Turk J Med Sci
30 (2000) 167–171
Alprazolam and Cognitive Behavior Therapy in
Treatment of Panic Disorder
Received: August 17, 1999
Abstract: Panic is an often incapacitating and
were assessed at the beginning of treatment,
chronic disorder. Cognitive behaviour therapy
and then at weeks 4,8,12 and 16 by means
(CBT) and alprazolam have been shown to be
of self-monitoring. On the basis of HAM-D,
effective in the treatment of panic disorder.
HAM-A, anxiety level, and panic number, the
Patients who met the DSM-III-R criteria for
CBT and alprazolam groups showed a
panic disorder, were randomized and given
significant improvement at the end of
16 weeks of double-blind treatment with
treatment. When compared to each other, the
CBT (n=16), or alprazolam of up to 6
groups showed no significant differences at
mg/day (n=18). The 17-item HAM-D and
the end of the treatment. In the last month,
HAM-A scales were administered to all the
10/16 (62.5%) of the CBT patients and
1Department of Psychiatry, Faculty of Medicine,
subjects before and after treatment, which
11/18 (61.1%) of the alprazolam patients
Abant ?zzet Baysal University, Düzce, Bolu,
took place over 16 weeks, and the changes in
2Department of Psychiatry, Faculty of Medicine,
the scores were analyzed. The patients’
Key Words: Alprazolam, Cognitive behavior
Dicle University, Diyarbak?r-Turkey
anxiety levels and numbers of panic attacks
therapy, Panic disorder.
To our knowledge, few reports have compared the
Panic disorder is a common anxiety disorder
efficiency of both treatment in patients with panic
associated with a great deal of distress as well as marked
disorder. In view of the effectiveness of this CBT and of
social and occupational disability (1,2). Such patients are
alprazolam in panic disorder, the purpose of this study
over-represented with regard to the use of medical
was to evaluate the effectiveness of each treatment.
services, such as emergency room visits, the number of
visits to physicians and the use of psychotropic
Materials and Method
medications (3,4,5,). In addition, their rate of attempted
suicide has been reported to be either greater to that of
Subjects: Patients were drawn from patients
the general population or equal to that of patients
attending the psychiatry clinic. All had been given a
suffering from major depression (6,7,8).
diagnosis of panic disorder with mild or no agoraphobic
avoidance, using DSM-III-R criteria. Only patients with at
Clinical evidence suggests that cognitive-behaviour
least four panic attacks within a four-week period, or
therapy (CBT) is an effective treatment for panic. For
those experiencing one or more attacks followed by a
example, Gitlin et al. reported that 10 out of 11 patients
period of at least a month of persistent fear of another
receiving CBT were not panicking by the end of treatment
attack were included.
(9). Beck, Ost, Craske have also reported nearly total
elimination of panic in patients suffering from panic
The general exclusion criteria were as follows: age
disorder using either cognitive behavioral or behaviorally-
below 18 or above 65 years, current drug or alcohol
based relaxation treatments (10,11,12).
abuse/dependency, principal diagnosis of major
depression, and any signs of psychosis or organic brain
In the 1980s, a new class of benzodiazepines, the
syndrome. Finally, subjects were excluded if they had
triazolobenzodiazepines, became available. One member
begun taking benzodiazepines or antidepressants within
of that class, alprazolam, has been reported to be
the previous six months.
effective in the treatment of panic disorder (13,14).
Alprazolam and Cognitive Behavior Therapy in Treatment of Panic Disorder
At the onset of treatment, the subjects comprised 40
therapy, we helped the patients to identify and modify
patients with panic disorder.
their negative thoughts. In addition, the patients were
The patients were treated with either CBT or
encouraged to expose themselves to situations or
alprazolam for two months, and then followed for two
activities which they were avoiding. They were also
months without CBT and alprazolam.
encouraged to modify behaviours which occur once
symptoms have started and which maintain a patient’s
Measures: Clinical assessment measures consisting of
belief that certain symptoms are highly dangerous.
the Hamilton Anxiety Rating Scale (HAM-A) and the
Hamilton Rating Scale for Depression (HAM-D) were
administered to all subjects before and after treatment,
and the changes in the scores were analyzed.
Out of 40 initial patients, 34 patients completed the
A self-monitoring measure was administered at the
study, and 6 patients dropped out. A higher rate of drop
beginning of treatment and assessed at 4-week periods
out was observed in the CBT group than in the other
throughout treatment. Patients monitored their current
group. Two patients out of 20 (10%) dropped out of the
levels of anxiety on a 0-to-8-point visual analogue scale,
alprazolam group, while 4 out of 20 (20%) dropped out
four times a day (morning, afternoon, evening and
of the CBT group.
bedtime), stating whether or not they experienced panic
A t-test analysis on these dorp-out frequencies
(patients were instructed and trained to define and
showed no significant differences between the CBT and
differentiate a panic attack from episodes of generalized
alprazolam group (t=1.03,p=0.314).
anxiety). The data from the visual analogue scale served
to measure the anxiety level and panic number
Patients who dropped out of the study were
questioned about their reasons. Of the 4 patients who
Alprazolam treatment group: Patients received
dropped out of the CBT group, 2 developed intense panic
1mg doses of alprazolam (1 or 2 mg) up to four times
attacks in the 1st week of the treatment, causing them to
daily. Medication was gradually increased until the
drop out of the study. Two were unavailable for interview
maximum benefit was achieved or dose-limiting side
after the second week of treatment. The 2 subjects who
effects occurred. Patients began taking one tablet per day
dropped out of the alprazolam treatment group stated
(for two days) and then this was increased to two tablets
that they disliked the side effects of the medication in the
(for three days), three tablets (for four days), four tablets
1 st week of treatment (1 reported over-sedation, and 1
(for four days), five tablets (for four days), and then six
reported suicidal ideation).
tablets per day on day 18. When side effects were
reported, these increases in medication were slowed or
In the CBT group, 9 men (56%) and 7 women (43%)
the dose was reduced. Every effort was made to achieve
completed the study. The mean age was 30.81 years. In
a dosage of six tablets per day.
the alprazolam group, 6 men (44%) and 12 women
(56%) completed the study. The mean age was 31.44
Patients were given an explanation of their condition,
years. The mean age difference between the groups was
including what could be expected of the medication. No
not significant (F=0.574, df=32, t=-0.234, p>0.05).
other centrally active medications were administered
during the trial.
In the CBT group (16 patients), the mean score on the
Hamilton Depression Scale at week 0 was 12.06 (range,
At the beginning of the 9th week of treatment, the
2 to 45), with only 5 patients (31.2%) scoring values
psychiatrist began to taper the doses of alprazolam at a
above 14. In the alprazolam group (18 patients), the
rate no faster than one tablet every 3 days. The
mean score on the Hamilton Depression Scale at week 0
psychiatrist continued meeting patients until they had
was 10.83 (range, 2 to 40), with only 6 patients
stopped taking medication completely.
(33.3%) scoring in the range above 14.
CBT group: The treatment consisted of a 2-month
In the study intake, no statistical difference between
course of CBT. The patients received 8 individual sessions
the two groups in the average HAM-D and HAM-A scores
of CBT for panic disorder in weekly meetings. Exposure
were found using the Mann-Whitney test (z=-0.657,
plus cognitive restructuring were applied in the case of
p>0.528), (z=-0.346, p>0.746).
these patients. Treatment comprised a rationale and
education concerning panic disorder, the components of
In terms of HAM-D scores, the CBT and alprazolam
anxiety and emphasized exposure to somatic cues.
groups showed a statistically significant improvement on
Cognitive approaches were also included. In cognitive
the Wilcoxon signed rank test at the end of the 4 months,
A. ATAO?LU, M. ÖZKAN, H. TUTKUN, A. MARA?
and there was no difference between the groups on the
When the treatments were compared in terms of
Mann-Whitney test (Table 1).
anxiety level, it was found that most improvement
The scores on HAM-A were found to have decreased
occurred with alprazolam in the first month, and then
significantly at the end of the treatment in the cognitive-
with CBT in the third and fourth months. This is
behavior and alprazolam groups on the Wilcoxon signed
described in Table 2.
rank test. This is described in Table 1. The differences in
Both CBT and alprazolam significantly reduced panic
anxiety scores in both groups found at the end of the
frequency at the end of the treatment according to the
study were compared, but the decrease in anxiety scores
results of the Friedman test (x2=26.160, df=4,
was not found to be significant on the Mann-Whitney
p<0.0001), (x2=16.987, df=4, p<0.002). In the end-
test. This is described in Table 1.
point analysis, 11/18 (61.1%) of the alprazolam patients
In the CBT group, anxiety level (on the 0-8 scale)
and 10/16 (62.5%) of the CBT patients had no panic
from baseline to end point was compared using the
attacks in the last month. The number of panic attacks
Friedman test and the decrease in anxiety level was found
did not show any statistically significant differences
to be significant (x2=50.888, df=4, p<0.0001). Similarly,
between the two groups throughout the study (except in
in the alprazolam group the decrease in anxiety level was
the first month) on the Friedman test This is described in
found to be significant on the Friedman test (x2=30.499,
The difference in anxiety and depression scores in both groups.
Before treat. after treat. Before treat. After treat.
anxiety score anxiety score depression score depression score
Mean SD Mean SD Mean SD Mean SD
Anxiety levels reported
Cog. treatment group Alp. treatment group
by each group.
Number of panic
Cog. treatment group Alp. treatment group
Alprazolam and Cognitive Behavior Therapy in Treatment of Panic Disorder
had no signs of cardiac disease, the real effect of the
When a person is anxious, there are three different
avoidance was to prevent him from learning that the
components to his/her reaction: a physiological
symptoms he was experiencing were innocuous.
component (e.g., increased heart rate, sweating, muscle
In this study, as the patients were prevented from
tension), a behavioural component (e.g. avoidance,
avoiding such situations, their negative thoughts about
attempts to escape), and a cognitive component (negative
body sensations changed, and these changed body
thoughts, such as “I am going to collapse”, “I cannot
sensations changed their cognition of the disease.
cope”). The relative strength of these components varies
Panic attacks were eliminated in a very large
from person to person, but it is common for people to
percentage of patients (in the CBT group, 62.5%; in the
experience a physiological change, followed by a negative
alprazolam group, 61.1%). These findings are similar to
thought, which increases the physiological reaction,
reports of long-term clinical outcome studies testing CBT
producing a vicious circle. To break this vicious circle we
for panic disorder in which nearly 70% of patients were
encouraged the patients to focus on and to expose
found to be panic-free (12, 15). These findings indicate
themselves to the physiological reaction which they were
that CBT is an effective short-term treatment of panic
avoiding. It was also important to modify behaviours
disorder. Studies comparing the long-term treatment and
which occur once symptoms have started and which
short-term treatment of CBT in patients who have panic
maintain the patients’ belief that certain symptoms are
disorder are needed to facilitate decision-making with
relation to therapy.
Cognitive-behavioral approaches are thought to have
At the end of study, improvement in the anxiety and
an impact on panic and anxiety by affecting cognitive
depression scores of the two groups were observed. In
rather than somatic symptoms. In this study, however, we
the number of panic attacks and in the anxiety level
saw that patients’ somatic sensations were reduced and
significant differences favoring alprazolam over CBT were
we considered that this was related to cognitive change
observed in the first month of the study. In the patients’
concerning the disease in the patients. The cognitive
reported anxiety levels, significant differences favoring
model of panic states that individuals experience panic
CBT over alprazolam were observed in the third and
attacks because they have a relatively enduring tendency
fourth months. It is important to emphasize that
to interpret a range of bodily sensations in a catastrophic
significant improvements observed clinically in the first
fashion. Sensations which are misinterpreted are mainly
month in the alprazolam group were probably due to the
those which can be involved in normal anxiety responses
action of the alprazolam. This observation is consistent
(e.g. palpitation, breathlessness, dizziness). The
with a slower onset of effects with CBT than with
catastrophic misinterpretation involves perceiving these
alprazolam (16 ).
sensations as indicative of an immediately impending
physical or mental disaster. For example, a patient who
These findings, suggest that it might be beneficial to
was preoccupied with the idea he may be suffering from
start patients on alprazolam with a therapeutic contract
cardiac disease avoided exercise whenever he noticed
in order to withdraw them from alprazolam as CBT
palpitations. He believed that this avoidance helped to
progresses. In this way, patients are protected from the
prevent him from having a heart attack. However, as he
long-term therapy risk of alprazolam.
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