Diabetes and Depresi

8/10/2019 Diabetes and Depresi

1/218

Diabetes and depresi1

Study protocol of the Diabetes andDepression Study (DAD): a multi-centerrandomized controlled trial to comparethe efficacy of a diabetes-specificcognitive behavioral group therapy versussertraline in patients with major

depression and poorly controlled diabetesmellitusran! "etra! 1*, Stephan #erpertz 1, $hristian Albus 2, %orbert #ermanns 3, $hristoph #iem!e 4, &olfgang #iller 5, 'ai 'ronfeld 6, ohannes 'ruse 7, ernd'ulzer 3, $hristian *uc!es 6 and +atthias +,ller 8

* Corresponding author: Frank Petrakmail dr!"rank!petrak#de

$uthor $""iliations

1 %epartment o" Ps&'hosomati' (edi'ine and Ps&'hotherap&, ) )!+ni ersit& Clini'-o'hum, .uhr!+ni ersit& -o'hum, -o'hum, /erman&

2 %epartment o" Ps&'hosomati' (edi'ine and Ps&'hotherap&, +ni ersit& o" Cologne,0 ln, /erman&

3 %ia etes Center (ergentheim, -ad (ergentheim, /erman&

4 %epartment o" Ps&'hiatr& and Ps&'hotherap&, +ni ersit& (edi'al Centre, ohannes/uten erg!+ni ersit&, (ain , /erman&

5 %epartment o" Clini'al Ps&'holog& and Ps&'hotherap&, ohannes /uten erg +ni ersit&(ain , (ain , /erman&

6 nterdis'iplinar& Centre "or Clini'al rials (ain 09 (ain , +ni ersit& (edi'alCentre, ohannes /uten erg!+ni ersit&, (ain , /erman&
http://www.biomedcentral.com/1471-244X/13/206/#ins1http://www.biomedcentral.com/1471-244X/13/206/#ins1http://www.biomedcentral.com/1471-244X/13/206/#ins2http://www.biomedcentral.com/1471-244X/13/206/#ins3http://www.biomedcentral.com/1471-244X/13/206/#ins3http://www.biomedcentral.com/1471-244X/13/206/#ins4http://www.biomedcentral.com/1471-244X/13/206/#ins5http://www.biomedcentral.com/1471-244X/13/206/#ins5http://www.biomedcentral.com/1471-244X/13/206/#ins6http://www.biomedcentral.com/1471-244X/13/206/#ins7http://www.biomedcentral.com/1471-244X/13/206/#ins3http://www.biomedcentral.com/1471-244X/13/206/#ins6http://www.biomedcentral.com/1471-244X/13/206/#ins8mailto:[email protected]://www.biomedcentral.com/1471-244X/13/206http://www.biomedcentral.com/1471-244X/13/206/#ins1http://www.biomedcentral.com/1471-244X/13/206/#ins2http://www.biomedcentral.com/1471-244X/13/206/#ins3http://www.biomedcentral.com/1471-244X/13/206/#ins4http://www.biomedcentral.com/1471-244X/13/206/#ins5http://www.biomedcentral.com/1471-244X/13/206/#ins6http://www.biomedcentral.com/1471-244X/13/206/#ins7http://www.biomedcentral.com/1471-244X/13/206/#ins3http://www.biomedcentral.com/1471-244X/13/206/#ins6http://www.biomedcentral.com/1471-244X/13/206/#ins8mailto:[email protected]://www.biomedcentral.com/1471-244X/13/206http://www.biomedcentral.com/1471-244X/13/206/#ins1


2/218

7 Clini' "or Ps&'hosomati' and Ps&'hotherap&, +ni ersit& Clini' /ie;en


3/218

0e& in'lusion 'riteria @ere: t&pe 1 or 2 dia etes, ma or depression diagnosed @ith the

9tru'tured Clini'al nter ie@ "or %9(! =, 9C % and hemoglo in $1 C G7#5H despite

'urrent insulin therap %uring the initial phase, patients re'ei ed either 5>I2>> mg C- sessions aiming at the remission o" depression and enhan'ed

adheren'e to dia etes treatment and 'oping @ith dia etes# -oth groups re'ei ed dia etes

treatment as usual# $"ter 12 @eeks o" this initial open!la el therap&, onl& the treatment!

responders 5>H depression s&mptoms redu'tion, Jamilton %epression .ating 9'ale, 17!

item ersion KJ$(%L @ere in'luded in the su seMuent one &ear stud& phase and

represented the primar& anal&sis population# C- !responders re'ei ed no "urther

treatment, @hile 9E.!responders o tained a 'ontinuous, "leNi le!dose 9E. regimen as

relapse pre ention# $dheren'e to treatment @as anal& ed using therapeuti' drugmonitoring measurement o" sertraline and D!desmeth&lsertraline 'on'entrations in lood

serum and & 'ounting the num ers o" C- sessions re'ei ed# ut'ome assessments

@ere 'ondu'ted & trained ps&'hologists linded to group assignment# /roup di""eren'es

in J $1' primar& out'ome and depression J$(%, se'ondar& out'ome et@een 1!

&ear "ollo@!up and aseline @ill e anal& ed & $DC =$ 'ontrolling "or aseline

alues# $s primar& h&pothesis @e eNpe't that C- leads to signi"i'antl& greater

impro ement o" gl&'emi' 'ontrol in the one &ear "ollo@!up in treatment responders o" theshort term phase#

Discussion

he %$% stud& is the "irst randomi ed 'ontrolled trial 'omparing antidepressants to a

ps&'hologi'al treatment in dia etes patients @ith depression#

he stud& is in estigator initiated and @as supported & the OF rderprogramm 0linis'he

9tudien Clini'al rials and the OCompeten'e Det@ork "or %ia etes mellitus "unded &

the Federal (inistr& o" Edu'ation and .esear'h F0 >10/>5>5 #

0rial registration

Current 'ontrolled trials 9.C D8Q333241 #
http://www.controlled-trials.com/ISRCTN89333241http://www.controlled-trials.com/ISRCTN89333241


4/218

ac!ground

Diabetes and depression

%ia etes mellitus is a highl& pre alent 'hroni' disease a""e'ting approNimatel& Q to 1>H

o" the glo al adult population K1L# -ased on estimates o" the nternational %ia etes

Federation there @ere 366 million people @ith dia etes in 2>11, and this rate is eNpe'ted

to rise to 552 million & 2>3> K2L# %ia etes is a ma or 'ause o" mor idit& and mortalit&

K3L and eNtremel& 'ostl& in e'onomi' terms K4L# People @ith dia etes are at t@i'e the risk

o" de eloping depression 'ompared @ith 'ontrol groups @ithout dia etes# $''ordingl&,

QH o" patients @ith dia etes meet the 'riteria "or ma or depression 'ontrols: 5H and

approNimatel& 25H o" patients @ith dia etes mellitus are su""ering "rom single or

multiple depression s&mptoms 'ontrols: 14H , @hi'h in'ludes ma or depression as @ell

as su 'lini'al depression K5L#

here is a strong od& o" e iden'e "or multiple ad erse intera'tions et@een dia etes and

depression# erall, the 'omor idit& o" depression and dia etes is asso'iated @ith

ad erse dia etes out'omes, espe'iall& higher hemoglo in $1' J $1' le els K 6L, mi'ro!

and ma'ro as'ular 'ompli'ations K 7L, mortalit& K8,QL, greater dia etes!related s&mptom

urden K1>L, in'reased "un'tional impairment, and poorer adheren'e to diet, eNer'ise, anddia etes sel"!management K11L# n addition, 'oeNisting depression in people @ith dia etes

is asso'iated @ith poorer mental and ph&si'al Mualit& o" li"e K12L and markedl& in'reased

health 'are 'osts K13,14L#

0reatment of depression in diabetes

$''ording to the a o e mentioned results, the treatment o" 'omor id depression is

'onsidered as essential "or the 'lini'al 'are o" dia etes patients K15L# hen treatingdepressed dia etes patients, there are t@o ma or treatment goals:

1 remission or impro ement o" depression, and
http://www.biomedcentral.com/1471-244X/13/206#B1http://www.biomedcentral.com/1471-244X/13/206#B2http://www.biomedcentral.com/1471-244X/13/206#B3http://www.biomedcentral.com/1471-244X/13/206#B4http://www.biomedcentral.com/1471-244X/13/206#B5http://www.biomedcentral.com/1471-244X/13/206#B6http://www.biomedcentral.com/1471-244X/13/206#B7http://www.biomedcentral.com/1471-244X/13/206#B8http://www.biomedcentral.com/1471-244X/13/206#B9http://www.biomedcentral.com/1471-244X/13/206#B9http://www.biomedcentral.com/1471-244X/13/206#B10http://www.biomedcentral.com/1471-244X/13/206#B11http://www.biomedcentral.com/1471-244X/13/206#B12http://www.biomedcentral.com/1471-244X/13/206#B13http://www.biomedcentral.com/1471-244X/13/206#B13http://www.biomedcentral.com/1471-244X/13/206#B14http://www.biomedcentral.com/1471-244X/13/206#B15http://www.biomedcentral.com/1471-244X/13/206#B1http://www.biomedcentral.com/1471-244X/13/206#B2http://www.biomedcentral.com/1471-244X/13/206#B3http://www.biomedcentral.com/1471-244X/13/206#B4http://www.biomedcentral.com/1471-244X/13/206#B5http://www.biomedcentral.com/1471-244X/13/206#B6http://www.biomedcentral.com/1471-244X/13/206#B7http://www.biomedcentral.com/1471-244X/13/206#B8http://www.biomedcentral.com/1471-244X/13/206#B9http://www.biomedcentral.com/1471-244X/13/206#B10http://www.biomedcentral.com/1471-244X/13/206#B11http://www.biomedcentral.com/1471-244X/13/206#B12http://www.biomedcentral.com/1471-244X/13/206#B13http://www.biomedcentral.com/1471-244X/13/206#B14http://www.biomedcentral.com/1471-244X/13/206#B15


5/218

2 impro ement o" the o"ten poor gl&'emi' 'ontrol# he se'ond goal is generall&

'onsidered as "undamental to the management o" dia etes, in order to pre ent or dela&

long!term 'ompli'ations K16L#

+p to no@, three di""erent approa'hes to treat depression in dia etes ha e een e aluated

in randomi ed 'ontrolled trials .C : $ntidepressant medi'ation, ps&'hologi'al

treatments e# g# 'ogniti e eha ioral therap&, 'ounseling, pro lem sol ing training and

a "leNi le 'om ination o" oth in stepped 'are approa'hes# n 2>1>, treatment e""e'ts

@ere summari ed in a meta!anal&sis o" 14 .C s K17L and in 2>12 in a s&stemati'

Co'hrane re ie@ in'luding 1Q .C s K18L#

$s a result o" oth anal&ses there is gro@ing e iden'e that depression 'an e treated @ithmoderate su''ess in patients @ith dia etes using either ps&'hologi'al, pharma'ologi'al

and stepped 'are inter entions 'om ined e""e't si es KE9L d R>#51B Q5H 'on"iden'e

inter al KC L !>#63 to R>#3Q # ith regard to the goal o" impro ed gl&'emi' 'ontrol the

results are 'ontro ersial: @hile the meta!anal&sis 'al'ulated small 'om ined e""e't si es

"or all treatments taken together E9 d R>#27B Q5H 0l R>#4> to R>#15 K17L, the Co'hrane

re ie@ 'on'luded that O glycemic control improved moderately in pharmacological trials,

while the evidence is inconclusive for psychological intervention. Overall, the evidence is

sparse and inconclusive due to several low-quality trials with substantial ris of bias and

the heterogeneity of e!amined populations and interventions K18L#

n sum, despite the rele an'e o" the topi' and the in'reased resear'h a'ti it& o er the last

t@o de'ades, there is still a 'onsidera le la'k o" kno@ledge @hen "a'ing the Muestion to

identi"& the most e""e'ti e treatment "or depression in dia etes# Espe'iall&, due to the

'om ination o" inter entions in the 'olla orati e 'are trials @ith sound methodolog&, e#g#K1Q!21L, it is impossi le to identi"& the e""e'ti e 'omponents o" 'ompound treatments or

to e aluate the superiorit& o" one treatment e#g# antidepressants a o e another e#g#

'ogniti e eha ioral therap&, pro lem sol ing training # Finall&, there eNist no pu lished

data to identi"& the est treatments among e""e'ti e treatmentsB and more spe'i"i'all&, to
http://www.biomedcentral.com/1471-244X/13/206#B16http://www.biomedcentral.com/1471-244X/13/206#B17http://www.biomedcentral.com/1471-244X/13/206#B18http://www.biomedcentral.com/1471-244X/13/206#B17http://www.biomedcentral.com/1471-244X/13/206#B18http://www.biomedcentral.com/1471-244X/13/206#B19http://www.biomedcentral.com/1471-244X/13/206#B21http://www.biomedcentral.com/1471-244X/13/206#B16http://www.biomedcentral.com/1471-244X/13/206#B17http://www.biomedcentral.com/1471-244X/13/206#B18http://www.biomedcentral.com/1471-244X/13/206#B17http://www.biomedcentral.com/1471-244X/13/206#B18http://www.biomedcentral.com/1471-244X/13/206#B19http://www.biomedcentral.com/1471-244X/13/206#B21


6/218

our kno@ledge no trial @as 'ondu'ted 'omparing pharma'ologi'al to ps&'hologi'al

inter entions in patients @ith dia etes and 'omor id depression#

o address this la'k o" kno@ledge @e 'ondu'ted the %ia etes and %epression 9tud&

%$% stud& , a randomi ed, multi'enter, 'ontrolled trial 'omparing a dia etes!spe'i"i'

C- to 9E. in poorl& 'ontrolled dia etes patients @ith ma or depression#

$urrent status of the trial

%ata anal&sis phase#

*esearch objectives and endpoints

"rimary objective

he aim o" the planned stud& is to e aluate the e""i'a'& o" a dia etes!spe'i"i' C-

'om ined @ith dia etes edu'ation ersus a 'ontinuous treatment @ith 99. 9E.

'om ined @ith dia etes edu'ation in high!risk patients @ith poorl& 'ontrolled insulin!

treated t&pe 1 or t&pe 2 dia etes mellitus and depression#

"rincipal research 1uestion

%oes a dia etes!spe'i"i' ps&'hotherap& C- or antidepressant medi'ation 9E.

impro e long!term gl&'emi' 'ontrol in patients @ith poorl& 'ontrolled dia etes and

depressionS

"rimary hypothesis

C- leads to a etter impro ement o" gl&'emi' 'ontrol @hen 'ompared @ith 9E. at the

one!&ear "ollo@!up in patients @ho initiall& responded to short!term therap& C- or

9E. @ith regard to impro ement in depression#

Primar& endpoint: Change o" gl&'emi' 'ontrol hemoglo in $1C #

Secondary objectives


7/218

o pro ide 'lear s'ienti"i' e iden'e @hether the t@o most @idel& esta lished treatments

99. and C- "or patients @ith depression ut @ithout additional somati' diseases 'an

e applied to high!risk patients @ith poor meta oli' 'ontrol o" insulin!treated dia etes

and 'omor id depression#

Secondary hypothesis

C- and 9E. are oth e""e'ti e in terms o" remission o" depression a"ter 12 @eeks in an

open la el trial as @ell as at the one!&ear "ollo@!up#

Secondary endpoints

a remission o" depression: no longer "ul"illing the %9(! =! . 'riteria "or depression

a''ording to the 9tru'tured Clini'al nter ie@ "or %9(! =, 9C % K 22L, and depression

s'ore a''ording to the J$(% I nter ie@ K 23L T U 7B

impro ement o" depression GH redu'tion o" J$(%! aseline s'ore B

' impro ed generi' J.Vo), per 9F!36 K 24LB and

d de'reased pro lems in dail& li ing @ith dia etes, per P$ % K25L#

+ethods/Design

Study design2 setting2 recruitment and procedures

his trial is a prospe'ti e, randomi ed, multi'enter, parallel arm 'ontrolled 'lini'al trial

that in ol ed the t@o treatment 'onditions C- s# 9E. in a parallel group design see

Figure 1 #

igure 3 Design of the DAD study3

he re'ruitment o" the patients took pla'e et@een $pril 2>>6 and (a& 2>>Q in 7> trial

'enters o" outpatient se'ondar& 'are spe'iali ed dia etologi'al pra'ti'es and am ulator&
http://www.biomedcentral.com/1471-244X/13/206#B22http://www.biomedcentral.com/1471-244X/13/206#B23http://www.biomedcentral.com/1471-244X/13/206#B24http://www.biomedcentral.com/1471-244X/13/206#B25http://www.biomedcentral.com/1471-244X/13/206/figure/F1http://www.biomedcentral.com/1471-244X/13/206/figure/F1http://www.biomedcentral.com/1471-244X/13/206/figure/F1http://www.biomedcentral.com/1471-244X/13/206#B22http://www.biomedcentral.com/1471-244X/13/206#B23http://www.biomedcentral.com/1471-244X/13/206#B24http://www.biomedcentral.com/1471-244X/13/206#B25http://www.biomedcentral.com/1471-244X/13/206/figure/F1http://www.biomedcentral.com/1471-244X/13/206/figure/F1


8/218


9/218

indi'ating that the raters @ere @ell trained e"ore the eginning o" their assessment in the

%$% stud Further ps&'hoso'ial aria les @ere assessed using ps&'hometri'

Muestionnaires des'ri ed in the O(easures se'tion #

Patients meeting all eligi ilit& 'riteria see OEligi ilit& 'riteria se'tion @ere o""ered a

short stru'tured dia etes edu'ation 2 Z 3 hours & trained dia etes edu'ators as an

update to ensure su""i'ient dia etes kno@ledge in all trial parti'ipants see O%ia etes

edu'ation se'tion # $ll patients 'ompleting the dia etes edu'ation program @ere

allo'ated randoml& to either 1> sessions o" group C- or an algorithm ased 9E.!

treatment @ith 5> to 2>> mgH redu'tion o" the J$(% aseline s'ore or J$(%

post!treatment s'ore \ 7 @ere in'luded in a 12!month long!term phase# hese patients

'onstituted the intention!to!treat population# Don!responders o" the short!term

phase @ere eN'luded "rom the treatment proto'ol and re"erred to the est a aila le

treatment using standard medi'al 'are# he general re'ommendation to the treating ph&si'ians @as to gi e 9E. or other medi'ation to C- !non!responders and to gi e C-

or other medi'ation to 9E.! non!responders#

$ll patients entering the long!term phase re'ei ed ongoing dia etologi'al treatment as

usual & their treating ph&si'ians in the dia etologi'al trial 'enter at 3!month inter als

during the "ollo@ing 12 months# 9E.!responders re'ei ed a 'ontinuous 9E.! treatment

as relapse pre ention# C- responders did not re'ei e "urther treatment ut @ereen'ouraged to @ork @ith a patients manual in the sense o" a i liotherap& K2QL during the

one &ear "ollo@!up phase# he di""eren'e in the a'ti e treatment duration et@een oth

inter entions 'orresponds to usual 'lini'al pra'ti'e and thus assure eNternal alidit

/enerall&, group C- is o""ered "or a limited period o" time assuming that O'arr& o er
http://www.biomedcentral.com/1471-244X/13/206#B29http://www.biomedcentral.com/1471-244X/13/206#B29


10/218


11/218

poorl& 'ontrolled t&pe 2 dia etes @ould ha e still een treated in primar& 'are settings

not parti'ipating in the %(Ps#

o enhan'e 'ompara ilit& @ith international studies and to pre ent a sele'tion ias, our

independent s'ienti"i' ad isor& oard see OVualit& assuran'e se'tion re'ommended

eN'luding patients onl& in 'ase o" 'lini'all& signi"i'ant sui'ide risk or histor& o"

attempted sui'ide in the past 12 months# he eN'lusion 'riterion regarding the 'urrent use

o" ps&'hotropi' drugs @as modi"ied to allo@ the in'lusion o" patients treated @ith lo@

poten'& neurolepti's in lo@ doses less than 3>> mg 'hlorproma ine dose eMui alents per

da& , as these drugs are o"ten used to treat sleeping disorders and restlessness in dia etes

patients, parti'ularl& in those su""ering "rom dia eti' neuropath %etailed in'lusion and

eN'lusion 'riteria are listed in a le 1#

0able 3 4ligibility criteria for the DAD study

*andomization and blinding

*andomization

Patients @ere randomi ed using lo'k randomi ation to ensure eMual group si es# For

ea'h 'oordinating institution, a separate randomi ation pro'edure strati"ied & t&pe o"dia etes @as per"ormed to ensure alan'ed treatment groups a'ross and @ithin

'oordinating institutions# .andomi ation lists @ere generated & the nterdis'iplinar&

Center "or Clini'al rials (ain 09 , +ni ersit& (edi'al Center (ain & means o" a

'omputer program# hese randomi ation lists in'luded the patient identi"i'ation num er

9+- % used "or identi"&ing all data 'olle'ted "rom the su e't during the stud& and "or

the treatment allo'ation# he randomi ation lists @ere maintained & the 09# he

treatment allo'ation at the 'oordinating institutions @as per"ormed using F$?randomi ation# $"ter 'he'king su e't s eligi ilit&, the in estigator "aNed a randomi ation

reMuest "orm to the 09 randomi ation 'enter# his "orm in'luded in"ormation on the

patient s seN, &ear o" irth and t&pe o" dia etes# he 09 randomi ation 'enter entered
http://www.biomedcentral.com/1471-244X/13/206/table/T1http://www.biomedcentral.com/1471-244X/13/206/table/T1http://www.biomedcentral.com/1471-244X/13/206/table/T1http://www.biomedcentral.com/1471-244X/13/206/table/T1http://www.biomedcentral.com/1471-244X/13/206/table/T1http://www.biomedcentral.com/1471-244X/13/206/table/T1


12/218

the 9+- % and treatment allo'ation on the reMuest "orm and "aNed the "orm a'k to the

in estigator s site#

linding

n the %$% stud&, ps&'hotherap& C- @as 'ompared to medi'ation and there @as no

pla'e o 'ondition# hus, a linding o" patients or health 'are pro iders @as not possi le#

Jo@e er, a linding o" all mem ers o" the resear'h team in ol ed in the assessment o"

out'omes @as 'arried out#

6nterventions

Diabetes education

/i en the poor gl&'emi' 'ontrol o" the patients and 'onsidering that most patients treated

@ith insulin had likel& undergone dia etes edu'ation pre iousl& a''ording to the

/erman e iden'e ased guidelines that @ere in "or'e at the time o" the patient

re'ruitment K36L , a short dia etes edu'ation program @as o""ered to all patients as an

update# Patients re'ei ed stru'tured dia etes edu'ation 2 Z 3 hours e"ore

randomi ation# he program in'luded the "ollo@ing modules: 1 insulin treatmentB 2

sel"!monitoring @ith regard to dia etes!rele ant eha ioral strategies e#g#, nutrition, ph&si'al a'ti it&, "oot 'are B 3 the re'ognition, treatment, and pre ention o" a'ute

'ompli'ationsB and 4 risk "a'tors e#g#, h&perlipidemia, arterial h&pertension, smoking

"or ma'roangiopathi' dia etes!related illnesses# his dia etes edu'ation @as o""ered &

trained dia etes edu'ators using a manual that @as esta lished "or the %$% stud& see

$dditional "ile1 O"tructured diabetes education manual for diabetes educators in

/erman #

Additional file 3 Structured diabetes education manual for diabetes educators (in7erman)3

Format: P%F 9i e: 2#8(- %o@nload "ile or displa& 'ontent in a ne@ @indo@

his "ile 'an e ie@ed @ith: $do e $'ro at .eader
http://www.biomedcentral.com/1471-244X/13/206#B36http://www.biomedcentral.com/1471-244X/13/206/suppl/S1http://www.biomedcentral.com/1471-244X/13/206/suppl/S1http://www.biomedcentral.com/content/supplementary/1471-244x-13-206-s1.pdfhttp://www.biomedcentral.com/content/supplementary/1471-244X-13-206-s1/http://www.adobe.com/products/acrobat/readstep.htmlhttp://www.adobe.com/products/acrobat/readstep.htmlhttp://www.biomedcentral.com/about/access/#opendatahttp://www.biomedcentral.com/1471-244X/13/206#B36http://www.biomedcentral.com/1471-244X/13/206/suppl/S1http://www.biomedcentral.com/content/supplementary/1471-244x-13-206-s1.pdfhttp://www.biomedcentral.com/content/supplementary/1471-244X-13-206-s1/http://www.adobe.com/products/acrobat/readstep.html


13/218

Diabetes specific cognitive behavioral group therapy ($ 0)

C- @as o""ered as manuali ed dia etes!spe'i"i' treatment deli ered & 'lini'al

ps&'hologist @ho had undergone a s&stemati' training regarding the manual# Ea'h

session @as ideotaped and a random sample o" 13H o" the sessions D U 32 sessions@as used in order to 'ontinuousl& e aluate and ensure the adheren'e to the manual and to

gi e 'ontinuous super ision & one o" the authors, @ho is a C- trainer and super isor

FP # e additionall& de eloped and e aluated a rating s&stem to assess the eNpertise o"

the therapists @ith a''epta le to good interrater relia ilit& intra'lass 'orrelation

'oe""i'ient, CC >#73 to >#Q6 # $ se'ond rating s&stem to assess adheren'e to the C-

manual @as also de eloped and sho@ed good to eN'ellent interrater relia ilit& 'oe""i'ient

>#74 to 1#> details o" the rating s&stems @ill e pu lished separatel& #

C- @as deli ered in groups o" 4 to 1> patients per group in an outpatient setting @ithin

a 12I@eek time period# his treatment 'onsisted o" 1> sessions 2> hours using a

manuali ed semi!stru'tured C- "or depression, in'luding di""erent dia etes!spe'i"i'

aspe'ts in order to impro e adheren'e to dia etes treatment and 'oping @ith dia etes see

$dditional "ile2 O #iabetes-specific CB$ manual for therapists , in /erman # he

ps&'hoedu'ation se'tion sessions 1I3 in'luded in"ormation a out the asso'iation o"mood and a'ti ities and the de elopment and maintenan'e o" depression# n addition,

parti'ipants learned a out the link et@een dia etes and mood and @a&s to in"luen'e

impaired mood @ith 'ogniti e te'hniMues# Furthermore, parti'ipants @ere en'ouraged to

dis'uss dia etes!spe'i"i' goals su'h as J $1 ' target alues @ith their dia etologists and

to spe'i"& eha ioral goals in order to impro e their gl&'emi' 'ontrol see $dditional "ile

3 O%or ing sheet for diabetologists and patients& strategies to improve glycemic control ,

in /erman # ndi idual goal a'hie ement @as assessed in sessions siN and ten and possi le arriers to the goal attainment @ere identi"ied and modi"ied i" possi le# o help

patients identi"&ing and redu'ing per'ei ed arriers to arious aspe'ts o" sel"!

management and to enhan'e 'oping skills, the pro lem!sol ing se'tion sessions 4I7

'o ered 'ogniti e and eha ioral te'hniMues e#g# 'ogniti e restru'turing, stress
http://www.biomedcentral.com/1471-244X/13/206/suppl/S2http://www.biomedcentral.com/1471-244X/13/206/suppl/S2http://www.biomedcentral.com/1471-244X/13/206/suppl/S3http://www.biomedcentral.com/1471-244X/13/206/suppl/S2http://www.biomedcentral.com/1471-244X/13/206/suppl/S3


14/218


15/218

supplementar& isits and telephone 'onta't @ere possi le at an& time# $dditionall& one o"

the authors, a ps&'hiatrist and 'lini'al ps&'hologist ( ( , o""ered ad i'e to the treating

dia etologists pro iding a ps&'hiatri' hotline i" Muestions regarding the medi'ation

o''urred# %uring the long!term phase o" the trial 9E. responders re'ei ed a 'ontinuous

9E. treatment as relapse pre ention#

0able 83 Algorithm for the sertraline treatment in the DAD trial

+easures

ut'ome measures @ere assessed at aseline, at the end o" the short!term phase

12 @eeks , at months 6, Q, 12 during the long!term phase and at the end o" the long!term

phase 15 months # For patients randomi ed to 9E. treatment, additional assessments@ere s'heduled at @eek 2 and 8 during the short term phase to deli er medi'ation and

monitor the response and side!e""e'ts# $t @eek 8 and 12 9E. and desmeth&lsertraline

lood le els @ere assessed# Figure 2 summari es all medi'al and ps&'hoso'ial aria les,

@hi'h @ere assessed in the 'urrent trial, & time o" data 'olle'tion# $d erse e ents @ere

monitored and re'orded 'ontinuousl& during the trial see $dditional "ile5 O"afety

manual , in /ermanB and O #efinitions and assessment of adverse events #

igure 83 +easurements in the DAD study3 Dote: P U isit to the'oordinating institutions @ere Muestionnaire and inter ie@s @ill e administered &mem ers o" the resear'h team resear'h assistants, ps&'hologists B % U isit to thetreating ph&si'ian or resear'h assistants in the dia etologi' trial 'entres# *=isit 92 isoptional & tele"one or personall

Additional file ;3 Safety manual (in 7erman)< and = Definitions and assessment ofadverse events 93

Format: P%F 9i e: 5230- %o@nload "ile or displa& 'ontent in a ne@ @indo@


"rimary outcome
http://www.biomedcentral.com/1471-244X/13/206/table/T2http://www.biomedcentral.com/1471-244X/13/206/table/T2http://www.biomedcentral.com/1471-244X/13/206/figure/F2http://www.biomedcentral.com/1471-244X/13/206/figure/F2http://www.biomedcentral.com/1471-244X/13/206/suppl/S5http://www.biomedcentral.com/1471-244X/13/206/figure/F2http://www.biomedcentral.com/content/supplementary/1471-244x-13-206-s5.pdfhttp://www.biomedcentral.com/content/supplementary/1471-244X-13-206-s5/http://www.adobe.com/products/acrobat/readstep.htmlhttp://www.adobe.com/products/acrobat/readstep.htmlhttp://www.biomedcentral.com/about/access/#opendatahttp://www.biomedcentral.com/1471-244X/13/206/table/T2http://www.biomedcentral.com/1471-244X/13/206/figure/F2http://www.biomedcentral.com/1471-244X/13/206/suppl/S5http://www.biomedcentral.com/1471-244X/13/206/figure/F2http://www.biomedcentral.com/content/supplementary/1471-244x-13-206-s5.pdfhttp://www.biomedcentral.com/content/supplementary/1471-244X-13-206-s5/http://www.adobe.com/products/acrobat/readstep.html


16/218

nitiall&, the primar& out'ome @as Oimpro ement o" gl&'emi' 'ontrol , de"ined as a

de'rease o" at least 1H in J $1 ' alue &es>8 into O'hange o"

gl&'emi' 'ontrol , de"ined as the di""eren'e in J $1 ' alue "rom aseline to the end o"

the long!term phase# -& 'hanging the di'hotomous endpoint into a 'ontinuous endpoint,

the statisti'al po@er o" the trial 'ould e enhan'ed and the planned num er o" trial

su e'ts had to e redu'ed see O9ample si e 'al'ulation se'tion #

Secondary outcomes

9e'ondar& out'omes @ere Oremission o" depression B i#e# not "ul"illing the %9(! =! .

'riteria "or depression a''ording to the 9C % and J$(% s'ores \ 7, Oimpro ement o"

depression , i#e# a redu'tion o" the J$(% s'ore "rom aseline to the end o" trial & at

least 5>H, Oimpro ement o" health!related Mualit& o" li"e J.Vo) , i#e# 'hange in

generi' J.Vo) "rom aseline to end o" trial as assessed per 9F!36 mental and ph&si'al

'omponent s'ores K24L, and Oimpro ement o" dia etes related stress , "rom aseline to

end o" trial as measured per P$ % K3QL# $s amended to the proto'ol, the pre ious primar&

out'ome impro ement o" gl&'emi' 'ontrol o" at least 1H in J $1 ' alue "rom aselineto the end o" the long!term phase @as assessed as a se'ondar& out'ome#

>ther psychometric measures

$ num er o" other ps&'hometri' aria les @ere in estigated and measured @ith alidated

/erman Muestionnaires or /erman ersions o" internationall& alidated Muestionnaires at

aseline, a"ter the end o" the short!term phase and in the one &ear "ollo@!up: %ia etes

kno@ledge @as measured @ith a %ia etes 0no@ledge Vuestionnaire "or &pe 1

%ia etes! issens! est &p! !, % ! K 4>L and &pe 2 %ia etes %ia etes! issens!

est &p! , % ! K 41L, dia etes sel"!'are & the 9ummar& o" dia etes sel"!'are

a'ti ities measure 9%9C$ K42L, dia etes!spe'i"i' lo'us o" 'ontrol & the PC!%ia etes!

Vuestionnaire PC!%1 K43L and ps&'hologi'al arriers to insulin therap& & the -arriers
http://www.biomedcentral.com/1471-244X/13/206#B24http://www.biomedcentral.com/1471-244X/13/206#B39http://www.biomedcentral.com/1471-244X/13/206#B40http://www.biomedcentral.com/1471-244X/13/206#B41http://www.biomedcentral.com/1471-244X/13/206#B42http://www.biomedcentral.com/1471-244X/13/206#B43http://www.biomedcentral.com/1471-244X/13/206#B24http://www.biomedcentral.com/1471-244X/13/206#B39http://www.biomedcentral.com/1471-244X/13/206#B40http://www.biomedcentral.com/1471-244X/13/206#B41http://www.biomedcentral.com/1471-244X/13/206#B42http://www.biomedcentral.com/1471-244X/13/206#B43


17/218

to nsulin herap& Vuestionnaire - K44L# Coping @as assessed using the Frei urger

Coping @ith llness Vuestionnaire 15!item ersion, F0=!15 K45L, sel"!esteem & the

.osen erg 9el"!Esteem 9'ale .9E K 46LB hopelessness & the Jopelessness 9'ale J!

9'ale K47LB in'ongruen'e & nkongruen'e Vuestionnaire 0! D0 K48L, 'hildhood

traumata & Childhood rauma Vuestionnaire C V K4Q,5>L ps&'hologi'al pro lems and

s&mptoms o" ps&'hopatholog& & the 9hort!Form o" the 9&mptom Che'klist 9C)!Q>!.

K51L /erman ersion, 9C)!0!Q K52LB and so'ial support & the Vuestionnaire o"

per'ei ed "amil& support and 'ommuni'ation PF+0 K53L#

Assessment of treatment preference

reatment pre"eren'e @as assessed as "ollo@s: O " &ou @ere depressed and &ou 'ould

'hoose et@een t@o eMuall& e""e'ti e treatments that might 'ure &our depression, @hi'h

DE @ould &ou 'hooseS

1 Free medi'ation dail& "or 15 months no or onl& minor side e""e'ts to e eNpe'ted B

2 1> sessions 2 hours ea'h, @ithin a 3Imonth time period o" group ps&'hotherap&

@ith a maNimum o" 1> group mem ers, @ith a "o'us on depression and dia etes!related

pro lemsB

3 do not pre"ere either treatment#

Assessment of the patient- and therapist perspectives of the ($ 0) sessions

Ea'h C- session @as rated & patients and therapists assessing the per'ei ed personal

in ol ement and 'on"iden'e regarding the group therap he group therapists and the

super isor re'ei ed the results as 'ontinuous "eed a'k e"ore the neNt session in order to

re"le't and i" ne'essar& to impro e the therapeuti' strateg& in the respe'ti e group# he

Muestionnaire @as alidated @ithin the %$% stud& @ith good ps&'hometri' results K54L#

Assessment of adherence to treatment
http://www.biomedcentral.com/1471-244X/13/206#B44http://www.biomedcentral.com/1471-244X/13/206#B45http://www.biomedcentral.com/1471-244X/13/206#B46http://www.biomedcentral.com/1471-244X/13/206#B47http://www.biomedcentral.com/1471-244X/13/206#B48http://www.biomedcentral.com/1471-244X/13/206#B49http://www.biomedcentral.com/1471-244X/13/206#B50http://www.biomedcentral.com/1471-244X/13/206#B50http://www.biomedcentral.com/1471-244X/13/206#B51http://www.biomedcentral.com/1471-244X/13/206#B52http://www.biomedcentral.com/1471-244X/13/206#B53http://www.biomedcentral.com/1471-244X/13/206#B54http://www.biomedcentral.com/1471-244X/13/206#B44http://www.biomedcentral.com/1471-244X/13/206#B45http://www.biomedcentral.com/1471-244X/13/206#B46http://www.biomedcentral.com/1471-244X/13/206#B47http://www.biomedcentral.com/1471-244X/13/206#B48http://www.biomedcentral.com/1471-244X/13/206#B49http://www.biomedcentral.com/1471-244X/13/206#B50http://www.biomedcentral.com/1471-244X/13/206#B51http://www.biomedcentral.com/1471-244X/13/206#B52http://www.biomedcentral.com/1471-244X/13/206#B53http://www.biomedcentral.com/1471-244X/13/206#B54


18/218

$dheren'e to treatment @as de"ined & measuring the re'ei ed therap& ]dose] see a le 3

"or an o er ie@ a out the de"inition o" adheren'e to C- and 9E. treatment #

0able .3 Definition of treatment adherence in the $ 0 and sertraline treatment

groupsAdherence to $ 0 @as assessed & the num er o" attended C- !sessions# $s there

eNists no esta lished measure o" adheren'e "or ps&'hotherap&, in the 'urrent trial

su""i'ient adheren'e to C- @as de"ined as parti'ipation in at least eight out o" ten

sessions#

Adherence to S4* treatment @as assessed & repeated measures o" serum 9E.

'on'entrations and the ratio o" meta olite to parent 'ompound, i#e# ratio o" D!desmeth&lsertraline %9E. to 9E. as re'ommended & .eis and 'olleagues K56L# $s

patients identi"ied as treatment non!responders a"ter the end o" the short!term phase @ere

eN'luded "rom the treatment proto'ol, 9E. adheren'e @as e aluated separatel& "or

randomi ed patients and patients# For randomi ed patients, adheren'e @as assessed

ased on 9E. 'on'entrations and %9E.: 9E. measured at @eek 8 and 12# For

patients, adheren'e @as assessed ased on 9E. 'on'entrations and %9E.: 9E. measured

at @eek 8, 12, 24, 36, 48 and 6># Dot@ithstanding initial planning and herapeuti' %rug(onitoring %( guidelines K 57L, @hi'h re'ommend 'on'entrations et@een 1>I

5> ngI1>> ng> ng


19/218

'on'entrations, %9E. 'on'entrations and ratios %9E.:9E., adheren'e @as estimated "or

these patients# " onl& one lood sample @as a aila le, the patient @as eN'luded "rom the

adheren'e rating# $s high 9E. 'on'entrations G 1>> ng>8, the po@er 'al'ulation @as 'hanged as "ollo@s: he po@er

'al'ulation @as ased on eNpe'ted di""eren'es in J $1 ' le els o" the 'omparison groups

in the sample# his sample 'onsisted o" all randomi ed patients @ho entered the 12!

month "ollo@!up phase# Considering .C s in @hi'h C- K58L or 99. s K5QL @ere

e aluated, a treatment di""eren'e o" 1#>H J $1' 'ould e assumed as rele ant# 9tandard

de iations o" J $1 ' alues o" 1#42 and 1#8 @ere o ser ed in these studies# For the

'urrent trial a standard de iation o" slightl& more than 1#4 'ould e eNpe'ted# Jo@e er, a

standard de iation o" 1#6 as a 'onser ati e approa'h @as taken# here"ore, @ith 2Z46

e alua le su e'ts, the trial @ill ha e 85H po@er to dete't a treatment di""eren'e o" 1#>H
http://www.biomedcentral.com/1471-244X/13/206#B58http://www.biomedcentral.com/1471-244X/13/206#B59http://www.biomedcentral.com/1471-244X/13/206#B58http://www.biomedcentral.com/1471-244X/13/206#B59


20/218

J $1 ' & means o" a t!test on a t@o!sided le el o" signi"i'an'e ^ U >#>5# $ssuming a

drop!out rate o" 6>H, 23> 2Z115 su e'ts had to e randomi ed#

$nal&ses @ill e per"ormed using an intent!to!treat prin'iple# Jo@e er, i" in the short!

term phase dropout rates in the t@o treatment groups di""er & more than 1>H, the

primar& anal&sis @ill emplo& all randomi ed patients# his @ould e done e'ause the

'omparison o" long!term treatment e""e'ts on gl&'emi' 'ontrol in patients @ho ha e an

initial short!term impro ement o" depressi e disorder J$(% redu'tion [ 5>H or

J$(% s'ore \ 7 a"ter the short!term phase is alid onl& i" the dropout rates in the short!

term phase are similar#

Analysis of outcome variables

Do interim anal&ses are planned# he primar& out'ome o" the trial O'hange o" gl&'emi'

'ontrol is de"ined as the di""eren'e in J $1 ' alue "rom aseline to the end o" the long!

term phase 'ompared "or the di""erent treatment groups using an anal&sis o" 'o arian'e

$DC =$ 'ontrolling "or aseline J $1 ' alue and aseline J$(% s'ore# he

primar& anal&sis @ill e "o'used on o ser ed 'ases# he anal&sis @ill e repeated a"ter

emplo&ing the last o ser ation 'arried "or@ard method "or missing J $1' and J$(%

s'ores# $n appropriate method has to e 'hosen on an indi idual asis @hen the missing

alue pattern e'omes kno@n# " more than 1>H ut less than 4>H o" the alues are

missing, multiple imputation methods @ill e 'onsidered#

he main se'ondar& anal&sis is ased on the num ers and proportions o" patients @ho

demonstrate impro ement o" gl&'emi' 'ontrol [ 1H impro ement in J $1 ' alues "rom

aseline to the end o" the long!term phase # %i""eren'es et@een treatment groups @ill e

tested using logisti' regression anal&sis 'ontrolling "or aseline J $1' alue and aselineJ$(%!s'ore# Further se'ondar& out'omes su'h as remission o" depression and

impro ement o" depression @ill e anal& ed using logisti' regression anal&sis 'ontrolling

"or aseline J $1 ' alue and aseline J$(% s'ore to e aluate treatment e""e'ts#

%i""eren'es et@een treatment groups in impro ement in JrVo) 9F!36 mental and


21/218

ph&si'al 'omponent s'ores and impro ement o" dia etes related distress as assessed &

P$ % @ill e anal& ed using anal&ses o" 'o arian'e 'ontrolling "or aseline J $1 '

alues and aseline 9F!36 s'ores mental and a''ordingl& ph&si'al 'omponent s'ore or

aseline P$ % s'ores, respe'ti el

$ll primar& and se'ondar& anal&ses @ill e repeated 'ontrolling "or potential

'on"ounders# o identi"& 'on"ounders su'h as age, seN, 'oordinating institution, dia etes

t&pe, dia etes 'ompli'ations, edu'ation &ears, in'ome, single @ith long!term out'ome aria les J $1 ' , J$(%

s'ore, 9F!36 'omponent s'ores and P$ % s'ore, respe'ti el& @ill then e in'luded as

"urther 'ontrol aria les#

$''ording to the intent!to!treat prin'iple all anal&ses @ill e 'ondu'ted "or the

population# he anal&ses "or sa"et& population, randomi ed population and per proto'ol

population @ill e 'onsidered as se'ondar

$n eNplorator& su group anal&sis "or t&pe o" dia etes @ill e emplo&ed "or the primar&

out'ome# here"ore, the primar& anal&sis @ill e repeated in'luding an intera'tion termo" dia etes t&pe and treatment group in the $DC =$# Further 'o ariates @ill e aseline

J $1 ' and aseline J$(% s'ore# For remission o" depression "rom the end o" the short!

term phase to the end o" "ollo@!up a logisti' regression in'luding an intera'tion term o"

dia etes t&pe and treatment group, aseline J $1 ' and aseline J$(% s'ore @ill e

per"ormed, respe'ti el hese anal&ses ha e to e 'onsidered eNplorator

$dheren'e to treatment @ill e displa&ed des'ripti el& o erall and "or ea'h treatment

group# %i""eren'es in adheren'e et@een oth treatment groups @ill e anal& ed using

'hi!sMuare tests# $n eNplorator& su group anal&sis "or adheren'e groups @ill e

emplo&ed "or 'hange in J $1 ' "rom the end o" short!term phase to the end o" the "ollo@!

up# here"ore, an $DC =$ @ill e per"ormed in'luding an intera'tion term o" adheren'e

group and treatment group# Further 'o ariates @ill e J $1' and J$(% s'ore at the end


22/218

o" the short!term phase# For remission o" depression "rom the end o" the short!term phase

to the end o" "ollo@!up a logisti' regression in'luding an intera'tion term o" adheren'e

group and treatment group, J $1 ' and J$(% s'ore at the end o" short!term phase @ill

e per"ormed, respe'ti el hese anal&ses ha e to e 'onsidered eNplorator&, as the

statisti'al po@er might not e su""i'ient#

Further eNplorator& se'ondar& anal&ses @ill e per"ormed su'h as the anal&sis, @hether

impro ement in depression sho@s a stronger asso'iation @ith etter J $1' in the C-

group than in the on!going medi'ation groupB and, i" this is the 'ase, to test, i" the degree

o" dia etes sel"!'are @ill in'rease more in the C- group than in the on!going medi'ation

group see $dditional "ile6 O #etailed statistical analysis plan #

Additional file ?3 Detailed statistical analysis plan3

Format: P%F 9i e: 2520- %o@nload "ile or displa& 'ontent in a ne@ @indo@


@uality assurance

Safety %i""eren'es et@een treatment groups regarding rates o" ad erse e ents su'h

ne@l& emerging tenden'& @ill e displa&ed des'ripti el Dum ers and per'entages o"ad erse e ents and num er and per'entage o" su e'ts @ith ad erse e ents @ill e

presented "or ea'h o''urring s&stem organ 'lass and "or ea'h pre"erred term @ithin

s&stem organ 'lass & treatment group and @ith a total 'olumn# $dditionall&, this @ill e

done "or relationship, intensit& and seriousness o" ad erse e ents# he results @ill e

displa&ed "or the sa"et& population see $dditional "ile 5 O"afety manual in /erman B

and O #efinitions and assessment of adverse events #

Data management $ data management plan %(P @as esta lished "or the %$% stud&

to spe'i"& ea'h data management pro'ess "or the %$% trial# he purpose o" the %(P is

to des'ri e the underl&ing data management pro'ess @hi'h go erns 'olle'tion,

management, re ie@ and reporting o" data "rom this 'lini'al trial# he 'ontent o" a %(P
http://www.biomedcentral.com/1471-244X/13/206/suppl/S6http://www.biomedcentral.com/content/supplementary/1471-244x-13-206-s6.pdfhttp://www.biomedcentral.com/content/supplementary/1471-244X-13-206-s6/http://www.adobe.com/products/acrobat/readstep.htmlhttp://www.adobe.com/products/acrobat/readstep.htmlhttp://www.biomedcentral.com/1471-244X/13/206/suppl/S5http://www.biomedcentral.com/1471-244X/13/206/suppl/S5http://www.biomedcentral.com/about/access/#opendatahttp://www.biomedcentral.com/1471-244X/13/206/suppl/S6http://www.biomedcentral.com/content/supplementary/1471-244x-13-206-s6.pdfhttp://www.biomedcentral.com/content/supplementary/1471-244X-13-206-s6/http://www.adobe.com/products/acrobat/readstep.htmlhttp://www.biomedcentral.com/1471-244X/13/206/suppl/S5


23/218

in'ludes, ut is not limited to, trial timelines, data management pro'edures in'luding data

'olle'tion and data "lo@ and the %ata =alidation Plan# he %(P do'uments the

alidation strateg& and tools, and re"eren'es responsi ilities "or di""erent tasks# $ll data

management a'ti ities @ere per"ormed a''ording to the 'urrent 9tandard perating

Pro'edures 9 Ps o" the 09 see $dditional "ile 7 O #ata management plan #

Additional file 3 Data management plan3

Format: P%F 9i e: 13Q0- %o@nload "ile or displa& 'ontent in a ne@ @indo@


+onitoring Clini'al on!site monitoring @as per"ormed & personal isits "rom a 'lini'al

monitor a''ording to 9 Ps o" the 09# o initiate the stud&, the monitor isited ea'h parti'ipating lo'al trial site and 'oordinating stud& 'enters# he monitors ensured that the

in estigators and their sta"" understand all reMuirements o" the proto'ol and their

regulator& responsi ilities# Ea'h site @as isited & the monitor at regular inter als to

ensure 'omplian'e @ith the stud& proto'ol, /CP and legal aspe'ts# he monitors

re ie@ed the entries into the Case .eport Forms C.F on the asis o" the sour'e

do'uments# he presen'e o" 'orre't in"ormed 'onsents @as 'he'ked "or e er& patient#

9our'e do'ument eri"i'ation 9%= @as per"ormed "or 1>>H o" 'ore data

randomi ation, primar& endpoint and 9$E and 2>H o" other data in this stud %etails

@ere spe'i"ied in the monitoring manual "or the %$% stud he in estigators had to

allo@ the monitor to look at all rele ant do'uments and @ere reMuested to pro ide support

at all times to the monitor# -& "reMuent 'ommuni'ations letters, telephone, "aN , the

monitors ensured that the trial @as 'ondu'ted a''ording to the proto'ol and regulator&

reMuirements#

Advisory board $n independent s'ienti"i' ad isor& oard @as esta lished to super ise

the 'ondu't o" the trial and to issue re'ommendations "or earl& termination, modi"i'ations

or 'ontinuation o" the trial, i" ne'essar

(em ers o" the $d isor& -oard are:
http://www.biomedcentral.com/1471-244X/13/206/suppl/S7http://www.biomedcentral.com/1471-244X/13/206/suppl/S7http://www.biomedcentral.com/content/supplementary/1471-244x-13-206-s7.pdfhttp://www.biomedcentral.com/content/supplementary/1471-244X-13-206-s7/http://www.adobe.com/products/acrobat/readstep.htmlhttp://www.adobe.com/products/acrobat/readstep.htmlhttp://www.biomedcentral.com/about/access/#opendatahttp://www.biomedcentral.com/1471-244X/13/206/suppl/S7http://www.biomedcentral.com/content/supplementary/1471-244x-13-206-s7.pdfhttp://www.biomedcentral.com/content/supplementary/1471-244X-13-206-s7/http://www.adobe.com/products/acrobat/readstep.html


24/218

I Pro"# %r# +lri'h Jegerl, Clini' and Poli'lini' o" Ps&'hiatr& and Ps&'hotherap& o" the

+ni ersit& o" )eip ig, /erman

I Pro"# %r# alter )ehma'her, nstitute "or (edi'al 9tatisti's, n"ormati's and

Epidemiolog& o" the +ni ersit& o" Cologne, /erman

I Pro"# %r# (artin Jaut inger, E erhard!0arls!+ni ersit&, nstitute o" Ps&'holog&,

%epartment o" Clini'al and %e elopmental Ps&'holog&, ue ingen, /erman

4thical aspects

he pro'edures set out in the trial proto'ol regarding the 'ondu't, e aluation, and

do'umentation o" this trial are designed to ensure that all persons in ol ed in the triala ide & /ood Clini'al Pra'ti'e /CP and the ethi'al prin'iples des'ri ed in the 'urrent

re ision o" the %e'laration o" Jelsinki# Clini'al monitoring, data management,

pharma'o igilan'e, regulator& a""airs and iometr& a''ording to /CP @ere 'ondu'ted &

the 09 (ain # he trial @as 'arried out in keeping @ith lo'al legal and regulator&

reMuirements# he reMuirements o" the $(/, the /CP regulation, and the Federal %ata

Prote'tion )a@ -%9/ ha e een kept# he trial @as appro ed & (edi'al Ethi's

Committee Jessen Ethikkommission der )andes_r tekammer Jessen no# 2>6 on143>6# he Federal nstitute "or %rugs and (edi'al %e i'es appro ed the trial on

173>6# hree su stantial amendments ha e een appro ed & oth institutions in

$ugust 2>>6, $pril 2>>7 and Do em er 2>>8# $ll patients @ere in treatment, regularl&

seen & dia etologists and ps&'hologists# -e"ore eing admitted to the 'lini'al trial, the

patients agreed to parti'ipate a"ter the nature, s'ope, and possi le 'onseMuen'es o" the

trial ha e een eNplained in a "orm understanda le to them# he patients ga e @ritten

in"ormed 'onsent and re'ei ed a 'op& o" the signed 'onsent do'ument# he do'uments@ere in language that @as understanda le to the patients and spe'i"ied @ho in"ormed

them# %uring the trial, patients @ere identi"ied solel& & means o" &ear o" irth and an

indi idual identi"i'ation 'ode patient num er, randomi ation num er #


25/218

Discussion

%espite the in'reasing num er o" studies e aluating treatment options "or depression in

dia etes, the e iden'e "or the identi"i'ation o" a single treatment, @hi'h 'ould

signi"i'antl& impro e ps&'hologi'al out'omes and gl&'emi' 'ontrol at the same timeremains in'on'lusi e K17,18L# Furthermore, as pointed out & (arko@iet and 'olleagues

K6>L, most inter entions @ere not designed to dire'tl& impro e dia etes sel"!'are and did

not e aluate e""e'ts on "urther out'ome aria les su'h as Mualit& o" li"e or remission o"

depression# he 'urrent trial attempts to address these limitations & in'luding onl&

patients @ith poor gl&'emi' 'ontrol J $1' G 7#5H , de eloping a 'ogniti e eha ioral

therap& 'o ering dia etes!spe'i"i' aspe'ts su'h as goal!setting to enhan'e dia etes!sel"!

'are, and & assessment o" "urther out'ome aria les su'h as remission o" depression,impro ement in Mualit& o" li"e and redu'tion o" dia etes!related distress# $s @as o ser ed

in the most re'ent s&stemati' re ie@ on this topi' the Mualit& o" the trials in this "ield is

er& heterogeneous and espe'iall& a'ti e 'omparison trials are rare K18L# here"ore, @e

'ondu'ted this trial 'omparing "or the "irst time the e""i'a'& o" a ps&'hologi'al treatment

to ps&'hopharma'ologi'al treatment "or depression in patients @ith depression @ith a

strong emphasis on sound methodolog hus, @e think that the %$% stud& @ill add

important kno@ledge to the "ield o" depression treatment in dia etes#

Status of the trial

he trial 'ommen'ed in $pril 2>>6, and patient re'ruitment @as 'ompleted in (a& 2>>Q,

resulting in a sample o" 251 randomi ed patients# $"ter rea'hing the 'al'ulated sample

si e o" 23> patients, all patients alread& under s'reening ha e een randomi ed

additionall Currentl& @e are in the anal&sis phase#

$ompeting interests

he authors de'lare that the& ha e no 'ompeting interests#

Authors9 contributions
http://www.biomedcentral.com/1471-244X/13/206#B17http://www.biomedcentral.com/1471-244X/13/206#B18http://www.biomedcentral.com/1471-244X/13/206#B18http://www.biomedcentral.com/1471-244X/13/206#B60http://www.biomedcentral.com/1471-244X/13/206#B18http://www.biomedcentral.com/1471-244X/13/206#B17http://www.biomedcentral.com/1471-244X/13/206#B18http://www.biomedcentral.com/1471-244X/13/206#B60http://www.biomedcentral.com/1471-244X/13/206#B18


26/218

FP prin'ipal in estigator P , ( ( 'oordinating in estigator, 00 'lini'al trialist, C.

iometri'ian# 9igni"i'ant 'ontri ution to the de elopment o" the stud& design and

methods: FP, 9J, DJ, CJ, 00B 0, -0, C., ( (B riting o" the manus'ript# FP# $ll

'o!authors read, edited, and appro ed the "inal manus'ript# .esponsi ilit& "or the

'oordination, re'ruitment and treatment in the 'oordinating regional trial 'enters: FP, 9J,

C$, DJ, J, 00, 0, -0# $ll authors parti'ipated in the @ork su""i'ientl& to take

pu li' responsi ilit& "or their respe'ti e parts o" the paper# 9igni"i'ant 'ontri ution to

iometri's: C., FP, ( (# 9igni"i'ant 'ontri ution to monitoring and Mualit& assuran'e o"

the trial: 00, FP, ( (#

Ac!nowledgments

he authors @ould like to thank all patients "or their parti'ipation in the %$% trial#

Furthermore, @e thank the dia etologists and ph&si'ians o" the dia etologi'al trial

'enters: Jeinke $dam' e@ski, (ar'us $ltmeier, -ernhard $ngelkort, Pa&am

$rd omand, Jolger $rndt, 0laus -adenhoop, $lain -arakat, -ernd -e'ker, +lla -ehlen!

ilm, Peter -erndt, .ainer -et hol , .alph -ier@irth, (atthias -oehme, 9tephan

-onnermann, -irgit - ttger, (arion -raun, Jelga -W'ker, 0laus -us'h, Frank

%emtroeder, $ndreas %erstro"", ris %onati!Jirs'h, (i'hael Engho"er, -erthold Fohr,

)ut Fri'ke, %irk /_'kler, /udrun /eier, 0ai / tte, .udol" /rodde'k, (artin

/rWne erg, E a Jaak, Wrgen Jaak, Ju ertus Jal"as, ol"gang Jauth, %orothea Jer er,

0arl!Jein Jer er, E a Jess, /regor Jess, /angol" Jeussen, homas Jipp, (i'hael

Juptas, 9a ine _kel, er & asinski, Cornelia aurs'h!Jan'ke, utta 0al"haus, (atthias

0altheuner, Jans! homas 0app, Jans!Peter 0empe, Jans! Wrgen 0issing, /erhard

0lausmann, %ieter 0lein, /uido 0lempt, erner 0leophas, -eate 0orth! iemann,

0laus!Peter 0reisselmeier, /eorg 0r_mer, 0laus 0usterer, (i'hael )ang, $li'e )ange,

0arin )anger, Claudia )e&er, (atthias )e&er, E'kart )ohr, -a ette )orra, /eorg (arMua,

9tephan (aNeiner, Frank (er"ort, /esine (e&er, 0athrin (e&er, $ngela (inor, ris

(its'hka, Jans rg (Whlen, +do (Wller, %ieter DeusW;, +lri'h DWhlen, Erika!(aria

erter, +rsula hndor", (an"red Plum, +@e Preu;, -eate Vuad e'k, ilhelm


27/218

.eden a'h, 0onrad .eimann, -ernadette .eins'h, $leNander .isse, 9te"an .oth"rit ,

Emilia .u"", 9tephanie .uppre'ht, Jein ! .W;mann, Dikolaus 9'heper, (i'hael 9'hilp,

(an"red 9'hlotmann, )othar 9'hramm, -enno 9'hul e!9'hleppingho"", (i'hael

9imonsohn, il"ried 9o e, 0lemens 9ondern, (i'hael 9tammen, Eugen 9te""ens, )ut

9temler, erner 9tWrmer, (artin 9ulliga, Claudia +l ri'h, 9imon =idal, Christian on

-oN erg, 9imone on Jaag, Ernst! tto on .eis, /eorg e er, (atthias e er,

Friedri'h orth, ose" immermannB and the parti'ipating ps&'hiatrists and the

ph&si'ians spe'iali ed in ps&'hosomati' medi'ine Christian $l us, ol" -resges,

9tephan Jerpert , ohannes 0ruse, (atthias (Wller, $leNander Die'ke, and -ernd

9onntag # e also thank the ps&'hologists in the 'oordinating trial 'enters, @ho helped in

the de elopment o" the trial design, patient re'ruitment and trial 'ondu't: Claudia-aNmann, sa el -engesser, $ndrea -enne'ke, Dor ert Jermanns, 9ophie anssen,

-ernhard 0ul er, (areike 0Wpper, -eatriN )ehnho"", +lrike ) @, (aria Digro, Esther

Petermann, Frank Petrak, 0ristin Pla'k, 0athrin Post, (onika .en ert, $nna .odrigue

.u io, Dadine .und, Jeike 9ager, Christopher 9'he"", -ar ara 9'hmidt, 9&l ia 9'hmidt,

0atharina 9'hnit ler, 9a ine agner, %aniela ahn, $ssad ahran, and 0athrin ou ek#

e are inde ted to Petra -irkner, =eronika -rill, $nne Ehrli'h, li ia Endress, Peter

Friedri'h!(ai, ana Jeuer, Petra 0rensel, 0ai 0ron"eld, .ol" (einert, 0ornelia P"ei""er,Christina .e'k, Christian .u'kes, %aniel a'htlin and 9a ine ol", nterdis'iplinar&

Centre o" Clini'al 9tudies 09 (ain "or 'lini'al monitoring, pharma'o igilan'e,

regulator& a""airs, data management and iometr e also thank "or the 'ontri utions o"

the %$% trial s'ienti"i' ad isor& oard (artin Jaut inger, +lri'h Jegerl and alter

)ehma'her # e @ould like to a'kno@ledge the te'hni'al sta"" o" the Deuro'hemi'al

)a orator&, %epartment o" Ps&'hiatr&, ohannes /uten erg +ni ersit& (ain , "or the

anal&sis o" sertraline 'on'entrations and (onika inter and her 'o!@orkers, -ios'ientiangelheim, "or the la orator& anal&sis o" endo'rinologi' parameters#

unding


28/218

his @ork @as supported & the `0ompeten net %ia etes mellitus Competen'e

Det@ork "or %ia etes mellitus ` "unded & the Federal (inistr& o" Edu'ation and

.esear'h Do# >10/>5>5 #

*eferences

3 %anaei /, Finu'ane ((, )u , 9ingh /(, Co@an ( , Pa'iorek C , )in 0,Far ad"ar F, 0hang J, 9te ens /$, et al #:%ational2 regional2 and globaltrends in fasting plasma glucose and diabetes prevalence since BC :systematic analysis of health e5amination surveys and epidemiologicalstudies with . country-years and 83 million participants3

'ancet 2>11,. C Q785:31!4>#Pu (ed $ stra't bPu lisher Full eNt

83 hiting %., /uariguata ), eil C, 9ha@ : 6D diabetes atlas: global estimatesof the prevalence of diabetes for 8 and 8 . 3

#iabetes (es Clin Pract 2>11,B 3 :311!321#Pu (ed $ stra't bPu lisher Full eNt

.3 0ilpatri'k E9, .ig & $9, $tkin 9): A $ variability and the ris! ofmicrovascular complications in type diabetes: data from the diabetescontrol and complications trial3

#iabetes Care 2>>8,. 11 :21Q8!22>2#Pu (ed $ stra't b Pu lisher Full eNt b

Pu (ed Central Full eNt 3 0oster , =on Fer er ), hle P, 9'hu ert , Jauner J: 0he cost burden of

diabetes mellitus: the evidence from 7ermanyEthe $oDi+ study3

#iabetologia 2>>6, B 7 :14Q8!15>4#Pu (ed $ stra't bPu lisher Full eNt

;3 $nderson . , Freedland 0E, Clouse .E, )ustman P : 0he prevalence ofcomorbid depression in adults with diabetes: a meta-analysis3

#iabetes Care 2>>1,8 6 :1>6Q!1>78#Pu (ed $ stra't bPu lisher Full eNt

?3 )ustman P , $nderson . , Freedland 0E, %e /root (, Carne& .(, Clouse .E:Depression and poor glycemic control: a meta-analytic review of theliterature3

#iabetes Care 2>>>,8. 7 :Q34!Q42#Pu (ed $ stra't bPu lisher Full eNt
http://www.biomedcentral.com/pubmed/21705069http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=21705069http://www.biomedcentral.com/pubmed/22079683http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=22079683http://www.biomedcentral.com/pubmed/18650371http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=18650371http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=18650371http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=18650371http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18650371http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B3http://www.biomedcentral.com/pubmed/16752168http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=16752168http://www.biomedcentral.com/pubmed/11375373http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=11375373http://www.biomedcentral.com/pubmed/10895843http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=10895843http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B6http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B5http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B4http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B3http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B2http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B1http://www.biomedcentral.com/pubmed/21705069http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=21705069http://www.biomedcentral.com/pubmed/22079683http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=22079683http://www.biomedcentral.com/pubmed/18650371http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=18650371http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18650371http://www.biomedcentral.com/pubmed/16752168http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=16752168http://www.biomedcentral.com/pubmed/11375373http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=11375373http://www.biomedcentral.com/pubmed/10895843http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=10895843


29/218

3 %e /root (, $nderson ., Freedland 0E, Clouse .E, )ustman P : Association ofdepression and diabetes complications: a meta-analysis3

Psychosom Med 2>>1,?. 4 :61Q!63>#Pu (ed $ stra't bPu lisher Full eNt

C3 Egede )E, Dietert P , heng %: Depression and all-cause and coronary heartdisease mortality among adults with and without diabetes3

#iabetes Care 2>>5,8C6 :133Q!1345#Pu (ed $ stra't bPu lisher Full eNt

B3 .i'hardson )0, Egede )E, (ueller (: 4ffect of race/ethnicity and persistentrecognition of depression on mortality in elderly men with type 8 diabetesand depression3

#iabetes Care 2>>8,. 5 :88>!881#Pu (ed $ stra't bPu lisher Full eNt

3 Jermanns D, 0ul er -, 0ri'h aum (, 0u iak , Jaak : #ow to screen fordepression and emotional problems in patients with diabetes: comparison ofscreening characteristics of depression 1uestionnaires2 measurement ofdiabetes-specific emotional problems and standard clinical assessment3

#iabetologia 2>>6, B 3 :46Q!477#Pu (ed $ stra't bPu lisher Full eNt

3 /on ale 9, Pe&rot (, ('Carl )$, Collins E(, 9erpa ), (imiaga ( , 9a"ren9$: Depression and diabetes treatment nonadherence: a meta-analysis3

#iabetes Care 2>>8,. 12 :23Q8!24>3#Pu (ed $ stra't bPu lisher Full eNt b

Pu (ed Central Full eNt 83 Egede )E, Ellis C: 0he effects of depression on metabolic control and 1uality

of life in indigent patients with type 8 diabetes3

#iabetes $echnol $her 2>1>, 8 4 :257!262#Pu (ed $ stra't bPu lisher Full eNt bPu (ed Central Full eNt

.3 Jutter D, 9'hnurr $, -aumeister J: #ealthcare costs in patients with diabetesmellitus and comorbid mental disordersEa systematic review3

#iabetologia 2>1>,;. 12 :247>!247Q#Pu (ed $ stra't bPu lisher Full eNt 3 -osmans E, $driaanse (C: >utpatient costs in pharmaceutically treated

diabetes patients with and without a diagnosis of depression in a Dutchprimary care setting3

BMC )ealth "erv (es 2>12, 8: 46#Pu (ed $ stra't b -io(ed Central Full eNt bPu (ed Central Full eNt
http://www.biomedcentral.com/pubmed/11485116http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=11485116http://www.biomedcentral.com/pubmed/15920049http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=15920049http://www.biomedcentral.com/pubmed/18332155http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=18332155http://www.biomedcentral.com/pubmed/16432706http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=16432706http://www.biomedcentral.com/pubmed/19033420http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=19033420http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19033420http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B11http://www.biomedcentral.com/pubmed/20210563http://www.biomedcentral.com/pubmed/20210563http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=20210563http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=20210563http://www.biomedcentral.com/pubmed/20700575http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=20700575http://www.biomedcentral.com/pubmed/22361361http://dx.doi.org/10.1186/1472-6963-12-46http://dx.doi.org/10.1186/1472-6963-12-46http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=22361361http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B14http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B14http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B13http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B12http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B11http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B10http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B9http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B8http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B7http://www.biomedcentral.com/pubmed/11485116http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=11485116http://www.biomedcentral.com/pubmed/15920049http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=15920049http://www.biomedcentral.com/pubmed/18332155http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=18332155http://www.biomedcentral.com/pubmed/16432706http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=16432706http://www.biomedcentral.com/pubmed/19033420http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=19033420http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19033420http://www.biomedcentral.com/pubmed/20210563http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=20210563http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=20210563http://www.biomedcentral.com/pubmed/20700575http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=20700575http://www.biomedcentral.com/pubmed/22361361http://dx.doi.org/10.1186/1472-6963-12-46http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=22361361


30/218

;3 Jolt . , 0aton : Dialogue on diabetes and depression: dealing with thedouble burden of co-morbidity3

* +ffect #isord 2>12, 8 9uppl :91!93#Pu (ed $ stra't bPu lisher Full eNt

?3 $meri'an %ia etes $sso'iation: 45ecutive summary: standards of medicalcare in diabetes-8 .3

#iabetes Care 2>13,.?: 4!1>#Pu (ed $ stra't bPu lisher Full eNt

3 an der Felt !Cornelis C(, Du&en , 9toop C, Chan , a'o son $(, 0aton ,9noek F, 9artorius D:4ffect of interventions for major depressive disorderand significant depressive symptoms in patients with diabetes mellitus: asystematic review and meta-analysis3

en )osp Psychiatry 2>1>,.8 4 :38>!3Q5#Pu (ed $ stra't b

Pu lisher Full eNt C3-aumeister J, Jutter D, -engel : "sychological and pharmacological

interventions for depression in patients with diabetes mellitus anddepression3

Cochrane #atabase "yst (ev 2>12, 8: C%>>8381#Pu (ed $ stra't bPu lisher Full eNt

B3Ell 0, 0aton , ?ie -, )ee P , 0apetano i' 9, /uterman , Chou CP:$ollaborative care management of major depression among low-income2

predominantly #ispanic subjects with diabetes: a randomized controlledtrial3

#iabetes Care 2>1>,.. 4 :7>6!713#Pu (ed $ stra't bPu lisher Full eNt bPu (ed Central Full eNt

8 3 0aton , )in EJ, =on 0or"" (, Cie'hano@ski P, )udman E , oung -,Peterson %, .utter C(, ('/regor (, ('Cullo'h %: $ollaborative care forpatients with depression and chronic illnesses3

ngl * Med 2>1>,.?. 27 :2611!262>#Pu (ed $ stra't b Pu lisher Full eNt b

Pu (ed Central Full eNt 8 3 0aton , =on 0or"" (, )in EJ, 9imon /, )udman E, .usso , Cie'hano@ski P,

alker E, -ush : 0he pathways study: a randomized trial of collaborativecare in patients with diabetes and depression3

+rch en Psychiatry 2>>4,? 1> :1>42!1>4Q#Pu (ed $ stra't bPu lisher Full eNt
http://www.biomedcentral.com/pubmed/23062852http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=23062852http://www.biomedcentral.com/pubmed/23264284http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=23264284http://www.biomedcentral.com/pubmed/20633742http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=20633742http://www.biomedcentral.com/pubmed/23235661http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=23235661http://www.biomedcentral.com/pubmed/20097780http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=20097780http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=20097780http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B19http://www.biomedcentral.com/pubmed/21190455http://www.biomedcentral.com/pubmed/21190455http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=21190455http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=21190455http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=21190455http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B20http://www.biomedcentral.com/pubmed/15466678http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=15466678http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B21http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B20http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B19http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B18http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B17http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B16http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B15http://www.biomedcentral.com/pubmed/23062852http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=23062852http://www.biomedcentral.com/pubmed/23264284http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=23264284http://www.biomedcentral.com/pubmed/20633742http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=20633742http://www.biomedcentral.com/pubmed/23235661http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=23235661http://www.biomedcentral.com/pubmed/20097780http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=20097780http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=20097780http://www.biomedcentral.com/pubmed/21190455http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=21190455http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=21190455http://www.biomedcentral.com/pubmed/15466678http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=15466678


31/218


32/218

n f1r die 'eitliniengruppe 8nipolare #epression& "4-'eitlinie9 ationale2ersorgungs'eitlinie 8nipolare #epression-'angfassung :2ersion 7.4; # 2>12#

http:1>, 1 :55#Pu (ed $ stra't b-io(ed Central Full eNt b Pu (ed Central Full eNt

.;3 9 e'sen&i , .osemann , oos 9, Peters!0limm F, (iks'h $: 7erman diabetesdisease management programs are appropriate for restructuring careaccording to the chronic care model: an evaluation with the patientassessment of chronic illness care instrument3

#iabetes Care 2>>8,. : 115>!1154#Pu (ed $ stra't bPu lisher Full eNt .?3 Petrak F, Jerpert 9, $l us C, Jirs'h $, 0ul er -, 0ruse : "sychosocial factors

and diabetes mellitus: evidence-based treatment guidelines3

Curr #iabetes (ev 2>>5, 3 :255!27>#Pu (ed $ stra't bPu lisher Full eNt

. 3 /u& : Clinical lobal 0mpressions :C 0; "cale. Modified from& (ush *, et al.& Psychiatric Measures # ashington %C: $P$B 2>>>#

.C3)ing aerde , $hl"ors +/, -e'h P, %en'ker 9 , Elgen 0: 0he G'G side effectrating scale3 A new comprehensive rating scale for psychotropic drugs and a

cross-sectional study of side effects in neuroleptic-treated patients3 +cta Psychiatr "cand "uppl 1Q87,.. : 1!1>>#Pu (ed $ stra't

.B30ul er -, Jermanns D, E ert (, 0empe , 0u iak , Jaak : "roblembereichebei Diabetes ("A6D)-ein neues +eJinstrument zur 4rfassung deremotionalen Anpassung an Diabetes3
http://www.versorgungsleitlinien.de/themen/depression/pdf/s3_nvl_depression_lang.pdfhttp://www.versorgungsleitlinien.de/themen/depression/pdf/s3_nvl_depression_lang.pdfhttp://www.webcitation.org/query.php?url=http://www.versorgungsleitlinien.de/themen/depression/pdf/s3_nvl_depression_lang.pdf&refdoi=10.1186/1471-244x-13-206http://www.biomedcentral.com/pubmed/23930150http://www.biomedcentral.com/pubmed/23930150http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=23930150http://dx.doi.org/10.1365/s10337-009-1003-5http://www.biomedcentral.com/pubmed/20199685http://dx.doi.org/10.1186/1472-6963-10-55http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=20199685http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=20199685http://www.biomedcentral.com/pubmed/18299443http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=18299443http://www.biomedcentral.com/pubmed/18220602http://www.biomedcentral.com/pubmed/18220602http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=18220602http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B36http://www.biomedcentral.com/pubmed/2887090http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B38http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B37http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B36http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B35http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B34http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B33http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B32http://www.versorgungsleitlinien.de/themen/depression/pdf/s3_nvl_depression_lang.pdfhttp://www.versorgungsleitlinien.de/themen/depression/pdf/s3_nvl_depression_lang.pdfhttp://www.webcitation.org/query.php?url=http://www.versorgungsleitlinien.de/themen/depression/pdf/s3_nvl_depression_lang.pdf&refdoi=10.1186/1471-244x-13-206http://www.biomedcentral.com/pubmed/23930150http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=23930150http://dx.doi.org/10.1365/s10337-009-1003-5http://www.biomedcentral.com/pubmed/20199685http://dx.doi.org/10.1186/1472-6963-10-55http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=20199685http://www.biomedcentral.com/pubmed/18299443http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=18299443http://www.biomedcentral.com/pubmed/18220602http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=18220602http://www.biomedcentral.com/pubmed/2887090


33/218

#iabetes und "toffwechsel 2>>2, 9uppl# 1:144#

3 .oth ., 0ul er -, eupe -, -orkenstein (: #er #iabetes-%issens-$est& $yp-0:#%$& $yp-0; # / ttingen: Jogre"eB 1QQ5#

3 Jermanns D, 0ul er -: 4ntwic!lung und 4valuation eines &issenstests f,r

nicht-insulinpflichtige 0yp-66b-Diabeti!er3 #iabetes und "toffwechsel 1QQ5,;: 183!1Q>#

83 oo ert %, Jampson 9, /lasgo@ .: 0he summary of diabetes self-careactivities measure: results from studies and a revised scale3

#iabetes Care 2>>>,8. 7 :Q43!Q5>#Pu (ed $ stra't bPu lisher Full eNt

.3 0ohlmann C, 0Wstner E, 9'huler (, aus'h $: #er 0PC-#iabetes-3ragebogen:0PC-#7;. )andbuch # est entrale: / ttingenB 1QQ4#

3 Petrak F, 9tridde E, )e erkus F, Crispin $$, Forst , P"ut ner $: Developmentand validation of a new measure to evaluate psychological resistance toinsulin treatment3

#iabetes Care 2>>7,. Q :21QQ!22>4#Pu (ed $ stra't bPu lisher Full eNt

;3 Jardt , Petrak F, Egle + , 0appis -, 9'hul /, 0Wstner E: &as misst der 'KL4ine Mberpr,fung des reiburger ragebogens zur 'ran!heitsverarbeitungbei "atienten mit unterschiedlichen 4r!ran!ungen3

< /lin Psychol Psychother 2>>3,.8 1 :41!5>#Pu lisher Full eNt

?3 Ferring %, Filipp 9J:+essung des Selbstwertgefuehls: efunde zu*eliabilitaet2 Kaliditaet und Stabilitaet der *osenberg-S!ala +easurement of self-esteem: indings regarding reliability2 validity2 and stability of the*osenberg Scale3

#iagnostica 1QQ6,. 3 :284!2Q2#

3 0rampen /: " alen 6ur rfassung von )offnungslosig eit :)-" alen; # / ttingen:Jogre"eB 1QQ4#

C3/rosse!Jolt"orth (, /ra@e 0, am'an : 0n ongruen6fragebogen # / ttingen:

Jogre"eB 2>>4#B3-ernstein %P, 9tein $, De@'om (%, alker E, Pogge %, $hlu alia , 9tokes, Jandelsman ), (edrano (, %esmond %, et al #:Development and validationof a brief screening version of the childhood trauma 1uestionnaire3

Child +buse egl 2>>3,8 2 :16Q!1Q># Pu (ed $ stra't bPu lisher Full eNt
http://www.biomedcentral.com/pubmed/10895844http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=10895844http://www.biomedcentral.com/pubmed/17575092http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=17575092http://dx.doi.org/10.1026/1616-3443.32.1.41http://www.biomedcentral.com/pubmed/12615092http://www.biomedcentral.com/pubmed/12615092http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=12615092http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B49http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B48http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B47http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B46http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B45http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B44http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B43http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B42http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B41http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B40http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B39http://www.biomedcentral.com/pubmed/10895844http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=10895844http://www.biomedcentral.com/pubmed/17575092http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=17575092http://dx.doi.org/10.1026/1616-3443.32.1.41http://www.biomedcentral.com/pubmed/12615092http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=12615092


34/218

; 3 ingen"eld 0, 9pit er C, (ense a'h C, /ra e J , Jill $, /ast +, 9'hlosser D,Jopp J, -e lo , %riessen (: 0he 7erman version of the childhood trauma1uestionnaire ($0@): preliminary psychometric properties3

Psychother Psychosom Med Psychol 2>1>,? 11 :442!45>#Pu (ed $ stra't b

Pu lisher Full eNt ; 3 Franke /J: "C'-=>-(. #ie "ymptom-Chec liste von #erogatis # / ttingen,

Jogre"e: %euts'he =ersionB 1QQ5#;830lagho"er ., -r_hler E: 'onstru!tion und teststatistische "r,fung einer

'urzform der S$H-B -*3

< /lin Psychol Psychiatr Psychother 2>>1, B:115!124#

;.3 $&manns P: #er ?3ragebogen 6ur rfassung der Per6ipierten 3amilialen8nterst1t6ung und /ommuni ation? :P38/;& $heoretischer )intergrund und

" alen onstru tion. 2olume 4@ # rier: +ni ersit_t rier, Fa'h erei'h !Ps&'hologieB 1QQ1#Pu (ed $ stra't bPu lisher Full eNt ; 3 ou ek 0, Jiller , .ie" , Petrak F: Development and validation of a process

evaluation 1uestionnaire for cognitive behavioral group therapy sessions3

< Psychosom Med Psychother

su mitted

;;3 Jiemke C, -aumann P, -ergemann D, Con'a $, %ietmaier , Eg erts 0, Fri' (,/erla'h (, /reiner C, /runder /, et al #:A7%" consensus guidelines fortherapeutic drug monitoring in psychiatry: update 8 3

Pharmacopsychiatry 2>11, 6 :1Q5!235# Pu (ed $ stra't

;?3 .eis (, $ erg! istedt $, $gren J, $ker lad $C, -engtsson F: $ompliancewith SS*6 medication during ? months of treatment for major depression: anevaluation by determination of repeated serum drug concentrations3

* +ffect #isord 2>>4,C83 :443!446#Pu (ed $ stra't bPu lisher Full eNt

; 3 -aumann P, Jiemke C, +lri'h 9, E'kermann /, /aertner , /erla'h (, 0uss J ,)auN /, (uller! erlinghausen -, .ao (), et al #:0he A7%"-0D+ e5pertgroup consensus guidelines: therapeutic drug monitoring in psychiatry3

Pharmacopsychiatry 2>>4,. 6 :243!265#Pu (ed $ stra't bPu lisher Full eNt
http://www.biomedcentral.com/pubmed/20200804http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=20200804http://www.biomedcentral.com/pubmed/23929743http://www.biomedcentral.com/pubmed/23929743http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=23929743http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B53http://www.biomedcentral.com/pubmed/22053351http://www.biomedcentral.com/pubmed/22053351http://www.biomedcentral.com/pubmed/15555696http://www.biomedcentral.com/pubmed/15555696http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=15555696http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B56http://www.biomedcentral.com/pubmed/15551191http://www.biomedcentral.com/pubmed/15551191http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=15551191http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B57http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B56http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B55http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B54http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B53http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B52http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B51http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B50http://www.biomedcentral.com/pubmed/20200804http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=20200804http://www.biomedcentral.com/pubmed/23929743http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=23929743http://www.biomedcentral.com/pubmed/22053351http://www.biomedcentral.com/pubmed/15555696http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=15555696http://www.biomedcentral.com/pubmed/15551191http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=15551191


35/218

;C3)ustman P , /ri""ith )9, Freedland 0E, 0issel 99, Clouse .E: $ognitivebehavior therapy for depression in type 8 diabetes mellitus3 A randomized2controlled trial3

+nn 0ntern Med 1QQ8,8B 8 :613!621#Pu (ed $ stra't bPu lisher Full eNt

;B3)ustman P , Clouse .E, DiN -%, Freedland 0E, .u in EJ, ('/ill -, illiams((, /elen erg $ , Cie'hano@ski P9, Jirs'h -: Sertraline for prevention ofdepression recurrence in diabetes mellitus: a randomized2 double-blind3"lacebo-controlled trial3

+rch en Psychiatry 2>>6,?. 5 :521!52Q#Pu (ed $ stra't bPu lisher Full eNt

? 3 (arko@it 9(, /on ale 9, ilkinson ), 9a"ren 9$: A review of treatingdepression in diabetes: emerging findings3

Psychosomatics 2>11,;8 1 :1!18#Pu (ed $ stra't bPu lisher Full eNt bPu (ed Central Full eNt

2

#igh prevalence of diagnosis of diabetes2depression2 an5iety2 hypertension2asthma and $>"D in the totalpopulation of Stoc!holm2 Sweden E achallenge for public health

A5el $ $arlsson 12*, "er &Nndell1, Grban Osby34, *amin Parrin!oub 15, jQrn&ettermar! 56 and 7unnar Hjunggren 57

* Corresponding author: $Nel C CarlssonaNel'e"am hotmail#'om

$uthor $""iliations

1 Centre "or Famil& (edi'ine, %epartment o" Deuro iolog&, Care 9'ien'es and 9o'iet&,0arolinska nstitutet, $l"red Do els $llf 12, 141 83 Juddinge, 9@eden

2 %epartment o" Pu li' Jealth and Caring 9'ien'es< 9e'tion o" /eriatri's, +ppsala+ni ersit&, +ppsala, 9@eden
http://www.biomedcentral.com/pubmed/9786808http://www.biomedcentral.com/pubmed/9786808http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=9786808http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B58http://www.biomedcentral.com/pubmed/16651509http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=16651509http://www.biomedcentral.com/pubmed/21300190http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=21300190http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=21300190http://www.biomedcentral.com/sfx_links?ui=1471-244X-13-206&bibl=B60http://www.biomedcentral.com/1471-

Diabetes and Depresi

Documents

Transcript of Diabetes and Depresi