Psychotherapy and antidepressant for panic disorder
Panic
disorder, with or without agoraphobia, is usually treated with psychotherapy,
with or without antidepressants. Deciding which is best is made difficult by
trials being generally small, testing different types of psychotherapy, with
different controls, and with endpoints at the end of treatment or at some later
time. Just as well that we have a systematic review [1] to help us get some grip.
Systematic review
Searching
used a specialised Cochrane register, supplemented with a series of other
electronic searches, plus hand searching of major journals, proceedings, and
trial registers, up to the end of 2003. Randomised trials were accepted. The
primary outcome was response, a substantial improvement from baseline,
equivalent to very much or much improved, derived by dichotomising results from
studies which used different measurement scales. Outcomes were assessed at the
end of the treatment phase, and at some longer follow up, typically 12-24
months later.
Results
Searching
found 23 randomised comparisons with 1,700 patients, in studies with treatment
duration of six to 26 weeks, but where most were of nine to 15 weeks. Different
types of psychotherapy were used. Behaviour therapy consisted of exposure, with
or without breathing retraining, with or without relaxation exercises.
Cognitive behavioural studies consisted of both cognitive and behavioural
elements. Antidepressants used included tricyclics (average dose 150 mg daily
of imipramine equivalents), or SSRIs (average dose 30 mg daily of fluoxetine
equivalents).
The
summary results are shown in Table 1. Overall, psychotherapy plus
antidepressant was better than antidepressant or psychotherapy alone at the end
of the treatment phase, with numbers needed to treat of 10 to produce one more
responder. At longer term follow up, psychotherapy plus antidepressant was
better than antidepressant alone, with an NNT of 5, but not psychotherapy
alone. Figure 1 shows the percentage of responders in the comparisons in a
truncated form, to emphasis the similarity between psychotherapy plus
antidepressant.
Table 1: Summary of pooled estimates of efficacy of psychotherapy plus antidepressants versus antidepressants alone or psychotherapy alone in treating panic disorder
| Comparison | (95% CI) |
(95% CI) |
||||
| End of treatment phase | ||||||
| Psychotherapy + antidepressant vs antidepressant | ||||||
| Psychotherapy + antidepressant vs psychotherapy | ||||||
| Longer term follow up | ||||||
| Psychotherapy + antidepressant vs antidepressant | ||||||
| Psychotherapy + antidepressant vs psychotherapy | ||||||
Figure 1: Percentage of responders in comparisons of psychotherapy plus antidepressants (PA) versus antidepressants alone (A) or psychotherapy alone (P)
Various
sensitivity analyses were performed. Omitting studies that included agoraphobia
made no difference, nor did comparison with different classes of
antidepressant, nor did analysis by different type of psychotherapy make much
difference. Additional analysis by size of trial made no difference.
Sensitivity analyses like this are important, given the small size of trials
generally, and the resultant scattering of results, possibly because of random
chance. Figures 2 and 3 show results for individual trials comparing
psychotherapy plus antidepressant with antidepressant at the end of treatment
(Figure 2) and at later follow up (Figure 3).
Figure 2: Responders at end of treatment phase with psychotherapy plus antidepressants (PA) or antidepressants alone (A)
Figure 3: Responders at longer term follow up with psychotherapy plus antidepressants (PA) or antidepressants alone (A)
Comment
These
results appeared pretty robust. One possible quibble is that the numbers given
in the paper for psychotherapy plus antidepressant compared with antidepressant
alone at the end of treatment had some obvious minor problems, like numbers not
adding up, and relative risks which were obviously wrong, but recalculating or
omitting problematic trials made no difference. The results were robust.
Bandolier
is always suspicious about results when we have only a scattering of small
studies, and where there is scope for clinical heterogeneity. That was the
situation here, and as we saw in Bandolier 139, that is a situation where even
a systematic review is more likely to be wrong than right. That is why
sensitivity analysis is important, and Figures 2 and 3 emphasise how much small
trials can contribute to an overall result.
Here
the results for psychotherapy plus antidepressant stood up to sensitivity
analysis. The question of whether the extent of advantage over antidepressant
alone is big enough, or big enough to make a cost effectiveness argument, is
another matter, and a difficult call. Two years after the event some 60% of
patients with panic disorder had not achieved a sustained response with any of
these treatments.
Reference:
- TA Furukawa et al. Psychotherapy plus antidepressants for panic disorder with or without agoraphobia. British Journal of Psychiatry 2006 188: 305-312.