Current Treatments of the Anxiety Disorders in Adults
James C. Ballenger
The progress in developing effective treatments for the five
principal anxiety disorders (ADs) in adults—panic disor-
der (PD), social phobia (SP), obsessive compulsive disor-
der (OCD), generalized anxiety disorder (GAD), posttrau-
matic stress disorder (PTSD)— has been rapid in the past
15 years. There are now well-controlled clinical trials
documenting effective pharmacological and psychological
treatments for all of these disorders, although generally
the evidence is better developed for some disorders than
for others.
Both the pharmacological treatments and the effective
psychological treatments for each disorder will be briefly
reviewed. The available data for combination treatment
will be reviewed and comparisons of the two types of
treatment will be made. This review will contain at least
brief reviews of what the treatments involve and attempt to
describe how well they work. Many studies unfortunately
report only the percentage of patients who “improve”
without quantifying the clinical significance of those
responses. Data underlining clinical response in terms of
the percentage of patients who have an “excellent,”
“marked,” or “moderate” response, and the percentage
of patients with a “clinically significant” response will be
reported whenever available. Other clinically relevant
issues such as length of treatment-relapse rates upon
discontinuation and side effects will be presented. As such,
this article should provide a brief but comprehensive
review of the treatment of these disorders in adults. Biol
Psychiatry 1999;46:1579 –1594 © 1999 Society of Biolog-
ical Psychiatry
Key Words: Anxiety disorders, cognitive behavioral ther-
apy, pharmacotherapy, treatments, adults
Panic Disorder (PD)
T he most well-developed literature on treatment of
the anxiety disorders is probably for panic disorder
(PD). It was the first to receive intense scientific
scrutiny, beginning in the 1960s. Investigation of the
treatment of PD has had a worldwide focus, particularly
From the Department of Psychiatry & Behavioral Sciences, Medical University of
South Carolina, Charleston.
Address reprint requests to Dr James C. Ballenger, Medical University South
Carolina, PO Box 250861, Charleston, SC 29425.
Received April 23, 1999; revised July 27, 1999; accepted August 4, 1999.
© 1999 Society of Biological Psychiatry
over the past 20 years. As with the other disorders, there
are a variety of effective psychopharmacologic agents
and several psychological approaches, especially cog-
nitive-behavioral therapy.
Pharmacologic Treatments
Early in the 1960s, investigators documented that imipra-
mine and the monoamine oxidase inhibitors (MAOIs),
particularly phenelzine, were both effective treatments of
PD (Ballenger et al 1997). As has been observed in all the
subsequent trials, effective treatments reduce all the symp-
toms of PD, the frequency and severity of panic attacks
(PAs), agoraphobic avoidance, anxiety, and comorbid
depression. Although there are different responses of each
of these symptoms to these treatments (e.g., agoraphobic
avoidance is the most difficult to treat), successful treat-
ments effectively reduce all these aspects of the PD
syndrome. The field has grappled with the problem of
appropriate outcome measures for PD (Shear et al 1998).
Reduction of PA frequency has been widely utilized but
has been unreliable as a single measure, and most inves-
tigators now use multidomain measures (Shear et al 1997).
The percentage of patients who become free of PAs is
generally 50 – 80% of patients studied in acute trials
lasting 6 – 8 weeks with multiple medications (Den Boer
1998). In patients who are treated for longer periods, this
percentage most often rises. It is generally true that the
longer PD patients are treated, the more complete and
comprehensive is their response. In the large cross-na-
tional trial, after 8 –12 months of treatment (Cross Na-
tional Collaborative Panic Study 1993), fully three fourths
of patients were free of PAs. In the recent large 12-month
comparison of paroxetine and clomipramine, the panic-
free rates respectively were 85% and 72%, rising from
⬇55% at 3 months (Lecrubier and Judge 1997).
As a group, PD patients continue to improve over time
both with and without treatment. During a random 4- to
6-year follow-up of a research trial followed by varied
treatment in the community, approximately one third of
patients had complete resolution of symptoms, 50% of
patients had mild intermittent symptoms, and 18% of
patients continued to do poorly after 8 weeks of treatment
with alprazolam, imipramine, or placebo (Katschnig et al
1995). The percentage of patients who had only mild
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1580 BIOL PSYCHIATRY
1999;46:1579 –1594
avoidance or less had increased from 40% immediately
after short-term treatment to 60% at 4 years. Those with
mild or less work impairment rose from 48% to 82%
(Katschnig et al 1995).
The anxiety that PD patients experience between PAs
can be considerable. This anxiety is reduced by all
effective therapies with little difference between treat-
ments (Cox et al 1992; Van Balkom et al 1997). In a
similar fashion, most effective treatments decrease the
common comorbid depressive symptoms, again generally
with little difference between treatments (Den Boer 1998).
Although some studies have failed to observe a difference
between alprazolam and imipramine in treatment of de-
pressive symptoms (Lesser et al 1989), several large
meta-analyses have suggested a reduced efficacy for the
benzodiazepines (BZs) compared to tricyclic antidepres-
sants (TCAs) (Cox 1992) and antidepressants in general
(Clum et al 1993; Van Balkom et al 1997). At this point,
patients with significant depressive symptoms are gener-
ally treated with an antidepressant rather than BZs.
Agoraphobia is probably the most treatment-resistant
symptom in PD. Although effective pharmacotherapy does
significantly reduce agoraphobia avoidance, in vivo expo-
sure is often employed to reduce avoidance behaviors.
There is no standard measure employed in the literature of
improvement in agoraphobic avoidance, making compar-
isons across studies and treatments difficult. Nonetheless,
in a review of 16 studies, remission of agoraphobia
occurred in ranges varying from 18 – 64% (Roy-Byrne and
Cowley 1995), and in a recent trial, 69% of patients
became free of avoidance (Marchesi et al 1997).
Improvement in agoraphobic avoidance occurs with all
the effective treatments, probably more or less equally,
although this has not been rigorously studied. The BZs are
as effective as antidepressants in reducing avoidance,
although effects begin earlier with the BZs (Van Balkom
et al 1997). Improvement is seen as early as the first or
second week with BZs and as early as the fourth week
with the antidepressants (Ballenger 1992; Ballenger et al
1998a), although improvement in agoraphobia is often the
last portion of the syndrome to respond, and patients
continue to improve for at least 3– 6 months. Recent trials
suggest that a significant response to antidepressants may
occur in the first 2– 4 weeks, which is earlier than
previously thought (Ballenger et al 1998a; Pohl et al
1998).
Length of Treatment
PD is now recognized to be a chronic disorder in most
patients. Most patients are now treated for at least 6
months, and generally 18 months, before consideration is
given to discontinuing active treatment (Ballenger 1992;
J.C. Ballenger
Ballenger et al 1998a). Relapse is the principal difficulty
with discontinuation and, until recently, was thought to
occur in 40 –90% of patients; however, a carefully con-
trolled trial of discontinuation of paroxetine documented
that the relapse rate was only 30% when patients were
blindly switched to placebo (Judge and Steiner 1996). This
is, in fact, similar to data observed by Clark and colleagues
1994 indicating a 40% relapse rate and to the 26% relapse
rate observed in the earliest imipramine trials (Zitrin
1978). Mavissakalian and Perel have suggested that the
longer treatment occurs before discontinuation, the lower
the relapse rate. In a small sample, they reported that
although there was an 80% response rate if imipramine
was discontinued after 6 months, that rate fell to 20% after
18 months of treatment (Mavissakalian and Perel 1992).
If discontinuation is to be attempted, it is suggested that
it involve choosing the correct time in which the patient is
stable and confident in his or her ability to manage the
anxiety. It should also involve family and patient educa-
tion, followed by a slow taper of the medication over 2– 6
months (Ballenger 1992). Group behavior therapy may be
helpful in managing emergent symptoms and increasing
the percentage of patients who successfully discontinue
medications (Otto et al 1993).
Comparison between Effective Medications
Certainly at this point in time, most experts agree that the
selective serotonin reuptake inhibitors (SSRIs) are the first
line of medication treatment (Ballenger et al 1998a; Boyer
1995; Jobson et al 1995). This is largely based on
controlled trials documenting the high tolerability of the
SSRIs and how they particularly appear to be associated
with a decreased rate of the hyperstimulation responses
(“jitteriness”) often observed initially with antidepres-
sants. These responses are often intolerable and are a
problematic side effect observed in as many as one third of
patients with TCAs, particularly if they are not started at
the lowest possible doses. This reaction appears to be
lower with the SSRIs, particularly if initial doses are quite
low (Ballenger 1999).
Most of the SSRIs, paroxetine (Ballenger et al 1998b,
Lecrubier and Judge 1997), fluvoxamine (Den Boer 1998),
citalopram (Wade 1997), fluoxetine (Michelson et al
1998), and sertraline (Pohl et al 1998), have been shown to
be effective in well-controlled trials with approximately
equal efficacy, although comparison trials are generally
lacking.
Side effects are the principal difference between the
medications, with more significant side effects in the
TCAs and MAOIs and greater tolerability in the BZs and
SSRIs. The SSRIs and BZs are also safer in overdose.
Although effective and well tolerated in short-term use,
Treatment of Anxiety Disorders in Adults
the BZs are associated with withdrawal symptoms, espe-
cially if not tapered slowly, and do carry some risk of
abuse in individuals who abuse alcohol or opiates. Al-
though the MAOIs are excellent therapeutic agents, par-
ticularly in depressed patients with PD, their need for
dietary restriction and the risk for hypertensive reactions
limit their use (Laird and Benefield 1995). The recent
work with reversible MAOIs (moclobemide and brofaro-
mine) have shown some promise (Jefferson 1997; Priest et
al 1995), but development of brofaromine has been dis-
continued, and moclobemide is not available in the United
States. The antidepressant nefazodone in open trials
(DeMartinis et al 1996) and an unpublished multicenter
trial has been shown to be effective and well tolerated.
Psychotherapeutic Treatments
A large number of studies have demonstrated the effec-
tiveness of exposure-based treatments of PD with agora-
phobia, showing improvement rates of 58 – 83% and pan-
ic-free status of 74% (Ballenger et al 1997). Applied
relaxation is also effective, although probably somewhat
less than in vivo exposure (Oest et al 1993). Researchers
have begun to generate a rapidly increasing body of
evidence supporting combinations of exposure-based
treatments and cognitive-behavioral therapy (CBT) in-
volving education about the disorder, breathing retraining,
cognitive restructuring, exposure to physical symptoms of
PAs (interoceptive exposure), and exposure in vivo (Bal-
lenger et al 1997; Chambless and Gillis 1993; Margraf et
al 1993). These treatments are based on theories empha-
sizing the catastrophic misinterpretation of physical symp-
toms and the “fear of fear cycle” in panic patients (Barlow
1986; 1988; Clark et al 1986). The treatments are well
accepted, with perhaps the best known in the United States
being Panic Control Therapy (PCT) (Barlow et al 1989;
Ballenger et al 1997).
Recent trials of CBT in panic have observed panic-free
rates of 71– 87%, averaging 83% in short-term trials
(Barlow et al 1989; Clark et al 1994; Margraf et al 1993).
Short-term gains are generally maintained even after
therapy is discontinued, although symptom levels clearly
wax and wane, and “booster sessions” are often helpful
(Brown and Barlow 1995). In a 2-year cross-sectional
follow-up, 80% of patients remained panic-free (Craske et
al 1991). This low relapse rate suggests a potential
advantage of CBT over medication treatments. It also
appears that CBT can augment medication responses
(Hegel et al 1994; Speigel et al 1994), and some studies
demonstrate that patients who are resistant to medication
subsequently respond to treatment with CBT (Pollack et al
1994).
Meta-analyses suggest that CBT is certainly as effective
BIOL PSYCHIATRY 1581
1999;46:1579 –1594
as, if not more effective, than pharmacotherapy (Cham-
bless and Gillis 1993; Clum et al 1993; Van Balkom et al
1997). There is also evidence that the combination of the
two is probably even more effective (Ballenger et al 1997;
Mattick et al 1990; Mavissakalian and Michelsen 1986;
Telch et al 1985; Van Balkom et al 1997).
In the most recent and best designed controlled multi-
center trial, however, the combination provided little
added benefit, perhaps because imipramine and CBT both
performed so well on their own (Barlow et al 1998). In this
11-week acute trial with a 6-month follow-up, CBT,
imipramine, and a combination of the two were compared.
CBT and imipramine performed equally well at 11 weeks
and 6 months, although responders to imipramine tended
to have a more robust response than CBT responders.
There was a nonsignificant trend for the combination of
CBT and imipramine to be more effective. Consistent with
other literature at follow-up, more imipramine patients had
relapsed 6 months after ending treatment.
Although traditional psychotherapy for PD has been
generally ineffective, focal psychodynamic therapy re-
cently has been demonstrated to be effective in clinical
trials (Milrod 1997).
Discussion
Most experts would agree that the treatment of PD with
pharmacotherapy or a CBT approach employing a combi-
nation of exposure and cognitive therapy are roughly
comparable in efficacy (Ballenger et al 1998a; Barlow et
al 1998). Not surprisingly, most cognitive or behavioral
therapists prefer a CBT-type approach, and most psychi-
atrists prefer a pharmacotherapy approach combined with
some elements of education and exposure. Treatment
choices are frequently made by patient preference or
availability of trained therapists, however. Because thera-
pists trained in CBT for PD are not widely available,
recent work has investigated whether other clinicians
without specific training can learn to apply this technique.
In one recent trial, pharmacologically oriented therapists
learned to be effective CBT therapists (Barlow and Leh-
man 1996; Welkowitz et al 1991). Also, recent efforts to
transport these treatments into routine practice have been
successful (Martinsen et al 1998) and have shown to be
less expensive in a group format than pharmacotherapy for
PD (Otto et al 1997).
An important issue that has been underemphasized but
is central in evaluating the treatment response to PD (and
to all of the anxiety disorders) is that not all patients, not
even the majority, completely recover with either pharma-
cotherapy or psychotherapy. For both types of treatment,
only 25– 45% of patients could be considered fully recov-
ered. Despite the excellent progress made in the last 15–20
1582 BIOL PSYCHIATRY
1999;46:1579 –1594
years, improvements in treatments to increase cure rates
are badly needed.
Social Phobia (SP)
Pharmacotherapy
Despite its high prevalence (5– 8% current, 10 –13% life-
time), social phobia (SP) is still widely undiagnosed: Only
2% of patients with SP are diagnosed (Ballenger et al
1998b). The generalized form of SP involving multiple
situations is now recognized to be the most debilitating
form. This review predominantly refers to the generalized
form of SP, rather than the less serious specific form.
Pharmacologic treatments of SP have paralleled those
of PD in many ways. There were three early controlled
trials (Gelernter et al 1991; Liebowitz et al 1992; Versiani
et al 1992) in which phenelzine was found to be quite
effective, with 64% of patients obtaining clinically signif-
icant responses, which increased when treatment was
extended to 4 months.
In a comparison between phenelzine and moclobemide,
phenelzine appeared roughly equivalent but appeared to
work faster (Versiani et al 1992). By week 16, 70% of the
phenelzine patients versus 54% of moclobemide patients
were nearly asymptomatic, although moclobemide was
better tolerated. In the Gelernter (1991) trial, phenelzine
was slightly better than alprazolam in terms of efficacy.
As mentioned, reversible MAOIs (RIMAs) have been
studied recently, although brofaromine is no longer under
development. Brofaromine was promising and roughly
comparable to moclobemide, with response rates of 77%
(Fahlen et al 1995) and 80% (Van Vliet et al 1992). In two
moclobemide trials, one half to two-thirds of patients
attained marked or moderate responses (1 or 2 on CGI) in
dosages ranging from 600 to 800 mg q.d. (Bisserbe et al
1994; Katschnig et al 1997; Versiani et al 1992).
The BZ clonazepam was also shown to be effective in
one trial, with 78% of patients responding to an average
dosage of 2.4 mg q.d. (Davidson et al 1991, 1993). Almost
85% of patients had some response, with 50% having a
marked response and 50% having a moderate one. Buspi-
rone has been shown to be effective as a primary treatment
in two-thirds of patients in early trials (Schneier et al 1993;
Munjack et al 1991; Van Ameringen et al 1993) and as an
augmenting agent with SSRIs (Van Ameringen et al
1996). One controlled trial failed to find significant
differences between buspirone and placebo (Van Vliet et
al 1997). In initial trials, venlafaxine has been shown to be
effective with 50 –70% of patients responding (Kelsey
1995).
Certainly the greatest amount of carefully controlled
data is with the recent paroxetine studies (Stein et al 1998).
In multicentered, double-blinded, placebo-controlled, 12-
J.C. Ballenger
week trials of severely symptomatic patients with social
phobia, 55% of patients had a marked or moderate
response at a mean dosage of 36.6 mg q.d. Scores on the
Liebowitz Social Anxiety Scale (LSAS) fell ⬇40% on
paroxetine (30.5 points on the LSAS). Differences were
observed in the second week and throughout the remainder
of the trial.
Other controlled trials of the other SSRIs include
fluvoxamine (Goodman et al 1989; Van Vliet et al 1994),
sertraline (Katzelnick et al 1995), fluoxetine (Van Am-
eringen et al 1993), and nefazodone (Van Ameringen et al
1999). In these trials, the clinically significant response
rates of patients were in the 42–77% range.
Psychological Treatments
As with PD, the psychological treatment of SP shown to
be effective is CBT (which involves exposure), cognitive
restructuring, and, in some cases, social skills training.
Exposure involves a confrontation with the feared situa-
tion in real life (in vivo), in imagination, or in role-playing
situations in therapy. Cognitive restructuring attempts to
change the patient’s interpretation of the feared situations
and the outcomes he or she thinks represent failures.
Social skills training tends to improve deficient social
skills and utilizes modeling of appropriate behavior, be-
havioral rehearsal, feedback, and homework (Turner et al
1994).
Combined exposure and CBT has been most successful,
particularly in a group setting (CBGT) supplemented by in
vivo (homework) exposures. In this context, 81% of
patients had clinically significant improvement, which was
maintained at follow-up 5.5 years later (Heimberg et al
1993). Long-term maintenance has been observed in
multiple studies (Heimberg et al 1993, 1998; Wlazlo et al
1990).
It remains controversial whether cognitive restructuring,
combined with exposure, is more effective than exposure
alone. Some studies suggest it is, and others do not (Juster
and Heimberg 1995; Mattick and Peters 1988; Shear and
Beidel 1998; Taylor et al 1996). It is clear that exposure is
a major component of treatment (Ballenger et al 1997); it
is less clear which cognitive components are important
additions. There is some evidence that a combination is
better, but evidence is mixed (Mersch 1995; Shear and
Beidel 1998; Taylor et al 1997). It is also not yet known
how many sessions are needed or for how long.
Turner and colleagues have developed social effective-
ness training (SET) that couples individual exposure with
direct social training. Training efforts involve understand-
ing the context of the social environment and utilizing
flexibility exercises to emphasize that there are many ways
to socially interact (e.g., how to start a conversation)
(Turner et al 1994).
Treatment of Anxiety Disorders in Adults
In an attempt to develop a cost-effective and more
widely available treatment, Marks has developed a self-
help approach, which employs daily exposure supple-
mented by tapes and diaries (Marks 1995).
Comparisons between Medications and
Psychotherapy
Recent trials suggest that the two approaches are roughly
comparable. One study compared CBGT and clonazepam
and found no significant difference between the two
treatments, although there was greater improvement on
patient-rated scales with clonazepam (Otto et al 1997). In
the most carefully performed trial, CBT in a group format
(CBGT) was compared to phenelzine and to the combina-
tion for 12 weeks (Heimberg et al 1998). At 12 weeks,
both conditions were approximately equal and signifi-
cantly better than pill placebo. Three-fourths of the pa-
tients responded to the two active conditions (vs. one third
on the control). The onset of action with phenelzine was
more rapid but involved more relapses after discontinua-
tion of phenelzine than with CBGT. Interestingly, the
supportive psychotherapy cell did not perform as well as
the placebo.
Relapse
In most studies, relapse after discontinuation of medica-
tions has been relatively high, ranging from one third to
three-fourths of patients (Liebowitz et al 1992; Stein et al
1996; Versiani et al 1992, 1997), which suggests that
patients should probably be treated for at least 6 months
after improvement. As with CBT in PD, maintenance of
gains and low relapse rates were observed (Heimberg et al
1993, 1998; Juster and Heimberg 1995; Wlazlo et al
1990). Recent studies suggest that medications may be
discontinued while maintaining improvements (Sutherland
et al 1996), although this requires replication.
Discussion
As in PD, evidence suggests that both pharmacotherapy
and CBT are approximately equally effective (Ballenger et
al 1998c). The choice of initial treatment is again domi-
nated by patient preference, availability of effective treat-
ment, and patient characteristics (e.g., whether patient is in
childbearing years). SP patients respond to an initial
course of treatment with continued improvement over
time. Patients treated with medication tend to improve
over the first year on medication, but there is a significant
chance of relapse if the medications are discontinued. One
of the clear advantages of effective CBT treatment is a
reduced need for continued treatment and a lower risk of
relapse. Most experts agree that the SSRIs are the first line
BIOL PSYCHIATRY 1583
1999;46:1579 –1594
of pharmacologic treatment in SP. This is based on
comparable efficacy and greater tolerability and safety of
the SSRIs when compared to other medications.
SP is associated with significant morbidity with 22%
receiving public assistance and 50% being moderately
disabled in educational and occupational areas. Successful
treatment does reverse these disabilities. Eighty percent of
SP patients are comorbid with other syndromes including
depression and substance abuse (Schneier et al 1989). It is
important that effective treatments either improve or not
complicate these frequently present comorbid conditions.
Depression and substance abuse comorbidity again argues
for use of the SSRI antidepressants rather than the MAOIs
or BZs.
Controlled data suggest that medication and CBT
treatments of SP are roughly equivalent, although there
is a lower relapse rate with CBT. Lack of available,
well-trained CBT therapists presents problems for pa-
tients, which have not yet been solved. Studies that
explore the “portability” of CBT treatment of SP
beyond centers with trained CBT therapists are not yet
available. As mentioned, the manual-driven, self-help
treatment program developed by Marks is potentially an
important step in this area.
Generalized Anxiety Disorder (GAD)
There are literally hundreds of studies documenting that
the BZs are more effective than placebo in GAD (Green-
blatt and Shader 1974a; 1974b; Greenblatt et al 1983a,
1983b). Results generally show moderate or marked im-
provement in 65–75% of patients. Forty percent of patients
have a moderate response, and 35% have a marked
response, essentially returning to a normal range of anxi-
ety (Sussman 1987; Uhlenhuth et al 1998). Most improve-
ment with the BZs occurs within the first 6 weeks. In
long-term use, tolerance to side effects does occur, but
tolerance to the anxiolytic effect of the BZs does not
appear.
Because as many as 50% of patients do not relapse
when BZs are discontinued after 6 weeks (Rickels et al
1983, 1993), a reasonable practice is to taper and discon-
tinue these after 6 weeks of treatment to identify who can
discontinue and who needs to rebegin treatment to manage
their anxiety. In those that need long-term treatment (6
months or longer), there is a high relapse rate when
medication is discontinued, and therefore chronic treat-
ment is appropriate for many patients (Rickels 1986).
It is prudent to reduce the dose of BZs to the lowest
possible effective dose and to use BZs as needed (p.r.n.)
whenever possible. Most patients without a history of
substance abuse treatment do not escalate the dose or
abuse the BZs in chronic use (Bowden and Fisher 1980;
1584 BIOL PSYCHIATRY
1999;46:1579 –1594
Ciraulo et al 1988; Hollister et al 1981; Jaffe et al 1983;
Sussman 1987). When abuse has been observed, it has
been primarily in alcoholics or opiate abusers, either as a
substitute drug of abuse or to self-medicate or regulate
withdrawal symptoms (Busto et al 1983; Ciraulo et al
1988; Smith 1988). The primary difficulty with the BZs is
the withdrawal reactions when they are discontinued too
rapidly; nonetheless, withdrawal difficulties were not rec-
ognized as significant problems until the introduction of
the recent high-potency BZs such as alprazolam and
triazolam, particularly in the treatment of panic disorder.
There is little difference in the BZs beyond price and
patient preference (Ballenger 1995). Some BZs like diaz-
epam and chlordiazepoxide are slowly metabolized and
have multiple active metabolites and long half-lives. These
BZs have the advantages of fewer intradose symptom
breakthroughs, less concern if one forgets a dose, and
can be tapered more rapidly without withdrawal symp-
toms. Because diazepam has been the principal BZ
abused over the years, the modern high-potency BZ,
clonazepam, is preferred by many clinicians because of
its longer half-life.
Oxazepam and lorazepam have a more rapid metabo-
lism (shorter half-lives) and no active metabolites. There-
fore, they are safer to use in patients with liver disease and
elderly patients who have slower metabolism of BZs.
Also, their shorter duration of action makes them better
suited for certain patients (e.g., when only a short period of
anxiolysis is needed).
It does appear that the more recently developed BZs like
alprazolam, triazolam, midazolam, or even clonazepam
are more potent anxiolytics, which has led them to be more
popular in the treatment of PD. With higher doses,
however, other BZs such as diazepam and lorazepam are
also effective.
Despite evidence that the BZs are probably underuti-
lized (Marks 1983) and that reports of widespread abuse
are unfounded, the media has generally painted them in a
negative light. The negative attitudes toward the BZs exist
in patients and physicians alike. In a large 1979 commu-
nity survey of 3161 individuals, more than 50% of
individuals who had taken and benefited from BZs had
negative attitudes toward them. These attitudes seemed to
stem from feelings that taking BZs prevented people from
“working on their problems” or were a sign of weakness
(Mellinger et al 1984).
For this reason, and because of problems with with-
drawal symptoms and the high prevalence of comorbid
depression, recent attention has focused on antidepressants
as potential treatment for GAD. There is promising evi-
dence that the TCAs imipramine, trazodone, desipramine,
amitriptyline, and doxepin are all effective in the treatment
of GAD (Hoehn-Saric et al 1988; Johnstone et al 1980;
J.C. Ballenger
Kahn et al 1981, 1986; Liebowitz et al 1988; Rickels et al
1993). In these trials, the antidepressants surprisingly have
been observed to be equal or even superior in efficacy to
the BZs in the treatment of GAD with the added benefit
that they were superior in reducing depressive symptoms
(Hoehn-Saric et al 1988; Rickels et al 1993).
Buspirone
The first pharmacologic treatment for GAD beyond the
BZs was the azapirone buspirone. It has been shown to be
just as effective as BZs in GAD multiple studies (Kasten-
holtz 1984; Rickels et al 1982; Sussman 1987). Buspirone
has gained considerable popularity because it is not
sedating like the BZs, does not cause psychomotor impair-
ment or withdrawal symptoms, and does not interact with
alcohol or have abuse potential. Buspirone is given in
divided doses with an average daily dosage of 20 –30 mg
q.d. (range 20 – 60 mg q.d.).
In contrast to the almost immediate effects of the BZs,
buspirone’s onset of action generally does not occur for 2
weeks and in some patients only after 3 to 6 weeks
(Sussman 1987). Also, patients who have responded to
BZs in the past appear to not respond as well to buspirone
(Sussman 1987). As experience has accumulated, enthu-
siasm has waned somewhat, primarily because of the slow
onset of action and concerns about its level of potency.
Antidepressants
The first trial of an SSRI compared paroxetine to the TCA
imipramine and a metabolite of diazepam, 2-chlordes-
methyldiazepam (CDZ), in an 8-week trial (Rocca et al
1997). All three drugs were effective in more than 60% of
patients. The percentage of patients who had a moderate or
marked response (CGI 1 or 2) was 68% on paroxetine,
67% on imipramine, and 60% on CDZ. Dosages were 20
mg q.d. for paroxetine, imipramine 75 ⫾ 16 mg q.d., and
4.2 ⫾ 1.1 q.d. for 2-chlordesmethyldiazepam. There is
also recent open data suggesting nefazodone is effective in
GAD (Hedges et al 1996). These trials with the antide-
pressants are all single trials and are in need of replication.
Certainly the most exciting recent development in the
pharmacotherapy of GAD has been the well-controlled,
comprehensive trials with venlafaxine. In five placebo-
controlled 8-week trials, venlafaxine has demonstrated
efficacy significantly greater than placebo in all five of
these trials. These studies represent the most compre-
hensive examination of the use of an antidepressant in
the treatment of GAD patients without accompanying
depression.
Venlafaxine effects were observed after one week to be
greater than placebo, and these improvements were main-
tained throughout the remainder of the trials (Haskins et al
Treatment of Anxiety Disorders in Adults
1999a). Dosages were 75, 150, and 225 mg q.d. In a
comparison trial with buspirone, efficacy of venlafaxine
was significantly greater than buspirone on the primary
outcome measure (Derivan et al 1997).
In the first trial evaluating long-term treatment of GAD
with venlafaxine, a large 6-month trial demonstrated
effects significantly greater than placebo, beginning at
week 1 and continuing throughout the 6-month trial.
Although most of the improvement occurred in the first 4
weeks on venlafaxine, patients continued to improve over
the six-month period (Haskins et al 1998, 1999b). At 6
months, 70% of the patients had reached a 40% improve-
ment on HAM-A criteria. In a second large trial, 80% of
the patients on venlafaxine experienced a 50% decrease in
their HAM-A with dosages of 35.5, 75, and 150 mg q.d.
Dosages of 75–250 mg q.d. have been studied, averaging
175 mg q.d.
Current trials have not established a definitive dosage of
venlafaxine for the treatment of GAD, and positive results
have been observed at dosages as low as 37.5 mg q.d.
There is a trend in the data suggesting that 75–150 mg q.d.
is probably the most appropriate dosage range, however.
Side effects are relatively mild and include nausea, dry
mouth, and somnolence. These are principally seen at the
initiation of treatment and clear over time.
Psychotherapy
Until recently, the psychotherapeutic approaches to
GAD have been nonspecific and consisted generally of
supportive or traditional psychodynamic approaches,
both of which seem to be reasonably effective. Rigorous
controlled data are not available for these modalities,
however.
More recently, the techniques of CBT and applied
relaxation shown to be effective in the other anxiety
disorders have also been extended to GAD patients.
Unlike PD patients who have a fear of symptoms that to
them seem to indicate physical danger and SP patients
who have fears of social humiliation, GAD patients have
a broader pattern of worries. Similar to CBT for these
other disorders, CBT for GAD generally involves explo-
ration of irrational anxiety-producing thoughts and then
attempts to modify them with positive thoughts or by
challenging the irrationality of these thoughts. This ap-
proach also frequently involves elements of in vivo expo-
sure to thoughts and worries coupled with relaxation.
In almost all controlled trials to date, CBT has been
shown to be significantly more effective than pill placebo
or wait-list control. Although the studies generally do not
use the same outcome measure as pharmacologic trials, the
effect sizes of psychotherapy are large and clearly docu-
ment the effectiveness of this treatment (Chambless and
BIOL PSYCHIATRY 1585
1999;46:1579 –1594
Gillis 1993). Similar to the psychotherapy of the other
conditions, gains from CBT treatment of GAD have been
maintained and extended for 6 –24 months posttreatment
(Barlow et al 1984; Borkovec and Matthews 1988; Butler
et al 1991).
Although it is clear that CBT, applied relaxation (AR)
treatments (Oest 1987), and behavior therapy are all
effective to varying degrees, the literature to date is
inconclusive as to the exact effects of each component,
and this question is currently under study (Borkovec and
Costello 1993). In a recent trial comparing CBT and AR to
nondirective therapy (ND), CBT and AR were equivalent
but significantly superior to the ND treatment. Follow-up
of the gains of CBT and AR were maintained with some
losses with ND, suggesting that the elements of cognitive
therapy, exposure, and relaxation are important. For both
CBT and AR, 75– 85% of patients had moderate or better
responses after treatment and at follow-up twelve months
later. Only one-third of the AR and half of the CBT
patients had excellent responses, however (Borkovec and
Costello 1993).
Discussion
The pharmacotherapy and psychotherapy of GAD appear
roughly equal in efficacy, although there are fewer data
supporting this conclusion as there are in PD and SP. It is
not clear how the new CBT treatments will work in
broader settings, how much treatment is needed, and
whether they will work with general populations and
nonexpert CBT therapists. Less than 50% of patients have
an excellent response, so it is clear that improvements in
treatment are badly needed.
Obsessive-Compulsive Disorder (OCD)
The first medication demonstrated to be effective in OCD
was chlorimipramine (150 –250 mg q.d.) with 40% (vs.
4% for placebo) having a clinically significant decrease in
symptoms (Chlorimiprimine Collaborative Study Group
1991). Subsequently, all of the SSRIs have been shown to
be effective, including fluvoxamine (100 –300 mg q.d.),
fluoxetine (20 – 80 mg q.d.), paroxetine (40 – 60 mg q.d.),
sertraline (50 –200 mg q.d.), and citalopram (20 – 60 mg
q.d.). Most recent controlled trials find that ⬇50% of
patients experience a 25% or 35% drop in scale scores of
OCD, primarily utilizing the Yale-Brown Obsessive Com-
pulsive Scale (Y-BOCS). A drop of 25–35% on the
Y-BOCS is clinically significant because the Y-BOCS is
not linear.
Relative efficacy between the SSRIs has been difficult
to determine. One meta-analysis suggested greater effi-
cacy for chlorimipramine (CMI) (Greist et al 1995);
1586 BIOL PSYCHIATRY
1999;46:1579 –1594
however, these trials were performed over a 7–10 year
time period during which placebo rates rose significantly,
making any conclusion suspect. In fact, in several head-
to-head trials, CMI was found to have equal efficacy to
fluoxetine (Piggot et al 1990), paroxetine (Zohar and
Judge 1996), with unpublished trials finding equal or
better efficacy of paroxetine to CMI and sertraline to CMI.
There was no observed difference in a trial comparing
fluvoxamine, paroxetine, and citalopram (Mundo et al
1997). A more recent meta-analysis generally failed to
find any significant difference between the SSRIs, al-
though it again suggested some advantage for CMI.
This meta-analysis involved many of the trials men-
tioned above and has the same problem in interpretation
(Kobak 1998).
Dosages of these medicines have often been described
as being significantly higher than antidepressant dosages
(e.g., 60 – 80 mg q.d. of fluoxetine); however, in large
carefully controlled trials, there has been no observed
significant difference between response to higher and
lower dosages for the SSRIs (e.g., 50 and 200 mg q.d. of
sertraline). This clinical impression may well relate to the
slow onset of effectiveness with many patients taking 10
to 12 weeks to improve, during which time physicians
continue to raise the patients’ doses, mistakenly thinking it
was the increased dose, not time, that was responsible for
improvement.
Many patients will not respond to the first SSRI but will
respond to another antiobsessional agent. Therefore, se-
quential trials are frequently required, which easily can
take up to a year to accomplish.
Limited available evidence suggests that when effective
pharmacotherapy is discontinued, most patients (90%) do
relapse (Pato et al 1988). Therefore, current practice is to
continue effective pharmacotherapy for at least 1–2 years
or indefinitely. One 44-week trial demonstrated that ther-
apy gains with sertraline are maintained with continued
medication (Greist et al 1992); another with paroxetine
demonstrated continued efficacy for 12 months in the
majority of patients (Steiner 1995).
Although as many as 70% of patients experience clin-
ically significant improvement, most trials demonstrate
that only about 10% of patients with OCD actually
experience a remission of their symptoms. For that reason,
attempts to augment or improve the average response are
routine. There is no agent that is routinely effective as an
augmenting agent, although there is some support for
clonazepam, clonidine, trazodone, fenfluramine, trypto-
phan, and pindolol (Jenike and Rauch 1994). There is clear
evidence of benefit for traditional neuroleptics and more
recently the atypical neuroleptics (e.g., risperidone), prin-
cipally in the patients with OCD who have comorbid tic
disorders (McDougle et al 1994).
J.C. Ballenger
Behavior Therapy
Prolonged exposure in vivo coupled with response (or
ritual) prevention are the critical elements of modern
effective behavior therapy of OCD. Exposure involves
prolonged confrontation with stimuli that normally pro-
voke obsessional thoughts or compulsive behaviors. Pa-
tients agree not engage in their usual ritualistic behavior or
cognitions and to remain in the situation for 60 –90 min
until their discomfort wanes. Homework extensions are
also generally utilized outside the therapist contact.
Success rates vary (50 – 80%) (Hand 1995). Some stud-
ies suggest that up to 90% of patients have achieved
clinically significant benefits from behavior therapy (Gre-
ist 1994). Generally, 70 – 80% maintain their acute gains at
one-year follow-up (Foa et al 1985).
Intensive behavior therapy over 3 weeks has produced
promising results, even in a very symptomatic group. Foa
and colleagues (1985) have reported that 51% of patients
experience at least a 70% drop in symptoms, with 35%
experiencing a 31– 69% reduction. These gains are gener-
ally (75%) maintained at 12-month follow-up. Most ex-
perts agree that massed sessions of exposure and response
prevention (two or three 60-minute sessions per week for
several weeks) are significantly more effective (Foa et al
1985). It is obviously difficult to arrange such extensive
exposure in an outpatient setting, however. Recent results
in one trial suggest that providing this treatment in a group
setting may be effective and more cost-effective (Fals-
Stewart et al 1993).
Relapse prevention programs have proved beneficial in
maintaining the gains of acute treatment (Hiss et al 1994).
Comparisons
In a meta-analysis comparing behavioral treatments and
SSRIs in OCD, which involved 77 studies in 4641
patients, effect sizes for behavior therapy were not signif-
icantly different from those of the SSRIs; however, clini-
cal opinion suggests that behavior therapy may produce
better and longer lasting results in those patients who can
complete the behavior therapy. There were also no signif-
icant differences between the SSRIs, although CMI ap-
peared to have some increased efficacy but not sufficient
enough to warrant favoring it over other SSRIs given its
side-effect spectrum and the dangers associated with use
in OD (Kobak et al 1997). The choice between these two
modalities is often dominated by the relatively limited
availability of behavioral therapists and by patient prefer-
ence. Up to 25% of individuals refuse behavioral therapy,
but likewise many others prefer a nonpharmacological
treatment. Recent efforts to develop a computer program,
which offers behavior therapy via 12 computer-controlled
interactive phone calls, are promising. Over two-thirds of
Treatment of Anxiety Disorders in Adults
patients involved in this program improved significantly,
and this approach could make effective behavior therapy
more easily available (Marks et al 1998).
In routine practice, some combination of pharmacother-
apy and behavioral therapy is often employed. Available
research is not yet clear on potential benefits of combined
medication and behavior therapy, either on response or on
relapse prevention. Nonetheless, most OCD patients on
medication should certainly be encouraged to practice
exposure-and-response prevention.
Neurosurgical Treatments
For patients who have failed all pharmacologic and be-
havioral treatments (and probably ECT), consideration
should be given to neurosurgical treatments of OCD
(Beale et al 1995; Maletzky et al 1994). Various proce-
dures in intractable cases have been surprisingly success-
ful, with 25–30% of patients experiencing significant
benefit without undue side effects. Certainly the most
common current neurosurgical procedure is cingulotomy,
either performed via craniotomy or with the considerably
less involved gamma-knife procedure. In the most recent
reported trial in the United States, 18 patients underwent
cingulotomy. At follow-up 2 years later, 28% met conser-
vative criteria as responders, with 17% more meeting
criteria as partial responders (Baer et al 1995). Although
neurosurgery is certainly an extreme measure and reserved
for a small percentage of patients, it should be considered
in such cases.
Posttraumatic Stress Disorder (PTSD)
PTSD is a complex syndrome occurring after one or more
traumatic events and involves multiple anxiety symptoms,
including flashbacks, emotional numbing, avoidance of
the reminders of the event, and so forth. This disorder was
first recognized after military combat but is now seen
frequently after rape, assault, and accidents. Although
there is no established pharmacotherapy for PTSD, there
are multiple medications that seem to be effective in
reducing these symptoms, particularly flashbacks, phobic
avoidance, depression, anxiety, startle reaction, impulsiv-
ity, and hypervigilance.
TCAs have been shown to be helpful in controlled trials.
Imipramine (200 –300 mg q.d.) decreased intrusive
thoughts, nightmares, and flashbacks with no effect on
numbing or avoidance. Amitriptyline (200 –300 mg q.d.)
has also been shown to reduce avoidance and anxiety
(Davidson et al 1993; Frank et al 1988). Nefazodone
(350 – 450 mg q.d.) has been shown to significantly
improve most symptoms, including intrusive thoughts,
avoidant behaviors, emotional numbing, sleep, depression,
and anger (Davidson et al 1998; Hertzberg et al 1998).
BIOL PSYCHIATRY 1587
1999;46:1579 –1594
MAOIs have also been shown to be effective (phenel-
zine 45–75 mg q.d.) in reducing intrusive thoughts and
flashbacks (Frank et al 1988), but other trials have failed
to observe positive effects (Shestatsky et al 1998). In
addition, the usual dietary and medication restrictions of
the MAOIs are more problematic in this patient group,
given the high incidence of substance abuse. Early trials
with combat veterans suggest the reversible MAOI mo-
clobemide appears promising (Neal et al 1997).
The SSRIs have been observed to be helpful in open
studies, especially with fluoxetine up to 80 mg q.d.
(McDougle et al 1991). This has been confirmed in a
controlled trial of veteran and civilian trauma victims
(Van der Kilk 1994). Approximately two-thirds of
patients experienced decreases in the core symptoms of
PTSD including avoidance, intrusive images, and pho-
bic avoidance.
The anticonvulsant carbamazepine (CBZ) has been
shown to decrease flashbacks, hyperarousal, and impul-
sivity (Davidson et al 1992). Valproic acid (VPA) may be
helpful as well (Keck et al 1992).
Empirical evidence indicates that ⬇70% of patients
benefit from some form of pharmacotherapy (Bleich et al
1986) with moderate to marked effects (Davidson et al
1997). Increasing recent evidence suggests that the anti-
depressants are most effective and that the SSRIs probably
have the greatest efficacy of any single class of medica-
tions, particularly against avoidance and numbing. BZs
such as clonazepam and buspirone may be particularly
helpful agents in suppressing hyperarousal symptoms.
Lithium, beta-blockers, and CBZ may be particularly
helpful in patients with poor impulse control (Sutherland
and Davidson 1994).
Psychotherapy
The psychotherapeutic approaches to PTSD have varied
and are generally different for victims of civilian and
military trauma. Evidence is also limited from controlled
clinical trials.
Experience and available evidence in the scientific
literature underscore how difficult it is to involve recent
victims of rape with any systematic and prolonged contact
with therapists (Kilpatrick et al 1982), presumably because
of general difficulties of severe symptomatology, as well
as the anxiety engendered by having to relate to therapists.
Kilpatrick and his colleagues (1982) have developed a
brief treatment based on evidence that rape victims have
difficulty conceptualizing and talking about their rape
experience and therefore lack information about problems
that are commonly observed and have difficulty coping
with these problems. Treatment involves talking to a peer
counselor about the rape experience, presentation of con-
1588 BIOL PSYCHIATRY
1999;46:1579 –1594
siderable material about the common misinformation
about rape, and conceptualization of the experience in
learning various terms and anxiety-coping strategies such
as deep breathing and self-dialogue (Kilpatrick et al 1982).
This has evolved into what is now called stress inoculation
training presented in 20 sessions beginning with an edu-
cational phase, connecting the symptomatology via learn-
ing theory to the trauma. Patients are then taught skills to
fight fear in autonomic, behavioral, and cognitive spheres.
The other principal technique is prolonged exposure in
which the patient relates the traumatic event in detail and
then listens to the audiotape of her account as homework.
In vivo exposure to feared situations is also part of the
treatment (Foa et al 1991).
Both stress inoculation training and prolonged exposure
treatments of rape-related PTSD have been shown to be
effective (Foa et al 1991, 1997), and treatment gains are
maintained in short-term follow-up. Stress inoculation
training appears to be more effective, but prolonged
exposure outcome is superior in some trials at 3– 6
follow-ups.
Reviews of different behavioral/exposure-based treat-
ments have documented effectiveness in reducing core
symptoms of PTSD (Boudewyns and Hyer 1996; Frueh et
al 1995). Reviews of the available studies on behavioral
treatments have suggested that their effectiveness is
largely against positive symptoms of PTSD (e.g., intrusive
thoughts, nightmares, etc.; Blake 1993).
Psychodynamic therapies have emphasized the need of
victims of trauma to integrate the event into their life and
personality (Horowitz 1974) and to work through what the
trauma means for them, ultimately leading to exposure to
the original traumatic experience in a supportive environ-
ment. These have led to many derivative individual and
group therapies (Frueh et al 1995; Shalev et al 1996;
Sherman 1998; Soloman et al 1992); most effective
therapies start with the model developed by Horowitz.
A recent meta-analysis clearly documented the effec-
tiveness of behavioral, cognitive, and psychodynamic
therapies with maintenance of gains at follow-up (Sher-
man 1998). Based on 17 controlled trials, it suggested that
the treatment effects are moderate in size and that 43% of
patients improve to the point where they no longer meet
criteria for diagnosis. Recently, a manual-driven, office-
based treatment was shown to be effective and suggests a
cost-effective therapy that could be administered in rou-
tine settings (Hickling and Blanchard 1997).
Treatment of military PTSD is not as well developed
because there are relatively few controlled experiments
published. Probably the best studied treatment techniques
have involved exposure to combat-related stimuli. Al-
though the number of studies is limited, there is clear
evidence that properly executed exposure treatments are
J.C. Ballenger
effective in significantly reducing nightmares, intrusive
thoughts, and startle reactions. Effective flooding or im-
plosion treatments have even involved flights on Huey
helicopters (Scurfield et al 1992). Some exposure pro-
grams have failed (e.g., the Koach program), however, and
effective treatments must involve relevant stimuli and
sufficient time in exposure for reductions in anxiety to
occur (Avraham et al 1992; Frueh et al 1995). Efforts have
varied but have centered on supportive techniques, gener-
ally group settings in the VA system (Hammarberg and
Silver 1994). Some of these have involved various meth-
ods of reliving the experience coupled with attempts to
increase coping skills. Many programs have also involved
efforts to reintegrate the veteran into civilian life and
occupational retraining and efforts aimed at reduction of
self-injurious behavior, particularly substance abuse.
The Yale VA program has specifically aimed “First
Generation” programs at accessing and integrating the war
experience and reducing core PTSD symptoms. The “Sec-
ond Generation” programs are then aimed at reintegration
into family, work, and society (Johnson et al 1994). A
controversial new treatment has evolved called Eye Move-
ment Desensitization and Reprocessing (EMDR) (Silver et
al 1995). The procedure involves coupling rhythmic sac-
cadic eye movements to thinking about salient aspects of
the trauma. EMDR has been reported to be effective in just
one session (Shapiro 1989; Vaughn et al 1994). Careful
analysis of these early results cast doubt on the enthusi-
astic reports (Acierno et al 1994), however.
Conclusion
There has been a clear expansion and consolidation of the
empirical evidence for the treatment of the anxiety disor-
ders in adults, and there is now empirical support for
effective pharmacotherapy and effective psychotherapeu-
tic techniques (mostly CBT) for all five of the adult ADs.
Certainly, the evidence is strongest for PD and OCD. The
recent evidence established for effective treatments for SP
is strong but will need replication and further refinement.
Important recent psychopharmacologic evidence of the
effectiveness of venlafaxine and other antidepressants in
treatment of GAD will substantially change the way this
disorder will be treated. Currently, the least amount of
controlled data is for treatment of PTSD. There are
controlled studies for both treatments in PTSD, but the
current evidence is less definitive for both types of
treatment in this disorder.
It is almost surprising the extent to which the psycho-
pharmacologic and psychotherapeutic treatments of these
disorders have evolved in parallel and resemble each
other. For all of the disorders except GAD, the psycho-
pharmacologic treatment of choice has become the SSRI
Treatment of Anxiety Disorders in Adults
class of antidepressants. Even in GAD, antidepressants
including the SSRIs and venlafaxine are emerging as the
most effective treatments. This is a somewhat surprising
outcome and probably would not have been predicted a
decade ago. For the same type of treatment to be so
effective across these disorders can certainly lend support
to those who believe that the anxiety disorders are all on a
single continuum. It also will lend support to evidence
suggesting that serotonin is involved in at least the
reduction of anxiety if not the etiology of pathological
anxiety.
In a similar fashion, CBT’s success in all five disorders
makes a similar argument. The elements of exposure to
situations causing anxiety and cognitive restructuring
around the anxious thoughts involved seem to be effective
therapeutic elements for all these disorders. This, too,
raises the possibility that these disorders are along a
continuum of sorts or involve many of the same psycho-
logical mechanisms.
The modern treatments of these disorders have become
increasingly effective from an era 25 years ago when most
estimates were that 80% of patients did not significantly
benefit from the available treatment. Almost the opposite
is true today. Treatment for all five of the disorders results
in clinically significant improvement in the majority of
patients. The estimates across the disorders vary, but there
is considerable evidence that 60 – 80% of patients respond
to either psychopharmacologic treatments, CBT, or their
combination. This has led to considerable therapeutic
excitement over the last two decades. Treatment of the
anxiety disorders has become a legitimate subspecialty.
The field has developed to a point where it has been
demonstrated, again and again, that specific employment
of treatments, which have been shown empirically to be
effective, does, in fact, result in significantly greater
improvement.
This raises significant issues for the field. Now that
there are effective treatments for the anxiety disorders,
public education or dissemination of this knowledge has
become more critical. This is equally true for professional
education. Because most physicians are unaware of the
significant advances in the treatment of these disorders,
most patients with anxiety disorders are still receiving
nonspecific treatment. This is particularly true in general
medicine or primary care, where 80% of these patients
receive their treatment. Unfortunately, the anxiety disor-
ders continue to be poorly recognized and treated in
primary care settings.
In a similar fashion, there is now increased responsibil-
ity to make these treatments available to the general
public. Whereas the medication treatments are generally
widely available, the sophisticated CBT treatments of
these disorders are not. Although there are beginning
BIOL PSYCHIATRY 1589
1999;46:1579 –1594
efforts to deal with this problem by increasing the training
in CBT in postgraduate training programs, availability of
well-trained therapists remains a large issue. Also the
recent efforts to make these treatments more cost-effective
are important.
Despite the justifiable optimism in now having effective
treatments for these disorders, it is a sobering realization
that not all patients benefit, and few patients have a
response approximating a complete recovery. It is cer-
tainly true that as many as one-third of patients in
controlled trials do not receive any significant benefit from
available treatments. This is obviously a large percentage
but one certainly comparable to the limitations of treat-
ment in other medical disorders (heart disease, arthritis,
etc.). Nonetheless, it is a distressingly high percentage and
provides impetus to the field to develop increasingly
effective treatments. The same could be said for the
marked responders (i.e., it is disappointing that only
30 – 45% of patients have a marked response to treatment
with reductions of their anxiety down into the normal or
nonaffected range. Even that figure is too high for OCD
and PTSD, where a much smaller percentage of patients
achieve anything like remission. Progress in the past
several decades has been impressive but is far from
complete.
This work was presented at the scientific satellite conference, “The Role
of Biological and Psychological Factors on Early Development and Their
Impact on Adult Life,” that preceded the Anxiety Disorders Association
of America (ADAA) annual meeting, San Diego, March 1999. The
conference was jointly sponsored by the ADAA and the National
Institute of Mental Health through an unrestricted educational grant
provided by Wyeth-Ayerst Laboratories.
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