10.1192/bjp.170.6.

549 Access the most recent version at doi:

1997 170: 549-553 The British Journal of Psychiatry

AG Wade, U Lepola, HJ Koponen, V Pedersen and T Pedersen

The effect of citalopram in panic disorder

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years. They had to give written informed
consent, have a score of less than 22 on the
Montgomery-Asberg Depression Rating
Scale (MADRS; Montgomery & Asberg,
1979), and fulfil DSMHIR criteria for
panic disorder. They must also have suffered
at least one panic attack per week with at
least three symptoms (as defined in the
DSMll1R criteria) during the three weeks
immediately prior to entering the study, and
to have suffered a further panic attack
during the one-week screening period of
the trial.
The exclusion criteria were: pregnancy
or intention to become pregnant, depres
sion, organic brain damage, neurological
disease, drug and/or alcohol misuse during
the past year, other severe psychiatric or
somatic disorders, orthostatic hypotension,
or hypersensitivity to the test preparations.
Prior to the screening assessment, all
patients were to have discontinued treat
ment with any psychotropic drugs (except
benzodiazepines), monoamineoxidaseinhi
bitors (MAOIs) or fluoxetine for at least
one, two or five weeks respectively.
Throughout the study, all psychotropic
drugs (with the exception of oxazepam)
were proscribed. Treatment with oxazepam
was permitted during the screening week
(up to a maximum daily dose of 30 mg) and
during Weeks 1 and 2 (a maximum dose of
20 mg daily). However, investigators were
advised to discontinue such treatment
during Weeks 3 and 4, and it was prohibited
during Weeks S to 8. Somatic disorders
could be treatedwithout limitation.
The intention-to-treat (ITT) population
was defined as all patients who received a
tablet of double-blind medication, and the
efficacy population (EFF) was defined as all
randomisedpatientswho had beentreated
for at least 28 days and had received no
prohibited concomitant medication cx
pected to influence treatment outcome.
The study followed the ethical guidelines
laid down by the Declaration of Helsinki
and was approved by the local ethics
committee of each participating centre.
Study design and assessments
This study was designedas a randomised,
double-blind, placebo and clomipramine
controlled, multicentre, flexible dose within
a fixed-dose range, parallel group, compara
tive study over an eight-week period, with a
preceding one week screening period. There
were three fixed dose levels for citalopram
and one fixed dose range for the active
Panic disorder (PD) has been recognised as a
separatepsychiatric illness in the DSM since
1980 (DSMIilR; American Psychiatric
Association, 1987). A chronic illness, it is a
disabling diseaseespecially when, as is often
the case, it is combined with agoraphobia
(DSMIV; American Psychiatric Association,
1994). Early pharmacological treatments
used benzodiazepines such as diazepam and
clonazepam, which were effective only at
high doses (Spier et a!, 1986; Kahn & van
Praag, 1992). The efficacy of the benzodia
zepine derivative alprazolam, which some
studies found to reduce panic attacks (Alex
ander & Alexander, 1986; Ballenger et a!,
1988; Cross-National Collaborative Panic
Study, 1992), may not be as effective as first
thought (Marks et a!, 1993). A number of
tricyclic antidepressants have also been
shown to be effective treatments, notably
clomipramine, which causes a statistically
significant decrease in the total number of
panic attacks compared with both placebo
and imipramine after 12 weeks of treatment
(Modigh et a!, 1992).
More recently, selective serotonin reup
take inhibitors (SSRIs) such as paroxetine,
fluvoxamine and sertraline, have appeared to
offer effective treatment of PD with a
superior tolerability profile to the classical
tricyclic antidepressants (Hoehn-Saric et a!,
1993; Oehrberg et a!, 199S; Nutt, 1995).
Citaloppram is a highly selective SSRI (Hyttel
et a!, 1995), and two previous open studies
have suggested that it is effective in the
treatment of panic disorder (Humble &
Wistedt, 1992; Lepola et a!, 1994). The
present study aimed to build upon these
findings by establishing and estimating a dose
relationship and optimal dose range of
citalopram in the acute treatment of panic
disorder.
METHOD
Subjects
To be included in the study, patients could
be of either sex and aged between 18 and 65
Background Citalopramisa serotonin
reuptake inhibitor which has been
demonstrated to be highlyselectiveand
with a superior tolerability profile to the
classicaltricyclic antidepressants.This study
wasdesignedto test whether there was
any difference in efficacy in the manage
mentofpanicdisorder (PD) between cita
lopram and placebo.
Method Thiswasadouble-blind,
placeboandclomipraminecontrolled,
parallelgroup eight-week study.Atotal of
475 patients with PD, with or without
agoraphobia, were randomisedto treat
ment with either placebo,clomipramine60
or 90 mg/day,orcitalopram 0 or IS mg/
day,20 or 30 mg/day,or 40 or 60 mg/day.
Doses were increased over the first three
weeks, stabilised during the fourth week
andfixed between weeksfive andeight.
Results Treatmentwithcitalopramat 20
or 30 mg, 40 or 60 mgandclomipramine
were significantly superior to placebo,
judged by the number ofpatients free of
panic attacks in the week prior to the final
assessment. All rating scalesexamined
suggestedthat citalopram 20 or 30 mg
was more effective than citalopram 40 or
60 mg.
Conclusion The mostadvantageous
benefit/risk ratio for the treatment of PD
was associated with citalopram 20 or
30 mg/day.
549
The effect of citalopram in panic disorder
A. G. WADE, U. LEPOLA, H. J. KOPONEN, V. PEDERSENand T. PEDERSEN
Pla ce boCita lopra mClomipra mine (n=96)
n (%)10IS
mg
(n=97) n (%)20 30
mg
(n=95) n (%)40-60
mg
(n=89) n (%)60 90
mg
(n=98) n (%)La ckofe ffica cy
Adve rs e e ve nts
Re fus e d ne xt tre a tme nt
Di dnot r et ur n
No longe r me t s tudy
crite ria
Non-complia nce
Concurre nt illne s s
Othe r
Tota l8(8)
7 (7)
5 (5)
I ( I )
0 (0)
0(0)
0 (0)
4(4)
25 (26)4(4)
8 (8)
3 (3)
8( 8)
2 (2)
I (I)
0 (0)
0(0)
26 (27)3(3)
5 (5)
I (I)
5( 5)
I ( I)
0(0)
I ( I)
4(4)
20 (2 I)3(3)
6 (7)
4 (5)
3( 3)
I ( I)
I (I)
0 (0)
I (I)
I9 (2l )4(4)
I0 ( I0)
5 (5)
I ( I )
0(0)
2(2)
0(0)
3(3)
25 (26)
group, whereas for differences between
citalopram groups and the clomipramine
group, 90% confidence intervals have been
used.
RESULTS
Pati ent numbers
Five hundred and forty-five patients were
screened, 475 of whom were randomi sed to
study treatment in 22 centres in four
countries (Finland, Sweden, the Netherlands
a nd the UK). The ma jority of ce ntre s we re
speci al i st psychi atri c cl i ni cs, but two general
practice centres were used in the UK.
Of the 475 pa tie nts ma king up the liT
population, 96 were randomised to receive
placebo and 98 were randomised to receive
clomipramine. The remaining 281 patients
we re ra ndomis e d to re ce ive cita lopra m: 97 in
the 1015mg group, 95 in the 2030mg
group a nd 89 in the 40 60mg group.
Demography
All patients recruited into the study, 70% of
whom we re fe ma le , we re ca uca s ia n. The
mean age of the population was 38 years.
There were no statistically significant differ
ences between the treatment groups i n any
demographic parameters measured.
A total of 355 patients (75%) were
re corde d a s ha ving pa nic dis orde r in
conjunction with agoraphobia, 117 patients
(25% ) did not have agoraphobia, and the
remaining three patients ( < 1%) did not
have the status of their agoraphobia
re corde d.
Starting from Week S the doses were
fixe d. In the cita lopra m 10 15mg group,
around 40% of patients took 10 mg, and in
comparator, clomipramine. These dose
ranges were mi rrored i n the untreated,
placebo control group.
After screening for eligibility (Day 7),
patients entered the screening period (Week
1 ) during which they received one tablet
of placebo, single-blind, each morning.
Those patients still fulfilling the entry
criteria and who did not respond to
pla ce bo in We e k 1 we re ra ndomis e d to
the double-blind phase of the study. This
consisted of a titration phase used to reduce
the number of withdrawals because of
adverse events (Weeks 1 to 4), and a fixed
dose phase (Weeks S to 8). Five treatment
groups were planned:
( a) pl acebo
(b) citalopram 10 mg (with the option of
increasing to 15 mg if efficacy was not
seen)
(c) citalopram titrated over three weeks to
20 mg (with the option of increasing to
30 mg if efficacy was not seen)
(d) citalopram titrated over three weeks to
40 mg (with the option of increasing to
60 mg if efficacy was not seen)
(e ) clomipra mine titra te d ove r thre e we e ks
to 60 mg (with the option of increasing
to 90 mg if e ffica cy wa s not s e e n).
The number of panic attacks was assessed
using the panic attack item of the Clinical
Anxie ty Sca le (CAS; Sna ith e t a !, 1982). The
general i mprovement i n a pati ent' s cl i ni cal
state was assessed by both the physician and
the patient using, respectively, the Physician's
Global Improvement Scale(PHYGIS)and the
Pa tie nt's Globa l Improve me nt Sca le
(PATGIS), both of which use a scale ranging
from 0 (very bad, could not be worse) to 10
(major improvement, back to normal)
(She e ha n, 1979). In a ddition, pa tie nts we re
assessed on the Hami l ton Anxi ety Rati ng
Scale (HAS; Hamilton, 1959; Maier et a!,
1988) and on the MADRS to exclude
depression (Maier & Philipp, 1985).
Sa fe ty a nd tole ra bility a s s e s s me nts
included a physical examination (at
s cre e ning), vita l s igns (blood pre s s ure a nd
puls e ra te ), a nd ha e ma tology a nd clinica l
che mis try te s ts (a t s cre e ning a nd vis it We e ks
6 and 8 or withdrawal). Adverse events,
either observed by the investigator or
reported by the patient following an open
question, were coded according to World
Health Organization terminology (WHO,
1989) and recorded. Any concomitant
medications were recorded at each visit.
Bl ood sampl es were taken from the
pati ents at screeni ng and at Weeks 6 and 8
for cita lopra m a nd cita lopra m me ta bolite
a s s a ys . Pa tie nts we re a ls o s cre e ne d for
benzodiazepines at this time to check that
oxazepam treatment had been withdrawn
after Week 4. General treatment compliance
was assessed by means of a tabl et count.
Stati sti cal anal yses
The primary analysis of efficacy was based
upon the relative number of responding
patients at Week 8 for the ITT population
a nd by us e of the la s t obs e rva tion ca rrie d
forwa rd' (LOCF). Re s pons ewa s de fine d a s a
score of 0 (no panic attacks) or I (no panic
attacks, but increased anxiety) for the panic
a tta ck ite m on the CAS s ca le , a nd a s core of
9 or 10 on the PHYGIS and PATGIS (major
improvement or normal). The active treat
ment groups and the placebo group were
compared using Fisher's exact test for
formatted scores (where pati ents were
defined as responders' or non-responders').
The proportion of re s ponde rs wa s
analysed as a secondary analysis by logistic
regression to test the baseline measurements
of demographi c and anamnesti c vari abl es
for thei r probabl e prognosti c val ue. Suppor
tive a na lys e s of PHYGIS a nd PATGIS we re
made by using the KruskalWallisscores for
overall comparisons and the Wilcoxon rank
s um te s t for pa irwis e compa ris ons . The
s e conda ry a na lys e s of tota l HAS a nd
MADRS were made by using analyses of
covariance (ANCOVA) with the baseline
score as covariate and supported by 95%
confide nce inte rva ls for diffe re nce s be twe e n
active treatment groups and the placebo
Tabl e I Summaryof prematuredi sconti nuati onby reason ITT popul ati on
550
Pla ce boCita lopra mClomipra mine (n=96)10 15
mg20 30 mg40 60 mg60 90 mg(n=97)(n=95)(n=89)(n=98)HAS
tota lBa s e line 23.023.522.923.024.2La s ta s s e s s me nt5.613.6**12.3***ll.4l2.7@HAS
ps ychicBa s e line 2.612.62.012.73.2La s t
a s s e s s me nt8.874*6.3@6.0*@6.7HAS
s oma ticBa s e line 10.410.910.910.3I
1.0La s t
a s s e s s me nt6.86.26.05.4@6.0i@*MADRSBa s e line 11.912.011.411.62.9La s t
a s s e s s me nt9.58.26.5***6.5@'6.9@P<0.l.
**p<@j5 P<0.Ol.
1* *
I
I
the 2030mg and 4060mg citalopram
groups , a round 60% of pa tie nts re ce ive d
the lowe r dos e .
At baseline, 11 (2.2%) of the patients
had a CAS panic attack item score rated at
level 1 (no panic attacks, but increased
anxiety), 143 (30.2%) at level 2 (12
attacks per week), 174 (36.6%) at level 3
(37attacks per week) and 147 (31.0%) at
level 4 (8 or more attacks per week). There
were no statistically significant differences
between the treatment groups in the baseline
panic attack item of CAS scores.
Wi thdrawal anal ysi s
From the s cre e ning popula tion, 70 pa tie nts
(12.8%) failed to progress, either because
they responded to placebo during the run-in
phase or they failed to meet the entry
criteria, leaving an ITT population of 475.
A total of 115 patients from this population
failed to complete the study (see Table 1).
There were no statistically significant differ
e nce s be twe e n the tota l numbe r of dis conti
nuati ons i n each group.
Effi cacy
Ana lys e s we re a ls o pe rforme d on the
efficacy population and the results were
comparable to the ITT population results
that are presented here.
The numbe r of pa tie nts fre e of s ymp
toms, as recorded by measurements of the
Ba s &In We e k I
Tabl e 2 MADRSandHASscoresat basel i neandfi nalassessment (LOCF)
CAS panic attack item, by visit week is
shown in Fig. 1.
Response rates wi th the PHYGIS and
PATGIS s ca le s we re de fine d a s a s core of 9
or 10, and the number of patients scoring
this wa s s ignifica ntly gre a te r with cita lo
pram 2030mg (PHYGIS 41 %; PATGIS
42%), 4060mg (34%; 27%) and clomi
pra mine (39%; 38%) tha n pla ce bo (21%;
21%) at Week 8. The citalopram 2030mg
treatment group showed a trend towards a
gre a te r e ffe ct tha n the highe r cita lopra m
dose. A large increase in placebo response
wa s s e e n be twe e n We e k 4 (PHYGIS 8%;
PATGIS 11%) and Week 6 (16%; 20%).
The CAS pa nic a tta ck ite m s core s ta ke n
toge the r with the PHYGIS a nd PATGIS
re s ults s howtwo dis tinct pa tte rns of e ffe ct.
(a) Citalopram appears to be more effica
cious tha n pla ce bo, with the 20 or
30 mg treatment group more effective
than the higher dose group.
(b) There is a large increase in the placebo
response between Week 4 and Week 6,
whi ch somewhat masks the effect of the
treatment groups at Week 6.
The HAS me a n tota l a nd me a n ps ychic
s core s s howe d a s ta tis tica lly s ignifica nt
improvement by the last assessment in the
citalopram 2030mg, 4060mg and clomi
pramine groups. Significant improvement
was also seen in the HAS mean somatic
score for the citalopram 4060mg group.
MADRS scores at the last assessment also
s howe d a s ta tis tica lly s ignifica nt de cre a s e
from baseline in the clomipramine and
citalopram 2030mg and 4060mg
groups (Table 2).
Safety and tol erabi l i ty
All 475 patients who were randomised to
s tudy tre a tme nt we re include d in the s a fe ty
a s s e s s me nt.A tota l of 36 pa tie nts re porte d
a dve rs e e ve nts tha t ca us e d or contribute d to
them withdrawing from the study. Adverse
events commonly associated with SSRI
tre a tme nt a nd occurring in a t le a s t S% of
patients in any treatment group are
WeekS WSek8
**
Week 2 Week 4
100% -@
60%
3O%@
*
**
Fi g. I Percentageof respondersmeasuredby the CAS pani cattack i tem, by vi si tweek.
*p<O.05, P<O.OI.
551
Adve rs e e ve ntPla ce boCita lopra mClomipra mine 60 90 mg
n(%)n
(%)I
0 I5 mg
n(%)2030
mg
n(%)4060
mg
n(%)He a da che
Na us e a
Mout hdr y
lncre a s e ds we a ting
Dizzine s s
Ins omnia
Abdomina l pa in
Tre mor
Cons tipa tion
Anorga s mia 27
(28)
7 (18)
14( 15)
7(7)
6(6)
7(7)
5 (5)
5(5)
2 (2)
0 (0)32
(33)'
26 (27)
12( 12) '
10(10)
9(9)
8(8)
4 (4)
3(3)'
I (I)
I (2)25
(26)
27 (28)
I l ( 12) '
17(18)2
13(14)
10(11)
5 (5)'
7(7)
3 (3)
6 (9)226
(29)'
26 (29)
15( 17) '
14(16)
6(7)'
6(7)
6 (7)'
2(2)
2 (2)
7 ( I0)2I
6 ( I6)
29 (30)
32( 33) 2
19(19)2
18(18)2
16(16)
0 (0)2
17(17)2
7(7)
6 ( I0)2
Tabl e 3 Number andpercentageof treatment-emergentadverseevents wa s no more e ffe ctive tha n pla ce bo, whe re a s
both citalopram 2030m g and 4060m g
were significantly m ore effective than
pl acebo i n treati ng PD. Interesti ngl y, the
2030m g dose tended to provide a better
response than the hi gher ci tal opram doses,
a lthough not s ignifica ntly s o. Clomipra mine
had a sim ilar efficacy to citalopram 20
30 m g. The results obtained with the three
different citalopram dose groups in the
prevention of panic attacks were sim ilar in
pattern to the responses obtained with
di fferent doses i n the treatment of depressi on
(M ontgom ery & Johnson, 1995).
The re s ults of this s tudy us ing cita lo
pram , where there is a 60% response rate
for the citalopram 2030m g group at eight
weeks, com pare favourably with other
placebo controlled studies perform ed with
SSRIs.Paroxetine has been shown to reduce
pani c attacks to ei ther zero or one per
three-week period in 36% of patients after
12 weeks (Oehrberg eta!, 1995), and after
e ight we e ks tre a tme nt of fluvoxa mine , 61%
ofpatients were free of m ajor panic attacks
(Hoehn-Saric eta!, 1993).
This study was not designed to report on
the onset of action of the active treatm ents,
but statistically significant differences
be twe e n cita lopra m a nd pla ce bo we re s e e n
atW eek 4,com pared with the reported six
week onset ofaction of both paroxetine and
fluvoxa mine . De s pite a continue d improve
m ent in all treatm ent groups at W eek 6,
stati sti cal si gni fi cance was masked by an
increase in placebo response from 19% at
We e k 4 to 33% a t We e k 6. Simila r pla ce bo
response rates are not uncom m on in panic
disorder patients and have been reported
before (M aier et a!, 1991; Andersch et a!,
1991). In a ddition to s ponta ne ous improve
m ent, trial factors such as patients receiving
an accurate diagnosis, explanation of the
nature of the disease, and greater investi
gator attention and support m ay explain this
finding.
Si de-effects
Citalopram is generally well tolerated, with
the adverse eventsseen in the study m ainly
those associated with the SSRIclass ofdrugs
such as nausea and increased sweating,
a lthough no diffe re nce wa s s e e n be twe e n
the incidence of these adverse events in the
citalopram groups and the clom ipram ine
group. Headache, which was seen in a
sim ilar frequency in the citalopram and
placebo groups, was significantly lower in
I. Significa ntlydiffe re nt from clomipra mine .
2. Significa ntly diffe re ntfrom pla ce bo.
pre s e nte d in Ta ble 3. Anorga s mia a ppe a rs to
be the only dose-related adverse event, with
pa tie nts re porting it more fre que ntly a s the
dos e of cita lopra m incre a s e d.
There was one suicide during the study
which occurred on day 3 of the run-in
pla ce bo pe riod. The re we re a ls o two
attem pted suicides: one patient overdosed
with oxazepam the day after screening, and
a nothe r re porte d ta king a n ove rdos eof 40
citalopram tablets (although a gastric lavage
fa ile d to confirm this ) thre e da ys be fore the
final assessm ent visit. Both patients fully
recovered and the latter continued open
tre a tme nt with cita lopra m.
The re we re a furthe r thre e s e rious
adverse events during the study: a death
from coronary atherom a, a patient diagnosed
with schizophrenia, and another patient who
de ve lope d de pre s s ion a fte r 46 da ys of
double-blind treatm ent with placebo. All
were wi thdrawn from treatment, together
with one patient taking clom ipram ine who
suffered a transient ischaem ic attack.
Two patients taking clom ipram ine were
seen to have clinically significant increases in
liver enzym es. Allthree liver enzym es (ALT,
AST and GGT) dem onstrated sm all overall
re ductions or we re uncha nge d during the
study for patients receiving citalopram or
pl acebo.
DISCUSSION
The aim of this study was to testwhether
the re wa s a ny diffe re nce in e ffica cy be twe e n
citalopram and placebo in the treatm ent of
PD and to establish an optim al dose-range
for the treatm ent of patients suffering from
PD. The me thods us e d ha d be e n te s te d in a
pilot study (Lepola eta!, 1994) and worked
well in this study. The study design used
both a ne ga tive control (pla ce bo) a nd
positive control (clom ipram ine), and the
val ue of thi s has been demonstrated by the
statistically significant im provem ent for
clom ipram ine treatm ent com pared with
placebo. This confirm s that the study as
de s igne d wa s s e ns itive to cha nge s in the
s e ve rity of pa nic dis orde r a nd thus s uita ble
to detect therapeutic response within the
e ight-we e ktre a tme ntpe riod.
None of the treatment groups reached a
plateau of efficacy after eight weeks and
the re fore it is pos s ible tha t the pa tie nts
would ha ve continue d to improve furthe r.
At the end of the study patients had the
option, after consultation with their indivi
dual i nvesti gators, of conti nui ng doubl e
blind treatm ent; 279 patients took up this
offer, and the results of this continuation
study will be reported in a separate paper.
The de mogra phic da ta s how tha t the
patients in this trial were typical of a
popula tion s uffe ring from PD, with a n
approxim ate 1:2 m ale/fem ale ratio, a m ean
age of 38, and three-quarters also suffering
from a gora phobia (DSM IV). Clinica l
depression was an exclusion criterion from
the s tudy, a nd the ba s e line MADRS s core s
in the treatm ent groups of between 11 and
13 strongly suggests that this was achieved.
Response to treatment
The results from the various efficacy scales
used show a si mi l ar pattern of response to
treatm ent. The 1015m g citalopram dose
552
pa i n.
Dry mouth and i nsomni a were reported
more often i n the cl omi prami ne group.
Al though these si de-effects are not seri ous,
they can be troubl esome for the pati ent, and
with citalopram they appear to be no more
preval ent than wi th pl acebo. Anorgasmi a
appears to be the only adverse event that is
dose-rel ated wi th ci tal opram treatment and
has a si gni fi cantl y hi gher i nci dence i n the
20 30mg and 40 60mg than i n the
pl acebo group. Anorgasmi a i s al so si gni fi
cantl y hi gher i n the cl omi prami ne group
when compared wi th pl acebo.
ACKNOWLEDGEMENTS
I A dose o12030 mg appears to be the most effective.
a The time toameasurable effect over placebo was four weeks.
S At eight weeks, efficacy was still improving. patients had not stabilised, and further
improvement might have beenexpected.
a The studydid not address phobic versus non-phobic symptoms.
S The study had a restricted age range ( <65 years old).
The authorswould liketo thankthe followingco-inves
tigators for their contribution to the study: Dr J. B.
Frazer, Dr E. Leinonen, Dr J. Penttinen, Dr K. Jirving,
Dr I Sjodin. Dr K. Yasin,Dr P. Svanborg. Dr Jussi
Turtonen, Dr Antti Liikkanen,Dr Mikko Naarala, Dr
Martti Jaskari, Dr Sirpa Korhonen, Dr Maritta
Loponen, Dr BOrjeWistedt,Dr MatsHumble,Dr
Kerstin Hedin, Dr Eli lsakson, Dr Marie Arned, Dr
TorbjrnOhrt, Dr GranBjarling. Dr Carl-Gustav
Eriksson, Dr IngegerdBergstrom. Dr AnnaAberg
Wetedt,Dr Ragni Olander, Dr M.J.A.J.M.Hoes,Dr
J.H.B.Ze@pveld, DrJ.H.M.vanLaarhoven. Dr P.J. H.
Notten, Dr G.C. Zwartjes. Dr H. N. Dijkstra, Dr H. A.
Droogleever Fortuyn. Dr B. Batelaan,Dr A. M. van
Langevelde. Dr K. Sundararajan, Dr R. H. Mahmood,
Dr P.Jauhar, Dr J.Luthra, DrI. Pinker,Dr S.Lynch,Dr
J.M.C. Holden,Dr K.Yasin, Dr B.S.Weerakoon, Dr
Mette Sndergaardand Mr Neil Morrison (medical
writer).
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the cl omi prami ne group, as was abdomi nal
CLINICAL IMPLICATIONS
a Citalopram ismore effective than placebo inthetreatment ofpanic disorder.
LIMITATIONS