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\pard\li4946\ri0\sl-360\slmult0 \fs24\cf1\f0\charscalex100 {Article}\par\pard\li
1053\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li1053\ri0\sl-213\slmult0 \fs18\cf0\p
ar\pard\li1053\ri0\sl-360\slmult0 \fs34\cf0\f0\charscalex100 {Are Benzodiazepine
s Still the Medication of Choice}\par\pard\li2666\ri0\sl-413\slmult0 \fs34\cf0\f
0\charscalex100 {for Patients With Panic Disorder}\par\pard\li2800\ri0\sl-386\sl
mult0 \fs34\cf0\f0\charscalex100 {With or Without Agoraphobia?}\par\pard\sect\se
ctd\sbknone\cols3\colno1\colw3853\colsr-0\colno2\colw3320\colsr-0\colno3\colw426
6\pard\li533\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li533\ri0\sl-213\slmult0 \fs1
8\cf0\par\pard\li533\ri0\sl-346\slmult0 \fs22\cf0\f0\charscalex100 {Steven E. Br
uce, Ph.D.}\par\pard\li533\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li533\ri0\sl-25
3\slmult0 \fs22\cf0\f0\charscalex100 {Russell G. Vasile, M.D.}\par\pard\li533\ri
0\sl-213\slmult0 \fs18\cf0\par\pard\li533\ri0\sl-240\slmult0 \fs22\cf0\f0\charsc
alex100 {Robert M. Goisman, M.D.}\par\pard\li533\ri0\sl-213\slmult0 \fs18\cf0\pa

r\pard\li533\ri0\sl-253\slmult0 \fs22\cf0\f0\charscalex100 {Carl Salzman, M.D.}\

par\pard\li533\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li533\ri0\sl-253\slmult0 \f
s22\cf0\f0\charscalex100 {Megan Spencer, B.S.}\par\pard\li533\ri0\sl-213\slmult0
\fs18\cf0\par\pard\li533\ri0\sl-240\slmult0 \fs22\cf0\f0\charscalex100 {Jason T
. Machan, Ph.D.}\par\pard\li533\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li533\ri0\
sl-240\slmult0 \fs22\cf0\f0\charscalex100 {Martin B. Keller, M.D.}\par\column\pa
rd\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\pa
r\pard\li0\ri0\sl-293\slmult0 \fs16\cf0\f0\charscalex100 {Objective:}{ }\fs16\cf
0\f0\charscalex100 {Recently, pharmacological}\par\pard\li0\ri0\sl-213\slmult0 \
fs16\cf0\f0\charscalex100 {treatment guidelines for panic disorder}\par\pard\li0
\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {have changed as newer treatment
options}\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100 {have become
available. The authors exam-}\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\char
scalex100 {ined how the use of psychotropic drugs}\par\pard\li0\ri0\sl-213\slmul
t0 \fs16\cf0\f0\charscalex100 {has shifted over the course of 10 years to}\par\p
ard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {determine if prescribing
patterns have}\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100 {chang
ed to reflect these revised treatment}\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf0
\f0\charscalex100 {guidelines.}\par\pard\li0\ri0\sl-280\slmult0 \fs16\cf0\f0\cha
rscalex100 {Method:}{ }\fs16\cf0\f0\charscalex100 {A total of 443 patients with}
\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100 {panic disorder were
enrolled in the Har-}\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex10
0 {vard/Brown Anxiety Research Project, a}\par\pard\li0\ri0\sl-213\slmult0 \fs16
\cf0\f0\charscalex100 {prospective longitudinal study of anxiety}\par\pard\li0\r
i0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {disorders. These patients were int
erviewed}\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100 {over the c
ourse of 10 years to examine}\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\chars
calex100 {their use of psychotropic medications.}\par\pard\li0\ri0\sl-293\slmult
0 \fs16\cf0\f0\charscalex100 {Results: }\fs16\cf0\f0\charscalex100 {Despite effo
rts aimed at increas-}\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex10
0 {ing the use of selective serotonin reuptake}\par\pard\li0\ri0\sl-200\slmult0
\fs16\cf0\f0\charscalex100 {inhibitors (SSRIs) in patients with panic dis-}\par\
pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100 {order (e.g., APA\uc1\u82
17Xs practice guideline for}\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\charsc
alex100 {panic disorder, Food and Drug Administra-}\par\pard\li0\ri0\sl-213\slmu
lt0 \fs16\cf0\f0\charscalex100 {tion approval of particular SSRIs for the}\par\c
olumn\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs1
8\cf0\par\pard\li0\ri0\sl-293\slmult0 \fs16\cf0\f0\charscalex100 {treatment of p
anic disorder), only a mod-}\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\charsc
alex100 {est increase in their use was found. Treat-}\par\pard\li0\ri0\sl-213\sl
mult0 \fs16\cf0\f0\charscalex100 {ment patterns for psychotropic drugs ap-}\par\
pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100 {pear to have remained st
able over the past}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {
decade, with benzodiazepines being the}\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf
0\f0\charscalex100 {most commonly used medication for}\par\pard\li0\ri0\sl-213\s
lmult0 \fs16\cf0\f0\charscalex100 {panic disorder. In comparison, SSRI use}\par\
pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100 {throughout the follow-up
period has re-}\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100 {mai
ned low. Patients using an SSRI did not}\par\pard\li0\ri0\sl-213\slmult0 \fs16\c
f0\f0\charscalex100 {have a more favorable clinical course than}\par\pard\li0\ri
0\sl-213\slmult0 \fs16\cf0\f0\charscalex100 {those using a benzodiazepine, nor w
ere}\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100 {there significa
ntly better rates of remission}\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\cha
rscalex100 {in patients using SSRIs and benzodiaz-}\par\pard\li0\ri0\sl-213\slmu
lt0 \fs16\cf0\f0\charscalex100 {epines concomitantly.}\par\pard\li0\ri0\sl-320\s
lmult0 \fs16\cf0\f0\charscalex100 {Conclusions:}{ }\fs16\cf0\f0\charscalex100 {T
hese results highlight a}\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\charscale
x100 {gap between pharmacological treatment}\par\pard\li0\ri0\sl-213\slmult0 \fs
16\cf0\f0\charscalex100 {guidelines and actual delivery of care in}\par\pard\li0
\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100 {that recommendations to use SSRI

s to}\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100 {treat panic di

sorder are not being fol-}\par\pard\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\charscal
ex100 {lowed. Factors potentially associated with}\par\pard\li0\ri0\sl-213\slmul
t0 \fs16\cf0\f0\charscalex100 {promoting and ignoring treatment recom-}\par\pard
\li0\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100 {mendations are discussed.}\p
ar\pard\li293\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li293\ri0\sl-226\slmult0 \fs
16\cf0\f0\charscalex100 {(Am J Psychiatry 2003; 160:1432\uc1\u8211X1438)}\par\pa
rd\sect\sectd\sbknone\cols2\colno1\colw5573\colsr-0\colno2\colw5866\pard\li533\r
i0\sl-213\slmult0 \fs18\cf0\par\pard\li533\ri0\sl-826\slmult0 \fs74\cf2\f0\chars
calex100 {P}\fs18\cf0\f0\charscalex100 {anic disorder is a disabling psychiatric
condition asso-}\par\column\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\
ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\
li0\ri0\sl-266\slmult0 \fs18\cf0\f0\charscalex100 {sants is low; the lethal dose
is approximately three times}\par\pard\sect\sectd\sbknone\cols2\colno1\colw5573
\colsr-0\colno2\colw5866\pard\li533\ri0\sl-173\slmult0 \fs18\cf0\f0\charscalex10
0 {ciated with significant impairment in psychosocial and}\par\pard\li533\ri0\sl
-173\slmult0 \fs16\cf0\f0\charscalex100 {occupational functioning. Epidemiologic
al studies have}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {c
onsistently estimated lifetime prevalence rates at 2%\uc1\u8211X4%}\par\pard\li5
33\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {(1, 2). Panic disorder is freq
uently accompanied by other}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\char
scalex100 {psychiatric disorders, notably depression; 55.6% of those}\par\pard\l
i533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {with panic disorder also mee
t lifetime criteria for major}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\ch
arscalex100 {depression (3). In recent years, particularly within the last}\par\
pard\li533\ri0\sl-253\slmult0 \fs16\cf0\f0\charscalex100 {decade, the pharmacolo
gical treatment of panic disorder}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f
0\charscalex100 {has changed as different treatment options have been de-}\par\p
ard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {veloped. The differing
efficacy and safety of these agents}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0
\f0\charscalex100 {presents the challenge of choosing the best medication for}\p
ar\pard\li533\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {those diagnosed wit
h panic disorder.}\par\pard\li720\ri0\sl-280\slmult0 \fs18\cf0\f0\charscalex100
{Historically, panic disorder was first treated with tricy-}\par\pard\li533\ri0\
sl-240\slmult0 \fs18\cf0\f0\charscalex100 {clic antidepressants and monoamine ox
idase inhibitors}\par\pard\li533\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {
(MAOIs). However, tricyclic antidepressants and MAOIs}\par\pard\li533\ri0\sl-240
\slmult0 \fs18\cf0\f0\charscalex100 {carry many intolerable side effects, from a
nticholinergic}\par\pard\li533\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {an
d adverse cardiovascular effects in tricyclic antidepres-}\par\pard\li533\ri0\sl
-240\slmult0 \fs18\cf0\f0\charscalex100 {sants to strict dietary restrictions an
d overall poor tolera-}\par\pard\li533\ri0\sl-240\slmult0 \fs18\cf0\f0\charscale
x100 {bility in MAOIs (4). These side effects are thought to de-}\par\pard\li533
\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {crease overall patient complianc
e. Several safety concerns}\par\pard\li533\ri0\sl-240\slmult0 \fs18\cf0\f0\chars
calex100 {also exist with tricyclic antidepressants and MAOIs. For}\par\pard\li5
33\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {example, the therapeutic margi
n of tricyclic antidepres-}\par\column\pard\li0\ri0\sl-173\slmult0 \fs18\cf0\f0\
charscalex100 {the maximum therapeutic dose. For MAOIs, a hyperten-}\par\pard\li
0\ri0\sl-173\slmult0 \fs18\cf0\f0\charscalex100 {sive crisis can occur from the
ingestion of foods contain-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charsc
alex100 {ing high levels of tyramine, which can be lethal.}\par\pard\li186\ri0\s
l-266\slmult0 \fs16\cf0\f0\charscalex100 {Benzodiazepines have been used as a tr
eatment for}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {panic d
isorder for the past 15 years. They have an advan-}\par\pard\li0\ri0\sl-240\slmu
lt0 \fs18\cf0\f0\charscalex100 {tage over MAOIs and tricyclic antidepressants in
their}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {rapid onset
of action in comparison to the relatively slow}\par\pard\li0\ri0\sl-240\slmult0
\fs18\cf0\f0\charscalex100 {onset of MAOIs and tricyclic antidepressants. Howeve
r,}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {the long-term us

e of benzodiazepines may lead to depen-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\c

f0\f0\charscalex100 {dency and withdrawal if they are not tapered properly, and}
\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {some patients who u
se benzodiazepines find their seda-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f
0\charscalex100 {tive side effect to be adverse. Benzodiazepines as a single}\pa
r\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {agent are also general
ly not effective in treating comorbid}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0
\f0\charscalex100 {major depression (5, 6) and also carry a potentially lethal}\
par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {danger in overdose w
hen combined with alcohol.}\par\pard\li186\ri0\sl-280\slmult0 \fs18\cf0\f0\chars
calex100 {Currently, selective serotonin reuptake inhibitors (SSRIs)}\par\pard\l
i0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {are indicated as the first-lin
e treatment for panic disorder}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\cha
rscalex100 {(8). The APA\uc1\u8217Xs }\fs18\cf0\f0\charscalex100\i {Practice Gui
deline for the Treatment of Pa-}\i0 \par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f
0\charscalex100\i {tients With Panic Disorder}\i0 \fs18\cf0\f0\charscalex100 { s
tates that SSRIs are likely to}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\cha
rscalex100 {have the most favorable balance of efficacy and adverse}\par\pard\li
0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {effects (7). SSRIs have an adva
ntage over other treatment}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charsca
lex100 {agents in that they are safer in overdose and have a signif-}\par\pard\s
ect\sectd\sbknone\cols3\colno1\colw1733\colsr-0\colno2\colw5853\colsr-0\colno3\c
olw3853\pard\li533\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li533\ri0\sl-280\slmult
0 \fs20\cf0\f0\charscalex100 {1432}\par\column\pard\li0\ri0\sl-213\slmult0 \fs18
\cf0\par\pard\li0\ri0\sl-266\slmult0 \fs16\cf0\f0\charscalex100 {http://ajp.psyc
hiatryonline.org}\par\column\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\
ri0\sl-266\slmult0 \fs16\cf0\f0\charscalex100 {Am J Psychiatry 160:8, August 200
3}\par\pard\sect\sectd\sbknone\pard\sect\sectd\sbkpage
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{\sp{\sn fLayoutInCell}{\sv 1}}}}\pgwsxn12240\pghsxn15840\marglsxn666\margrsxn13
3\margtsxn653\margbsxn186\cols2\colno1\colw5693\colsr-0\colno2\colw5746\pard\li6
53\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li653\ri0\sl-213\slmult0 \fs18\cf0\par\
pard\li653\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {icantly lower rate of
adverse events, particularly fewer car-}\par\column\pard\li2093\ri0\sl-146\slmul
t0 \fs16\cf2\f0\charscalex100 {BRUCE, VASILE, GOISMAN, ET AL.}\par\pard\li0\ri0\
sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-293\slmult0 \fs14\cf0\f0\charscalex
100 {TABLE 1. Psychiatric Status Rating Scale for Panic Disorder}{\super \fs10\u
p2\cf0\f0\charscalex100 {a}}\par\pard\sect\sectd\sbknone\pgwsxn12240\pghsxn15840
\marglsxn666\margrsxn133\cols4\colno1\colw5693\colsr-0\colno2\colw1813\colsr-0\c
olno3\colw1240\colsr-0\colno4\colw2693\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f
0\charscalex100 {diovascular symptoms, than tricyclic antidepressants and}\par\c
olumn\pard\li0\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {Panic Disorder}\pa
r\column\pard\li0\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {Code}\par\colum
n\pard\li0\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {Agoraphobia}\par\pard\
sect\sectd\sbknone\pgwsxn12240\pghsxn15840\marglsxn666\margrsxn133\cols3\colno1\
colw5693\colsr-0\colno2\colw1946\colsr-0\colno3\colw3800\pard\li653\ri0\sl-240\s
lmult0 \fs16\cf0\f0\charscalex100 {no dietary restrictions, as do MAOIs. When co
mpared with}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {benzo
diazepines, SSRIs carry a lower risk of causing phys-}\par\pard\li653\ri0\sl-240
\slmult0 \fs16\cf0\f0\charscalex100 {iological dependence, although there are st
udies that have}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {f
ound a discontinuation syndrome upon abrupt discon-}\par\pard\li653\ri0\sl-240\s
lmult0 \fs16\cf0\f0\charscalex100 {tinuation of SSRIs (9, 10), which is associat
ed with dizzi-}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {ne
ss, nausea, lethargy, and headaches. Finally, the use of}\par\pard\li653\ri0\sl240\slmult0 \fs16\cf0\f0\charscalex100 {SSRIs may be advantageous because of the
ir ease of ad-}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {mi
nistration by primary care providers and their ability to}\par\pard\li653\ri0\sl
-240\slmult0 \fs16\cf0\f0\charscalex100 {effectively treat comorbid disorders (d
epression, obses-}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100
{sive-compulsive disorder [OCD], social anxiety disorder)}\par\pard\li653\ri0\sl
-240\slmult0 \fs18\cf0\f0\charscalex100 {that commonly accompany panic disorder
(7).}\par\pard\li840\ri0\sl-266\slmult0 \fs18\cf0\f0\charscalex100 {The purpose
of this study was to examine the long-term}\par\pard\li653\ri0\sl-226\slmult0 \f
s18\cf0\f0\charscalex100 {use of psychotropic medications in patients with panic
}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {disorder who wer
e enrolled in the Harvard/Brown Anxi-}\par\pard\li653\ri0\sl-253\slmult0 \fs18\c
f0\f0\charscalex100 {ety Research Project. Specifically, the use of SSRIs and}\p
ar\pard\li653\ri0\sl-226\slmult0 \fs18\cf0\f0\charscalex100 {benzodiazepines was
examined over 10 years to deter-}\par\column\pard\li0\ri0\sl-213\slmult0 \fs16\
cf0\f0\charscalex100 {One panic attack or }\par\pard\li120\ri0\sl-186\slmult0 \f
s16\cf0\f0\charscalex100 {more per day}\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf
0\par\pard\li0\ri0\sl-320\slmult0 \fs16\cf0\f0\charscalex100 {One panic attack p
er }\par\pard\li120\ri0\sl-186\slmult0 \fs16\cf0\f0\charscalex100 {week}\par\par
d\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par
\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-253\slmult0 \fs16\cf0
\f0\charscalex100 {Persistent fear of panic }\par\pard\li120\ri0\sl-186\slmult0
\fs16\cf0\f0\charscalex100 {attacks}\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\p
ar\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-293\slmult0 \fs16\c
f0\f0\charscalex100 {Limited symptom}\par\pard\li120\ri0\sl-173\slmult0 \fs16\cf
0\f0\charscalex100 {attacks}\par\pard\li0\ri0\sl-186\slmult0 \fs16\cf0\f0\charsc
alex100 {No attacks; patient}\par\pard\li120\ri0\sl-173\slmult0 \fs16\cf0\f0\cha

rscalex100 {sometimes feels on }\par\pard\li120\ri0\sl-186\slmult0 \fs16\cf0\f0\

charscalex100 {the verge of attack but}\par\pard\li120\ri0\sl-173\slmult0 \fs16\
cf0\f0\charscalex100 {is able to control it}\par\column\pard\li0\ri0\sl-213\slmu
lt0 \*\tx333\fs16\cf0\f0\charscalex100 {6}\tab \fs16\cf0\f0\charscalex100 {Avoid
ance results in patient being}\par\pard\li453\ri0\sl-186\slmult0 \fs16\cf0\f0\ch
arscalex100 {nearly or completely }\par\pard\li453\ri0\sl-173\slmult0 \fs16\cf0\
f0\charscalex100 {housebound or unable to leave}\par\pard\li453\ri0\sl-186\slmul
t0 \fs16\cf0\f0\charscalex100 {home unaccompanied}\par\pard\li0\ri0\sl-173\slmul
t0 \*\tx333\fs16\cf0\f0\charscalex100 {5}\tab \fs16\cf0\f0\charscalex100 {Avoida
nce resulting in constricted}\par\pard\li453\ri0\sl-186\slmult0 \fs16\cf0\f0\cha
rscalex100 {lifestyle or endurance with great}\par\pard\li453\ri0\sl-173\slmult0
\fs16\cf0\f0\charscalex100 {anxiety; e.g., patient is able to }\par\pard\li453\
ri0\sl-186\slmult0 \fs16\cf0\f0\charscalex100 {leave house alone but unable}\par
\pard\li453\ri0\sl-173\slmult0 \fs16\cf0\f0\charscalex100 {to go more than a few
miles }\par\pard\li453\ri0\sl-186\slmult0 \fs16\cf0\f0\charscalex100 {unaccompa
nied}\par\pard\li0\ri0\sl-173\slmult0 \*\tx333\fs16\cf0\f0\charscalex100 {4}\tab
\fs16\cf0\f0\charscalex100 {Some avoidance; a relatively }\par\pard\li453\ri0\s
l-186\slmult0 \fs16\cf0\f0\charscalex100 {normal lifestyle; e.g., travels }\par\
pard\li453\ri0\sl-173\slmult0 \fs16\cf0\f0\charscalex100 {unaccompanied when nec
essary, }\par\pard\li453\ri0\sl-186\slmult0 \fs16\cf0\f0\charscalex100 {such as
to work or shopping but }\par\pard\li453\ri0\sl-173\slmult0 \fs16\cf0\f0\charsca
lex100 {otherwise avoids traveling alone}\par\pard\li0\ri0\sl-186\slmult0 \*\tx3
33\fs16\cf0\f0\charscalex100 {3}\tab \fs16\cf0\f0\charscalex100 {Moderate anxiet
y when in such a }\par\pard\li453\ri0\sl-173\slmult0 \fs16\cf0\f0\charscalex100
{situation but no avoidance}\par\pard\li0\ri0\sl-186\slmult0 \*\tx333\fs16\cf0\f
0\charscalex100 {2}\tab \fs16\cf0\f0\charscalex100 {Slight anxiety in such a sit
uation (or}\par\pard\li453\ri0\sl-173\slmult0 \fs14\cf0\f0\charscalex100 {in ant
icipation of a situation) but }\par\pard\li453\ri0\sl-186\slmult0 \fs16\cf0\f0\c
harscalex100 {no avoidance}\par\pard\sect\sectd\sbknone\pgwsxn12240\pghsxn15840\
marglsxn666\margrsxn133\cols2\colno1\colw5693\colsr-0\colno2\colw5746\pard\li653
\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {mine if prescribing patterns shi
fted during the past de-}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charsca
lex100 {cade because of the availability of newer pharmacological}\par\pard\li65
3\ri0\sl-253\slmult0 \fs16\cf0\f0\charscalex100 {agents, as well as revised trea
tment guidelines for panic}\par\pard\li653\ri0\sl-226\slmult0 \fs16\cf0\f0\chars
calex100 {disorder. Pharmacological treatment patterns were also}\par\pard\li653
\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {examined in patients with panic
disorder and other co-}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscale
x100 {morbid disorders.}\par\pard\li653\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li
653\ri0\sl-346\slmult0 \fs24\cf0\f0\charscalex100 {Method}\par\pard\li840\ri0\sl
-360\slmult0 \fs16\cf0\f0\charscalex100 {The Harvard/Brown Anxiety Research Proj
ect is a prospective,}\par\pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex
100 {naturalistic, longitudinal, multicenter study of adults with a cur-}\par\pa
rd\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {rent or past history of
anxiety disorders. A total of 711 subjects en-}\par\pard\li653\ri0\sl-200\slmult
0 \fs16\cf0\f0\charscalex100 {tered this study from more than 30 clinicians}\fs1
6\cf0\f0\charscalex100 {\uc1\u8217X}\fs16\cf0\f0\charscalex100 { practices at 11
dif-}\par\pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {ferent clin
ical treatment facilities in the New England area. The}\par\pard\li653\ri0\sl-20
0\slmult0 \fs16\cf0\f0\charscalex100 {methods are described in detail elsewhere
(11). Inclusion criteria}\par\pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\charsca
lex100 {for participation included a past or current diagnosis of the fol-}\par\
pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {lowing at intake: pani
c disorder with or without agoraphobia, ag-}\par\pard\li653\ri0\sl-200\slmult0 \
fs16\cf0\f0\charscalex100 {oraphobia without panic disorder, social phobia, or g
eneralized}\par\pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {anxiet
y disorder. Insufficient for inclusion, but frequently seen as}\par\pard\li653\r
i0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {comorbid conditions, were diagnose
s of simple phobia, posttrau-}\par\pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\ch
arscalex100 {matic stress disorder, OCD, or anxiety disorder not otherwise}\par\

pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {specified. Participant

s must have been at least 18 years of age at}\par\pard\li653\ri0\sl-200\slmult0
\fs16\cf0\f0\charscalex100 {intake, have been willing to voluntarily participate
in the study,}\par\pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {an
d have signed a written consent form. Exclusion criteria con-}\par\pard\li653\ri
0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {sisted of the presence of an organi
c brain syndrome and a history}\par\pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\c
harscalex100 {of schizophrenia or current psychosis at intake; otherwise, any}\p
ar\pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {comorbidity was all
owed. A total of 443 patients at intake met the}\par\pard\li653\ri0\sl-200\slmul
t0 \fs16\cf0\f0\charscalex100 {criteria for panic disorder with or without agora
phobia.}\par\pard\li840\ri0\sl-213\slmult0 \fs14\cf0\f0\charscalex100 {The prese
nt data derive from the structured diagnostic inter-}\par\pard\li653\ri0\sl-200\
slmult0 \fs16\cf0\f0\charscalex100 {view administered at intake (1989}\fs16\cf0\
f0\charscalex100 {\uc1\u8211X}\fs16\cf0\f0\charscalex100 {1991) and subsequent s
emian-}\par\pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {nual and a
nnual follow-up interviews over 10 years (1991}\fs16\cf0\f0\charscalex100 {\uc1\
u8211X}\fs16\cf0\f0\charscalex100 {2001).}\par\pard\li653\ri0\sl-200\slmult0 \fs
16\cf0\f0\charscalex100 {The initial comprehensive evaluation assessed lifetime
history}\par\pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {with the
Structured Clinical Interview for DSM-III-R Non-Affective}\par\pard\li653\ri0\sl
-200\slmult0 \fs16\cf0\f0\charscalex100 {Disorders, Patient Version (SCID), and
the Research Diagnostic}\par\pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\charscal
ex100 {Criteria (RDC) Schedule for Affective Disorders and Schizophre-}\par\pard
\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {nia}\fs16\cf0\f0\charscale
x100 {\uc1\u8212X}\fs16\cf0\f0\charscalex100 {Lifetime Version (SADS-L) (12). It
ems on the SCID and}\par\pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex10
0 {SADS-L were combined to create the Scalup, a structured inter-}\par\pard\li65
3\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {view used to assess diagnoses a
t intake (available from M.B.K.}\par\pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\
charscalex100 {upon request). The instrument yielded both present and past RDC}\
par\pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {diagnoses for affe
ctive disorders and DSM-III-R diagnoses for}\par\pard\li653\ri0\sl-200\slmult0 \
fs16\cf0\f0\charscalex100 {nonaffective (including anxiety) disorders. Interview
s, conducted}\par\pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {by t
rained research assistants, usually took place in single sessions}\par\pard\li65
3\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {lasting 2}\fs16\cf0\f0\charscal
ex100 {\uc1\u8211X}\fs16\cf0\f0\charscalex100 {4 hours. Follow-up evaluations we
re conducted at 6-}\par\pard\li653\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100
{month intervals for the first 2 years, annually for years 3}\fs16\cf0\f0\chars
calex100 {\uc1\u8211X}\fs16\cf0\f0\charscalex100 {7, and}\par\column\pard\li0\ri
0\sl-146\slmult0 \*\tx1946\*\tx2280\fs16\cf0\f0\charscalex100 {None of the prece
ding}\tab \fs16\cf0\f0\charscalex100 {1}\tab \fs16\cf0\f0\charscalex100 {None of
the preceding}\par\pard\li0\ri0\sl-240\slmult0 \fs12\cf0\f0\charscalex100 {a}{
}\fs16\cf0\f0\charscalex100 {From the Longitudinal Interval Follow-Up Evaluation
\uc1\u8212XUpjohn}\par\pard\li106\ri0\sl-173\slmult0 \fs12\cf0\f0\charscalex100
{(LIFE-UP) (3).}\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-3
20\slmult0 \fs16\cf0\f0\charscalex100 {semiannually for years 8}\fs16\cf0\f0\cha
rscalex100 {\uc1\u8211X}\fs16\cf0\f0\charscalex100 {10 with the Upjohn version o
f the Longi-}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {tudina
l Interval Follow-Up Evaluation (13). The evaluation gath-}\par\pard\li0\ri0\sl200\slmult0 \fs16\cf0\f0\charscalex100 {ered weekly information about the presen
ce of specific symptom}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex1
00 {criteria, psychiatric comorbidity, and psychosocial functioning.}\par\pard\l
i0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {Additionally, information rega
rding pharmacological treatment}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\ch
arscalex100 {from the patients was collected every 6}\fs16\cf0\f0\charscalex100
{\uc1\u8211X}\fs16\cf0\f0\charscalex100 {12 months, retrospec-}\par\pard\li0\ri0
\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {tively, for each week during the int
erval and included medication}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\char

scalex100 {type, average daily dose, and whether patients were taking it as}\par
\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {needed.}\par\pard\li186
\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {The Longitudinal Interval Follow
-Up Evaluation assesses psy-}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\chars
calex100 {chopathology with a 6-point psychiatric status rating scale that is}\p
ar\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {scored for each week
of the follow-up interval. Psychiatric status}\par\pard\li0\ri0\sl-200\slmult0 \
fs16\cf0\f0\charscalex100 {ratings for panic disorder and agoraphobia are presen
ted in Table}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {1. For
example, a psychiatric status rating of 6, representing the}\par\pard\li0\ri0\s
l-200\slmult0 \fs16\cf0\f0\charscalex100 {greatest severity of illness, requires
meeting the full DSM-III-R}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charsc
alex100 {criteria in addition to having severely disrupted psychosocial}\par\par
d\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {and/or occupational functio
ning. A psychiatric status rating of 5}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf
0\f0\charscalex100 {for panic disorder requires meeting the full DSM-III-R crite
ria}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {and having at l
east one panic attack per week. For agoraphobia, a}\par\pard\li0\ri0\sl-200\slmu
lt0 \fs16\cf0\f0\charscalex100 {psychiatric status rating of 5 includes active a
voidance, resulting}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100
{in a constricted lifestyle or endurance with great anxiety (e.g.,}\par\pard\li0
\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {able to leave house alone but no
t able to go more than a few miles}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0
\charscalex100 {unaccompanied). A participant was considered to have remitted}\p
ar\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {panic disorder if he/
she experienced 8 consecutive weeks of psy-}\par\pard\li0\ri0\sl-200\slmult0 \fs
16\cf0\f0\charscalex100 {chiatric status ratings of 2 or fewer. This definition
of remission}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {has be
en widely used in studies of affective and other disorders.}\par\pard\li0\ri0\sl
-200\slmult0 \fs16\cf0\f0\charscalex100 {Additionally, patients with remission f
rom panic disorder were}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex
100 {judged to have relapsed if their psychiatric status rating increased}\par\p
ard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {to a score of 5 or 6 for
2 consecutive weeks.}\par\pard\li186\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex1
00 {Three studies have been conducted with participants already}\par\pard\li0\ri
0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {enrolled in Harvard/Brown Anxiety R
esearch Project to assess in-}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\char
scalex100 {terrater reliability, subject recall, and validity of psychiatric sta
tus}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {ratings from th
e Longitudinal Interval Follow-Up Evaluation used}\par\pard\li0\ri0\sl-200\slmul
t0 \fs16\cf0\f0\charscalex100 {to assess the course of all disorders (14). Asses
sment of interrater}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100
{reliability of the psychiatric status ratings for anxiety disorder and}\par\par
d\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {the other instruments found
good-to-excellent reliability. The}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f
0\charscalex100 {long-term test-retest study conducted to assess the reliability
of}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {using subjects}
\fs16\cf0\f0\charscalex100 {\uc1\u8217X}\fs16\cf0\f0\charscalex100 { retrospecti
ve recall to assess psychiatric status rat-}\par\pard\li0\ri0\sl-200\slmult0 \fs
16\cf0\f0\charscalex100 {ings over 1 year found very good to excellent reliabili
ty for anxiety}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {diso
rders and major depressive disorder. A separate external va-}\par\pard\li0\ri0\s
l-200\slmult0 \fs16\cf0\f0\charscalex100 {lidity assessment comparing psychiatri
c status ratings with other}\par\pard\sect\sectd\sbknone\pgwsxn12240\pghsxn15840
\marglsxn666\margrsxn133\cols3\colno1\colw6920\colsr-0\colno2\colw2933\colsr-0\c
olno3\colw1586\pard\li653\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li653\ri0\sl-266
\slmult0 \fs16\cf0\f0\charscalex100 {Am J Psychiatry 160:8, August 2003}\par\col
umn\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-266\slmult0 \fs16\
cf0\f0\charscalex100 {http://ajp.psychiatryonline.org}\par\column\pard\li0\ri0\s
l-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-280\slmult0 \fs20\cf0\f0\charscalex1

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found re-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {garding
demographic characteristics between the patients}\par\pard\sect\sectd\sbknone\pg
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\fs18\cf0\par\pard\li0\ri0\sl-346\slmult0 \fs16\cf0\f0\charscalex100 {70}\par\p
ard\li0\ri0\sl-360\slmult0 \fs16\cf0\f0\charscalex100 {85}\par\pard\li0\ri0\sl-1
73\slmult0 \fs16\cf0\f0\charscalex100 {82}\par\column\pard\li66\ri0\sl-226\slmul
t0 \fs16\cf0\f0\charscalex100 {%}\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\
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\fs16\cf0\f0\charscalex100 {22.8}\par\column\pard\li0\ri0\sl-186\slmult0 \fs18\c
f0\f0\charscalex100 {cantly different demographic characteristics were found}\pa
r\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {between the patients w
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harscalex100 {those who experienced subsequent onset at some point}\par\pard\li0
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6\ri0\sl-280\slmult0 \fs18\cf0\f0\charscalex100 {An examination of clinical feat
ures showed a high level}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscale
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00 {Major depressive }\par\pard\li653\ri0\sl-173\slmult0 \*\tx2480\fs16\cf0\f0\c
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mult0 \fs16\cf0\f0\charscalex100 {Score on Global }\par\column\pard\li0\ri0\sl-1
73\slmult0 \fs16\cf0\f0\charscalex100 {17.9}\par\pard\li93\ri0\sl-360\slmult0 \f
s16\cf0\f0\charscalex100 {7.1}\par\pard\li0\ri0\sl-360\slmult0 \fs16\cf0\f0\char
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33\slmult0 \fs16\cf0\f0\charscalex100 {70.2}\par\pard\li80\ri0\sl-213\slmult0 \f
s18\cf0\par\pard\li80\ri0\sl-160\slmult0 \fs16\cf0\f0\charscalex100 {SD}\par\col
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\pard\li0\ri0\sl-333\slmult0 \fs16\cf0\f0\charscalex100 {181}\par\pard\li0\ri0\s
l-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-160\slmult0 \fs16\cf0\f0\charscalex1
00 {Mean}\par\column\pard\li0\ri0\sl-173\slmult0 \fs16\cf0\f0\charscalex100 {11.
7}\par\pard\li80\ri0\sl-360\slmult0 \fs14\cf0\f0\charscalex100 {8.1}\par\pard\li
0\ri0\sl-360\slmult0 \fs16\cf0\f0\charscalex100 {26.5}\par\pard\li0\ri0\sl-213\s
lmult0 \fs18\cf0\par\pard\li0\ri0\sl-333\slmult0 \fs16\cf0\f0\charscalex100 {50.
4}\par\pard\li26\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li26\ri0\sl-160\slmult0 \
fs16\cf0\f0\charscalex100 {SD}\par\column\pard\li0\ri0\sl-173\slmult0 \fs18\cf0\
f0\charscalex100 {tients with panic disorder (Table 2). The most commonly}\par\p
ard\li0\ri0\sl-226\slmult0 \fs18\cf0\f0\charscalex100 {occurring comorbid condit
ion was major depressive dis-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\char
scalex100 {order (28.0%), followed by generalized anxiety disorder}\par\pard\li0
\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {(24.2%), and social phobia (20.1
%). A total of 54.2% of the}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charsc
alex100 {patients also met criteria for a lifetime history of alcohol or}\par\pa
rd\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {substance use/dependence.
The age at onset of panic dis-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\cha
rscalex100 {order was significantly earlier in the patients with agora-}\par\par
d\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {phobia (mean=27.2 years) th

an in those without agora-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charsca

lex100 {phobia (mean=34.1 years). Additionally, the length of the}\par\pard\sect
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\li653\ri0\sl-146\slmult0 \*\tx2480\fs16\cf0\f0\charscalex100 {Assessment Scale}
\tab \fs16\cf0\f0\charscalex100 {59.6}\par\pard\li533\ri0\sl-146\slmult0 \fs16\c
f0\f0\charscalex100 {Length of intake }\par\column\pard\li0\ri0\sl-146\slmult0 \
fs16\cf0\f0\charscalex100 {12.0}\par\column\pard\li0\ri0\sl-146\slmult0 \*\tx706
\fs16\cf0\f0\charscalex100 {60.1}\tab \fs16\cf0\f0\charscalex100 {10.0}\par\colu
mn\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {intake episode was si
gnificantly longer in the patients with}\par\pard\sect\sectd\sbknone\pgwsxn12240
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653\ri0\sl-186\slmult0 \fs16\cf0\f0\charscalex100 {episode (years)}{\super \fs12
\up2\cf0\f0\charscalex100 {a}}\par\pard\li533\ri0\sl-173\slmult0 \fs16\cf0\f0\ch
arscalex100 {Age at first onset }\par\pard\li653\ri0\sl-186\slmult0 \fs16\cf0\f0
\charscalex100 {(years)}{\super \fs12\up2\cf0\f0\charscalex100 {b}}\par\column\p
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-360\slmult0 \fs16\cf0\f0\charscalex100 {34.1}\par\column\pard\li0\ri0\sl-186\sl
mult0 \fs16\cf0\f0\charscalex100 {12.7}\par\pard\li0\ri0\sl-360\slmult0 \fs16\cf
0\f0\charscalex100 {12.3}\par\column\pard\li0\ri0\sl-186\slmult0 \*\tx706\fs16\c
f0\f0\charscalex100 {17.1}\tab \fs16\cf0\f0\charscalex100 {14.1}\par\pard\li0\ri
0\sl-360\slmult0 \*\tx706\fs16\cf0\f0\charscalex100 {27.2}\tab \fs16\cf0\f0\char
scalex100 {11.1}\par\column\pard\li0\ri0\sl-186\slmult0 \fs18\cf0\f0\charscalex1
00 {panic disorder with agoraphobia (mean=17.1 years) than}\par\pard\li0\ri0\sl240\slmult0 \fs18\cf0\f0\charscalex100 {in those without agoraphobia (mean=11.8
years). No other}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {si
gnificant differences were found across clinical features.}\par\pard\sect\sectd\
sbknone\pgwsxn12240\pghsxn15840\marglsxn666\margrsxn133\cols2\colno1\colw5573\co
lsr-0\colno2\colw5866\pard\li533\ri0\sl-200\slmult0 \fs12\cf0\f0\charscalex100 {
a}{ }\fs16\cf0\f0\charscalex100 {Significant difference between groups (t=2.93,
df=443, p}\fs16\cf0\f1\charscalex100 {<}\fs16\cf0\f0\charscalex100 {0.01).}\par\
pard\li533\ri0\sl-200\slmult0 \fs12\cf0\f0\charscalex100 {b}{ }\fs16\cf0\f0\char
scalex100 {Significant difference between groups (t=4.64, df=443, p}\fs16\cf0\f1
\charscalex100 {<}\fs16\cf0\f0\charscalex100 {0.001).}\par\pard\li533\ri0\sl-213
\slmult0 \fs18\cf0\par\pard\li533\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100
{psychosocial measures found good concurrent and discriminant}\par\pard\li533\ri
0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {validity.}\par\pard\li720\ri0\sl-21
3\slmult0 \fs14\cf0\f0\charscalex100 {Statistical analyses were conducted by usi
ng SAS version 6.07}\par\pard\li533\ri0\sl-200\slmult0 \fs14\cf0\f0\charscalex10
0 {(15) and the procedures PROC FREQ, PROC MEANS, and PROC T-}\par\pard\li533\ri
0\sl-200\slmult0 \fs14\cf0\f0\charscalex100 {TEST. Additionally, proportional ha
zards regressions (PROC}\par\pard\li533\ri0\sl-200\slmult0 \fs14\cf0\f0\charscal
ex100 {PHREG) with time-varying covariates were conducted to examine}\par\pard\l
i533\ri0\sl-200\slmult0 \fs14\cf0\f0\charscalex100 {significant predictors of SS
RI and benzodiazepine use over the}\par\pard\li533\ri0\sl-200\slmult0 \fs14\cf0\
f0\charscalex100 {10-year follow-up period. These analyses allowed us to examine
}\par\pard\li533\ri0\sl-200\slmult0 \fs14\cf0\f0\charscalex100 {how variations w
ithin a predictor variable over time influenced}\par\pard\li533\ri0\sl-200\slmul
t0 \fs14\cf0\f0\charscalex100 {the use of an SSRI or benzodiazepine. For example
, for the partic-}\par\pard\li533\ri0\sl-200\slmult0 \fs14\cf0\f0\charscalex100
{ipants who started using an SSRI during our period of observa-}\par\pard\li533\
ri0\sl-200\slmult0 \fs14\cf0\f0\charscalex100 {tion, we designated the month the
use started for that individual}\par\pard\li533\ri0\sl-200\slmult0 \fs14\cf0\f0
\charscalex100 {as 0. Ratings were then assembled relative to that time, from 1}
\par\pard\li533\ri0\sl-200\slmult0 \fs14\cf0\f0\charscalex100 {year before use o
f that SSRI until 1 year afterward. Proportional}\par\pard\li533\ri0\sl-200\slmu
lt0 \fs14\cf0\f0\charscalex100 {hazards regressions were also conducted for the
patients whose}\par\pard\li533\ri0\sl-200\slmult0 \fs14\cf0\f0\charscalex100 {il
lness was in remission from panic disorder to examine if receiv-}\par\pard\li533

\ri0\sl-200\slmult0 \fs14\cf0\f0\charscalex100 {ing various types of psychotropi

c treatment (SSRIs, benzodiaz-}\par\pard\li533\ri0\sl-200\slmult0 \fs14\cf0\f0\c
harscalex100 {epines, monotherapy, combined pharmacological treatment) in-}\par\
pard\li533\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {creased the likelihood
of remission.}\par\pard\li533\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li533\ri0\s
l-293\slmult0 \fs24\cf0\f0\charscalex100 {Results}\par\pard\li720\ri0\sl-360\slm
ult0 \fs18\cf0\f0\charscalex100 {For the analyses in this article, our study gro
up con-}\par\pard\li533\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {sisted of
443 patients with panic disorder (with or without}\par\pard\li533\ri0\sl-240\sl
mult0 \fs18\cf0\f0\charscalex100 {agoraphobia) who had at least 6 months of foll
ow-up. An}\par\pard\li533\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {additio
nal 44 subjects had a new onset of panic disorder}\par\pard\li533\ri0\sl-240\slm
ult0 \fs18\cf0\f0\charscalex100 {(with or without agoraphobia) during subsequent
follow-}\par\pard\li533\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {up perio
ds and were included in these follow-up analyses.}\par\pard\li533\ri0\sl-240\slm
ult0 \fs18\cf0\f0\charscalex100 {Inspection of demographic characteristics of th
e 443 sub-}\par\pard\li533\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {jects
at intake indicated that the majority of the patients}\par\pard\li533\ri0\sl-240
\slmult0 \fs18\cf0\f0\charscalex100 {were Caucasian (89%) and female (68%) and h
ad a high}\par\pard\li533\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {level o
f education (38% had a college education or higher).}\par\pard\li533\ri0\sl-240\
slmult0 \fs18\cf0\f0\charscalex100 {Slightly more than one-half were married at
intake,}\par\pard\li533\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {whereas 2
7% of the participants reported having never}\par\column\pard\li0\ri0\sl-400\slm
ult0 \fs20\cf0\f0\charscalex100 {Medication Doses}\par\pard\li186\ri0\sl-320\slm
ult0 \fs18\cf0\f0\charscalex100 {Average doses of specific SSRIs and benzodiazep
ines are}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {reported i
n Table 3. The average daily dose at the 10-year}\par\pard\li0\ri0\sl-240\slmult
0 \fs18\cf0\f0\charscalex100 {follow-up is reported since some of the medication
s were}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {not yet deve
loped or approved at intake or in earlier fol-}\par\pard\li0\ri0\sl-253\slmult0
\fs18\cf0\f0\charscalex100 {low-up years. Additionally, the proportion of patien
ts tak-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {ing benzodi
azepines on an as-needed basis is reported.}\par\pard\li0\ri0\sl-240\slmult0 \fs
18\cf0\f0\charscalex100 {The average daily dose of benzodiazepines was within th
e}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {lower range that
is typically prescribed, although there}\par\pard\li0\ri0\sl-240\slmult0 \fs18\c
f0\f0\charscalex100 {were large standard deviations in dose because some of}\par
\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {the patients were takin
g extremely low or extremely high}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\
charscalex100 {doses. Approximately one-half of the patients taking a}\par\pard\
li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {benzodiazepine were taking it
as needed, with the excep-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charsc
alex100 {tion of clonazepam (10.5%). For the SSRIs, the average}\par\pard\li0\ri
0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {doses were also in the lower typica
l range. Most of the pa-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscale
x100 {tients reported taking fluoxetine, followed by paroxetine}\par\pard\li0\ri
0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {and sertraline. The patients who we
re taking a benzodiaz-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex1
00 {epine on an as-needed basis were no more likely to be tak-}\par\pard\li0\ri0
\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {ing a daily SSRI than were those who
were taking a daily}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100
{benzodiazepine.}\par\pard\li0\ri0\sl-400\slmult0 \fs20\cf0\f0\charscalex100 {U
se of Pharmacological Agents Over Follow-Up}\par\pard\li186\ri0\sl-333\slmult0 \
fs18\cf0\f0\charscalex100 {Ten-year use of SSRIs and benzodiazepines in patients
}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {with panic disorde
r is reported in Table 4. The results indi-}\par\pard\li0\ri0\sl-240\slmult0 \fs
18\cf0\f0\charscalex100 {cated a slight decline in benzodiazepine use across the
fol-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {low-up interv
al, although overall use of benzodiazepines}\par\pard\li0\ri0\sl-240\slmult0 \fs

18\cf0\f0\charscalex100 {has remained high, with over one-half of the patients r

e-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {porting use of a
benzodiazepine during each of the follow-}\par\pard\li0\ri0\sl-240\slmult0 \fs1
8\cf0\f0\charscalex100 {up years. A moderate incremental increase in SSRI use wa
s}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {found over time i
n the patients with panic disorder, from}\par\pard\li0\ri0\sl-240\slmult0 \fs18\
cf0\f0\charscalex100 {13.3% at intake to 32.9% at the 10-year follow-up. How-}\p
ar\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {ever, of the patients
taking an SSRI, approximately two-}\par\pard\sect\sectd\sbknone\pgwsxn12240\pgh
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http://ajp.psychiatryonline.org}\par\column\pard\li0\ri0\sl-213\slmult0 \fs18\cf
0\par\pard\li0\ri0\sl-266\slmult0 \fs16\cf0\f0\charscalex100 {Am J Psychiatry 16
0:8, August 2003}\par\pard\sect\sectd\sbknone\pgwsxn12240\pghsxn15840\marglsxn66
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0\charscalex100 {tients who were experiencing current episodes (psychiat-}\par\c
olumn\pard\li0\ri0\sl-173\slmult0 \*\tx1666\*\tx2440\fs16\cf0\f0\charscalex100 {
Paroxetine (N=39)}\tab \fs16\cf0\f0\charscalex100 {21.77}\tab \fs16\cf0\f0\chars
calex100 {16.55}\par\column\pard\li0\ri0\sl-173\slmult0 \fs16\cf0\f0\charscalex1
00 {0}\par\column\pard\li0\ri0\sl-173\slmult0 \fs16\cf0\f0\charscalex100 {0.0}\p
ar\pard\sect\sectd\sbknone\pgwsxn12240\pghsxn15840\marglsxn666\margrsxn133\cols5
\colno1\colw5813\colsr-0\colno2\colw1666\colsr-0\colno3\colw1800\colsr-0\colno4\
colw720\colsr-0\colno5\colw1440\pard\li653\ri0\sl-173\slmult0 \fs18\cf0\f0\chars
calex100 {ric status rating of 5 or higher) of panic disorder during}\par\column
\pard\li0\ri0\sl-186\slmult0 \fs16\cf0\f0\charscalex100 {Sertraline (N=35)}\par\
column\pard\li0\ri0\sl-186\slmult0 \*\tx773\fs16\cf0\f0\charscalex100 {64.36}\ta
b \fs16\cf0\f0\charscalex100 {65.06}\par\column\pard\li0\ri0\sl-186\slmult0 \fs1
6\cf0\f0\charscalex100 {0}\par\column\pard\li0\ri0\sl-186\slmult0 \fs16\cf0\f0\c
harscalex100 {0.0}\par\pard\sect\sectd\sbknone\pgwsxn12240\pghsxn15840\marglsxn6
66\margrsxn133\cols4\colno1\colw5813\colsr-0\colno2\colw3466\colsr-0\colno3\colw

706\colsr-0\colno4\colw1453\pard\li653\ri0\sl-226\slmult0 \fs16\cf0\f0\charscale
x100 {each follow-up period. Comparisons of the patients who}\par\column\pard\li
0\ri0\sl-173\slmult0 \*\tx1666\*\tx2440\fs16\cf0\f0\charscalex100 {Citalopram (N
=13)}\tab \fs16\cf0\f0\charscalex100 {27.14}\tab \fs16\cf0\f0\charscalex100 {15.
90}\par\column\pard\li0\ri0\sl-173\slmult0 \fs16\cf0\f0\charscalex100 {0}\par\co
lumn\pard\li0\ri0\sl-173\slmult0 \fs16\cf0\f0\charscalex100 {0.0}\par\pard\sect\
sectd\sbknone\pgwsxn12240\pghsxn15840\marglsxn666\margrsxn133\cols2\colno1\colw5
693\colsr-0\colno2\colw5746\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscale
x100 {were having panic attacks at follow-up with the patients}\par\pard\li653\r
i0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {who were in remission indicated th
at experiencing a panic}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscal
ex100 {attack did not increase the overall rate of receiving either}\par\pard\li
653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {an SSRI or a benzodiazepine (
use at 10 years: 33.7%, 66 of}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\ch
arscalex100 {196, and 62.2%, 122 of 196, respectively).}\par\pard\li840\ri0\sl-2
53\slmult0 \fs16\cf0\f0\charscalex100 {Next, analyses were conducted to examine
the effect of}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {com
orbid major depressive disorder on the patterns of}\par\pard\li653\ri0\sl-240\sl
mult0 \fs16\cf0\f0\charscalex100 {psychotropic prescriptions. Our findings showe
d that the}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {presen
ce of major depressive disorder slightly increased}\par\pard\li653\ri0\sl-240\sl
mult0 \fs16\cf0\f0\charscalex100 {the overall percent of patients receiving an S
SRI, although}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {not
significantly. Only one-quarter to one-third of the pa-}\par\pard\li653\ri0\sl240\slmult0 \fs16\cf0\f0\charscalex100 {tients with comorbid major depressive di
sorder reported}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {r
eceiving an SSRI. Of interest, the use of benzodiazepines}\par\pard\li653\ri0\sl
-240\slmult0 \fs16\cf0\f0\charscalex100 {in the patients with comorbid major dep
ressive disorder}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {
also increased. For example, 72.1% (N=44) of the patients}\par\pard\li653\ri0\sl
-240\slmult0 \fs16\cf0\f0\charscalex100 {with panic disorder and comorbid major
depressive disor-}\par\pard\li653\ri0\sl-253\slmult0 \fs16\cf0\f0\charscalex100
{der reported taking a benzodiazepine at the 10-year fol-}\par\pard\li653\ri0\sl
-240\slmult0 \fs16\cf0\f0\charscalex100 {low-up compared with 61.5% (N=83) of th
e nondepressed}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {pa
tients with panic disorder.}\par\pard\li840\ri0\sl-253\slmult0 \fs18\cf0\f0\char
scalex100 {Proportional hazards regressions with time-varying co-}\par\pard\li65
3\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {variates were conducted to exam
ine predictors of SSRI}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscale
x100 {and benzodiazepine use in the patients with panic disor-}\par\pard\li653\r
i0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {der. The results indicated that co
morbid major depressive}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscal
ex100 {disorder was a significant predictor of SSRI use during fol-}\par\pard\li
653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {low-up. The patients with pan
ic disorder and comorbid}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charsca
lex100 {major depressive disorder were 3.5 times more likely to}\par\pard\li653\
ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {use an SSRI than those without ma
jor depressive disorder}\par\pard\li653\ri0\sl-266\slmult0 \fs18\cf0\f0\charscal
ex100 {(risk ratio=3.6, p}\fs18\cf0\f1\charscalex100 {<}\fs18\cf0\f0\charscalex1
00 {0.0001). Additionally, previous use of a}\par\pard\li653\ri0\sl-213\slmult0
\fs18\cf0\f0\charscalex100 {benzodiazepine significantly reduced the likelihood
that a}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {patient wo
uld receive an SSRI during future follow-ups}\par\pard\li653\ri0\sl-266\slmult0
\fs16\cf0\f0\charscalex100 {nearly fourfold (risk ratio=0.3, p}\fs16\cf0\f1\char
scalex100 {<}\fs16\cf0\f0\charscalex100 {0.0001). Other comorbid}\par\pard\li653
\ri0\sl-213\slmult0 \fs18\cf0\f0\charscalex100 {conditions, such as alcohol/subs
tance use disorders and}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscal
ex100 {additional comorbid anxiety disorders, did not signifi-}\par\pard\li653\r
i0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {cantly predict SSRI use in patient
s. No significant predic-}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charsc

alex100 {tors of benzodiazepine use were found.}\par\pard\li653\ri0\sl-400\slmul

t0 \fs20\cf0\f0\charscalex100 {Pharmacological Treatment and Clinical Course}\pa
r\pard\li840\ri0\sl-320\slmult0 \fs18\cf0\f0\charscalex100 {Proportional hazards
regressions analyses were con-}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\
charscalex100 {ducted to determine if types of psychotropic treatment}\par\pard\
li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {improved rates of remission
in patients with panic disor-}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\c
harscalex100 {der. Overall, the patients whose illness remitted were no}\par\par
d\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {more likely to be taking
an SSRI the week before remission}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f
0\charscalex100 {nor were they more likely to be receiving a benzodiazepine}\par
\column\pard\li0\ri0\sl-186\slmult0 \fs12\cf0\f0\charscalex100 {a}{ }\fs16\cf0\f
0\charscalex100 {Only medications given to 10 or more patients are shown.}\par\p
ard\li0\ri0\sl-186\slmult0 \fs12\cf0\f0\charscalex100 {b}{ }\fs16\cf0\f0\charsca
lex100 {Average dose was calculated by using all patients, including those}\par\
pard\li106\ri0\sl-173\slmult0 \fs16\cf0\f0\charscalex100 {taking medications on
an as-needed basis.}\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\
sl-333\slmult0 \fs18\cf0\f0\charscalex100 {the week before remission. Moreover,
results indicated}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {t
hat patients who were in remission were no more likely to}\par\pard\li0\ri0\sl-2
40\slmult0 \fs18\cf0\f0\charscalex100 {be receiving combination treatment (SSRIs
and benzodi-}\par\pard\li0\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {azepi
nes) the week before remission. Finally, analyses ex-}\par\pard\li0\ri0\sl-240\s
lmult0 \fs18\cf0\f0\charscalex100 {amining the intensity of treatment, including
dose and}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {whether p
atients were taking a medication as needed,}\par\pard\li0\ri0\sl-240\slmult0 \fs
18\cf0\f0\charscalex100 {were conducted to see if there were any effects on clin
ical}\par\pard\li0\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {outcome. Again
, the patients whose disorder remitted}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf
0\f0\charscalex100 {were no more likely to be receiving higher doses of benzo-}\
par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {diazepines or SSRIs
or to be taking a benzodiazepine as}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f
0\charscalex100 {needed the week before remission than those whose ill-}\par\par
d\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {ness had not remitted.}\par
\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-360\slmult0 \fs24\cf0
\f0\charscalex100 {Discussion}\par\pard\li186\ri0\sl-386\slmult0 \fs16\cf0\f0\ch
arscalex100 {Results from this prospective longitudinal study of anx-}\par\pard\
li0\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {iety disorders indicate that
despite attempts aimed at in-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\char
scalex100 {creasing the use of SSRIs to treat panic disorder (e.g., APA}\par\par
d\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {practice guideline), there
has only been a modest increase}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\ch
arscalex100 {in the proportion of patients receiving such treatment.}\par\pard\l
i0\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {Psychotropic treatment pattern
s appear to have remained}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscal
ex100 {relatively stable over the past decade (1989}\fs18\cf0\f0\charscalex100 {
\uc1\u8211X}\fs18\cf0\f0\charscalex100 {2001), with}\par\pard\li0\ri0\sl-240\slm
ult0 \fs18\cf0\f0\charscalex100 {benzodiazepines being the most common class of
drugs}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {used to treat
panic disorder. In comparison, the use of SS-}\par\pard\li0\ri0\sl-240\slmult0
\fs18\cf0\f0\charscalex100 {RIs throughout the follow-up period has remained low
. A}\par\pard\li0\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {majority of the
patients taking an SSRI also reported tak-}\par\pard\li0\ri0\sl-240\slmult0 \fs
18\cf0\f0\charscalex100 {ing a benzodiazepine concomitantly. A closer inspection
}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {of the patients wh
o were experiencing an episode of panic}\par\pard\li0\ri0\sl-253\slmult0 \fs18\c
f0\f0\charscalex100 {disorder at each of the follow-up intervals revealed simila
r}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {psychotropic trea
tment patterns over time. These results}\par\pard\li0\ri0\sl-240\slmult0 \fs18\c
f0\f0\charscalex100 {are consistent with those of Uhlenhuth and colleagues}\par\

pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {(16), who reported a neg

ligible decrease in the overall fre-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\
f0\charscalex100 {quency of expert recommendations for benzodiazepines}\par\pard
\li0\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {as a first-line treatment fo
r panic disorder over a 5-year in-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0
\charscalex100 {terval in the 1990s.}\par\pard\li186\ri0\sl-280\slmult0 \fs18\cf
0\f0\charscalex100 {The effect of comorbid major depressive disorder on}\par\par
d\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {medication treatment patter
ns in patients with panic dis-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\cha
rscalex100 {order was found to be a significant predictor of greater use}\par\pa
rd\li0\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {of SSRIs. This is consiste
nt with an earlier study that exam-}\par\pard\sect\sectd\sbknone\pgwsxn12240\pgh
sxn15840\marglsxn666\margrsxn133\cols3\colno1\colw6920\colsr-0\colno2\colw2933\c
olsr-0\colno3\colw1586\pard\li653\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li653\ri
0\sl-266\slmult0 \fs16\cf0\f0\charscalex100 {Am J Psychiatry 160:8, August 2003}
\par\column\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-266\slmult
0 \fs16\cf0\f0\charscalex100 {http://ajp.psychiatryonline.org}\par\column\pard\l
i0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-280\slmult0 \fs20\cf0\f0\cha
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w5866\pard\li533\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li533\ri0\sl-373\slmult0
\fs18\cf0\f0\charscalex100 {ined pharmacological treatment of generalized anxiet
y}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {disorder (17),
in which we also found significant increases}\par\pard\li533\ri0\sl-240\slmult0
\fs16\cf0\f0\charscalex100 {in the use of SSRIs when accompanied by comorbid de}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {pression. Howeve
r, the presence of other comorbid condi-}\par\pard\li533\ri0\sl-240\slmult0 \fs1
6\cf0\f0\charscalex100 {tions, such as alcohol or substance use, did not increas
e}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {SSRI use. This
was unexpected since we had initially hy-}\par\pard\li533\ri0\sl-240\slmult0 \fs
16\cf0\f0\charscalex100 {pothesized that use of SSRIs would be greater in these
pa-}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {tients becaus
e of concerns associated with the combina-}\par\pard\li533\ri0\sl-240\slmult0 \f
s18\cf0\f0\charscalex100 {tion of alcohol and benzodiazepines.}\par\pard\li720\r
i0\sl-253\slmult0 \fs16\cf0\f0\charscalex100 {Overall, we were somewhat surprise
d by these findings.}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex1
00 {With the advent of several new SSRIs during the 1990s, we}\par\pard\li533\ri
0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {had anticipated a marked increase i
n the use of SSRIs over}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscal
ex100 {time, particularly during the most recent follow-up inter-}\par\pard\li53
3\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {vals. Why would a high percenta
ge of these patients}\fs16\cf0\f0\charscalex100 {\uc1\u8217X}\fs16\cf0\f0\charsc
alex100 { phy-}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {si
cians not prescribe SSRIs for panic disorder, despite}\par\pard\li533\ri0\sl-240
\slmult0 \fs16\cf0\f0\charscalex100 {treatment guidelines endorsing SSRIs as }\f
s16\cf0\f0\charscalex100 {\uc1\u8220X}\fs16\cf0\f0\charscalex100 {the most favor
-}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {able balance of
efficacy and adverse effects}\fs16\cf0\f0\charscalex100 {\uc1\u8221X}\fs16\cf0\
f0\charscalex100 { in many pa-}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\c
harscalex100 {tients with panic disorder (8)? Potential connections for}\par\par
d\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {the observed low levels o
f use of SSRIs have been posited}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0
\charscalex100 {by researchers, and collectively, they may help explain the}\par
\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {observed levels of SS
RI use in patients with panic disorder.}\par\pard\li533\ri0\sl-240\slmult0 \fs16
\cf0\f0\charscalex100 {For example, Lomas and colleagues (18) examined the in-}\
par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {fluence of practic
e guidelines on a group of physicians.}\par\pard\li533\ri0\sl-240\slmult0 \fs16\
cf0\f0\charscalex100 {Their findings indicated that although physicians}\fs16\cf
0\f0\charscalex100 {\uc1\u8217X}\fs16\cf0\f0\charscalex100 { self-re-}\par\pard\
li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {ports indicated a change in
the way in which they practice,}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0
\charscalex100 {actual behavior had changed little. Other studies have}\par\pard
\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {found resistance to practi
ce guidelines, particularly with}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0
\charscalex100 {more experienced physicians (19, 20). Resistance appears}\par\pa
rd\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {to be due, in part, to f
ear of loss of autonomy and clinical}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf
0\f0\charscalex100 {judgment, as well as to problems with the practical appli-}\

par\pard\li533\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {cation of such gui

delines.}\par\pard\li720\ri0\sl-266\slmult0 \fs16\cf0\f0\charscalex100 {Dugan an
d Cohen (21) suggested that }\fs16\cf0\f0\charscalex100 {\uc1\u8220X}\fs16\cf0\f
0\charscalex100 {before physi-}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\c
harscalex100 {cians view guidelines as precise tools to use in the con-}\par\par
d\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {struction of optimal pati
ent care, they must be convinced}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0
\charscalex100 {that guidelines contain clear, evidence-based recommen-}\par\par
d\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {dations, and that there i
s a distinct advantage to them in}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f
0\charscalex100 {changing practice styles to follow guidelines}\fs16\cf0\f0\char
scalex100 {\uc1\u8221X}\fs16\cf0\f0\charscalex100 { (pp. 284}\fs16\cf0\f0\charsc
alex100 {\uc1\u8211X}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex1
00 {285). For some physicians and patients, the rapid onset of}\par\pard\li533\r
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their use more favor-}\par\pard\li533\ri0\sl-240\slmult0 \fs16\cf0\f0\charscale
x100 {able than the newer SSRIs, which can take weeks to pro-}\par\pard\li533\ri
0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {vide any benefit. This may be shown
by the high rate of pa-}\par\column\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\p
ard\li0\ri0\sl-373\slmult0 \fs18\cf0\f0\charscalex100 {tients using benzodiazepi
nes on an as-needed basis.}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charsca
lex100 {Additionally, the comparatively high rates of noncompli-}\par\pard\li0\r
i0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {ance with the taking of SSRIs foun
d in some studies be-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex10
0 {cause of unwanted sexual side effects may make the }\fs18\cf0\f0\charscalex10
0 {\uc1\u8220X}\fs18\cf0\f0\charscalex100 {dis-}\par\pard\li0\ri0\sl-240\slmult0
\fs18\cf0\f0\charscalex100 {tinct advantage}\fs18\cf0\f0\charscalex100 {\uc1\u8
221X}\fs18\cf0\f0\charscalex100 { of using an SSRI murkier. For example,}\par\pa
rd\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {discontinuation of SSRIs i
n patients with panic disorder}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\cha
rscalex100 {has been attributed to adverse side effects 52% of the time,}\par\pa
rd\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {in contrast to benzodiazep
ines, for which adverse side ef-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\c
harscalex100 {fects were responsible for only 7% of the discontinuation}\par\par
d\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {(22). In a recent study of
6,299 primary care outpatients,}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\ch
arscalex100 {36%}\fs18\cf0\f0\charscalex100 {\uc1\u8211X}\fs18\cf0\f0\charscalex
100 {43% of the patients taking an SSRI reported sexual}\par\pard\li0\ri0\sl-240
\slmult0 \fs18\cf0\f0\charscalex100 {dysfunction (23), which is much higher than
the rate of}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {sexual
dysfunction reported in the product literature. A}\par\pard\li0\ri0\sl-240\slmu
lt0 \fs18\cf0\f0\charscalex100 {physician who has had multiple patients stop usi
ng SSRIs}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {because of
sexual dysfunction or other side effects may}\par\pard\li0\ri0\sl-240\slmult0 \
fs18\cf0\f0\charscalex100 {find these treatment guidelines overly theoretical an
d too}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {divorced from
their patients}\fs18\cf0\f0\charscalex100 {\uc1\u8217X}\fs18\cf0\f0\charscalex1
00 { concerns regarding quality of}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0
\charscalex100 {life.}\par\pard\li186\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex
100 {Two important observations must be noted. First, since}\par\pard\li0\ri0\sl
-240\slmult0 \fs18\cf0\f0\charscalex100 {this study did not include data from pa
tients}\fs18\cf0\f0\charscalex100 {\uc1\u8217X}\fs18\cf0\f0\charscalex100 { trea
ting phy-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {sicians,
it is impossible to determine whether SSRIs were}\par\pard\li0\ri0\sl-240\slmult
0 \fs18\cf0\f0\charscalex100 {not being prescribed to the patients or whether th
e physi-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {cians pres
cribed SSRIs, but the patients failed to take them}\par\pard\li0\ri0\sl-240\slmu
lt0 \fs18\cf0\f0\charscalex100 {because of concerns regarding potential unwanted
side}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {effects. Lack
of patient education surrounding these pos-}\par\pard\li0\ri0\sl-240\slmult0 \f

s18\cf0\f0\charscalex100 {sible side effects and education regarding the 4}\fs18

\cf0\f0\charscalex100 {\uc1\u8211X}\fs18\cf0\f0\charscalex100 {6-week}\par\pard\
li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {time period for the medicatio
n to become effective may}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscal
ex100 {also play a part in the low rates of SSRI use. Second, the pa-}\par\pard\
li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {tients recruited for this stu
dy had a long history of panic}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\cha
rscalex100 {disorder and originally sought treatment more than a de-}\par\pard\l
i0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {cade ago. Since the patients w
ere recruited from treatment}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\chars
calex100 {settings from 1989 to 1991, most SSRIs had not yet become}\par\pard\li
0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {available, and thus, many were
initially treated with a ben-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\char
scalex100 {zodiazepine. Therefore, the findings from this study may}\par\pard\li
0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {not be indicative of individual
s who are newly diagnosed}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscal
ex100 {with panic disorder and seeking treatment for the first}\par\pard\li0\ri0
\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {time.}\par\pard\li186\ri0\sl-266\slm
ult0 \fs16\cf0\f0\charscalex100 {These results highlight an existing gap between
recom-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {mended phar
macological treatment guidelines and actual}\par\pard\li0\ri0\sl-240\slmult0 \fs
18\cf0\f0\charscalex100 {delivery of care for the treatment of panic disorder. I
t ap-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {pears that th
e recommendation to use SSRIs as a first}\par\pard\sect\sectd\sbknone\pgwsxn1224
0\pghsxn15840\marglsxn666\margrsxn133\cols3\colno1\colw1733\colsr-0\colno2\colw5
853\colsr-0\colno3\colw3853\pard\li533\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li5
33\ri0\sl-280\slmult0 \fs20\cf0\f0\charscalex100 {1436}\par\column\pard\li0\ri0\
sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-266\slmult0 \fs16\cf0\f0\charscalex
100 {http://ajp.psychiatryonline.org}\par\column\pard\li0\ri0\sl-213\slmult0 \fs
18\cf0\par\pard\li0\ri0\sl-266\slmult0 \fs16\cf0\f0\charscalex100 {Am J Psychiat
ry 160:8, August 2003}\par\pard\sect\sectd\sbknone\pgwsxn12240\pghsxn15840\margl
sxn666\margrsxn133\pard\sect\sectd\sbkpage
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53\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li653\ri0\sl-213\slmult0 \fs18\cf0\par\
pard\li653\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {choice is not being fo
llowed rigorously. Future studies}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f
0\charscalex100 {should address this apparent gap, including whether or}\par\par
d\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {not the clinical guidelin
e to use SSRIs as a first-line treat-}\par\pard\li653\ri0\sl-240\slmult0 \fs16\c
f0\f0\charscalex100 {ment is premature. In an effect-size analysis of SSRIs for}
\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {the treatment of
panic disorder, Otto and colleagues (24)}\par\pard\li653\ri0\sl-240\slmult0 \fs1
6\cf0\f0\charscalex100 {found no evidence to support the hypothesis that SSRIs}\
par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {are more effective
than older antidepressants for the treat-}\par\pard\li653\ri0\sl-240\slmult0 \f
s16\cf0\f0\charscalex100 {ment of panic disorder. They suggest that earlier stud
ies}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {with small sa
mple sizes may have led to an initial overesti-}\par\pard\li653\ri0\sl-240\slmul
t0 \fs16\cf0\f0\charscalex100 {mation of the efficacy of SSRIs for panic disorde
r. To our}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {knowled
ge, no large controlled comparison study has}\par\pard\li653\ri0\sl-240\slmult0
\fs16\cf0\f0\charscalex100 {been conducted to examine the superiority of SSRIs o
ver}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {benzodiazepin
es for the treatment of panic disorder.}\par\pard\li653\ri0\sl-240\slmult0 \fs16
\cf0\f0\charscalex100 {Thus, it may be difficult for some physicians to alter pr
e-}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {scribing patte
rns until such firm evidence exists for the su-}\par\pard\li653\ri0\sl-240\slmul
t0 \fs18\cf0\f0\charscalex100 {periority of SSRIs.}\par\pard\li840\ri0\sl-266\sl
mult0 \fs16\cf0\f0\charscalex100 {Although our results indicate that the patient
s whose}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {panic dis
order remitted were no more likely to be taking}\par\pard\li653\ri0\sl-240\slmul
t0 \fs16\cf0\f0\charscalex100 {SSRIs or benzodiazepines (or both in combination)
before}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {remission
, the lack of treatment effects on their illness}\fs16\cf0\f0\charscalex100 {\uc
1\u8217X}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {clinical
course was not unexpected. Since the Harvard/}\par\pard\li653\ri0\sl-240\slmult
0 \fs16\cf0\f0\charscalex100 {Brown Anxiety Research Project is an observational
study}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {of anxiety
disorders by design, it observes but does not}\par\pard\li653\ri0\sl-240\slmult
0 \fs16\cf0\f0\charscalex100 {manipulate the treatment received by its patients.
Treat-}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {ment anal
yses performed by the Harvard/Brown Anxiety}\par\pard\li653\ri0\sl-240\slmult0 \
fs16\cf0\f0\charscalex100 {Research Project to date have shown that the treatmen
t}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {the patients re
ceived does not play a decisive role in im-}\par\pard\li653\ri0\sl-240\slmult0 \
fs16\cf0\f0\charscalex100 {proving the course of their anxiety disorders, since
we}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {have shown rel
atively slow rates of recovery and/or high}\par\pard\li653\ri0\sl-240\slmult0 \f
s16\cf0\f0\charscalex100 {rates of recurrence (11). This could be because of our
find-}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {ings of lo

w doses of medication for the treatment of anxi-}\par\pard\li653\ri0\sl-240\slmu

lt0 \fs16\cf0\f0\charscalex100 {ety disorders and minimum treatment with empiric
ally}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {based psycho
therapies with demonstrated efficacy or be-}\par\pard\li653\ri0\sl-240\slmult0 \
fs16\cf0\f0\charscalex100 {cause of self-selective biases that make treatment ap
pear}\par\pard\li653\ri0\sl-240\slmult0 \fs16\cf0\f0\charscalex100 {to have nega
tive effects because there is no experimental}\par\pard\li653\ri0\sl-240\slmult0
\fs18\cf0\f0\charscalex100 {control over treatment.}\par\pard\li840\ri0\sl-280\
slmult0 \fs18\cf0\f0\charscalex100 {It is important to note that a substantial n
umber of pa-}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {tien
ts in this study were not taking a benzodiazepine or an}\par\pard\li653\ri0\sl-2
40\slmult0 \fs18\cf0\f0\charscalex100 {SSRI. A few patients were receiving older
medications,}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {suc
h as MAOIs (2%), imipramine (9%), and buspirone}\par\pard\li653\ri0\sl-240\slmul
t0 \fs18\cf0\f0\charscalex100 {(5%), at intake. Additionally, other newer medica
tions,}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {such as ve
nlafaxine, also had low rates of use during fol-}\par\pard\li653\ri0\sl-240\slmu
lt0 \fs16\cf0\f0\charscalex100 {low-up (5% at the 10-year follow-up). Recruitmen
t oc-}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {curred in s
pecialized treatment settings, so individuals re-}\par\pard\li653\ri0\sl-240\slm
ult0 \fs18\cf0\f0\charscalex100 {ceiving somatic treatment for their panic disor
der is likely}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {to
be lower in community settings. These results, when}\par\pard\li653\ri0\sl-240\s
lmult0 \fs18\cf0\f0\charscalex100 {combined with those from earlier studies repo
rting the}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {low rat
es of patients from the Harvard/Brown Anxiety Re-}\par\pard\li653\ri0\sl-240\slm
ult0 \fs18\cf0\f0\charscalex100 {search Project who were receiving empirically s
upported}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {psychoso
cial treatment for their panic disorder (e.g., cog-}\par\pard\li653\ri0\sl-240\s
lmult0 \fs18\cf0\f0\charscalex100 {nitive behavior therapy) (25, 26), indicate t
hat a substan-}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {ti
al number of patients in our group were not receiving}\par\pard\li653\ri0\sl-240
\slmult0 \fs18\cf0\f0\charscalex100 {any of the recommended treatment for their
panic disor-}\par\pard\li653\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {der
symptoms. Although the continuation of controlled}\par\pard\li653\ri0\sl-226\slm
ult0 \fs18\cf0\f0\charscalex100 {clinical trials is paramount, these findings al
so highlight}\par\pard\li653\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {the
need for increased effectiveness research to examine}\par\column\pard\li2093\ri0
\sl-146\slmult0 \fs16\cf2\f0\charscalex100 {BRUCE, VASILE, GOISMAN, ET AL.}\par\
pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-320\slmult0 \fs16\cf0\
f0\charscalex100 {the factors associated with promoting and inhibiting the}\par\
pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {implementation of treatm
ent guidelines for panic disor-}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\ch
arscalex100 {der in real-world settings. These factors may help improve}\par\par
d\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {and modify existing treatme
nt guidelines and thus help}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charsc
alex100 {minimize the gap between clinical research and actual de-}\par\pard\li0
\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {livery of care.}\par\pard\li0\ri
0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\f0\charscal
ex100 {Acknowledgments}\par\pard\li0\ri0\sl-373\slmult0 \fs16\cf0\f0\charscalex1
00 {The Harvard/Brown Anxiety Disorder Research Program is con-}\par\pard\li0\ri
0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {ducted with the participation of th
e following investigators: M.B.}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\ch
arscalex100 {Keller, M.D., Chair: M.T. Shea, Ph.D. (Veterans Administration}\par
\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {Hospital, Providence, R
I; Brown Medical School); J. Eisen, M.D., K.}\par\pard\li0\ri0\sl-200\slmult0 \f
s16\cf0\f0\charscalex100 {Phillips, M.D., R. Stout, Ph.D. (Butler Hospital, Brow
n Medical}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {School);
S.E. Bruce, Ph.D., R.B. Weisberg, Ph.D., M.G. Warshaw,}\par\pard\li0\ri0\sl-200\
slmult0 \fs16\cf0\f0\charscalex100 {M.S.S., M.A. (Brown Medical School); R.M. Go

isman, M.D. (Mas-}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {s

achusetts Mental Health Center, Harvard Medical School); A.}\par\pard\li0\ri0\sl
-200\slmult0 \fs16\cf0\f0\charscalex100 {Massion, M.D. (University of Massachuse
tts Medical Center); M.P.}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscal
ex100 {Rogers, M.D. (Brigham and Women}\fs16\cf0\f0\charscalex100 {\uc1\u8217X}\
fs16\cf0\f0\charscalex100 {s Hospital, Harvard Medical}\par\pard\li0\ri0\sl-200\
slmult0 \fs16\cf0\f0\charscalex100 {School); C. Salzman, M.D. (Massachusetts Men
tal Health Center,}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {
Harvard Medical School); G. Steketee, Ph.D. (Boston University}\par\pard\li0\ri0
\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {School of Social Work); K. Yonkers,
M.D. (Yale University School of}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\ch
arscalex100 {Medicine); I. Goldenberg, Psy.D.; G. Mallya, M.D. (McLean Hospi-}\p
ar\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {tal, Harvard Medical
School); T. Mueller, M.D. (Butler Hospital,}\par\pard\li0\ri0\sl-200\slmult0 \fs
16\cf0\f0\charscalex100 {Brown Medical School); F. Rodriguez-Villa, M.D. (McLean
Hospi-}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {tal, Harvar
d Medical School); R. Vasile, M.D. (Beth Israel Deacon-}\par\pard\li0\ri0\sl-200
\slmult0 \fs16\cf0\f0\charscalex100 {ess Medical Center, Harvard Medical School)
; C. Zlotnick, Ph.D.}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100
{(Butler Hospital, Brown Medical School); E. Fierman, M.D. Addi-}\par\pard\li0\
ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {tional contributions were from th
e following: P. Alexander, M.D.}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\ch
arscalex100 {(Butler Hospital, Brown Medical School); J. Curran, M.D.; J. Cole,}
\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {M.D. (McLean Hospit
al, Harvard Medical School); J. Ellison, M.D.,}\par\pard\li0\ri0\sl-200\slmult0
\fs16\cf0\f0\charscalex100 {M.P.H. (Harvard Pilgrim Health Care, Harvard Medical
School); A.}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {Gordon
, M.D., S. Rasmussen, M.D. (Butler Hospital, Brown Medi-}\par\pard\li0\ri0\sl-20
0\slmult0 \fs16\cf0\f0\charscalex100 {cal School); R. Hirschfeld Ph.D. (Universi
ty of Texas, Galveston); J.}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charsc
alex100 {Hooley, D.Phil. (Harvard University); P. Lavori, Ph.D. (Stanford}\par\p
ard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {University); J. Perry, M.
D. ( Jewish General Hospital, McGill}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\
f0\charscalex100 {University School of Medicine, Montreal); L. Peterson (Midcoas
t}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {Medical Group, Ro
ckport, Maine); J. Reich, M.D., M.P.H.; J. Rice,}\par\pard\li0\ri0\sl-200\slmult
0 \fs16\cf0\f0\charscalex100 {Ph.D. (Renard Hospital, Washington University Scho
ol of Medi-}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {cine);
H. Samuelson, M.A. (Brigham and Women}\fs16\cf0\f0\charscalex100 {\uc1\u8217X}\f
s16\cf0\f0\charscalex100 {s Hospital); D.}\par\pard\li0\ri0\sl-200\slmult0 \fs16
\cf0\f0\charscalex100 {Shera, M.S. (Harvard School of Public Health); N. Weinshe
nker,}\par\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {M.D. (New Jer
sey Medical School); M. Weissman, Ph.D. (Colum-}\par\pard\li0\ri0\sl-200\slmult0
\fs16\cf0\f0\charscalex100 {bia University); K. White, M.D.}\par\pard\li120\ri0
\sl-213\slmult0 \fs18\cf0\par\pard\li120\ri0\sl-226\slmult0 \fs12\cf0\f0\charsca
lex100 {Presented in part at the 22nd national conference of the Anxiety}\par\pa
rd\li0\ri0\sl-173\slmult0 \fs14\cf0\f0\charscalex100 {Disorders Association of A
merica, Austin, Tex., March 21\uc1\u8211X24, 2002.}\par\pard\li0\ri0\sl-186\slmu
lt0 \fs14\cf0\f0\charscalex100 {Received July 31, 2002, revision received Feb. 1
2, 2003, accepted}\par\pard\li0\ri0\sl-173\slmult0 \fs14\cf0\f0\charscalex100 {F
eb. 22, 2003. From Brown University; Beth Israel Deaconess Medical}\par\pard\li0
\ri0\sl-186\slmult0 \fs14\cf0\f0\charscalex100 {Center, Boston; Massachusetts Me
ntal Health Center, Boston; and the}\par\pard\li0\ri0\sl-173\slmult0 \fs14\cf0\f
0\charscalex100 {Department of Psychiatry, Harvard Medical School, Boston. Addre
ss}\par\pard\li0\ri0\sl-186\slmult0 \fs14\cf0\f0\charscalex100 {reprint requests
to Dr. Bruce, Department of Psychiatry and Human}\par\pard\li0\ri0\sl-173\slmul
t0 \fs14\cf0\f0\charscalex100 {Behavior, Box G-BH, Brown University, Providence,
RI 02906; Steven_}\par\pard\li0\ri0\sl-186\slmult0 \fs14\cf0\f0\charscalex100 {
Bruce_PhD@brown.edu (e-mail). }\par\pard\li120\ri0\sl-200\slmult0 \fs12\cf0\f0\c
harscalex100 {Funded in part by Wyeth-Ayerst Laboratories through its Global Re-

}\par\pard\li0\ri0\sl-186\slmult0 \fs14\cf0\f0\charscalex100 {search Program on

Anxiety and Depression and by NIMH grant MH-}\par\pard\li0\ri0\sl-173\slmult0 \f
s14\cf0\f0\charscalex100 {51415.}\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\
pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-226\slmult0 \fs18\cf0\
f0\charscalex100 {References}\par\pard\li160\ri0\sl-333\slmult0 \fs12\cf0\f0\cha
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ar\column\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-280\slmult0
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33\ri0\sl-146\slmult0 \fs16\cf2\f0\charscalex100 {BENZODIAZEPINES FOR PANIC DISO
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0\ri0\sl-253\slmult0 \fs16\cf0\f0\charscalex100 {Am J Psychiatry 160:8, August 2
003}\par}