Asian Journal of Psychiatry 6 (2013) 364–368

Diabetes with comorbid depression: Role of SSRI in better glycemiccontrol

Pratibha Gehlawat a,*, Rajiv Gupta a, Rajesh Rajput b, Deepak Gahlan b,Virender Kumar Gehlawat c

a Department of Psychiatry, Pt.B.D.Sharma PGIMS, Rohtak, Haryana, Indiab Department of Medicine, Pt.B.D.Sharma PGIMS, Rohtak, Haryana, Indiac Deparment of Paediatrics, Pt.B.D.Sharma PGIMS, Rohtak, Haryana, India

A R T I C L E I N F O

Article history:

Received 23 August 2012

Received in revised form 23 February 2013

Accepted 30 March 2013

Keywords:

Depression

Diabetes

Glycemic control

SSRI

A B S T R A C T

Introduction: The presence of depression in patients with diabetes mellitus is reported to be associated

with poor glycemic control and an increased risk of diabetic complications. Treatment of depression with

selective serotonin reuptake inhibitors (SSRIs) may improve glycemic control and may be beneficial for

patients with comorbid depression and diabetes.

Aims and objective: To study the effect of Escitalopram (SSRI) in patients with diabetes mellitus with

comorbid depression and the relationship of treatment response for depression and glycemic control.

Research design and methods: 40 patients received open-label Escitalopram therapy for up to 12 weeks.

Clinical outcome measures included Hamilton Depression rating scale (HAM-D) assessment at 3, 6, and

12 weeks. In addition, fasting and post-prandial plasma glucose level, weight and waist circumference,

glycosylated hemoglobin level (HbA1C), lipid profile, renal function test and fundus examination were

done before and during Escitalopram therapy.

Results: A significant decline in mean HAM-D scores was observed 3 weeks onwards till the end of the

study during Escitalopram therapy. There was a corresponding decline in mean fasting and post-prandial

plasma glucose level at 6 and 12 weeks respectively and glycosylated hemoglobin level at 12 weeks was

observed.

Conclusion: Escitalopram is effective in treating depression in patients with diabetes mellitus, and has

beneficial effects on glycemic control.

� 2013 Published by Elsevier B.V.

Contents lists available at SciVerse ScienceDirect

Asian Journal of Psychiatry

jo u rn al h om epag e: ww w.els evier .c o m/lo cat e/a jp

1. Introduction

The frequency of co-morbid depression in patients with diabetesrange from 10 to 40% (Goodnick and Hernandez, 2000; Rubin et al.,2005). It is estimated that the likelihood of having co-morbiddepression with diabetes is double that seen in the non-diabeticmedical population (Anderson et al., 2001). The prevalence ofdepression was found 14.7% amongst those with diabetes asopposed to 4.9% amongst those without diabetes and also itsprevalence to be high in Type 2 diabetes mellitus in the studies donein the Indian sub-continent (Zahid et al., 2008; Raval et al., 2010).

Depressive disorder may have a negative impact on manage-ment and recovery from comorbid medical disorder (Lustmanet al., 1988; Katon et al., 2005). It was found that comorbiddepression with diabetes was associated with an increased risk forall-cause mortality over 2 year period of approximately 36–38%

* Corresponding author. Tel.: +91 9671615649.

E-mail address: hunt4prat_01@rediffmail.com (P. Gehlawat).

1876-2018/$ – see front matter � 2013 Published by Elsevier B.V.

http://dx.doi.org/10.1016/j.ajp.2013.03.007

(Katon et al., 2005). Depression is unrecognized and untreated inapproximately two thirds of patients with both conditions(Lustman and Harper, 1987). A worldwide survey (Moussaviet al., 2007) evaluated the effect of depression alone or comorbidwith other chronic conditions (i.e., diabetes, asthma, arthritis, andangina) on overall health status among respondents aged >18years from 60 countries. Depression produced the greatestdisability in health when compared with the other 5 chronicconditions surveyed; the combination of diabetes and depressionwas also the most disabling of the comorbidities surveyed.Comorbid depression is associated with an increased numberand severity of diabetic symptoms and complications. Thesedepressive symptoms are severe enough to warrant treatment,adequate treatment of the affective component of this comorbidityis lacking. Studies suggest that the recognition and treatment ofdepression is less than optimal, with only 25% of depresseddiabetics receiving care (Rubin et al., 2004).

Although tricyclic antidepressants (TCAs) and monoamineoxidase inhibitors appear to be effective therapy for depressionin patients with diabetes, but there is evidence that these agents

Table 2Diabetic characteristics and complications.

Family history of diabetes, present (%) 23 (57.5)

Duration of diabetes (years)

0–5 no. (%) 21 (52.5)

6–10 no. (%) 9 (22.5)

>10 no. (%) 10 (25)

Diabetes management

Oral hypoglycemic no. (%) 35 (87.5)

Insulin therapy 13 (32.5)

Both 8 (20)

Complications present (%)

Retinopathy 28 (70)

Neuropathy 18 (45)

Nephropathy 20 (50)

Macrovascular (IHD) 7 (17.5)

Hypertension 24 (60)

Table 1Sociodemographic characteristics of the study group.

Age, mean � SD, (years) 50.75 � 8.88

Female no. (%) 30 (75)

Male no. (%) 10 (25)

Married no. (%) 36 (90)

Unmarried no. (%) 2 (5)

Lifestyle

Physically active no. (%) 20 (50)

Sedentary no. (%) 20 (50)

Alcohol use no. (%) 5 (12.5)

Smoking no. (%) 9 (22.5)

Body mass index mean � SD (kg/m2) 26.83 � 4.41

Obese no. (%) 24 (60)

Overweight no. (%) 6 (15)

Normal no. (%) 10 (25)

P. Gehlawat et al. / Asian Journal of Psychiatry 6 (2013) 364–368 365

may destabilize glycemic control in some diabetic patients(Goodnick et al., 1995; Lustman et al., 1997; Ghaeli et al., 2004).In contrast, there is growing evidence that selective serotoninreuptake inhibitor (SSRI) antidepressants may facilitate glyce-mic control in some patients with co-morbid diabetes anddepression (Ghaeli et al., 2004; Winokur et al., 1988). Thefavourable profiles of SSRIs make them the preferred pharma-cologic interventions for patients with depression and diabetes(Katon et al., 2005).

Among SSRIs, Escitalopram has high selectivity for theserotonin transporter (with little or no affinity for noradrenergicand dopaminergic transporters) (Klein et al., 2006). Escitalopramhas minimal inhibitory effect on the cytochrome P-450 2D6 and3A4 iso-enzymes that are responsible for the metabolism of manydrugs used in the treatment of diabetes (Greenblatt et al., 1999).Escitalopram causes significant reduction in depression withoutrisk of hyper or hypoglycemia or weight gain. The present studyexamines the effect of Escitalopram therapy on depressivesymptoms and on glycemic control in patients with co-morbiddepression and diabetes mellitus.

2. Methods

2.1. Sample

The study was conducted over a period of 12 months in theEndocrine OPD and Department of Psychiatry in a tertiary carecentre of northern India 410 patients attending Endocrine outpatient department were screened.

2.1.1. Inclusion criteria

Patients having diabetes mellitus receiving anti-diabetictreatment for 3 months from endocrine OPD and were not intarget HbA1C (<7%), of either gender, age �18 years of age andfulfilling ICD-10 criteria for depressive episode were included inthe study. The diagnosis of depression was arrived at by the routineclinical interview method by the principal investigator andconfirmed by consensus with the Senior Professor.

2.1.2. Exclusion criteria

Patients with chronic medical or surgical illness other thandiabetes mellitus and on long term treatment for other medicalillness, who were terminally ill, having renal, neurological orcardiovascular dysfunction and required immediate hospitali-zation, who were currently using corticosteroids or psychotropicdrugs, who had history of mania or any other psychiatricdisorder and who were having suicidal risk were excluded fromthe study. 53 patients had moderate to severe depressiveepisode, 10 did not give consent. A total of 43 patients wereincluded in the study sample and 3 dropped out. All patientsprovided signed informed consent. Approval from Ethical boardof Post Graduate Institute of Medical Sciences, Rohtak, Haryanawas granted.

2.2. Measures

A semi-structured clinical interview was designed to collectsociodemographic variables, relevant past medical and psychiatrichistory, medications received.

HAM-D (Hamilton, 1960): it is a multiple choice questionnaireto rate the severity of depression and was used as the primaryclinical outcome measure.

Secondary outcome measures included the fasting and post-prandial plasma glucose level and glycosylated hemoglobin HbA1clevels.

2.3. Study design

Patients were maintained on their established oral hypoglyce-mic and insulin therapy. All patients were started on 10 mg/day ofEscitalopram and all the baseline investigations were done. After 3weeks of therapy at this dose, patients with less than a 50%reduction in baseline HAMD score had their Escitalopram doseincreased to 15 mg daily and at 6 weeks, patients who still had lessthan 50% reduction in baseline HAM-D score, dose was furtherincreased to 20 mg daily for rest of the study period. TheEscitalopram dose could be reduced in case of adverse events.Efficacy measures were obtained at baseline and after 3, 6 and 12weeks of treatment. The details regarding the ongoing treatmentfor diabetes was taken as shown in Table 2 and no change in anti-diabetic treatment was done during 3 months of study period.Weight, waist circumference, fasting plasma glucose, post-prandial plasma glucose were obtained at baseline, at 6 weeksand at 12 weeks of treatment. Glycosylated hemoglobin-A 1Clevels, lipid profile, serum creatinine, spot urine for microalbumi-nuria and fundoscopy were done at baseline and at 12weeks.Safety measures were obtained at each study visit and includedreported and elicited adverse events and vital signs.

2.4. Statistical analysis

The data collected during the study was entered in theMicrosoft excel format and was analyzed using SPSS.14 versionMicrosoft software. Descriptive statistical analysis was done forcontinuous and categorical variables. The data was tested fornormality by using Kolmogrov-Smirnov test. RM-ANOVA was

P. Gehlawat et al. / Asian Journal of Psychiatry 6 (2013) 364–368366

applied for repeated measures of continuous variables. Forcategorical variables ‘Chi Square test’ was used and unpaired t-test was used for intra-group comparisons. The p values were twotailed and probability level of significant difference was set at<0.05.

3. Results

3.1. Sociodemographic variables

Table 1 shows sociodemographic variables of the study group.The mean age � SD of the study group is 50.75 � 8.88 years. Themean � SD body mass index of the patients was 26.83 � 4.41 kg/m2

indicating that majority of the patients were overweight and obese.Table 2 shows that 35 (87.5%) were on oral hypoglycemics, 13 (32.5%)were on insulin therapy and 8 (20%) were taking both.

3.2. Antidepressant efficacy

The mean dose was 11.16 � 2.25 mg/day. In 9 patients, the doseof Escitalopram was raised upto 20 mg/day accordingly who did notshow improvement with 10 mg/day of Escitalopram.

There was statistically significant mean decrease in HAM-Dscores at 3, 6 and 12 weeks follow up respectively (p < 0.001). Themean � SD decrease in HAM-D score at 12 weeks from baseline was17.38 � 4.25 (Table 3).

3.3. Glycemic control

There was no significant decline of weight at 6 and 12 weeksafter treatment (p > 0.05). There was statistically significant(p < 0.001) decline in fasting (mean decrease at 12 weeks was68.72 � 40.53 mg/dl) and post-prandial plasma glucose level (meandecrease at 12 weeks was 109.95 � 55.32 mg/dl) at 6 weeks and 12weeks after treatment as compared with baseline (Table 3). Astatistically significant decline in mean glycosylated hemoglobinlevel (HbA1C) at 12 weeks (mean decrease at 12 weeks was1.36 � 0.63) (p < 0.001) after treatment was also observed(Table 3). No statistical significant change was observed in meancholesterol, triglyceride, LDL, HDL and VLDL levels at 12 weeks aftertreatment. There was non-significant change in renal parameters at12 weeks (p > 0.05) (Table 3). The response to treatment was alsocompared between the group of patients who showed positiveresponse without dose increment of Escitalopram (statatic dosegroup) and the group of patients who showed positive response withdose increment (titrating dose group). A significant difference was

Table 3Response to treatment on anthropometric variables, glycemic control, HAM-D scores a

At baseline mean � SD At 3 weeks mean � SD At

Weight (kg) 66.38 � 10.42 –

Waist circumference (cm) 96.20 � 11.82 –

FPG (mg/dl) 177.66 � 57.81 –

PPPG (mg/dl) 254.63 � 71.23 –

HbA1c (%) 9.88 � 1.73 –

HAM-D scores 22.33 � 5.22 12.53 � 4.70

Lipid profile

TG level (mg/dl) 181.28 � 84.70 –

CH level (mg/dl) 195.63 � 51.22 –

HDL (mg/dl) 42.53 � 7.58 –

LDL (mg/dl) 109.98 � 33.30 –

VLDL (mg/dl) 39.13 � 14.05 –

Creatinine (mg/dl) 0.85 � 0.14 –

* significant (<0.05).** highly significant (<0.01).*** very highly significant (<0.001).

found on comparison of alcohol use and duration of diabetes betweenthe two groups. Most of the patients were alcohol users and hadduration of diabetes over 6 years in the titrating dose group. Also,most of the patients in titrating dose group had associated diabeticcomplications including retinopathy, neuropathy, nephropathy,hypertension and macrovascular complications (Table 4). All thepatients in the titrating dose group had severe depression i.e. �19 onHAM-D score. A significant difference found between the static doseand the titrating dose group on comparing change in HAM-D scores(p < 0.001) Also, a significant difference was found on comparingfasting and post-prandial plasma glucose level and glycosylatedhaemoglobin level at baseline and end of the study between the twogroups (p < 0.001) (Table 4).

4. Discussion

Over the past decade, researchers have gained ground to clearlyelucidate the link between diabetes and depression. It is suggestedthat each disease is a risk factor for developing the other, and thetwo disorders may share similar pathophysiological mechanisms(Ajilore et al., 2007). Comorbid depression may indicate particu-larly severe underlying diabetic illness (Black et al., 2003).

This was an open label, longitudinal study, studying thetreatment effects in patients of diabetes mellitus with comorbiddepression. Of the 410 diabetic patients screened, there were 52%females and 48% males. However, in the study group, 30 (75%) ofpatients were females and 10 (25%) were males. Earlier, it wasfound nearly one third (29% males and 30% females with diabeteshad clinically significant levels of depression, compared with 6%males and 15% females without diabetes) (Asghar et al., 2007).

The mean age � SD was 50.75 � 8.88 years. 80% of the patientswere between 41 and 60 years. Another study found mean age ofpatients with comorbid diabetes and depression was 50.8 years with60.1% females (Lustman et al., 2007).

Equal number of patients i.e. 20 (50%) had sedentary life styleand 20 (50%) were physically active, thus minimizing theconfounding effect of lifestyle of patient on the glycemic statusof the patients. Majority of the patients (52.5%) were suffering fromdiabetes for less than 5 years suggesting that depression may bethe outcome of behavioral effects regarding diabetes selfmanagement and adjustment problem to recently diagnoseddisease. The mean body mass index was 26.83 � 4.42 kg/m2 atbaseline. In a previous study, the mean BMI was 30.4 kg/m2

comparable to the present study (Abrahamian et al., 2009). Thisindicate that majority of the patients having comorbid diabetes anddepression were overweight and obese.

nd biochemical variables of all patients completing the study (n = 40).

6 weeks mean � SD At 12 weeks mean � SD F critical value P value

66.05 � 9.89 65.95 � 10.01 1.14 >0.05

95.90 � 11.51 95.83 � 11.44 1.587 >0.05

134.55 � 39.79 108.95 � 25.84 59.685 <0.001***

177.35 � 50.65 146.27 � 25.69 38.000 <0.001***

– 8.53 � 1.34 178.133 <0.001***

8.18 � 4.34 4.75 � 2.24 413.435 <0.001***

– 179.20 � 83.55 3.705 >0.05

– 192.10 � 50.73 3.555 >0.05

– 44.75 � 11.52 2.187 >0.05

– 108.48 � 32.23 3.710 >0.05

– 38.95 � 12.17 0.096 >0.05

– 0.85 � 0.10 0.328 >0.05

Table 4Comparison between the static dose group (n = 31) Vs titrating dose group (n = 9).

Characteristics Static dose group Titrating dose group T value P value

Lifestyle

Physically active 14 3 – >0.05

Sedentary 17 6

Family history of diabetes, present 17 6 – >0.05

Alcohol use 1 4 – <0.001***

Smoking 5 4

Duration of diabetes (years)

0–5 21 0 – <0.001***

6–10 5 4

>10 5 5

Complications

Retinopathy 20 (64.5) 8 (88.8) –

Neuropathy 11 (35.4) 7 (77.7) <0.05*

Nephropathy 14 (45.1) 6 (66.6)

Macrovascular 4 (12.9) 3 (33.3)

Hypertension 18 (58.1) 6 (66.6)

FPG (mg/dl)

Baseline 160.95 � 49.94 235.22 � 46.14 3.583 <0.05*

6 weeks 118.96 � 24.19 188.22 � 36.64 3.962 <0.05*

12 weeks 97.74 � 13.28 147.55 � 20.78 4.584 <0.05*

PPPG (mg/dl)

Baseline 239.49 � 67.53 306.77 � 60.72 2.618 <0.05*

6weeks 158.94 � 32.78 240.77 � 51.39 3.525 <0.05*

12 weeks 136.97 � 19.19 178.33 � 18.59 4.558 <0.05*

HbA1c (%)

Baseline 9.62 � 1.81 10.75 � 1.08 2.254 <0.05*

12 weeks 8.31 � 1.34 9.27 � 1.12 2.050 <0.05*

HAM-D scores

Baseline 21.74 � 5.42 24.33 � 4.12 1.323 >0.05

3 weeks 10.58 � 2.81 19.22 � 3.56 7.63 <0.001***

6 weeks 6.61 � 2.60 13.56 � 4.93 5.66 <0.001***

12 weeks 4.10 � 1.56 7.00 � 2.83 4.04 <0.001***

* significant (<0.05).** highly significant (<0.01).*** very highly significant (<0.001).

P. Gehlawat et al. / Asian Journal of Psychiatry 6 (2013) 364–368 367

The mean � SD dose of Escitalopram used was 11.16 � 2.25 mg/day. Most of the patients (77.5%) patients showed positive responsewith a dose of 10 mg/day. Previous studies also found that 10 mg/dayof Escitalopram (10 mg/day) caused a significant decline in depres-sion rating scales 2–3 weeks onwards (Wade et al., 2002; Burke et al.,2002). Therefore, these findings suggest the efficacy of Escitalopramat a dose of 10–20 mg/day for the treatment of depression andtheurapeutic effect appears as early as 3 weeks onwards.

The mean fasting and post-prandial plasma glucose leveldecreased significantly from baseline level at 6 and 12 weeksrespectively. The mean decrease at 12 weeks was 68.72 � 40.53mg/dl and 109.95 � 55.32 mg/dl respectively. A recent study foundstatistically significant difference of fasting plasma glucose andpostprandial plasma glucose at 8th week when compared withbaseline after Escitalopram treatment (p < 0.05) (Hun-Li et al., 2009).Another study also found a statistically significant decrease of meanfasting plasma glucose level 155.0–113 mg/dl at 6 months aftertreatment with antidepressant (Abrahamian et al., 2009).

The change in HbA1c level was found to be significant at 12weeks with a mean decrease of 1.36 � 0.63%. In a study usingEscitalopram therapy for 16 weeks in 14 patients with comorbiddepression and diabetes, a modest reduction in fasting glucose,fructosamine and glycosylated hemoglobin levels was observed, butthe reduction was found to be non-significant. However, the samplesize was too small to be generalized to all patients (Amsterdam et al.,2006). Another study observed a statistically significant meanreduction in HbA1c levels (mean � SD HbA1c reduction�0.4 � 1.5%) at 16 weeks after treatment with Sertraline (Lustman

et al., 2006) which supports findings of present study. A statisticallysignificant reduction was found in mean HbA1c level from 7.9 to 6.9 at6 months after treatment with Milnacipran in patients with comorbiddiabetes and depression (Abrahamian et al., 2009). Also, improve-ment in glycemic control was reported using fluoxetine for treatmentof comorbid diabetes (Lustman et al., 2000). Therefore, present studyand data from previous study favors the efficacy of Escitalopram toimprove glycemic control in comorbid depression and diabetes.

The mean change of weight and waist circumference at 6 and 12weeks respectively were not found to be statistically significant inthe present study. This shows that Escitalopram does not pose riskof weight gain and likely a weight neutral drug and the change inanthropometric parameters did not cause glycemic control in thestudy group while glycemic control being a part of recovery fromdepressive illness. Conversely, previously it was reported astatistically significant mean decrease in body weight at 6 monthsafter treatment with Milnacipran (Abrahamian et al., 2009).

On comparison of static dose group and titrating dose group, astatistically significant difference was found on comparing on basisof smoking and alcohol use as well as duration of diabetes. All thepatients in titrating dose group had diabetes for a longer duration(�6 years) and majority of them used smoking and alcohol. Thesefactors could have been confounded the results and controlled for.The data also revealed that most of the patients among the titratingdose group had diabetic complications. The presence of complica-tions in the titrating dose group may be explained by the longerduration of diabetes (>6 years) in this group. Earlier, it was alsofound that the prevalence of depression was significantly higher

P. Gehlawat et al. / Asian Journal of Psychiatry 6 (2013) 364–368368

among diabetic subjects with diabetic complications (Poongothaiet al., 2011; Yoshida et al., 2009). Fasting and post-prandial plasmaglucose level and HbA1C level were also significantly higher in thetitrating dose group. This suggests that the glycemic control waspoor in the titrating dose group during the study period.

Thus, the present study favors SSRI Escitalopram as effectivepharmacological treatment in patients of diabetes with comorbiddepression.

5. Conclusion

Based on analysis of the data and comparing with the previousliterature, it was found that Escitalopram is efficacious at a dose of10 mg/day for treating depression in most patients of diabetesmellitus and a higher dose is required for response in more severeform of depression in diabetic patients. Alcohol use, prolongedduration of diabetic illness and presence of diabetic complicationsadversely affects the efficacy of Escitalopram in comorbid diabetesand depression. Treatment of depression in patients of diabetesmellitus is helpful to achieve glycemic control and the findings ofthe present study are in line with the data supporting use of SSRI incomorbid depression and diabetes. Therefore, we can concludethat screening of all diabetic patients for depression and depressivepatient for diabetes is useful indicator for planning treatment.

6. Limitations

Though the present study was conducted using soundmethodology, there are certain limitations. A small sample sizeand single-cited study limits the generaliziblity of the results. Asthis was open label study, lack of blinding is also a limitation. Aplacebo control group could have increased the reliability of resultsas there are certain confounding variables like smoking, alcoholuse and duration of diabetes in the study group. Further multi-central studies or metaanalysis studies in different geographicalareas should be considered to establish the effective treatmentoptions for the patients of comorbid diabetes and depression.

Conflict of interest

None.

Funding of study

None.

Acknowledgements

None.

References

Abrahamian, H., Peter, H., Rudolf, P., Herman, T., 2009. Diabetes mellitus andcomorbid depression: treatment with milnacipran result in significant im-provement of both diseases (results from the Austrian MDDM study group).Journal of Neuropsychiatric Disease and Treatment 5, 261–266.

Ajilore, O., Haroon, E., Kumaran, S., Darwin, C., Binesh, N., Mintz, J., Miller, J., Thomas,M.A., Kumar, A., 2007. Measurement of brain metabolites in patients with Type2 diabetes and major depression using proton magnetic resonance spectrosco-py. Neuropsychopharmacology 32 (6) 1224–1231.

Amsterdam, J.D., Shults, J., Rutherford, N., Schwartz, S., 2006. Safety and efficacy ofs-citalopram in patients with co-morbid major depression and diabetes melli-tus. Neuropsychobiology 54, 208–214.

Anderson, R.J., Freedland, K.E., Clouse, R.E., Lustman, P.J., 2001. The prevalence ofcomorbid depression in adults with diabetes. Diabetes Care 24, 1069–1078.

Asghar, S., Hussain, A., Ali, S.M., Khan, A.K., Magnusson, A., 2007. Prevalence ofdepression and diabetes: a population-based study from rural Bangladesh.Diabetic Medicine 24 (8) 872–877.

Black, S.A., Markides, K.S., Ray, L.A., 2003. Depression predicts increased incidence ofadverse health outcomes in older Mexican Americans with Type 2 diabetes.Diabetes Care 26 (10) 2822–2828.

Burke, W.J., Gergel, I., Bose, A., 2002. Fixed-dose trial of the single isomer SSRIescitalopram in depressed out-patients. Journal of Clinical Psychiatry 63, 331–336.

Ghaeli, P., Shahsavand, E., Mesbahi, M., Kamkar, M.Z., Sadeghi, M., Dashti-Khavidaki,S., 2004. Comparing the effects of 8-week treatment with fluoxetine andimipramine on fasting blood glucose of patients with major depressive disorder.Journal of Clinical Psychopharmacology 24, 386–388.

Goodnick, P.J., Henry, J.H., Buki, V.M.V., 1995. Treatments of depression in patientswith diabetes mellitus. Journal of Clinical Psychiatry 56, 128–136.

Goodnick, P.J., Hernandez, M., 2000. Treatment of depression in comorbid medicalillness. Expert Opinion on Pharmacotherapy 1, 1367–1384.

Greenblatt, D.J., Von Moltke, L.L., Harmatz, J.S., Shader, R.I., 1999. Human cyto-chromes and some newer antidepressants: kinetics, metabolism and druginteractions. Journal of Clinical Psychopharmacology 19 (Suppl. 1) 23S–35S.

Hamilton, M., 1960. Rating scale for depression. Journal of Neurology, Neurosurgeryand Psychiatry 23, 56–62.

Hun-Li, J.I.S., Yong-Li, S.H.I., Lei et, S.O.N.G., 2009. Analysis on clinical anti-depres-sion effectiveness of escitalopram for Type2 diabetes patients. Practical Journalof Medicine and Pharmacy 60, 27–35.

Katon, W.J., Rutter, C., Simon, G., Lin, E.H., Ludman, E., Ciechanowski, P., Kinder, L.,Young, B., Von Korff, M., 2005. The association of comorbid depression withmortality in patients with type 2 diabetes. Diabetes Care 28, 2668–2672.

Klein, N., Sacher, J., Geiss-Granadia, T., Attarbaschi, T., Mossaheb, T., Lanzenberger,R., Potzi, C., Holik, A., Spindelegger, C., Asenbaum, S., Dudczak, R., Tauscher, J.,Kasper, S., 2006. In vivo imaging of serotonin transporter occupancy by meansof SPECT and [123 I]ADAM in healthy subjects administered different doses ofescitalopram or citalopram. Psychopharmacology (Berl) 188, 263–272.

Lustman, P.J., Harper, G.W., 1987. Nonpsychiatric physicians’ identification andtreatment of depression in patients with diabetes. Comprehensive Psychiatry28, 22–27.

Lustman, P.J., Griffith, L.S., Clouse, R.E., 1988. Depression in adults with diabetes.Results of 5-year follow-up study. Diabetes Care 11, 605–612.

Lustman, P.J., Griffith, L.S., Clouse, R.E., Freedland, K.E., Eisen, S.A., Rubin, E.H.,Carney, R.M., McGill, J.B., 1997. Effects of nortriptyline on depression andglycemic control in diabetes: results of a double-blind, placebo-controlled trial.Psychosomatic Medicine 59, 241–250.

Lustman, P.J., Freedland, K.E., Griffith, L.S., Clouse, R.E., 2000. Fluoxetine for depres-sion in diabetes: a randomized double-blind placebo-controlled trial. DiabetesCare 23, 618–623.

Lustman, P.J., Clouse, R.E., Nix, B.D., 2006. Sertraline for prevention of depressionrecurrence in diabetes mellitus: a randomized, double-blind, placebo-con-trolled trial. Archives of General Psychiatry 63, 521–529.

Lustman, P.J., Williams, M.M., Sayuk, G.S., 2007. Factors influencingglycemic control in type 2 diabetes during acute- and maintenance-phasetreatment of major depressive disorder with bupropion. Diabetes Care 30,459–466.

Moussavi, S., Chatterji, S., Verdes, E., 2007. Depression, chronic diseases, anddecrements in health: results from the World Health Surveys. Lancet 370,851–858.

Poongothai, S., Anjana, R.M., Pradeepa, R., Ganesan, A., Unnikrishnan, R., Rema, M.,Mohan, V., 2011. Association of depression with complications of type-2diabetes – the Chennai Urban Rural Epidemiology Study (CURES-102). Journalof the Association of Physicians of India 59, 640–644.

Raval, A., Dhanraj, E., Bhansali, D., Grover, S., Tiwari, P., 2010. Prevalence anddeterminents of depression in patients with type2 diabetes in a tertiary carecentre. The Indian Journal of Medical Research 132, 195–200.

Rubin, R.R., Ciechanowski, P., Egede, L.E., Lin, E.H., Lustman, P.J., 2004. Recognizingand treating depression in patients with diabetes. Current Diabetes Reports 4(2) 119–125.

Rubin, R.R., Knowler, W.C., Ma, Y., Marrero, D.G., Edelstein, S.L., Walker, E.A.,Garfield, S.A., Fisher, E.B., 2005. Depressive symptoms and antidepressantmedicine use in diabetes prevention program participants. Diabetes Care 28,830–837.

Wade, A., Lemming, M.O., Hedegaard, B.K., 2002. Escitalopram 10 mg/day is effec-tive and well tolerated in a placebo-controlled study in depression in primarycare. International Clinical Psychopharmacology 17, 95–102.

Winokur, A., Maislin, G., Amsterdam, J.D., 1988. Insulin resistance after oral glucosetolerance testing in patients with major depression. American Journal ofPsychiatry 145, 325–330.

Yoshida, S., Hirai, M., Suzuki, S., Awata, S., Oka, Y., 2009. Neuropathy is associatedwith depression independently of health-related quality of life in Japanesepatients with diabetes. Psychiatry and Clinical Neurosciences 63, 65–72.

Zahid, N., Asghar, S., Claussen, B., Hussain, A., 2008. Depression and diabetes inarural community in Pakistan. Diabetes Research and Clinical Practice 79 (1)124–127.