Attribution of Improvement to Medication and Increased Risk of Relapse of Panic Disorder with Agoraphobia

We have read with great interest the recent article of Bakker et al. [1] who reported a differential effect on panic locus of control in favor of cognitive therapy as compared to medication. Differently from patients treated with psychotherapy, at the end of treatment patients who received antidepressant drugs did not exhibit a decrease in the attribution of anxiety control to medication or chance, and an increase in the internal anxiety control orientation. We have recently completed a follow-up study of a private practice sample of consecutive patients with DSM-III-R panic disorder with agoraphobia who achieved remission after drug treatment with or without concurrent cognitive-behavioral psychotherapy [2]. Although some methodological limitations suggest caution in interpreting our results, the long-term outcome was much better among patients who received integrated treatment as compared to patients who received medication alone. The advantage of integrated treatment over medication alone was large and independent from known prognostic factors. We report here the results of an additional analysis that we performed on the relationship between outcome and attributing improvement to medication. This analysis took advantage of the fact that during the first visit each patient had been rated on a brief checklist assessing his or her attitude towards drug treatment [3]. A key item of this instrument refers to the following belief: ‘I will improve, but well-being will last only until I will continue taking medication. ’ The design of the study will only be summarized briefly here. In all patients, the drug dose was titrated individually, and medication was maintained until patients reached a satisfactory improvement. Then, it was gradually tapered off over a period of 1–2 months. Patients who received concurrent psychotherapy were seen at weekly intervals during the first 6 months, then at bimonthly intervals for other 3–6 months. Only a few patients required to be treated for longer periods of time. Patients were assessed before treatment, after treatment, and at each follow-up contact with the Marks-Sheehan Phobia Scale, the Hamilton Anxiety Rating Scale, and the Hamilton Depression Rating Scale. Follow-up contacts consisted of a brief update of clinical state, including any treatment request or use of medications. Followup assessments were performed after 4–6 months, after about 1 year, and subsequently on a yearly basis. In addition, patients were instructed to call if any new symptoms appeared. Relapse was defined as the reappearance of symptoms of panic disorder or agoraphobia prompting the patient to seek treatment, causing considerable distress, or reducing substantially his or her psychosocial functioning. The outcome of patients treated with medication alone was so bad (about 4 of 5 of those who reached remission subsequently relapsed) that there was no room to test for an association between attribution and relapse. Therefore, we restricted the analysis to patients who received integrated treatment (n = 34). Of these, 6 (17.6%) dropped out, 2 (5.9%) discontinued treatment before reaching remission, 5 (14.7%) were lost to follow-up, and 1 (3.0%) was not rated on the attitude towards medication. Of the remaining 20 patients, 14 were rated at the first visit as holding the belief that their possible improvement would have lasted only until medication was maintained. However, in 9 of them this belief changed over the course of psychotherapy. The follow-up time ranged from 2 to 86 months, with a mean of 20.7 months. Kaplan-Meier survival analysis was performed on the time to panic disorder relapse. Among the 5 patients who believed that remission and medication were strongly related, 3 (60%) relapsed, the 1st patient after 6 months, and the other 2 after 24 months. No patient relapsed among patients who did not hold this belief or among patients in whom this belief changed during psychotherapy. In spite of the small sample size, the difference in survival distributions between groups is borderline significant (log-rank test = 4.95, d.f. = 2, p = 0.08). Our findings are in line with previous indications that patients strongly attributing their improvement to medication seem to be at increased risk of relapse [4]. They also suggest that the long-term prophylactic effect of psychotherapy in patients with panic disorder [5– 7] might be related to the effect of cognitive therapy on the locus of control orientation that Bakker et al. [1] demonstrated in their study. Working on patients’ attributions with the aim of favoring a shift towards a more internal orientation is considered essential in the treatment of phobic patients [8]. The poor outcome that we observed in patients attributing improvement to medication suggests that particular efforts should be devoted to such patients in order to reduce their external attributions of control and improvement.