Serial dexamethasone suppression tests in depressed patients treated only with electroconvulsive therapy

Journal of Affective Elsevier

Disorders,

13 (1987) 233-240

233

JAD 00494

Serial dexamethasone suppression tests in depressed treated only with electroconvulsive therapy Leon Grunhaus, Clmcal

Thomas Zelnik, A. Ariav Albala, David Rabin, Athanasios P. Zis and John F. Greden

Studies Unit, Department

of Pqxhintv,

patients

Roger F. Haskett,

ffmuerslt? of Michigan Mediccrl Center. Ann Arbor, MI 48109, U.S.A. (Received (Accepted

1 April 1987) 10 June 1987)

Summary

Several systematic studies have evaluated serial dexamethasone suppression tests (DST) in patients with major depression who were treated with antidepressant medications. DST changes were noted to parallel clinical improvement in most recovering patients. If serial DSTs are a valid state-related correlate of depressive pathophysiology, all types of effective antidepressant treatment should result in DST ‘normalization’. However, no treatment modalities other than antidepressant medications have been studied serially with systematic assessments. To test whether serial DSTs reflect clinical progress in depressives treated solely with electroconvulsive therapy (ECT), we studied weekly DSTs and Hamilton Rating Scales for Depression (HRSD) in 22 drug-free depressed patients. We observed progressive DST ‘normalization’ in most patients and moderately high correlations between weekly DST and HRSD values throughout treatment. Most patients receiving ECT became DST suppressors. In most patients the DST appeared to reflect the severity of depressive pathophysiology, perhaps providing serial feedback to clinicians monitoring the progress of treatment with ECT.

Key fiords:

Dexamethasone

suppression

test; Major depression;

Introduction

A number of investigators have reported on the patterns of dexamethasone suppression test (DST) Address for correspondence: Leon Grunhaus, M.D., Assistant Professor of Psychiatry, Department of Psychiatry, University of Michigan Medical Center, Ann Arbor, MI 481090118, U.S.A. Supported in part by NIMH Grants MH28294 and MH39593, and by the University of Michigan Mental Health Research Institute and Department of Psychiatry.

0165.0327/87/$03.50

0 1987 Elsevier Science Publishers

Electroconvulsive

therapy

results in depressed patients during treatment with antidepressant medications (Carroll 1972; De La Fuente and Rosenbaum 1980; Greden et al. 1980, 1983; Holsboer et al. 1982, 1983; Targum 1983; Gerken et al. 1985; Bowie and Beaini 1985; Baumgartner et al. 1986; Grunhaus et al. 1987). From these studies it appears that the normalization of a previously nonsuppressive DST parallels a successful course of antidepressant treatment. Initial reports suggested that similar patterns of normalization occurred during electroconvulsive

B.V. (Biomedical

Division)

ther+

(ECT)

(D>Aen

1979

1979

1981)

Hweler

more

recent

demon>trrlted

dn

a>cwatmn

not

4lbA.1

et aI

Carroll

normahzdtmn 19%.

aid

Debanand

To

et al

further

1981

outcome

et al

Greden

ECT

the eftects

rewlt,

\\\r \tudwd

22 wrrelv

deprewd

N Ith

onI\

ueehl\

mctdlatrl> follw

cbnlcal dfter

prr\>l\r

DST\

ECT

(2)

,tJte-relatlonshp Are

absolute

TABLE

Do

If

so

b’e

cner do

tlmr

>ensl

cllnlcal

of pa&nts

treated

plana

In monitoring mlth

lJnl\erslt\

of

the

ECT hale

~mpro~rment”

po\t-dexamethasone meaningful

A DSTb

tCSL[)

and

patients

Studw~

or

the

1984

Selected patent

patlent

recel\rd

Pschatq

bledlcal

Center

AND

CLINICAL

Each dw+xtlc

13

prnod

a

cl~mcal

ot e\aluatmn lnten~as

cortlal

dmgno>tlc

cllnic~l

the Schedule phrrrua

OF

INDIi

our

In TabIs

standard

dt IeJ\t

stdff psjchatnst)

Intrnwc

b\

for

tSpltzsr

da

IDCIAL

a tramrd

4tfectl\e and

Intenw\er

Dlsorda

Endlcott

one

NR

4 b

2 5

R

NR NR

20

1

R

NR

1

R

NR

2

and

1975).

(4)

(1

NR

(1

NR

1

L

1

-I

2

6 U> 3 2

NR

Phl Phl Phi T4H

R

Phi Phi

1

Phi NR

R

4 TAH

>

Phi

II ?

R

NR

r’ 10

R

NR

4

R

Phi

5

R

Phi

tt 4 NR

-’ 1fJ

NR

>

T4H R

Phi Phi

R

ealua-

(3) a a-uctured

PATIENTS

NR

research drug-free

(2) [HO or three unstructured (Including

13

12

the

and clinical

(1) ct lo-13

r\aluatmn

tmn h\ a w-uor

(3)

ECT’

FEATLIRES

of

hetL\een

are wmmanzed

I

DEhlOGRAPHIC

Attcctl\e

Ps>chobmlog>

of

dcmographc

for rJch

hobpltal-

tar

Chrucal

Department

Mlch+yn

\\err:

Llrut

1

lm-

nonsup-

depressed Clm~csl

In the

features

and

addressed

pretreatment

the

Program 1979

pnt~entb and

In

Dlsordrr~

on DST

DSTb

dunng

treatment (1)

\\lth

cliruc,~ll~

progrre

betore

normahze

,idnunl>tered”

\alueb

nlth

ratlngb

Ing questions

lzed

DST

tCor\ell

ot ECT

treated

concurrent

Twsnt>-two

ha\e

het\Jeen

1987)

t~anune ECT

t31 al

pubhcatmn\ from

Methods

and

Papakostd,

Phi

usmg Sch~zoph\wxl

exdmlnatlon

and

xreemng fanuly dnd

lntenwts

(6)

collection \\ere

Crlterta 1980)

medical

of Informatmn

using

cornplIed

(RDC)

(Spltzer

Dlqgnostlcran~

lllne>ses

longltudm~l

ot pre\ mus

Research

hston

\ierr:

Carroll blind

Incluslon DSTh

cntetw treated

pnor

techmcnl

bource\

medlcal

Ic)s~ (greater

here dunng

Illnrs~

than

205

or drug

no

Hlth

AND

choactl\e (other In

to DST

research

tre:atment

that Hould

et al

1981).

no hstoq helo~

FOR

hod\

INDIi

drugs

IDL’AL

HRSD

no

12

rllnzbs

and

mere

rncludlng

P-\TIENTS

HRSD

Patent Sr\ent>-one

female

ST-\ND-\RDIZED

T\ro third. DST

drpre>rsl\e Of

ani

psi-

course

of

ECT

to pxtlclpatz

met

these

cntena

The

SERIAL

(Table

1) met

disorder

(hlDD)

thsse

Four

d dlagnosls

deprewd

ibetght)

Hho

ot 21 pattents

18 and 22) iterr

9 recel\cd

rrwltb

nlth

In the sample

s\mptoms

17

to DST

consent

patlent>

&xvpr

luwnnl

no

the

~~eeehlb

Deprrwon

tar the ddnum,tratlon

Informed

for major

dogenous

v,rlpht

no pregnarq

Included

cnterld

Iniahdate

lncludlng

Ons-IhId DST L1

(3)

of seers

normal

abuse

Prr- ECT *

ECT

All

Tmentv-one

(2) ueehl\

(6)

blind

dunng

(4)

for

no treatment

those necsssan

and

1982)

Scale

b> raters (5)

mrdlcntmn

than

et cil

Rating

1960)

of ECT).

deprxwl\e

ECT

lmalldatlng

HRSD \ ALLIES

HRSD

score

ulth

of \anance (Cxroll

no alcohohsm trtxtment

(1)

exclu~~rlv

to and

of the DSTs

serious

C.1.r:

completed

\cere

s\mptoms

DST

(HRSD)

dlag-

reults

an\

Hanulton

(Harmlton

et aI

(Pri\ltera

17-item

Fol-

Dagno\tlc

1975

al\\a>h

(5)

records

conemus

et al

carbJmazepine

laboratory

mrdcal

to knItdate

rc\ Iens

lo\\lng noses

comprehen~l\r

to rule out sertous

17

(815)

umpolar

6 had

mean

TlhlE

age

the

( f SD)

of bipolar total

barnpIe

for the rntlrc

POINTS

Post ECT DST

HR3D

DST

WdI\d

1 !I I

No

tdlsordrr)

,I Astor! of

dr-

(No.\

Patent

of sctuzoaffcctl\e percent

sn-

had

patlent.

nondeltwonal

No

RDC

w.pnn,< R R NR R R R R P.ml_ll R NR Dl.~\~IlllllUd R R R R \\ ithdreu NR P.ifll&il R R R P.lrlldl

outcome

\arlable\

points tr~;ltmrnr

the

dctrrnuned

upon

course

group

prior

(2) upon completion

clInIcall\ (3)

tar

tl I rmmrdlatelv ECT

Lompletmn

four

11mr

flrbt

ECT

ot one-llurd

cow,2

ot

Jnd (41 \slthln

at

LO the

tHo-thirds

l-3

of the

for each pa~rsn~

dd\>

ot

the

tollwIng

ECT

thr: 1~151

EC T trtxtmrnt

ElectrIcal

Impul>rb

In>trument but

\\\rt:

one

L~YZ (patient

tredfment4)

s‘1e3

kzure

\\lth

the

~lmultaneou~

to

succln!

(average

dohe = 1

No

the

The

17-11em

DSTh

and

brl\\een

lI1lWl 1rt11iullILl~t?lt'

1 IlI,Jllll

HRSD

both

ECT

\\ere

w~nc~dsd ‘~l\\a>h

\rlth

dntldrpresbant 10 da>> pnor

treatment The

on da\>

Indicated

b>

patlent

docrlnr

CW~CO~S~ \\ertl

u,~l patient\ The wxdl

Jnd

total

ternunsd

JXOZIJI~~ d,lta

r\aluated

tar the group

number

LLIIuc~II~

aseh>mrnt\

clinical

of To

ECT

tor both

No

11 and

Senal

DST

ECT,

treat-

trqurnc\ No

fl\s

15

au>

tar

11 tredl-

ECT

due

16 \\lthdre\t

Fmal

In

Inds-

outcome

to

con\arld-

16 are excluded

from

data

data

In an earlier

The

patient

311 ECT

of aggregate

dppexed

For

not

15 listed

honzontal

after

all analyses

\\ertl

adrrunlstered

the

dt

treatment4

patwnt

results on

Nos

for

dunng

electrocon~ul~r~r

Patlent

rscelvlng

sedatrle-

pomt

condltlonb

Mere

2

or

tram

report

one patlent

( 4lbala

(No

et al

2)

1981)

IndI\~d-

a> LoI\ hole tredtmrnts

btandardlze

ate nnalbzed

111th IWIJ~CI~ and wurnsn-

31s

to treatment)

bornatlc

dwxntlnued

blzs for paitlents problem\

paral\

gl!copvrrolatc

or at an\

each

DST

arro\\>

confuwm

>ent after

ot group

of to

In Fig

lrert:

mental

mlmITuzs

dose = C, 75

admuubtered

Thu,

treatnlents

from

msnt>

To

and

conconutant

number

ECT

pendent

~nt~rprelation

short-acting

mubcle

hg)

to ECT

ddnurustrred 2

each

for

\\ere

course: b\

total

ments Table

treatments

a

or

anesthetIc

(alerage

antlpsbchotlc

medlcatlonb

cnntounded \rerl,l\

prtrlormsd

of

and

wxetmns

hipnotlc

tllrrllys

111 all

rscorded

doss = 0 3 mg 45 nun prior

to reduce

c Irtllllll

use

lchohns

111 alI unilateral

Standard

krp

mg/

hledcralr

tournrqurt

rscordlngs

mg ‘kg) (aLwage

\\A

J Irmb

Induce

a

8 rrce:l\cd

actl\ll\

Included

prztrralment

b>

bltrmporall>

No

~13s of

El33

barblturatc

Isa>t

generaled

admlmslrrrd

the

HRSD

M~S drtlrmng and

of

DST

-Ill

DST

normAt> before

\Aues

\\t3re log-transformed

ot dlbtnbutmn btatr>tlcal

analtses

and ctquaht> \\ere

10 obwn ot variance>

pertormed

To

de-

termlnr the slgnlflcance of decreases 111DST Calue\ end HRSD scores o\er ttmr dunng ECT treatmen t one-\\ a> ANOVA \\ Ith re:peJted meahurrz \b,l~\ used palred r-tests aere used tar paramrtnc compxlrons bet\iren pre- and posttreatment DST and HRSD rebulth. rehpcctl\elv For dtchotomous \arl&le> HT used either the chl-bquxed tebt or Fl3her.s exact prob&tlltk tebt Pcx>on’> product-moment correlatlon~ Here used to J~VZM the relatron\hlp betireen DST values and HRSD score> tar each Indlvldual patlent dunng the course of ECT treatment Rewlts

STANDARDIZED

hlean post-deuamethasone plasma cortlsol \alues and HRSD scores at the four standardized serial time points dunng ECT treatment are sho\sn In Fig 1 These aggregate data mdlcate that progressive normahzatlon of the DST occurred dunng resolutlon of the depressl\e syndrome mlth treatment One-wav ANOL’A alth repeated measures conflrmed qnlflcant reductions m these score5 oker time (P < 0 001) PaIrwise compansons between pre- and post-ECT treatment Lalues confIrmed tughI> slgruflcant reductions (P < 0 001) In both DST and HRSD bcores

POINTS

pressed \s euthynuc) there wa5 a stead! decrease In the percentage of both nonsupprebsors and depressed patients dunng treatment Thus categoncal analyses hupported trend.4 from mean data

Ttwteen patients (Nos 1 2 4 5 6. 7. 9 12 13 14. 15. 20 21) had pohttredtment DST supprewon DSTs and good response Three pattents (NOS 3.8.10) had posttreatment DST huppresslon but only partral or nonresponse Three patrents had posttreatment DST nonsuppresslon. of these

Table 3 re\eals that \\hen data \\ere annl>zrd categoncxll!, (wppressors \s nonwppressors deTABLE

ASSESSMENT

3

NLlhfBERS

-ZND

DARDIZED

SERIAL

PERCENTAGES TIhlE

OF

PATIENTS

WHO

4RE

DST

NONSLtPPRESSORS

lmmedm1e

One-thud

ECT

T\ro-rlurd>

pre-ECT DST non,uppreas,\e

l

AND

DEPRESSED

ECT

Immedk~le posl-ECT

,> /I’B dl,

n

lO,f 22

l-l,?1

s

9

90 9

bb 7

38 1

13 8

22,::. loo

lb 21 76 2

13 71 61 9

6, 20

Deprrwd

**

(HRSD

* C~I-quxr

= 26 74

21

3 19

> 101

II 4

“Ch-quare=2457

d/ =

d/=3

AT

POINTS

3

P < 0 001 P
30

STAN-

0

20406080130

0

20406OLam

40

so

80

I no

TREATMENT COURSE

(Days)

239 tuo

(Nos

call\

17

~hlle

patwnts cme

22) had pxt~al

one (No

\\ert:

not

their

(Nob

11

a

ml\,lng

data

patlent

(81%)

31on had three

III

treatments

ekplalned

(No

a good

or the\

In amman

I?

outcome and

DST

compared

\\ho

had

good

outcome

among

rrjpondm

13 of 14 (934)

DST

\\ere

ot

DST \ e:\xt

good

These

16

one

(FIbher

J Stated dIfferentI>

DST

ECT

wpprch>ors

apt

data

Induce>

and

that

anal\sls

tlons

o\er \\e

anuned

(1984)

of mean time

values

may

ulthm-subject blhty.

Daw

lead

senal

values

and

rather

strong

values

and

each

of repeated To

parable

post-deuamethasone matching

HRSD

temporal HRSD

wares

assoclatlon

scores

and

plasma

uas

ex-

cortlbol

(Fig

2)

between

elident

A

DST

m

man!

patients Indlrldual HRSD

plots

betueen-subject tlon

meekI\

\anation

between

DST

terns

that

ot DST

ment

wluch

m

patwnts

m Fig

Suggestlbe methasone

had

paralleled

of

absocld-

2)

Inspect-

Indl\Idual

cl~rucal

pat-

Improve-

the aggregate

pat-

1

ot

1980

bald

1981

et

al

plasma

rhythms

cortlsol

Nos

tient>

10. 17

of

\\ere

post-dexa-

noted

htudled

subjects

in ths

\\eekl!

ot

Our

m

4ome

study

uh~h

they Influenced

et al

1982.

Carroll group 61 5

1984)

The

hg

63 8

one-tlurd.

serial

DST

et al mean

from kg

each

to deterrmne

Edelstem

changed

for

and

fmdmgs

1983

for

kg

the

and

and

sect

respectl\ely

m

Ilmlted

number

farlure

ot

ment>

most

ma\

Jgalnbt

re-

Thlb I e

the

pro-

that

ob-

onI>

to normalize

d

when

poHer

of

about

Jnd poor outcome

greatly

lIkeI>

to

and

de\amethasone

during

while

mean

DST

values

depression

to normahze

(Figs

1 2)

Thus

aggre-

depressr\e

of

obwn

It I> uell eplbode

ac’robs patients

more

buppressorb

DST

but

\\e

good

ot

chnlcJ

lng

that

doe> not folio\\ It ma>

the out-

dunng Improve-

ot the dlscrepancles be clanfled

follou

known

cllmcal

of

cdutlon

nonsuppre>hlon

might

atlon

report5

Normallzatlon

Some

studies

pilot

conflrmatlon

predict

treatment

bet\keen

In

treat-

are

patlent>

DST

ment

~lnu~s

ECT or

ECT

ECT

brologlcal

in mo5t

AUI

of

to

to

1982)

strengthen

r preclude

at

rebpond

number

data

rndrpen-

aId Identrtlca-

Albald

responders

pro\ Ide

from

that uould

not

does

tern

patients to

perwstent

and

ECT

treatments

d lack of assoclatlon

mo>t

~m~llar

not

periods

HRSD

moderateI\

conslderatlonb

O\er-lnterpretatlon

e\en

\\eekl>

btudleh

does

ECT

conflrmed

DST that

progress

tound

antlde-

are

llrrutlng

optImaI

to become

mltlal

generalI>

the

come

after

that

benefit

Hahkett

These

treatment

normal-

ot

buppreshorh

ot the DST

1982

\\eelght

gate data

fall

that

DST

patlents

change5

DST

and DST

markers’

buggest

clinical

that

to be tenuoub

obJectl\e

tlon

pa-

a cnnlounded

Lalues

Thub

C I~n~ctans could dent

DST

treatment

to normahze

conttnue

of

ot depreh-

tlms

Illustrate

analws

1983

proportlon

ot h,ubJects tall

eftectlle

statrst~cal

\I-

1981

admlnlhtratron

senal

and

1983

marher

d problem

most

Fuente

al

hImpI\

o\er

also

encountered

mean begun

to

tram

become

bened gILen

I> not

correlated

ECT

La

\ilth

hupportb

1980

et

com-

treated

It also \uggchth

DST

matching

to htrongli ce~\lng

(De et al

In a large

medlcdtlon~

Thus had

the

to

entlre

treatment

post-ECT

contmued

to

(Berger

Felnberg

weight

65 1 and

the

the extent

62 6 kg before

t\\o-thrds

of

report>

that

ther-

tmdlng

15 a state-related

FIndIngs

\core>

This

Holsboer

\temmlng

prebsant

that

\\elghts

during

normallz~tlon

In patlent>

Grrdcn

pathophk,lolog>

Ilhel>

We

1983)

determlmng

21)

pnor

the DST

I Hashett

oscdlatmg

(eg.

(Fig

and

and

slgruflcant

patterns

normallratlon roughI>

shoHn

patients

most

values

relealed

these two ianables

1011 re\eals

tern

of

scores for each patlent

change

that electrocon\ul~l\e of DST

medrcatlon

Robenbaum

result

thus possl-

separate11

\\rlght

to tho>e obsened

lzatlon

loss of

lndlcate

a collectIon

~\t:

obsena-

address

patlent

ttteo-

emphasized

to d slgrufrcant

InformatIon

plotted

have

Jnd

patterns

antldepresbant

Targum

/t~ciuvhul purlertu of set-t& DST uttd HRSD swettretm durrt~g ECT rrearntettt Glbbonb

value,

treatment

DiscussIon

ot

po\ttredtment

= 0 15 N S

ECT

hJd

buppres-

\rlth

betiteen

bc-

dwxmtlnurd

po>ttreatment

(335)

nonapprraron

thlh anal>~~

\\ert:

pre\~ousl>)

18)

\\lth

patlent

cllnlThree

corwdrrrd

ECT

16

or nonre~pone

19) had good outcome

i\ell

b\. longer

reco\en

renu,slon a uniform be that

from from

a

pat-

J slnular

240 process occurs with the DST. Further refinements of research strategies are needed to address unanswered questions. For example, this study should be repeated with concomitant plasma dexamethasone levels to control for the possibility that repeated administration of barbiturates for ECT might change dexamethasone metabolism. If so. however, we would have expected to find progressively more nonsuppression, exactly opposite to what we observed. Finally, serial DSTs in untreated patients, i.e., those involved in placebocontrolled studies, may provide information on ‘naturalistic’ the course of hypothalamicpituitary-adrenal axis dysfunction in depression.

enous

deprewon

loss.

and

Gerken,

A., Maler.

DST

docrinology. Gibbon\, aalarieb

depressives chiatry.

16 (1981)

of

Gredcn.

Biol.

Psy-

Kurten,

I., Serial

dexametha-

in psychiatric

illness,

Psychiat.

(1979)

R. et al., Neuroendocrinological

neurophysiological are

there

Biol.

P.C.S.

in

major

markers

Psychiatry,

and

xamethasone

studies

biological

17 (1982)

Beaini,

A.Y.,

suppression

test,

the

dis-

endogenoua

Greden.

1217-1242.

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