1. Interpersonal Psychotherapy and Antidepressants in Major Depression in Type 2 Diabetes Patients International Society for Interpersonal Psychotherapy 4th International Conference Amsterdam,2011 Gois C*, Duarte R**, Carmo I***, Barbosa A* *Psychiatry Department, Hospital de Santa Maria, Lisbon **Portuguese Diabetes Association, Lisbon ***Endocrinology, Diabetes and Metabolism Department, Hospital de Santa Maria, Lisbon

2. Background Type 2 diabetes (90%) adult metabolic disease lack or dysfunctional insulin (resistance) life style association (obesity) treatment: oral hypoglycemic/insulin, diet, exercise, self management Type 1 diabetes young metabolic disease lack of insulin (B cell pancreatic autoimune failure) treatment: insulin, diet, exercise, self management Type 2 Diabetes Mellitus: prevalence 12,9% Cowie et al, 2009

3. Background Depression and Diabetes Mellitus Two pandemic morbidities WHO predictions 2020 depression from 4th to 2nd main cause of disability 2030 diabetes doubles to 366 millions persons worldwide

4. Depression prevalence in chronic somatic diseases Somatic Disease Major Depression Cancer 1,5 – 50% Post stroke 9 – 31% Parkinson 20 – 30% Multiple sclerosis 16 – 30% Coronary Disease 15 – 23% Diabetes Mellitus 11 – 15% HIV 4 – 23% Raison et al, 2005 Background

5. Ramalheira, 1996; DSM IV-TR, 2000; Anderson, 2001; Jacobson, 2002; Nichols, 2003; Gusmão, 2005 GeneralPopulation Type 1 Diabetes Type 2 Diabetes MajorDepression 3 – 9% 13 - 29% 11 - 33% Prevalence Background 2 – 3 times more Depression with Diabetes

6. Background DepressionDiabetes Behavioral: ↓ self-care Biologic: hormonal, glucose disfunction, neuroinflammation may affect

7. Major Depression in Diabetes ↓ Healthier behaviors: treatment adherence, smoking ↓ Healthier behaviors: treatment adherence, smoking ↑ Wasting with health, ↑ Inpatient admittances ↑ Wasting with health, ↑ Inpatient admittances ↑ Morbidity - chronic complications (severity and number) ↑ Morbidity - chronic complications (severity and number) ↑ Mortality - Cardio Vascular Diseases ↑ Mortality - Cardio Vascular Diseases DM + DEP = 2,4 x Only DEP = 1,3 x Only DM = 2,3 x Egede et al, 2005 Background

8. Comorbity depression and diabetes: worse decrements in health Moussavi et al, 2007 Background

9. Explains 3% of HbA1c variance (more in type 1 diabetes) Depression treatment: ↑ 41 to 58% persons with a good control < 1% redution in HbA1c → 33% decrease of retinophaty (DCCT) < 1% redution in HbA1c → 33% decrease of retinophaty (DCCT) Lustman et al, 2000 Background Depression and metabolic control in diabetes

10. Hamem, 2005; Kendler, 1999; Ludman et al, 2004 Background 2 – 3 times more Depression with Diabetes, WHY? illness intrusivenness inflamation ↑cortisol attachment social support

11. Background Type 2 Diabetes Attachment Dismissing attachment ↓ Self-care Ciechanowski et al, 2004 ↓ depressive symptoms Others more reliable ( ↓ avoidance) Self more worthy of attention ( ↓ anxiety) Ciechanowski et al, 2005

12. Background Major Depression Attachment Murphy & Bates, 1996 Negative view of self independently of view of other Self-criticism Anxiety/preoccupation and fearfull attachment Positive association with depression Dismissing attachment Secure attachment No association with depression Negative association with depression

13. Depression treatment (≈ non diabetes) 11 RCTs, Petrak & Herpetz, 2009 Type 1 & 2 diabetesDepressionMetabolic control Psychological (3, n=140) yesyes (except 1) Pharmacological (4, n=289) yes (except 1) no Mixed (4, n=954) Yes (except 1) no (excepto 1) 11 RCTs e 3 Collaborative care, Katon & van der Feltz-Cornelis, 2010 Type 1 & 2 diabetesDepression (ef size) Metabolic control (ef size) Psychological (5, n=310)moderate-large Pharmacological (6, n=215)moderatesmall Collaborative care (3)moderate-largeno effect

14. Cognitive – behavior therapy vs control Solution focused therapy vs usual DM2, ↓ dep, ↓ HbA1c follow-up DM2, ↓ dep, HbA1c ns Background Psychotherapy for Major Depression in Type 2 Diabetes Citalopram vs Interpersonal Psychotherapy T vs usual Katon et al, 2004; Bogner et al, 2007;Lustman et al,1998 Age 60 – 80 yrs, follow-up 5 yrs, ↓ mortality

15. Lustman et al, 1997,2000,2006,2007; Paile- Hyvarinen et al, 2003; Amsterdam et al, 2006; Goodnick et al, 1997 Acute Dep Recor Dep DepHbA1c nortriptilineyesno ↓↑ fluoxetineyesno ↓ ns; ↓ paroxetineyesno ↓ ns escitalopramyesno ↓ ns sertralineyes ↓↓ bupropionyes ↓↓ Antidepressants for Major Depression in Type 2 Diabetes Background

16. IPT Theory: attachment communication theory social theory IPT Objectives IPT Objectives: ↑ relationships IP Communication Problem solutions Acute Major Depression Adapt Stuart S, 2008

17. Acute Depression and Interpersonal Psychotherapy 1st RCT: IPT+Amitriptiline > IPT = Amitriptiline Weissman et al, 1979 RCT: NIMH – TDCRP (Efficacy Evidence) IPT=CBT=Imipramine Elkin et al,1989 13 RCTs: Meta analisys Remission: IPT=Antidepressant=IPT+Antidepressant Symptom reduction: IPT > CBT de Mello et al, 2005 Decrease in Symptoms, IP Problems and Attachment (anxiety and avoidance): IPT = IPT + Antidepressants Outcome: symptoms Outcome: symptoms + attachment + IP problems Ravitz et al, 2008

18. Acute Depression in Somatic Patients and Interpersonal Psychotherapy Outcome: symptoms RCT: HIV patients IPT = Imipramine > CBT Markowitz et al, 1998 RCT: Coronary Artery Patients Citalopram > IPT = Clinical Management Lespérance F et al, 2007

19. Questions 1st outcome eficiency of treatment of major depression in type 2 diabetes patients with IPT or sertraline or combo and detect diferences between /within them 2nd outcomes detecting changes in attachment, diabetes adaptation, diabetes self efficacy and metabolic control after treatment by the three treatment groups and differences between them

20. Exclusion Criteria 65 years acute suicidality antidepressant therapy other somatic chronic condition other mental disorder alcohol or others drugs abuse/dependence illiteracy, visual handicap

21. Clinical - Experimental Study

22. Methodology Consecutive screening of type 2 diabetes patients in two outpatient clinics (self-rated) HADS Hetero-evaluation: MDD Exclusion criteria revised MADRS MINI Clinical evaluation, IP inventory ITP Area Problem, Other instruments Informed consent EVA ATT DSES HbA1c IPT 3 months weekly sessions SSRI - Sertraline (usual) Dose: 50-150mg 3 months fortnightly consultation Randomization

23. Methodology Combo procedure week 6thMADRS IPT till 3 months weekly Sertraline (usual) till 3 months fortnightly ≤ 25% initialno 25% reduction IPT + Sertraline till 3 months fortnightly Sertraline + ITP till 3 months weekly more 3 months follow-up monthly IPT weekly Sertraline (usual) fortnightly Randomization

24. raters don´t treat patients, are blind to treatment type and inter-rater attuned Methodology MADRS regular evaluations Data concerning COMBO intervention include baseline data (before COMBO formal beginning ) as a third treatment group Same care provider for all patients

25. Some instruments description ATT 18 EVA Methodology Diabetes adaptation, Core Diabetes Integration Concept Portuguese short version of ATT39 (Dunn et al, 1986) high values – better adaptation, correlates with HbA1c Portuguese version Adult Attachment Scale – R (Collins & Read, 1990) 3 attachment dimensions: Close, Anxiety and Depend Close/Secure; Anxiety/Insecure; Depend/ ↓ Avoidant (confidante) DSES Portuguese version of Diabetes Self-Efficacy Scale (Crabtree 1986) 2 dimensions: diet and exercise

26. Results Global sample = 34 Age 55.17 ± 5.9 yrs Education 6.85 ± 3.07 yrs ♀ 30 (88.2%) ≥ 2 chronic complications 14 (41.2%) Insulin users 18 (52.9%) Diabetes duration 12.55 ± 5.75 yrs HADS dep 10.44 ± 2.87 HADS anx 13.14 ± 4.05 MADRS 24.32 ± 5.27 HbA1c 9.05 ± 2.13

27. Results TIP=17 USUAL=17 No differences between patients at baseline: age, gender, diabetes duration, ≥2 chronic complications, insulin users, diabetes adaptation, depression, anxiety,attachment, sub-scales,diabetes,self-efficacy, HbA1c

28. Treatment sub-groups: TIP – 10 USUAL – 12 COMBO - 8 (Usual – 3 IPT – 5) Drop-outs: USUAL – 3 Combo IPT - 1 Results (COMBO data analyzed altogether) No differences between patients at baseline: Except COMBO: < HADS depression < secure attachment

29. Results TIP - USUAL Total patients Area Problem Problem IP AreaNumber% Mourning64,3 IP conflicts1828,3 Role Transition (3 DM) adaptation 1010,9

30. MADRS * * * ** * * *

31. Adjustment to diabetes *

32. Preoccupied Attachment *P<0.05 **P<0.01 ***P<0.001 * *

33. Secure Attachment *P<0.05 **P<0.01 ***P<0.001

34. Trusting others (reversed dismissing attachment) *P<0.05 **P<0.01 ***P<0.001

35. Diabetes Self-efficacy DIET *P<0.05 **P<0.01 ***P<0.001

36. Diabetes Self-efficacy EXERCISE *P<0.05 **P<0.01 ***P<0.001 *

37. Glicohemoglobin A1c *P<0.05 **P<0.01 ***P<0.001

38. IPT n=10 USUAL n=12 COMBO n=8 MADRS 0-4 m0.0110.0030.028 MADRS 0-6 m0.0210.005 ATT 0-4 m (1) ATT 0-6 m0.025 Preoc attach 0-4 m (1) Preoc attach 0-6 m0.0190.044 Secure attach 0-4 m0.027 Secure attach 0-6 m0.042 Trust others 0-4 m Trust others 0-6 m S Effic diet 0-4 m (1) 0.018 S Effic diet 0-6 m (1) 0.018 S Effic exercise 0-4 m (1) (1) 0.012 (KW*) S Effic exercise 0-6 m0.005 HbA1c 0-6 m (1) 0.045 (1) Wilcoxon signed ranks test. KW*= Kruskall Wallis test; p<=0.05 Results: only P significant. Significant differences between/within groups

39. Conclusions Preliminary results, small sample Both IPT and USUAL reduce MADRS score Both COMBO and IPT better decrease insecure attachment COMBO better increase secure attachment COMBO was not related to depression and metabolic outcome IPT was not related with metabolic control USUAL better with diabetes adaptation, self-efficacy and metabolic control