The Journal for Nurse Practitioners
Volume 5, Issue 7 , Pages 523-535, July 2009

Depression as a Comorbidity to Diabetes: Implications for Management

  • Andrea A. Riley

      Affiliations

    • Andrea A. Riley, MSN, MS, CNP, RD, is a family nurse practitioner at Hidalgo Medical Services in Lordsburg, NM.
    • ,
  • Mindy L. McEntee

      Affiliations

    • Mindy L. McEntee, MA, is a research assistant, in the Department of Health Systems and Outcomes at Johns Hopkins University School of Nursing in Baltimore, MD.
    • ,
  • Linda Gerson

      Affiliations

    • Linda D. Gerson, PhD, RN, PMHCNS-BC, is an assistant professor, in the Department of Health Systems and Outcomes at Johns Hopkins University School of Nursing in Baltimore, MD.
    • ,
  • Cheryl R. Dennison

      Affiliations

    • Cheryl R. Dennison, RN, ANP, PhD, FAHA is an associate professor in the Department of Health Systems and Outcomes at Johns Hopkins University School of Nursing in Baltimore, MD.

Article Outline

Abstract 

Research has established a link between depression and diabetes, even though the underlying mechanisms in this relationship remain unclear. Primary care providers are often responsible for managing these conditions and are well positioned to provide integrated care improving patients' physical and mental health outcomes, yet they face a number of barriers contributing to the inadequate management of depression in primary care. All diabetic patients should be routinely screened for depression; management of these concomitant conditions should use a comprehensive approach that may include medication or referral for psychotherapy. This paper explores the relationship between depression and diabetes and implications for practice in the areas of screening, diagnosis, and management of depression in diabetic patients.

Keywords:  depression , diabetes , management , primary care , screening

 

The odds of having depression among individuals with type 1 or 2 diabetes are more than twice that of non-diabetics,1 with an estimated 33% of diabetics experiencing depressive symptoms severe enough to warrant treatment at any single point in time.2 The course of depression in these individuals is often chronic3 and may adversely affect the course of coexisting medical conditions.4, 5, 6 A number of studies have found depression to be associated with poor self-care in people with diabetes.7, 8, 9, 10, 11, 12, 13 Decreased adherence to medication,7, 10, 13, 14, 15 diet,7, 8, 13, 14 exercise,8, 11, 13 and blood glucose monitoring13 may contribute to increased diabetic symptoms,8, 16 glucose dysregulation,17, 18, 19 diabetic complications,18, 20, 21 mortality,22, 23, 24 decreased physical7, 8, 25 and mental functioning,7, 26 lower quality of life,7, 27 and increased healthcare utilization7, 26, 28 associated with comorbid diabetes and depression.

Because primary care providers (PCPs) are frequently charged with the management of type 2 diabetes and uncomplicated unipolar depression, they are well positioned to provide integrated care for these concomitant disorders.29 While the co-occurrence of these conditions is a widely known clinical phenomenon, depression remains under-recognized and inadequately treated in primary care.2, 13, 29, 30, 31, 32 To provide high-quality care optimizing physical and mental health outcomes for their patients, it is important that PCPs understand the relationship between depression and diabetes. This paper examines the etiologies of these comorbid conditions and discusses implications for practice in the areas of screening, diagnosis, and management of depression in the diabetic population.

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Relationship Between Diabetes and Depression 

The high prevalence of comorbid depression and diabetes suggests that these disorders may be related.33 Depression has been proposed as both a result of and precursor to diabetes, with this relationship attributed to a variety of mechanisms. Studies have examined a number of psychosocial and biological correlates of depression and diabetes, yet the causal relationship between these disorders, its direction, and underlying mechanisms remain unclear.31, 34

Depression as a Result of Diabetes 

Some authors have proposed that depression may stem from the psychosocial burden and/or biochemical changes related to diabetes and its treatment.1, 17, 18 This hypothesis may help explain why depression is more prevalent in diabetics than in the general population and is supported by the temporal finding among type 1 diabetics, in which diabetes typically precedes the onset of major depressive disorder (MDD).34 While there is little empirical data on the psychosocial facet of this theory, there is some evidence that emotional distress is mediated by perceived threat of illness,35, 36 self-esteem,37, 38 self-efficacy,35 coping skills,39 and social support.35, 37

Sociodemographic factors including younger age,21, 26, 40 female gender,1, 21, 26, 40, 41, 42, 43, 44 low socioeconomic status,26, 43, 45 ethnic minority status,21, 31, 41, 46 chronic stressors, and negative life events47 have also been identified as predictors of depression among individuals with diabetes, although a causal relationship has not been established.

The biological component of this hypothesis speculates that the metabolic consequences of diabetes lead to structural and functional changes in the brain that increase susceptibility to stress and depression,48 although data thus far have been inconclusive. The relationship between depression and glycemic control remains subject to debate; a meta-analysis of 26 studies found a significant relationship with comparable effect sizes in both type 1 and type 2 diabetes,17 yet other research did not find this correlation,42, 49, 50 or found it significant only for individuals with type 1 diabetes.51, 52 The connection between diabetic complications and depression has also produced mixed results;18, 31, 44, 53, 54, 55, 56, 57 these discrepancies may suggest that biochemical mechanisms have greater influence on the duration of depression rather than its initial onset.34

Depression as a Precursor to Diabetes 

An alternative hypothesis in which depression precedes and predisposes individuals to diabetes may explain the development of type 2 diabetes among patients diagnosed with depression several years earlier.58 This theory proposes that diabetes may develop via the psychosocial effects of depression, including adiposity and negative health behaviors like poor diet, physical activity, smoking, and medication adherence; and/or as a result of biological mechanisms such as activation of the HPA axis45, 59, 60, 61, 62 and inflammatory responses63, 64, 65, 66 that contribute to insulin resistance and decreased glucose uptake. A meta-analysis of 9 longitudinal studies showed that adults who were depressed were 37% more likely to develop type 2 diabetes than their non-depressed counterparts.67 Other studies have shown that this increased risk remains significant after controlling for known demographic and clinical risk factors.57, 68, 69, 70, 71, 72, 73, 74, 75 Adults receiving treatment for depression were still prone to developing diabetes,75, 76 with those taking a tricyclic antidepressant (TCA) and a selective serotonin reuptake inhibitor (SSRI) concurrently at greater risk (60%) than those prescribed either a TCA (44%) or SSRI (37%) alone.77

While research supports a trend in which depression precedes type 2 diabetes, causal mechanisms for this association remain speculative. A recent meta-analysis of 13 prospective studies found that while adverse psychosocial factors were associated with poor diabetes control in both type 1 and type 2 diabetes, they were not related to incidence of diabetes.78 Variations in the extent to which depression increased the risk of type 2 diabetes after accounting for known risk factors suggest that additional factors affect this relationship.44, 57, 70 Inflammatory markers interleukin-6 and C-reactive protein were elevated in depressed individuals and have been identified as risk factors for developing type 2 diabetes, yet models accounting for these variables were still unable to explain the association between depression and the incidence of type 2 diabetes in Golden et al.44 Knol et al found that insulin resistance was not related to depressive symptoms, further challenging the proposed mechanisms underlying this relationship.79

A Bidirectional Relationship 

Contradictory research findings suggest the relationship between depression and diabetes is complex and may differ for type 1 and type 2 diabetes. The factors underlying this relationship may be bidirectional and consist of multiple mechanisms and/or indirect causation. Golden et al found evidence for a bidirectional relationship within the same cohort; adults with treated type 2 diabetes who were depression-free at baseline were 52% more likely to experience depressive symptoms than non-diabetics, while adults with elevated depression scores were 21% more likely than those with low or normal symptoms to develop type 2 diabetes after adjusting for clinical, demographic, and lifestyle risk factors.44

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Screening and Diagnosis 

Although the link between depression and diabetes remains elusive, adverse effects can be minimized by adequate recognition and treatment. Because both conditions can produce similar somatic symptoms, concern has been raised that current diagnostic criteria for depression are not appropriate for the diabetic population.80 While rates of sympathetic arousal, gastrointestinal complaints, and fatigue are higher in depressed individuals with co-occurring medical conditions, the differences are modest and did not significantly affect the diagnostic process.81, 82 Depressed diabetics experienced a similar course of depression and were just as likely to respond to treatment as depressed individuals without diabetes, even though they reported lower levels of somatic well-being and contentment.83 Moreover, mean scores and symptom profiles on the Beck Depression Inventory (BDI) did not significantly differ between depressed individuals with diabetes and those without.80 These findings suggest that diagnostic criteria and screening methods currently accepted for use in the general population are also suitable for diabetic patients.

Current research suggests only 25% to 50% of diabetic patients with depression are identified in primary care.32, 84, 85 The American Diabetes Association (2008) advises regular screening throughout the course of diabetes management: at diagnosis, routine management visits, hospitalizations, when complications develop, or when problems with glucose control, quality of life, or adherence to self-care are identified.86 Administration of a brief depression screening tool should be included with annual screening for diabetes-related parameters.

Selectively screening individuals based on the presence of known risk factors alone is not recommended, as presence of these factors is not as reliable as use of brief screening tools in detecting depression.87 Providers should, however, be mindful of certain triggers in patients' medical history that may warrant additional screening, including unexplained psychosomatic symptoms, history of depression, comorbid psychological illnesses, chronic pain, substance abuse,87 or reported diabetes symptoms disproportionately high with respect to the course of diabetes.16 Patients with a personal history of depression or current anxiety disorder are significantly more likely to have depression and may warrant a diagnostic interview instead of initial screening.87

Depression Screening Tools 

While guidelines agree routine screening for depression is necessary, they provide little guidance on selecting the best measure(s) to do so.86, 87 Several self-report questionnaires have been validated to assess depressive symptoms in primary care patients, although their use in diabetic populations has received considerably less study. Nevertheless, several screening tools have demonstrated sound psychometric properties detecting depression in samples of primary care patients with diabetes (Table 1). In spite of differences in length, wording, and scoring criteria, each of these measures can be completed and scored within 5 to 10 minutes, allowing providers to follow up on the results of screening during the same visit.

Table 1. Depression Screening Tools for Use in Primary Care
Screening ToolPublic DomainNo. of ItemsTime to AdministerScore RangeUsual Cut-pointReliability & Validity in Primary Care PatientsReliability & Validity in Diabetic Patients
Beck Depression

Inventory II (BDI-II)

Beck et al 1996

No212–5 minutes0–63
14–19 = Mild

20–28 = Moderate

29–63 = Severe
Arnau 2001 – cutoff 18
Sensitivity 94%

Specificity 92%

AUC = 0.96


Dutton 2004 – cutoff 14
Cronbach α = 0.90

Sensitivity 88%

Specificity 84%

AUC = 0.91
Lustman 1997** – cutoff 13
Sensitivity 85%

Specificity 88%

AUC 0.94


**only original BDI

validated in this population

Beck Depression

Inventory for Primary Care (BDI-PC)

Beck et al 1997

No7<2 minutes0–21≥4
Steer 1999 – cutoff 4
Cronbach α = 0.85

Sensitivity 97%

Specificity 99%

AUC = 0.99


Beck 1997 outpatient – cutoff 6
Cronbach α = 0.88

Sensitivity 83%

Specificity 95%


n/a
Center for Epidemiological Studies

Depression Scale (CES-D)

Radloff et al 1977

Yes202–5 minutes0–60≥16
Whooley 1997 – cutoff 16
Sensitivity 88%

Specificity 74%

AUC = 0.89
Hermanns 2006 – cutoff 14
Sensitivity 79%

Specificity 89%

AUC = 0.80


McHale 2000 – cutoff 16
Sensitivity 71%

Specificity 71%

AUC = 0.81


Zauszniewski 2008 cutoff 16
Cronbach α = 0.87


Patient Health

Questionnaire – 9 (PHQ-9)

Kroenke 2001

Yes9<2 minutes0–27
5–9 = Mild

10–14 = Moderate

≥15 = Severe
Kroenke 2001 – cutoff ≥ 10
Cronbach α = 0.89

Sensitivity 88%

Specificity 88%

AUC = 0.95


Lowe 2002 – cutoff ≥10
Cronbach α = 0.88

Sensitivity 81%

Specificity 82%

AUC = 0.95
Kahn 2008 – cutoff ≥10
Sensitivity 66%

Specificity 52%


Lamers 2008 – cutoff ≥7
Sensitivity 92%

Specificity 81%


Patient Health

Questionnaire – 2 (PHQ-2)

Kroenke 2003

Yes2<1 minute0–6≥3
Kroenke 2003 – cutoff ≥3
Sensitivity 83%

Specificity 92%

AUC = 0.93


Brody 1998 – cutoff ≥ 3
Sensitivity 65%

Specificity 99%
Daly 2007 – cutoff ≥3
Sensitivity 83%

Specificity 92%


WHO-Five

Well-being Index (WHO-5)

World Health

Organization 1998

Yes5<2 minutes0–25<13
Henkel 2004 – cutoff <13
Sensitivity 94%

Specificity 63%

AUC = 0.91


Lowe 2002 – cutoff <13
Cronbach α = 0.91

Sensitivity 94%

Specificity 78%

AUC = 0.91
De Wit 2007 – cutoff <13
Cronbach α = 0.82

Sensitivity 89%

Specificity 86%


Awata 2007 – cutoff <13
Cronbach α = 0.89

Sensitivity 100%

Specificity 78%

AUC = 0.92


Zung Self-Rating

Depression Scale (SDS)

Zung 1965

Yes202-5 minutes0–100
50–59 = Mild

60-69 = Moderate

≥70 = Severe
Okimoto 1982 – cutoff ≥ 60
Sensitivity 82%

Specificity 87%
Rajala 1997 – cutoff > 55
Sensitivity 72%

Specificity 83%


AUC Area under the curve index for receiver operating characteristics (ROC) curve.

Beck Depression Inventory II

Beck AT, Steer RA, Brown GK. Beck Depression Inventory II Manual. San Antonio: The Psychological Corporation; 1996.

Arnau RC, Meagher MW, Norris MP, Bramson R. Psychometric evaluation of the Beck Depression Inventory-II with primary care medical patients. Health Psychol 2001;20:112-119.

Dutton GR, Grothe KB, Jones GN, Whitehead D, Kendra K, Brantley PJ. Use of the Beck Depression Inventory-II with African American primary care patients. Gen Hosp Psychiat 2004;26:437-442.

Lustman PJ, Clouse RE, Griffith LS, Carney RM, Freedland KE. Screening for depression in diabetes using the Beck Depression Inventory. Psychosomatic Med 1997;59:24-31.

Beck Depression Inventory for Primary Care (BDI-PC)

Beck AT, Guth D, Steer RA, Ball R. Screening for major depression disorders in medical inpatients with the Beck Depression Inventory for Primary Care. Behav Res Ther 1997;35:785-791.

Steer RA, Cavalieri TA, Leonard DM, Beck AT. Use of the Beck Depression Inventory for Primary Care to screen for major depression disorders. Gen Hosp Psychiat 1999;21(2):106-111.

Beck AT, Steer RA, Ball R, Ciervo CA, Kabat M. Use of the Beck Anxiety and Beck Depression Inventories for Primary Care with medical outpatients. Assessment 1997;4:211-219.

CES-D

Radloff LS. The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Measur 1977;1:385-401.

Whooley MA, Avins AL, Miranda J, Browner WS. Case-finding instruments for depression: two questions are as good as many. J Gen Intern Med 1997;12:439-445.

Hermanns N, Kulzer B, Krichbaum M, Kubiak T, Haak T. How to screen for depression and emotional problems in patients with diabetes: comparison of screening characteristics of depression questionnaires, measurement of diabetes-specific emotional problems and standard clinical assessment. Diabetologia 2006;49:469-477.

McHale M, Hendrikz J, Dann F, Kenardy J. Screening for depression in patients with diabetes mellitus. Psychosomatic Med 2008;70:869-874.

Zauszniewski JA, Graham GC. Comparison of short scales to measure depressive symptoms in elders with diabetes. West J Nurs Res 2009;31(2):219-34.

PHQ-9

Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001;16(9):606-613.

Löwe B, Spitzer RL, Gräfe K, Kroenke K, Quenter A, Zipfel S, et al. Comparative validity of three screening questionnaires for DSM-IV depressive disorders and physicians' diagnoses. J Affective Disorders 2004;78:131-140.

Kahn LS, Fox CH, McIntyre RS, Tumiel-Berhalter L, Berdine DE, Lyle H. Assessing the prevalence of depression among individuals with diabetes in a Medicaid managed-care program. Intern J Psychiat Med 2008;38:13-29.

Lamers F, Jonkers CCM, Bosma H, Penninx BWJH, Knottnerus JA, van Eijk JTM. Summed score of the Patient Health Questionnaire-9 was a reliable and valid measure for depression screening in chronically ill elderly patients. J Clin Epidemiol 2008;61:679-687.

PHQ-2

Kroenke K, Spitzer RL, Williams JB. The Patient Health Questionnaire-2: validity of a two-item depression screener. Med Care 2003;41:1284-1292.

Brody DS, Hahn SR, Spitzer RL, Kroenke K, Linzer M, deGruy FV et al. Identifying patients with depression in the primary care setting: a more efficient method. Arch

Intern Med 1998;158:2469-2475.

Daly EJ, Trivedi MH, Raskin P, Grannemann BD. Screening for depression in a diabetic outpatient population. Intern J Psychiatry Clin Pract 2007;11:268-272.

WHO-5

World Health Organization: Regional Office for Europe. Well-being measures in primary healthcare: the DepCare Project. 1998. Stockholm, Consensus meeting.

Henkel V, Mergl R, Kohnen R. Identifying depression in primary care: a comparison of different methods in a prospective cohort study. BMJ 2003;326:200-201.

Löwe B, Spitzer RL, Gräfe K, Kroenke K, Quenter A, Zipfel S, et al. Comparative validity of three screening questionnaires for DSM-IV depressive disorders and physicians' diagnoses. J Affective Disorders 2004;78:131-140.

de Wit M, Pouwer F, Gemke RJBJ, Delemarre-van de Waal HA, Snoek FJ. Validation of the WHO-5 Well-Being Index in adolescents with type 1 diabetes. Diabetes Care 2007;30:2003-2006.

Awata S, Bech P, Yoshida S, Hirai M, Suzuki S, Yamashita M et al. Reliability and validity of the Japanese version of the World Health Organization-Five Well-Being

Index in the context of detecting depression in diabetic patients. Psych Clin Neurosci 2007;61(1):112-119.

Zung (SDS)

Zung WW. A self-rating depression scale. Arch Gen Psychiatry 1965;12:63-70.

Okimoto JT, Barnes RF, Veith RC, Raskind MA, Inui TS, Carter WB. Screening for depression in geriatric medical patients. Am J Psych 1982;139:799-802.

Rajala U, Keinänen-Kiukaanniemi S, Kivelä S-L. Non-insulin-dependent diabetes mellitus and depression in a middle-aged Finnish population. Social Psychiatry Psychiatric Epidem 1997;32:363-367.

Reliability and validity data for these instruments is also summarized in Table 1. Cutoff scores optimizing the sensitivity and specificity of these measures were determined through receiving operator characteristics (ROC) analysis, while area under the ROC curve (area under the curve [AUC] index) assessed how well an instrument could discriminate between depressed and nondepressed individuals. Small variations in these statistics were reported across studies, though overall there was little difference between primary care (sensitivity 81-97%, specificity 63-99%, AUC 0.89-0.95) and diabetic patients (sensitivity 66-100%, specificity 52-92%, AUC 0.80-0.94). Because there is little evidence to suggest that any one of these measures is superior to the others, PCPs may wish to use the 2-item Patient Health Questionnaire (PHQ-2) as an initial screening tool for diabetic patients (Table 2). For those who indicate they have been bothered in the last 2 weeks from either “little interest or pleasure in doing things” or “feeling down, depressed, or hopeless,” providers can investigate further by administering the 9-item Patient Health Questionnaire-9 (PHQ-9) (Table 3). This combination of tools, available in public domain, provides an effective method of screening for depression that also addresses time constraints frequently encountered by PCPs.

Table 2. Patient Health Questionnaire-2 (PHQ-2)
Over The Past 2 Weeks, How Often Have You Been Bothered By Any Of The Following Problems?
Not At AllSeveral DaysMore Than Half The DaysNearly Every Day
Little interest or pleasure in doing things0123
Feeling down, depressed, or hopeless0123

Developed by Drs. Robert L. Spitzer, Janet B.W. Williams, and Kurt Kroenke and colleagues, with an educational grant from Pfizer Inc. For research information, contact Dr. Spitzer at rls8@columbia.edu.

Copyright © 2005 Pfizer, Inc. All rights reserved. Reproduced with permission.

Table 3. Patient Health Questionnaire-9 (PHQ-9)
Over The Last 2 Weeks, How Often Have You Been Bothered By Any Of The Following Problems?
Not At AllSeveral DaysMore Than Half The DaysNearly Every Day
1. Little interest or pleasure in doing things0 1 2 3
2. Feeling down, depressed, or hopeless0 1 2 3
3. Trouble falling or staying asleep, or sleeping too much0 1 2 3
4. Feeling tired or having little energy0 1 2 3
5. Poor appetite or overeating0 1 2 3
6. Feeling bad about yourself- or that you are a failure or have let yourself or your family down0 1 2 3
7. Trouble concentrating on things, such as reading the newspaper or watching television0 1 2 3
8. Moving or speaking so slowly that other people could have noticed? Or the opposite — being so fidgety or restless that you have been moving around a lot more than usual0 1 2 3
9. Thoughts that you would be better off dead or of hurting yourself in some way0 1 2 3
Office coding: Total Score _____________ =0+ + +
If you checked off any problems, how difficult have these problems made it for you to do your work, take care of things at home, or get along with other people?
Not difficult at allSomewhat difficultVery difficultExtremely difficult

Developed by Drs. Robert L. Spitzer, Janet B.W. Williams, and Kurt Kroenke and colleagues, with an educational grant from Pfizer Inc.

Copyright © 2005 Pfizer, Inc. All rights reserved. Reproduced with permission.

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Management of Depression in Diabetes 

To optimize patient outcomes, PCPs should have a thorough understanding of research findings related to the treatment of depression in diabetes. While necessary, provider education and screening alone had little impact on patient outcomes and other barriers to management.14, 87, 88 Depression remains inadequately treated in primary care,2, 13, 31, 89 with patients receiving inappropriately titrated doses of antidepressants90 and up to 50% discontinuing use prior to achieving remission.91 Both psychopharmacology92, 93, 94, 95, 96, 97, 98, 99, 100, 101 and psychotherapy102, 103, 104, 105, 106, 107 have been shown to effectively treat depression in diabetic patients, yet studies estimate only 33% to 52% of these patients were prescribed antidepressants,2, 32, 108 while less than 20% completed 4 or more counseling sessions.32

Antidepressants are the most common pharmacological treatment option, although PCPs class selection must take into account a patient's presenting symptoms, comorbid medical conditions, drug interactions, and side effects. Because most antidepressants have little impact on the course of depression once discontinued and relapse following successful treatment is common,89 a comprehensive treatment approach by the PCP should consider a referral for psychotherapy in addition to initial treatment and maintenance with medication. Both psychotherapy and medications are effective treating depression in diabetics, although the combination of these approaches has been shown to be more effective than either treatment alone in nondiabetic samples.109 Monoamine oxidase inhibitors (MAOIs) are not recommended in diabetic patients due to associated dietary restrictions, weight gain, and the potential for sudden, severe hypoglycemia.97, 99 Research findings and considerations for the use of TCAs, SSRIs, newer antidepressants, and cognitive behavior therapy (CBT) are summarized below.

Tricyclic Antidepressants 

TCAs are the oldest class of antidepressants and were commonly prescribed in primary care before the development of safer alternatives like SSRIs. Serious risks associated with the use of TCAs limit their current use, most notably due to cardiac effects92, 110, 111, 112 and lethality in overdose.113 Weight gain,92, 97, 110, 114 hyperglycemia,92, 97 anticholinergic effects,110 and impaired memory97 also contribute to the limited use of these medications in patients with diabetes. In spite of their side effects, TCAs may aid in regulating sleep110, 112 and are well established as a treatment for diabetic neuropathy; both desipramine and amitriptyline were shown to be more effective treating neuropathy than the SSRI fluoxetine in a randomized, double-blind, placebo-controlled study.115 While the TCA nortriptyline effectively reduced depressive symptoms among diabetics in a double-blind, placebo-controlled trial, it produced an adverse hyperglycemic effect unrelated to the drug's effect on weight. A similar increase in fasting blood glucose was found in nondiabetic patients following treatment with imipramine,116 adding to the concern of TCAs in individuals with diabetes. Consequently, TCAs are not recommended as a first-line treatment for this population, and should only be considered when patients are unresponsive to trials of at least 2 newer antidepressants.

Selective Serotonin Reuptake Inhibitors 

SSRIs are frequently a first-line choice of antidepressants in primary care, treating depression as effectively as TCAs with fewer adverse effects.112, 117, 118 SSRIs have received a significant amount of study in diabetic patients, examining the effect of these drugs on depression as well as diabetes outcomes and self-care. Fluoxetine,93, 100, 116 sertraline,95, 98, 119 and paroxetine100, 101, 120 were all effective treating depression in this population; fluoxetine and paroxetine were also associated with improved quality of life.100 There was little evidence for superior effectiveness of one SSRI over another in any study, although patients treated with fluoxetine experienced a reduction in depression severity 2 weeks earlier than those receiving paroxetine.100 Fluoxetine has also been associated with moderate weight loss,121 though the effect of other SSRIs on weight has been inconsistent.114 While SSRIs are associated with substantially fewer anticholinergic and cardiovascular effects, side effects such as sexual dysfunction, gastrointestinal distress, and agitation remain fairly common in diabetics and should be taken into consideration.110

Several randomized controlled trials have demonstrated a trend toward improvement in HgbA1c levels with SSRI treatment,93, 95, 100, 120 with statistically significant change in 2 open-label studies.95, 98 Musselman et al noted that the metabolic effect of SSRIs on certain oral antihyperglycemic agents may increase the risk of hypoglycemia, yet no clinical interaction of these drugs have been reported.68 While the majority of treatment studies ranged from 8 to 12 weeks, a year-long maintenance regimen of sertraline following successful treatment found patients taking the drug were less likely to experience recurring depression than those receiving placebo.95 Moreover, the initial improvement in glycemic control during treatment was sustained throughout the maintenance phase.95 Based on this research, PCPs can prescribe an SSRI to treat depression with reasonable confidence that the medication will not worsen the course of diabetes and may even contribute to better glycemic control.

Research examining the use of SSRIs in the treatment of diabetic neuropathy is limited. Randomized, double-blind, placebo-controlled trials have demonstrated the effectiveness of paroxetine122 and citalopram,123 although a number needed to treat analysis suggests they were less effective than TCAs.124 Two 8-week open trials found sertraline improved neuropathic symptoms, yet its effectiveness has not been compared to other treatments.125 Fluoxetine was the only SSRI studied in the treatment of depressed patients with neuropathy; although the drug was associated with improved neuropathic symptoms, its effects were no different than placebo.115 Thus, while SSRIs are better tolerated than TCAs and have been well established to effectively treat depression, they are not deemed a sufficient choice for neuropathy.126

Newer Antidepressants 

Several other new antidepressants are widespread in use, including serotonin-norepinephrine reuptake inhibitors (SNRIs), norepinephrine-dopamine reuptake inhibitors (NDRIs), and noradrenergic and specific serotonergic antidepressants (NASSAs). Like SSRIs, antidepressants in these classes are generally considered safer alternatives to TCAs for the treatment of depression. Many of these newer drugs may have indications for use either as a first-line treatment or when patients do not respond to SSRIs, although research on their use in diabetic patients is extremely limited.

SNRIs have been shown to effectively treat diabetic neuropathy in addition to depression. Duloxetine was approved by the FDA for this purpose in 2004 and is generally well-tolerated, with fewer adverse events than routine care.127, 128 While associated with a modest increase in fasting glucose and A1C, long-term studies have found no adverse effects of duloxetine on lipid profiles or weight.127, 128, 129 The relative efficacy of another SNRI, venlafaxine, was comparable to TCAs and gabapentin for the treatment of neuropathy,130 although this drug was associated with higher rates of adverse serotonergic effects and dose-dependent hypertension than duloxetine.131

Other side effects are similar to SSRIs and remain more conducive to use in diabetic patients than TCAs,132 although these drugs should not be abruptly discontinued due to risk of serious withdrawal symptoms. These findings suggest that SNRIs may be a viable treatment option for depressed patients with diabetic neuropathy, although these drugs have yet to be studied in patients with comorbid diabetes and depression.

The NDRI bupropion is the only newer antidepressant to be studied in diabetic patients with depression. Unlike SSRIs, bupropion effectively treated depression without sexual side effects96, 133 or concern of altering the metabolism of oral hypoglycemic medications,68 although increased anxiety, nausea, dizziness, and skin irritation were reported. Implications for long-term use of bupropion were promising: patients who stayed on maintenance treatment of the drug had no recurring depression.96 Bupropion has also been shown to be useful for smoking cessation in diabetics and has minimal impact on weight, ranging from no change to modest loss.96, 133 Only one study has examined the effects of this NDRI on neuropathy, although the drug was more effective than placebo with nearly 70% of patients reporting improvement.134 Like SNRIs, the NDRI bupropion may be an alternative to SSRIs in diabetic patients with neuropathy, although it should be noted that this is the only antidepressant not effective in relieving symptoms of anxiety.135

The NASSA mirtazapine has received the least study in the diabetic population. A randomized double-blind trial found mirtazapine relieved depressive symptoms significantly earlier than fluoxetine and was equally tolerable without sexual side effects or other adverse events related to serotonin.136 Commonly reported side effects of somnolence, hyperphagia, and weight gain have led to some concern using mirtazapine in patients with diabetes; although patients taking the drug have experienced significant weight gain, glycemic control actually improved.137, 138 While no research to date has examined the use of mirtazapine in diabetic neuropathy, the drug has been shown to increase pain tolerance in healthy individuals139 and provide significant relief to depressed patients with chronic pain.140

Cognitive Behavior Therapy 

Several studies have shown CBT and its variants to be successful in relieving symptoms of depression in diabetics.102, 103, 104, 105, 106, 141 Unlike antidepressants, there is evidence that the beneficial effects of CBT are maintained for up to a year past the end of treatment.103, 105 Therapy has also been shown to improve patients' self-efficacy 104 and diabetes management,102 while glycemic control improved in some102, 105, 106, 141 but not all103, 104, 105, 141 studies. Psychotherapeutic approaches are beneficial in that they lack the side effects of medication, but require active patient participation and may not be well received in all patients. Poor integration with specialty mental health care and the stigma associated with mental illness are also barriers to this form of treatment.29, 89 Providers should discuss the option of psychotherapy with depressed diabetic patients as a part of a comprehensive treatment plan, but be aware of potential barriers to this course of treatment.

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Implications for the PCP 

Research supports a clear association between diabetes and depression, even though the mechanisms underlying this relationship are not well understood. PCPs are frequently responsible and well positioned to manage these comorbid disorders and are advised to proactively screen for, diagnose, and treat depression to optimize patient outcomes, yet a number of barriers contribute to depression being inadequately managed in primary care. Suboptimal recognition can be addressed by increasing provider knowledge and following current treatment guidelines for routine depression screening of all diabetic patients, whether or not known risk factors for depression are present. Several screening tools have been validated in diabetic patients that can be completed in less than 10 minutes; use of the PHQ-2 to determine whether further investigation with PHQ-9 is warranted may help optimize the efficiency of the screening process. Providers should also be aware that presenting symptoms of depression can differ and should be sensitive to patients' gender, race, ethnicity, and individual values and beliefs.2, 108, 142

Management of depression in diabetes should be approached in a comprehensive manner, which potentially includes both medication and referral for psychotherapy such as CBT. Patients resistant to treatment should be educated to understand that benefits extend beyond improved mood and may include pain relief; decreased anxiety; improved social, occupational, and physical activity; enhanced general and sexual functioning; decreased preoccupation with somatic symptoms; more normal sleep and eating habits; improved coping skills; and better diabetes care.2, 94 Other patient barriers can be circumvented by selecting a treatment(s) that match an individual's symptoms, taking his or her preferences into consideration,2 and including patients' partners or other key family members whenever possible.112 Management barriers imposed at the system level include time constraints limiting close follow-up and monitoring, competing clinical priorities, and poor integration with mental health care. Treatment studies have demonstrated a clear need for PCPs to have additional mental health support,12 which may relieve some of the burden experienced by providers in primary care. Treatment algorithms for pharmacological treatment of depression in primary care patients with diabetes provide further assistance for PCPs clinical decisions.31, 89 Concordant with the research summarized here, these guidelines recommend initial treatment with an SSRI or other new antidepressant, taking into account patients' personal or familial responses to specific medications, in addition to side effects.31, 89 The timeline and further indications for follow-up assessment based on these recommendations are listed in Figure 1.

PCPs are also likely to be aided by future research addressing gaps in the current body of literature. Much of the research on comorbid depression in diabetic patients is limited to MDD; treatment for subclinical or other depressive disorders has received little study, even though these conditions may produce similar effects to MDD. Trials of newer antidepressants are promising, although there is little research on their use in the diabetic population. Antidepressant maintenance therapy has been identified as necessary, yet the long-term outcomes associated with it are unknown. Moreover, there is a need for collaborative care programs to identify effective and efficient ways to integrate treatment for these conditions in primary care.

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Conclusion 

Family and adult NPs and other PCPs can optimize health outcomes by increasing their understanding of the relationship between depression and diabetes and by systematically screening for, diagnosing, and managing depression in diabetic patients. While research in the area is limited, appropriate screening strategies have been identified and benefits and risks of certain pharmacological and psychotherapeutic treatments have been shown. Findings presented in this paper should serve as a guide in clinical decision making for the diagnosis and treatment of primary care patients with comorbid depression and diabetes.

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References 

  1. Anderson RJ , Freedland KE , Clouse RE , Lustman PJ . The prevalence of comorbid depression in adults with diabetes: a meta-analysis . Diabetes Care . 2001;24:1069–1078
  2. Lustman PJ , Clouse RE . Section III: practical considerations in the management of depression in diabetes . Diabetes Spectr . 2004;17:160–166
  3. Lustman PJ , Griffith LS , Freedland KE , Clouse RE . The course of major depression in diabetes . Gen Hosp Psychiatry . 1997;19:138–143
  4. DiMatteo MR , Lepper HS , Croghan TW . Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence . Arch Intern Med . 2000;160:2101–2107
  5. Katon W , Sullivan MD . Depression and chronic medical illness . J Clin Psychiatry . 1990;51:3–11
  6. Ford DE . Optimizing outcomes for patients with depression and chronic medical illnesses . Am J Med . 2008;121:S38–S44
  7. Ciechanowski PS , Katon WJ , Russo JE . Depression and diabetes: impact of depressive symptoms on adherence, function, and costs . Arch Intern Med . 2000;160:3278–3285
  8. Ciechanowski PS , Katon WJ , Russo JE , Hirsch IB . The relationship of depressive symptoms to symptom reporting, self-care and glucose control in diabetes . Gen Hosp Psychiatry . 2003;25:246–252
  9. McKellar JD , Humphreys K , Piette JD . Depression increases diabetes symptoms by complicating patients' self-care adherence . Diabetes Educ . 2004;30:485–492
  10. Park H , Hong Y , Lee H , Ha E , Sung Y . Individuals with type 2 diabetes and depressive symptoms exhibited lower adherence with self-care . J Clin Epidemiol . 2004;57:978–984
  11. Lin EHB , Katon W , Von Korff M , et al.   Relationship of depression and diabetes self-care, medication adherence, and preventive care . Diabetes Care . 2004;27:2154–2160
  12. Anderson D , Horton C , O'Toole ML , et al.   Integrating depression care with diabetes care in real-world settings: lessons from the Robert Wood Johnson Foundation Diabetes Initiative . Diabetes Spectr . 2007;20(1):10–16
  13. Gonzalez JS , Safren SA , Cagliero E , et al.   Depression, self-care, and medication adherence in type 2 diabetes: relationships across the full range of symptom severity . Diabetes Care . 2007;30:2222–2227
  14. Lin EH , Simon GE , Katzelnick DJ , Pearson SD . Does physician education on depression management improve treatment in primary care? . J Gen Intern Med . 2001;16:614–619
  15. Kilbourne AM , Reynolds CF , Good CB , et al.   How does depression influence diabetes medication adherence in older patients? . Am J Geriatr Psychiatry . 2005;13:202–210
  16. Ludman EJ , Katon W , Russo J , et al.   Depression and diabetes symptom burden . Gen Hosp Psychiatry . 2004;26(6):430–436
  17. Lustman PJ , Anderson RJ , Freedland KE , et al.   Depression and poor glycemic control: a meta-analytic review of the literature . Diabetes Care . 2000;23:934–942
  18. De Groot M , Anderson R , Freedland KE , Clouse RE , Lustman PJ . Association of depression and diabetes complications: a meta-analysis . Psychosom Med . 2001;63:619–630
  19. Rush WA , Whitebird RR , Rush MR , Solberg LI , O'Connor PJ . Depression in patients with diabetes: does it impact clinical goals? . J Am Board Fam Med . 2008;21(5):392–397
  20. Clouse RE , Lustman PJ , Freedland KE , et al.   Depression and coronary heart disease in women with diabetes . Psychosom Med . 2003;65:376–383
  21. Katon W , Von Korff M , Ciechanowski P , et al.   Behavioral and clinical factors associated with depression among individuals with diabetes . Diabetes Care . 2004;27:914–920
  22. Zhang X , Norris SL , Gregg EW , et al.   Depressive symptoms and mortality among persons with and without diabetes . Am J Epidemiol . 2005;161:652–660
  23. Katon WJ , Rutter C , Simon G , et al.   The association of comorbid depression with mortality in patients with type 2 diabetes . Diabetes Care . 2005;28:2668–2672
  24. Egede LE , Nietert PJ , Zheng D . Depression and all-cause and coronary heart disease mortality among adults with and without diabetes . Diabetes Care . 2005;28:1339–1345
  25. Egede LE . Diabetes, major depression, and functional disability among U.S. adults . Diabetes Care . 2004;27:421–428
  26. Egede LE , Zheng D , Simpson K . Comorbid depression is associated with increased health care use and expenditures in individuals with diabetes . Diabetes Care . 2002;25:464–470
  27. Goldney RD , Phillips PJ , Fisher LJ , Wilson DH . Diabetes, depression, and quality of life . Diabetes Care . 2004;27:1066–1070
  28. Finkelstein EA , Bray JW , Chen H , et al.   Prevalence and costs of major depression among elderly claimants with diabetes . Diabetes Care . 2003;26:415–420
  29. Williams JW , Katon W , Lin EHB , et al.   The effectiveness of depression care management on diabetes-related outcomes in older patients . Ann Intern Med . 2004;140:1015–1024
  30. Lustman PJ , Clouse RE . Identifying depression in adults with diabetes . Clin Diabetes . 1997;15:78–81
  31. Egede LE , Simpson K . Epidemiology, treatment and costs of depression in adults with type 2 diabetes . Expert Rev Pharmacoeconomics Outcome Res . 2003;3:251–262
  32. Katon WJ , Simon G , Russo J , et al.   Quality of depression care in a population-based sample of patients with diabetes and depression . Med Care . 2004;42:1222–1229
  33. Eaton WW . Epidemiologic evidence on the comorbidity of depression and diabetes . J Psychosom Res . 2002;53:903–906
  34. Talbot F , Nouwen A . A review of the relationship between depression and diabetes in adults: is there a link? . Diabetes Care . 2000;23:1556–1562
  35. Connell CM , Davis WK , Gallant MP , Sharpe PA . Impact of social support, social cognitive variables, and perceived threat on depression among adults with diabetes . Health Psychol . 1994;13:263–273
  36. Talbot F , Nouwen A , Gingras J , Belanger A , Audet J . Relations of diabetes intrusiveness and personal control to symptoms of depression among adults with diabetes . Health Psychol . 1999;18:537–542
  37. Bailey BJ . Mediators of depression in adults with diabetes . Clin Nurs Res . 1996;5:28–42
  38. De Groot M , Auslander W , Williams JH , Sherranden M , Haire-Joshu D . Depression and poverty among African American women at risk for type 2 diabetes . Ann Behav Med . 2003;25:172–181
  39. Macrodimitris SD , Endler NS . Coping, control, and adjustment in type 2 diabetes . Health Psychol . 2001;20:208–216
  40. Egede LE , Zheng D . Independent factors associated with major depressive disorder in a national sample . Diabetes Care . 2003;26:104–111
  41. Li C , Ford ES , Strine TW , Mokdad AH . Prevalence of depression among U.S. adults with diabetes: findings from the 2006 Behavioral Risk Factor Surveillance System . Diabetes Care . 2008;31:105–107
  42. Peyrot M , Rubin RR . Levels and risks of depression and anxiety symptomatology among diabetic adults . Diabetes Care . 1997;20:585–590
  43. Bell RA , Smith SL , Arcury TA , et al.   Prevalence and correlates of depressive symptoms among rural older African Americans, Native Americans, and whites with diabetes . Diabetes Care . 2005;28:823–829
  44. Golden SH , Lazo M , Carnethon M , et al.   Examining a bidirectional association between depressive symptoms and diabetes . JAMA . 2008;299(23):2751–2759
  45. Everson SA , Maty SC , Lynch JW , Kaplan GA . Epidemiologic evidence for the relation between socioeconomic status and depression, obesity, and diabetes . J Psychosom Res . 2002;53:891–895
  46. Kessler RC , Berglund P , Demler O , et al.   National Comorbidity Survey Replication: the epidemiology of major depressive disorder: results from the National Comorbidity Replication (NCS-R) . JAMA . 2003;289:3095–3105
  47. Fisher L , Chesla CA , Mullan JT , Skaff MM , Kanter RA . Contributors to depression in Latino and European-American patients with type 2 diabetes . Diabetes Care . 2001;24:1751–1757
  48. Jacobson AM , Samson JA , Weinger K , Ryan CM . Diabetes, the brain, and behavior: is there a biological mechanism underlying the association between diabetes and depression? . Int Rev Neurobiol . 2002;51:455–479
  49. Rubin RR , Peyrot MF . Quality of life and diabetes . Diabetes Metab Res Rev . 1999;15:205–218
  50. Rajala U , Keinänen-Kiukaanniemi S , Kivelä S-L . Non-insulin-dependent diabetes mellitus and depression in a middle-aged Finnish population . Soc Psychiatry Psychiatr Epidemiol . 1997;32:363–367
  51. De Groot M , Jacobson AM , Samson JA , Welch G . Glycemic control and major depression in patients with type 1 and type 2 diabetes mellitus . J Psychosom Res . 1999;46:425–435
  52. van Tilburg MAL , McCaskill CC , Lane JD , et al.   Depressed mood is a factor in glycemic control in type 1 diabetes . Psychosom Med . 2001;63:551–555
  53. Lustman PJ , Freedland KE , Griffith LS , Clouse RE . Predicting response to cognitive behavior therapy of depression in type 2 diabetes . Gen Hosp Psychiatry . 1998;20:302–306
  54. Lustman PJ , Griffith LS , Clouse RE , Cryer PE . Psychiatric illness in diabetes mellitus: relation to symptoms and glucose control . J Nerv Mental Dis . 1986;174:736–746
  55. Katon WJ . The comorbidity of diabetes mellitus and depression . Am J Med . 2008;121:S8–S15
  56. Yoshida S , Hirai M , Suzuki S , Awata S , Oka Y . Neuropathy is associated with depression independently of health-related quality of life in Japanese patients with diabetes . Psychiatry Clin Neurosci . 2009;63:65–72
  57. Engum A . The role of depression and anxiety in onset of diabetes in a large population-based study . J Psychosom Res . 2007;62:31–38
  58. Lustman PJ , Griffith LS , Clouse RE . Depression in adults with diabetes: results of 5-yr follow-up study . Diabetes Care . 1988;11:605–612
  59. Cameron OG , Kronfol Z , Greden JF , Carroll BJ . Hypothalamic-pituitary-adrenocortical activity in patients with diabetes mellitus . Arch Gen Psychiatry . 1984;41:1090–1095
  60. Björntorp P , Holm G , Rosmond R . Hypothalamic arousal, insulin resistance and type 2 diabetes mellitus . Diabet Med . 1999;16:373–383
  61. Rosmond R , Björntorp P . The hypothalamic-pituitary-adrenal axis activity as a predictor of cardiovascular disease, type 2 diabetes and stroke . J Intern Med . 2001;247:188–197
  62. Brown ES , Varghese FP , McEwen BS . Association of depression with medical illness: does cortisol play a role? . Biol Psychiatry . 2004;55:1–9
  63. Schmidt MI , Duncan BB , Sharrett AR , et al.   Markers of inflammation and prediction of diabetes mellitus in adults (Artherosclerosis Risk in Communities Study): a cohort study . Lancet . 1999;353:1649–1652
  64. Dandona P , Aljada A , Bandyopadhyay A . Inflammation: the link between insulin resistance, obesity and diabetes . Trends Immunol . 2004;25:4–7
  65. Pradhan AD , Manson JE , Rifai N , Buring JE , Ridker PM . C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus . JAMA . 2001;286:327–334
  66. Han TS , Sattar N , Williams K , Gonzalez-Villalpando C , et al.   Prospective study of C-reactive protein in relation to the development of diabetes and metabolic syndrome in the Mexico City Diabetes Study . Diabetes Care . 2002;25:2016–2021
  67. Knol MJ , Twisk JWR , Beekman ATF , et al.   Depression as a risk factor for the onset of type 2 diabetes melitus: a meta-analysis . Diabetologia . 2006;49:837–845
  68. Musselman DL , Betan E , Larson H , Phillips LS . Relationship of depression to diabetes types 1 and 2: epidemiology, biology, and treatment . Biol Psychiatry . 2003;54:317–329
  69. Williams MM , Clouse RE , Lustman PJ . Treating depression to prevent diabetes and its complications: understanding depression as a medical risk factor . Clin Diabetes . 2006;24:79–86
  70. Eaton WE , Armenian H , Gallo J , Pratt L , Ford DE . Depression and risk of onset of type II diabetes: a prospective population-based study . Diabetes Care . 1996;19:1097–1102
  71. Kawakami N , Takatsuka N , Shimizu H , Ishibashi H . Depressive symptoms and the occurrence of type 2 diabetes among Japanese men . Diabetes Care . 1999;22:1071–1076
  72. Arroyo C , Hu FB , Ryan LM , et al.   Depressive symptoms and risk of type 2 diabetes in women . Diabetes Care . 2004;27:129–133
  73. Carnethon MR , Biggs ML , Barzilay JI , et al.   Longitudinal association between depressive symptoms and incident type 2 diabetes mellitus in older adults . Arch Intern Med . 2007;167:802–807
  74. van den Akker M , Schuurman A , Metsemakers J , Buntinx F . Is depression related to subsequent diabetes mellitus? . Acta Psychiatr Scand . 2004;110:178–183
  75. Palinkas LA , Lee PP , Barrett-Connor E . A prospective study of type 2 diabetes and depressive symptoms in the elderly: the Rnacho Bernardo Study . Diabet Med . 2004;21:1185–1191
  76. Brown LC , Majumdar SR , Newman SC , Johnson JA . Type 2 diabetes does not increase risk of depression . Can Med Assoc J . 2006;175:42–46
  77. Brown LC , Majumdar SR , Johnson JA . Type of antidepressant therapy and risk of type 2 diabetes in people with depression . Diabetes Res Clin Pract . 2008;79:61–67
  78. Chida Y , Hamer M . An association of adverse psychological factors with diabetes mellitus: a meta-analytic review of longitudinal cohort studies . Diabetologia . 2008;51:2168–2178
  79. Knol MJ , Heerdink ER , Egberts ACG , et al.   Depressive symptoms in subjects with diagnosed and undiagnosed type 2 diabetes . Psychosom Med . 2007;69:300–305
  80. Lustman PJ , Freedland KE , Carney RM , Hong BA , Clouse RE . Similarity of depression in diabetic and psychiatric patients . Psychosom Med . 1992;54:602–611
  81. Simon GE , Von Korff M . Medical co-morbidity and validity of DSM-IV depression criteria . Psychol Med . 2005;35:1–10
  82. Yates WR , Mitchell J , Rush AJ , et al.   Clinical features of depressed outpatients with and without co-occurring general medical conditions in STAR*D . Gen Hosp Psychiatry . 2004;26(6):421–429
  83. Peterson T , Iosifescu DV , Papakostas GI , Shear DL , Fava M . Clinical characteristics of depressed patients with comorbid diabetes mellitus . Int Clin Psychopharmacol . 2006;21:43–47
  84. Hermanns N , Kulzer B , Krichbaum M , Kubiak T , Haak T . How to screen for depression and emotional problems in patients with diabetes: comparison of screening characteristics of depression questionnaires, measurement of diabetes-specific emotional problems and standard clinical assessment . Diabetologia . 2006;49:469–477
  85. Lustman PJ , Griffith LS , Clouse RE . Depression in adults with diabetes . Semin Clin Neuropsychiatry . 1997;2:15–23
  86. American Diabetes Association  . Standards of medical care in diabetes — 2008 . Diabetes Care . 2008;31:S12–S54
  87. U.S. Preventive Services Task Force (USPSTF)  . Screening for depression: recommendations and rationale . Ann Intern Med . 2002;136:760–764
  88. Kroenke K , Taylor-Vaisey A , Dietrich AJ , Oxman TE . Interventions to improve provider diagnosis and treatment of mental disorders in primary care. A critical review of the literature . Psychosomatics . 2000;41:39–52
  89. Rubin RR , Ciechanowski P , Egede LE , Lin EHB , Lustman P . Recognizing and treating depression in patients with diabetes . Curr Diabetes Rep . 2004;4:119–125
  90. Katon W , Von Korff M , Lin E , Bush T , Ormel J . Adequacy and duration of antidepressant treatment in primary care . Med Care . 1992;30:67–76
  91. Nau DP , Chao J , Aikens JE . The relationship of guideline-concordant depression treatment and patient adherence to oral diabetes medications . Res Social Adm Pharm . 2005;1:378–388
  92. Lustman PJ , Griffith LS , Clouse RE , et al.   Effects of nortriptyline on depression and glycemic control in diabetes: results of a double-blind, placebo-controlled trial . Psychosom Med . 1997;59:241–250
  93. Lustman PJ , Freedland KE , Griffith LS , Clouse RE . Fluoxetine for depression in diabetes: a randomized double-blind placebo-controlled trial . Diabetes Care . 2000;23:618–623
  94. Lustman PJ , Clouse RE . Treatment of depression in diabetes: impact on mood and medical outcome . J Psychosom Res . 2002;53:917–924
  95. Lustman PJ , Clouse RE , Nix BD , et al.   Sertraline for prevention of depression recurrence in diabetes mellitus: a randomized, double-blind, placebo-controlled trial . Arch Gen Psychiatry . 2006;63:521–529
  96. Lustman PJ , Williams MM , Sayuk GS , Nix BD , Clouse RE . Factors influencing glycemic control in type 2 diabetes during acute- and maintenance-phase treatment of major depressive disorder with bupropion . Diabetes Care . 2007;30:459–466
  97. Goodnick PJ , Henry JH , Buki VM . Treatment of depression in patients with diabetes mellitus . J Clin Psychiatry . 1995;56:128–136
  98. Goodnick PJ , Kumar A , Henry JH , Buki VMV , Goldberg RB . Sertraline in coexisting major depression and diabetes mellitus . Psychopharmacol Bull . 1997;33:261–264
  99. Goodnick PJ . Use of antidepressants in treatment of comorbid diabetes mellitus and depression as well as in diabetic neuropathy . Ann Clin Psychiatry . 2001;13:31–41
  100. Gülseren L , Gülseren S , Hekimsoy Z , Mete L . Comparison of fluoxetine and paroxetine in type II diabetes mellitus patients . Arch Med Res . 2005;36:159–165
  101. Paile-Hyvärinen M , Wahlbeck K , Eriksson JG . Quality of life and metabolic status in mildly depressed women with type 2 diabetes treated with paroxetine: a double-blind randomised placebo controlled 6-month trial . BMC Fam Pract . 2007;8:34
  102. Lustman PJ , Griffith LS , Freedland KE , Kissel SS , Clouse RE . Cognitive behavior therapy for depression in type 2 diabetes mellitus: a randomized, controlled trial . Ann Intern Med . 1998;129:613–621
  103. Georgiades A , Zucker N , Friedman KE , et al.   Changes in depressive symptoms and glycemic control in diabetes mellitus . Psychosom Med . 2007;69:235–241
  104. van der Ven NC , Hogenelst MH , Tromp-Wever AM , et al.   Short-term effects of cognitive behavioural group training (CBGT) in adult type 1 diabetes patients in prolonged poor glycaemic control. A randomized controlled trial . Diabetic Med . 2005;22:1619–1623
  105. Snoek FJ , van der Ven NCW , Twisk JWR , et al.   Cognitive behavioural therapy (CBT) compared with blood glucose awareness trainign (BGAT) in poorly controlled type 1 diabetic patients: long-term effects on HbA1c moderated by depression. A randomized controlled trial . Diabetic Med . 2008;25:1337–1342
  106. Ismail K , Winkley K , Rabe-Hesketh S . Systematic review and meta-analysis of randomised controlled trials of psychological interventions to improve glycaemic control in patients with type 2 diabetes . Lancet . 2004;363:1589–1597
  107. Katon WJ , Von Korff M , Lin EHB , et al.   The Pathways Study: a randomized trial of collaborative care in patients with diabetes and depression . Arch Gen Psychiatry . 2004;61:1042–1049
  108. De Groot M , Pinkerman B , Wagner J , Hockman E . Depression treatment and satisfaction in a multicultural sample of type 1 and type 2 diabetic patients . Diabetes Care . 2006;29:549–553
  109. Keller MB , McCullough JP , Klein DN , et al.   A comparison of nefazodone, the cognitive-behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression . New Engl J Med . 2000;342:1462–1470
  110. Lustman PJ , Anderson R . Depression in adults with diabetes . Pychiatric Times . 2002;19(1): http://www.psychiatrictimes.com/display/article/10168/47911
  111. Roose SP , Spatz E . Treating depression in patients with ischaemic heart disease: which agents are best to use and to avoid? . Drug Safety . 1999;20:459–465
  112. Clark M . Identification and treatment of depression in people with diabetes . Diabetes Primary Care . 2003;5:124–127
  113. Mason J , Freemantle N , Eccles M . Fatal toxicity associated with antidepressant use in primary care . Br J Gen Pract . 2000;50:366–370
  114. Zimmermann U , Kraus T , Himmerlich H , Schuld A , Pollmächer T . Epidemiology, implications, and mechanisms underlying drug-induced weight gain in psychiatric patients . J Psychiatr Res . 2003;37:193–220
  115. Max MB , Lynch SA , Muir J , et al.   Effects of desipramine, amitriptyline, and fluoxetine in diabetic neuropathy . New Engl J Med . 1992;326:1250–1256
  116. Ghaeli P , Shahsavand E , Mesbahi M , et al.   Comparing the effects of 8-week treatment with fluoxetine and imipramine on fasting blood glucose of patients with major depressive disorder . J Clin Psychopharmacol . 2004;24:386–388
  117. Rambelomanana S , Depont F , Forest D , et al.   Antidepressants: general practitioners' opinions and clinical practice . Acta Psychiatr Scand . 2006;113:460–467
  118. Stafford RS , Ausiello JC , Misra B , Saglam D . National patterns of depression treatment in primary care . Prim Care Companion J Clin Psychiatry . 2000;2:211–216
  119. Williams MM , Clouse RE , Nix BD , et al.   Efficacy of sertraline in prevention of depression recurrence in older versus younger adults with diabetes . Diabetes Care . 2007;30:801–806
  120. Paile-Hyvärinen M , Wahlbeck K , Eriksson JG . Quality of life and metabolic status in mildly depressed women with type 2 diabetes treated with paroxetine: a single-blind randomised placebo controlled trial . BMC Fam Pract . 2003;4:7–12
  121. Norris SL , Zhang X , Avenell A , et al.   Efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes mellitus: a meta-analysis . Arch Intern Med . 2004;164:1395–1404
  122. Sindrup SH , Gram LF , Brøsen K , Eshøj O , Mogensen EF . The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms . Pain . 1990;42:135–144
  123. Sindrup SH , Bjerre U , Dejgaard A , et al.   The selective serotonin reuptake inhibitor citalopram relieves the symptoms of diabetic neuropathy . Clin Pharmacol Ther . 1992;52:547–552
  124. Sindrup SH , Jensen TS . Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action . Pain . 1999;83:389–400
  125. Goodnick PJ , Jimenz I , Kumar A . Sertraline in diabetic neuropathy: preliminary results . Ann Clin Psychiatry . 1997;9:255–257
  126. Duby JJ , Campbell RK , Setter SM , White JR , Rasmussen KA . Diabetic neuropathy: an intensive review . Am J Health Syst Pharm . 2004;61:160–173
  127. Raskin J , Pritchett YL , Wang F , et al.   A double-blind, randomized multicenter trial comparing duloxetine with placebo in the management of diabetic peripheral neuropathic pain . Pain Med . 2005;6:346–356
  128. Raskin J , Smith TR , Wong K , et al.   Duloxetine versus routine care in the long-term management of diabetic peripheral neuropathic pain . J Palliat Med . 2006;9:29–40
  129. Hardy T , Sachson R , Shen S , Armbruster M , Boulton AJM . Does treatment with duloxetine for neuropathic pain impact glycemic control? . Diabetes Care . 2007;30:21–26
  130. Rowbotham MC , Goli V , Kunz NR , Lei D . Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study . Pain . 2004;110:697–706
  131. Stahl SM , Grady MM , Moret C , Briley M . SNRIs: their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants . CNS Spectr . 2005;10:732–747
  132. McKeage K . Treatment options for the management of diabetic painful neuropathy: best current evidence . Curr Opin Neurol . 2007;20:553–557
  133. Rowland DL , Myers L , Culver A , Davidson JM . Bupropion and sexual function: a placebo-controlled prospective study on diabetic men with erectile dysfunction . J Clin Psychopharmacol . 1997;17:350–357
  134. Semenchuk MR , Sherman S , Davis B . Double-blind, randomized trial of bupropion SR for the treatment of neuropathic pain . Neurology . 2001;57:1583–1588
  135. Hilty DM , McCarron RM , Ton H . Management of mental illness in patients with diabetes . Prim Care Clin Office Pract . 2007;34:713–730
  136. Fawcett J , Barkin RL . Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression . J Affect Disord . 1998;51:267–285
  137. Himmerich H , Fulda S , Schaaf L , et al.   Changes in weight and glucose tolerance during treatment with mirtazapine . Diabetes Care . 2006;29:170–171
  138. Weber-Hamann B , Gilles M , Schilling C , et al.   Improved insulin sensitivity in 51 nondiabetic depressed inpatients remitting during antidepressive treatment with mirtazapine and venlafaxine . J Clin Psychopharmacol . 2008;28:581–584
  139. Arnold P , Vuadens P , Kuntzer T , Gobelet C , Deriaz O . Mirtazapine decreases the pain feeling in healthy participants . Clin J Pain . 2008;24:116–119
  140. Freynhagen R , Muth-Selbach U , Lipfert P , et al.   The effect of mirtazapine in patients with chronic pain and concomitant depression . Curr Med Res Opin . 2006;22:257–264
  141. Winkley K , Landau S , Eisler I , Ismail K . Psychological interventions to improve glycaemic control in patients with type 1 diabetes: systematic review and meta-analysis of randomised controlled trials . BMJ . 2006;333:65–68
  142. Wagner J , Tsimikas J , Abbott G , De Groot M , Heapy A . Racial and ethnic differences in diabetic patient-reported depression symptoms, diagnosis, and treatment . Diabetes Res Clin Pract . 2007;75:119–122

 In compliance with national ethical guidelines, the authors report no relationships with business or industry that would pose a conflict of interest.

PII: S1555-4155(09)00198-6

doi:10.1016/j.nurpra.2009.03.020

The Journal for Nurse Practitioners
Volume 5, Issue 7 , Pages 523-535, July 2009

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