Psychiatric Times.
No. 2
Treatment Planning for Panic Disorder
By Yujuan Choy, MD |
February 1, 2008
Dr Choy is in private practice (general adult psychiatry and cognitive-behavioral therapy) in Irvine, Calif, and works as staff psychiatrist at the University of California, Irvine (UCI) Student Health Center. She is assistant clinical professor of psychiatry and human behavior at UCI. The author reports no conflicts of interest concerning the subject matter of this article.
DURATION OF PHARMACOTHERAPY
Acute treatment with medication should be at least 8 to 12 weeks' duration to ensure optimal response. CBT treatment can range from 8 to 12 weekly sessions. Most maintenance studies lasting 6 months to 1 year have largely found that gains achieved during acute treatment with CBT or pharmacotherapy are either sustained or improved during the maintenance phase.19,23,24,26,27,42,43 However, one naturalistic long-term, follow-up study reported that survival probability decreased over time even with continued treatment, from 87% at 1 year to 64% at 4 years following a 3-year maintenance period.44
Relapse is common on medication discontinuation, with the highest rates (up to 88%) reported for benzodiaz-epines45-47 and the lowest rates (15% to 30%) for SSRIs.48,49 The American Psychiatric Association guidelines recommend that treatment be maintained for at least 1 year,35 and the international consensus group recommends 1 to 2 years.13 Subsequent to these guidelines, a series of controlled discontinuation studies suggest that the length of maintenance treatment is not predictive of relapse. For example, the relapse rate (37%) within 1 year of medication discontinuation was the same after 6 months or 18 months of maintenance with imipramine(Drug information on imipramine).50-52 In an SSRI discontinuation study, relapse rates within 1 year of discontinuation did not differ between those who received treatment over 1 or 2 years with paroxetine(Drug information on paroxetine) (18% vs 15%).49 Similarly, another study found a high relapse rate (46% within 1 year of discontinuation) even after 3 years of maintenance treatment in a select group of moderately healthy patients.44
Given that a longer length of maintenance treatment does not seem to protect against relapse, medication discontinuation can be considered 6 months after full and sustained remission is obtained. Discontinuation should be conducted slowly over 2 to 6 months.13 Clinicians should prepare patients for what to expect following discontinuation so that treatment can be reinstituted promptly should relapse occur. Patients should also be advised to consider adjunctive CBT to optimize their chance of maintaining improvement after medication discontinuation. There is extensive evidence that CBT reduces the chance of relapse after medication discontinuation.53-55 One study also showed that brief psychodynamic psychotherapy reduces the incidence of relapse.56 Treatment should be continued in patients with significant residual anxiety or depressive symptoms, because premature medication discontinuation in these patients is less successful.57 Treatment should also be continued in patients with a history of relapse after discontinuation, in those with significant comorbidities, and in those with current severe life stressors.13
Treatment for NONRESPONDERS
A substantial number of patients do not completely recover from panic disorder with either CBT or pharmaco-therapy; in fact, only 25% to 45% of treated patients are considered to be in remission.58
The reasons for failure to respond to CBT have not been adequately studied.59 In a group of patients who received in vivo exposure, those who were treatment resistant (n = 21) were younger, more likely to be male and unmarried, and had a longer duration of illness, greater baseline depression, and poorer adherence to exposure homework than those who were successfully treated (n = 81).60
A limited number of studies suggest that the addition of medication or prolonged treatment with CBT may help patients who do not respond to CBT. An early, small study (N = 18) found that augmentation with clomipramine(Drug information on clomipramine) resulted in significant but modest improvement in patients who failed exposure therapy.61In a later study with SSRIs, patients who did not adequately respond to CBT (n = 43) were given additional CBT with or without paroxetine.59 Adjunctive paroxetine improved 3 of 7 outcome measures, including agoraphobic symptoms and anxiety discomfort. A greater proportion of patients in the CBT plus paroxetine group were panic-free compared with the CBT alone group (74% vs 47%), but this finding was not statistically significant. On the other hand, one study of 21 patients who were treatment-resistant suggested that prolonged (at least an additional 8 weeks) exposure to treatment alone can achieve a greater chance of panic-free status than augmentation with either imipramine or cognitive therapy.60 However, imipramine was not given a fair trial since many of the patients (6 of the 14) could not tolerate imipramine, and the medication had to be discontinued prematurely.
One of the most common reasons for drug treatment failures is inadequate dose and/or duration of treatment. True treatment resistance is found in only 24% of adequate medication trials.62 Thus, it is important to first optimize treatment by ensuring an adequate trial of medication. This may require improving tolerability by initiating treatment at low doses and aggressively managing adverse effects. For treatment-refractory situations, one strategy is to augment treatment with psychotherapy.
Three small open trials have shown that CBT can reduce panic symptoms in patients who are not responding. In the first study, patients (N = 15) who had an incomplete response to pharmacotherapy were given 12 weeks of group CBT treatment.63 These patients reported a decrease in panic frequency and improved global functioning. There also appeared to be a greater response to CBT in those who received an inadequate trial of medication compared with those who were treatment refractory.
A later study (N = 24) by the same group of researchers confirmed that CBT was an effective strategy in patients who were not responding to medication, but there was no significant difference in response between those who received an adequate trial and those who received an inadequate trial of medication.64 However, there was a greater effect size for those who were adequately treated relative to those who were in the inadequately treated sample. Approximately 60% of the adequately treated sample responded to treatment and had lower PDSS scores compared with 43% of the inadequately treated sample.
In addition, researchers in Brazil found CBT reduced panic symptoms in patients (N = 71) who were resistant to an adequate trial of SSRI, with gains maintained at 1-year follow-up. A little over 80% of patients were panic-free after CBT, and medication use decreased over time. In addition, the presence of baseline comorbid dysthymia, social anxiety disorder, and generalized anxiety disorder predicted worse outcomes.65
Most recently, a short-term, panic-focused psychodynamic psychotherapy has been shown to be effective in the treatment of panic disorder.66 Psychodynamic psychotherapy reduced the severity of panic symptoms compared with applied relaxation. The response rate was 73% for psychodynamic therapy versus 39% for applied relaxation in the intent-to-treat group. However, this difference was no longer significant when comparing only the patients who completed treatment. Although there are no augmentation studies with psychodynamic psychotherapy, it may be a good alternative for those who cannot tolerate medication or who do not respond to CBT.
Another strategy for patients who do not respond to pharmacotherapy is to switch to another medication that has proved effective for panic disorder, be it an SSRI, venlafaxine ER, a TCA, a benzodiazepine, or a combination of antidepressant and benzodiazepine. However, these strategies are largely based on clinical practice.13,36 The efficacy of switching from one antidepressant to another has not been examined in any controlled studies. There are also limited studies on combination pharmacotherapy for patients who are treatment refractory. Although b-blockers are not generally used in panic disorder, one controlled study (N = 25) looked at augmentation with pindolol(Drug information on pindolol) versus augmentation with placebo in patients who did not respond to fluoxetine(Drug information on fluoxetine).67 Compared with placebo, the addition of pindolol decreased overall anxiety, but the panic-free rates were not reported. Treatment with fluoxetine was also not optimized in this study because 20 mg was the maximum dose. A clinical trial is under way at Massachusetts General Hospital in Boston to determine whether the addition of clonazepam(Drug information on clonazepam) or CBT would benefit patients who did not respond to sertraline(Drug information on sertraline) (clinicaltrials.gov: NCT00118417).
In patients who do not respond even after switching to a different medication or the addition of adjunctive treatment, clinicians should consider the presence of comorbid conditions, such as personality disorder, mood disorder, substance abuse, or another anxiety disorder that may complicate the treatment of panic disorder. The Figure presents a suggested treatment algorithm.
Conclusion
Panic disorder is a chronic, debilitating psychiatric illness that should be recognized and adequately treated with CBT, SSRIs, or a combination of both. Combination treatment is effective in the short term but may not confer any additional benefits compared with CBT alone in the long term. Most recently, psychodynamic psychotherapy and venlafaxine ER have also been shown to be effective. During acute treatment, both dosage and duration of medication should be optimized to maximize the chance of recovery. Patients should be given medication for at least 6 months after they have achieved full sustained remission. Relapse is common after medication discontinuation, and measures to decrease the chance of relapse include slow discontinuation of medication and the addition of CBT. Switching medications or adjunctive CBT or SSRI may help with patients who do not respond to monotherapy.
- Ballenger JC. Remission rates in patients with anxiety disorders treated with paroxetine. J Clin Psychiatry. 2004;65:1696-1707.
- Barlow DH, Gorman JM, Shear MK, Woods SW. Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: a randomized controlled trial. JAMA. 2000;283:2529-2536.
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