomized, double-blind, placebo-controlled trial. Diabetes Care. 2009;32(12):2156–60.PubMedCrossRefGoogle Scholar
  82. 82.
    Bogner HR, de Vries HF. Integrating type 2 diabetes mellitus and depression treatment among African Americans: a randomized controlled pilot trial. Diabetes Educ. 2010;36(2):284–92.PubMedCrossRefGoogle Scholar
  83. 83.
    Ell K et al. Collaborative care management of major depression among low-income, predominantly Hispanic subjects with diabetes: a randomized controlled trial. Diabetes Care. 2010;33(4):706–13.PubMedCrossRefGoogle Scholar
  84. 84.
    • Ismail K et al. A randomised controlled trial of cognitive behaviour therapy and motivational interviewing for people with Type 1 diabetes mellitus with persistent sub-optimal glycaemic control: a Diabetes and Psychological Therapies (ADaPT) study. Health Technol Assess. 2010; 14(22):1–101, iii-iv. This article demosntates the importnace of nonpharmacologic interventions in diabetes. PubMedGoogle Scholar
  85. 85.
    van Bastelaar K et al. Development and reach of a web-based cognitive behavioural therapy programme to reduce symptoms of depression and diabetes-specific distress. Patient Educ Couns. 2010.Google Scholar
  86. 86.
    Kuritzky L. Managing diabetic peripheral neuropathic pain in primary care. J Fam Pract. 2010;59(5 Suppl):S15–22.PubMedGoogle Scholar
  87. 87.
    Tesfaye S. Advances in the management of diabetic peripheral neuropathy. Curr Opin Support Palliat Care. 2009;3(2):136–43.PubMedCrossRefGoogle Scholar
  88. 88.
    Greist JH et al. Depression and pain. J Clin Psychiatry. 2008;69(12):1970–8.PubMedCrossRefGoogle Scholar
  89. 89.
    Smink BE, Egberts ACG, Lusthof KJ. The relationship between benzodiazepine use and traffic accident: a systematic litreature review. CNS Drugs. 2010;24(8):639–53.PubMedCrossRefGoogle Scholar
  90. 90.
    Uzun S et al. Side effects of treatment with benzodiazepines. Psychiatr Danub. 2010;22(1):90–3.PubMedGoogle Scholar
  91. 91.
    Skljarevski V et al. Evaluating the maintenance of effect of duloxetine in patients with diabetic peripheral neuropathic pain. Diabetes Metab Res Rev. 2009;25(7):623–31.PubMedCrossRefGoogle Scholar
  92. 92.
    Rynn M et al. Efficacy and safety of duloxetine in the treatment of generalized anxiety disorder: a flexible-dose, progressive-titration, placebo-controlled trial. Depress Anxiety. 2008;25(3):182–9.PubMedCrossRefGoogle Scholar
  93. 93.
    Kornstein SG et al. A randomized, double-blind study of increasing or maintaining duloxetine dose in patients without remission of major depressive disorder after initial duloxetine therapy. J Clin Psychiatry. 2008;69(9):1383–92.PubMedCrossRefGoogle Scholar
  94. 94.
    Abrahamian H et al. Diabetes mellitus and co-morbid depression: treatment with milnacipran results in significant improvement of both diseases (results from the Austrian MDDM study group). Neuropsychiatr Dis Treat. 2009;5:261–6.PubMedCrossRefGoogle Scholar
  95. 95.
    Lieberman DZ, Massey SH. Desvenlafaxine in major depressive disorder: an evidence-based review of its place in therapy. Core Evid. 2010;4:67–82.PubMedGoogle Scholar
  96. 96.
    Pae CU et al. Milnacipran: beyond a role of antidepressant. Clin Neuropharmacol. 2009;32(6):355–63.PubMedCrossRefGoogle Scholar
  97. 97.
    Golden RN, Nicholas L. Antidepressant efficacy of venlafaxine. Depress Anxiety. 2000;12 Suppl 1:45–9.PubMedCrossRefGoogle Scholar
  98. 98.
    Di Guilmi MN et al. Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of CaV2.1 calcium channels. J Pharmacol Exp Ther. 2010.Google Scholar
  99. 99.
    Satosh J, Yagihashi S, Baba M, Suzuki M. Efficacy and safety of pregabalin for treating neuropathic pain associated with diabetic peripheral neuropathy: a 14 week, randomized, double blind, placebo-controlled trial. Diabet Med. 2011;28(1):109–16.CrossRefGoogle Scholar
  100. 100.
    Montgomery SA, Herman BK, Schweizer E. The efficacy of pregabalin and benzodiazepines in generalized anxiety disorder presenting with high levels of insomnia. Int Clin Psychopharmacology. 2009;24(4):214–22.CrossRefGoogle Scholar
  101. 101.
    Bryan C et al. The impact of diabetes on depression treatment outcomes. Gen Hosp Psychiatry. 2010;32(1):33–41.PubMedCrossRefGoogle Scholar
  102. 102.
    Osborn CY, Kozak C, Wagner J. Theory in practice: helping providers address depression in diabetes care. J Contin Educ Health Prof. 2010;30(3):172–9.PubMedCrossRefGoogle Scholar
  103. 103.
    Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Arlington, VA: APA Press; 2000.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Rakesh Jain
    • 1
    • 6
  • Shailesh Jain
    • 2
  • Charles L. Raison
    • 3
  • Vladimir Maletic
    • 4
    • 5
  1. 1.Department of PsychiatryTexas Tech Health Sciences Center Medical School at Permian BasinMidlandUSA
  2. 2.Department of PsychiatryTexas Tech Health Sciences Center Medical School at Permian BasinMidlandUSA
  3. 3.Department of Psychiatry and Behavioral SciencesEmory University School of MedicineAtlantaUSA
  4. 4.Department of Neuropsychiatry and Behavioral SciencesUniversity of South Carolina School of MedicineColumbiaUSA
  5. 5.GreerUSA
  6. 6.Lake JacksonUSA

Personalised recommendations