Efficacy of Aerobic Exercise Added to Alprazolam in Panic Disorder Treatment: Clinical Randomized Trial

Abstract

Objective: The purpose of this study is to determine whether the combination of aerobic physical
exercise and alprazolam in patients with panic disorder has a better therapeutic response than treatment
with alprazolam alone.

Description: We have observed in our clinical practice that patients who practiced aerobic physical
exercise had faster remissions and better improvement in their treatments than those who did not.
The objective is to compare the efficacy of a pharmacological monotherapy (alprazolam), which is one
of the options for the pharmacological treatment of panic disorder, with another treatment such as the
combination of aerobic physical exercise and alprazolam, and to determine if this combination results
in a better therapeutic response.

Methods: 150 outpatients with panic disorder were randomly assigned to 4 mg of alprazolam or 4 mg
of alprazolam associated to a programmed aerobic exercise reaching a heart rate between 50% and
75% of their maximum. Both groups completed their treatments in 12 weeks and were scored using
the Hamilton Anxiety Rating Scale (H.A.R.S./14) and the Clinical Global Impression (CGI) before the
study and during weeks 1, 4, 8, and 12.
Patients assigned to the pharmacological plan received 4 mg alprazolam daily for 12 weeks. Two weeks
after the first interview they had their first baseline psychiatric control, where all the patients were
evaluated. Then, at the same visit, all the patients were prescribed 4 mg of alprazolam. The dose was
gradually increased from 1 to 4 mg throughout the first week of treatment. The test was repeated during
weeks 2, 4, 8 and 12.
Patients assigned to exercise had to pass an ergometric test to determine their functional capacity
expressed in METs for future indication of exercise. Two weeks after the first interview they had
their first baseline psychiatric control and at the same time a 4 mg dose of alprazolam was prescribed,
gradually increased from 1 to 4 mg along the first week of treatment. The test was repeated during weeks
2, 4, 8 and 12. Then they followed a protocolized aerobic exercise plan for this study for 12 weeks. The
type of exercise consisted of a brisk walk for 30 minutes divided into stages. After each stage, the patient
must control his own heart frequency, which must be between 50 and 75% of its maximum to ensure an
aerobic condition (according yo American Cardiological Association criteria)

Results: 106 of the 150 selected patients managed to fulfill both treatments: 51 for the alprazolam +
exercise group (dropout rate 32%) and 55 for the alprazolam group (dropout rate 27 %).
The group treated with alprazolam + exercise experienced a significant improvement (p < 0.001) respect
to the group treated only with alprazolam, reaching lower Hamilton Anxiety Scale scores (4,16 ± 1,06
and 8.57 ± 2,39 respectively) and Global Clinical Evaluation scores (Severity 1,86 ± 0,60 and 2.71 ±
0,62 ; Improvement 2,19 ± 0,49 and 2,87 ± 0,63 respectively for each group). Also, the remission rates
were higher for the first group.

Conclusion: Aerobic physical exercise in addition to pharmacological treatment (alprazolam) is more
effective than the alprazolam treatment alone, and could be a useful alternative to treat this disorder.