TCR: Dr. Pollack, as the head of the Anxiety Disorders Program at Mass General, you’ve had the opportunity to evaluate thousands of patients with panic disorder. Do have any practical tips for those of us with less experience?
Dr. Pollack: It’s important not to focus just on panic attacks. It’s critical to look at anticipatory anxiety, agoraphobia, and the presence of comorbid depression. These will all influence both your choice of treatment and treatment outcome. The agoraphobic fear and avoidance is often the most disabling aspect of the panic disorder syndrome.

TCR: How do you actually ask patients if they have had panic attacks?
Dr. Pollack: I often will use the term “anxiety” rather than panic, because many patients associate “panic” with a level of severity that they may not have experienced. So I’ll ask, “have you had episodes of marked anxiety that have come on very quickly, and that have been associated with hyperventilation, racing heart beat, tingling in the extremities,” and I might include other examples of somatic symptoms like nausea or irritable bowel. One thing that you often get is that patients will say they have panic all day long, which generally isn’t panic but more typically generalized anxiety. I’ll often actually draw a picture for patients, with a saw tooth pattern that emphasizes that panic attacks are discrete episodes which may occur on top of a baseline of persistent anxiety.

TCR: As you proceed with your evaluation, are there any questions you ask to distinguish patients who might benefit more from medication vs. Cognitive Behavior Therapy (CBT)?
Dr. Pollack: There used to be this idea floating around that patients with phobic avoidance were better candidates for CBT whereas patients with discrete panic attacks did better with medications, but this has been largely discredited by research. Both CBT and medications are effective for various aspects of the panic disorder syndrome. In my experience, patients usually have a strong preference for one modality or the other before they walk in your door. We did a study of 100 new, treatment-seeking patients and found that 90% came to our clinic with a strong preference for either meds or therapy, and this was pretty evenly divided—at least initially these individuals would not have accepted a referral to the alternative modality. It’s important that both psychopharmacologists and behavior therapists avoid explicitly or implicitly devaluing the alternative treatment with their patients, as incomplete responders may benefit down the road from a referral for combined treatment.

Wellbutrin? For Panic?
“The evidence that Wellbutrin does not work for panic was based on a single-blind trial that was done 20 years ago....We just submitted a paper on an open trial with 20 patients showing Wellbutrin to be effective in panic disorder ”

TCR: In my experience, it can be very hard to find a good cognitive behavioral therapist to refer patients to, even in Newburyport which is only an hour north of Boston!
Dr. Pollack: Yes, that can be a problem, and for patients who want CBT but can’t find a therapist, there are good self-help books that can, in a sense, extend the reach of behavior therapy.

TCR: Any specific suggestions?
Dr. Pollack: Yes, we use David Barlow’s Mastering Anxiety and Panic, and Dr. Michael Otto’s book Stopping Anxiety Medication, which he developed here to help patients use cognitive behavior therapy techniques to get off anxiolytics like benzodiazepines.

TCR: Moving to medication treatment, what is your typical approach to medication treatment of panic disorder?
Dr. Pollack: Very commonly, we will start with both an antidepressant and a benzodiazepine (as long as there is no substance abuse history) with the idea that the benzodiazepine will work quickly to reduce the anxiety while we’re waiting for the antidepressant to kick in, and that it will also cover some of the initial stimulation that people sometimes get with antidepressants.

TCR: Is there any actual research data to back up that approach?
Dr. Pollack: Yes, there are two studies, one that we did here combining Paxil with Klonipin, and the other by Andrew Goddard at Yale combining Zoloft and Klonipin. Both of these studies suggested that people on the combinations get better faster. But in our study, which included a continuation phase, there was no evidence after 6 to 10 weeks that there was any additional benefit to being on combined treatment vs. antidepressant alone, so it may make sense for many individuals to taper slowly off the benzodiazepine at that point and see if they can maintain benefit on monotherapy with the antidepressant.

TCR: What were the doses you used in your combined study?
Dr. Pollack: Patients were on 1.5 to 2 mg of Klonipin daily and 30-40 mg of Paxil.

TCR: How do you usually dose Klonipin in your practice?
Dr. Pollack: I’ll usually start patients on 0.25 mg QHS, and then titrate up to 0.25 mg BID and so on. It’s important to remember that Klonipin is quite potent, in fact twice as potent as Xanax. Most patients end up in the 1 to 4 mg range with one study using a fixed dose design suggesting that 1 mg is as effective as 2 mg daily.

TCR: Do you prefer Klonipin over the other benzodiazepines?
Dr. Pollack: Generally yes, because it can be dosed BID, so patients don’t start watching the clock in anticipation of their next dose. Also, since it has a more gradual onset patients don’t report feeling light-headed as they often do with more rapid acting agents. But its important to remember that for older patients with slower metabolism, short-acting agents become, effectively, long-acting agents which hang around for a very long time, so shorter half-life agents may be better in the geriatric population.

TCR: In terms of SSRIs, there is a sense among practitioners that you have to get the doses up higher for treating anxiety disorders than for depression. Is that borne out by the research?
Dr. Pollack: In a fixed dose study of paroxetine for panic disorder, 40 mg worked better than 20 mg/day but there are trials with other SSRIs like Zoloft where 50 mg and 200 mg were equivalently effective.

TCR:So what’s the bottom line on dosing?
Dr. Pollack: It’s hard to know. John Greist and Jeff Jefferson have argued with OCD (obsessive-compulsive disorder) that the apparent need for much higher doses partly reflects the natural impatience of both patients and clinicians in treating the disorder. That is, it takes a while to respond and in order for the patient and clinician to feel they’re actually actively intervening the doses will get raised perhaps higher than they actually need to be had more time been given.

TCR: So a greater tincture of patience is important?
Dr. Pollack: Yes, especially with panic disorder and other phobic disorders. These patients really have two challenges to face in moving to recovery: first, they have to stop having panic attacks, and second, they have to feel less anxious and avoidant in general. It may take panic patients quite a long period of time without having panic attacks before they feel safe exposing themselves to situations that caused anxiety in the past.

TCR: Do you think that non-SSRI antidepressants are effective for panic disorder?
Dr. Pollack: Yes, there is good evidence that Effexor is effective, and there is even some recent evidence that Wellbutrin works. We just submitted a paper in collaboration with the group at Medical University of South Carolina on an open trial with 20 patients showing Wellbutrin to be effective in panic disorder.

TCR: That’s interesting, because Wellbutrin definitely has the reputation of being an anxiogenic antidepressant, which is unfortunate because panic patients are often asking for something that will not cause sexual side effects.
Dr. Pollack: Yes, and it’s still an open question. The evidence that Wellbutrin does not work for panic was based on a single blind trial that was done 20 years ago by David Sheehan with 12 patients. And that small study has strongly influenced the field to the idea that Wellbutrin is ineffective for panic. In fact, it may well be effective after all, although at this point there isn’t enough data to recommend it routinely as a first line agent compared to some of the other better vetted pharmacotherapies.

TCR: What do you suggest for treatment-resistant panic patients?
Dr. Pollack: In our clinic, we certainly add behavior therapy, and we also add some of the novel anticonvulsants like gabapentin (Neurontin), tiagabine (Gabitril), and levetiracetam (Keppra), and we also add the atypical antipsychotics, like risperidone (Risperdal), olanzapine (Zyprexa) and quetiapine (Seroquel), all of which seem to be effective as add-on therapy for treatment-resistant patients.

TCR: Gabapentin is a widely used medication now, and it has a very wide dose range, making it confusing to dose. What’s your approach to dosing it?
Dr. Pollack: I’ll usually start patients at 300 mg at HS, and then have them titrate up to BID or TID after a couple of days. Most of our patients end up at a dose of around 1800 mg QD. In studies of panic the average daily dose was around 2000 mg, and for social phobia around 3000 mg.

TCR: Anything new and exciting coming down the pike?
Dr. Pollack: Yes, there’s pregabilin, which is the next generation of gabapentin-type d shows a lot of promise as an anxiolytic though there’s not much data panic yet. There are also CRH (corticotrophin-releasing hormone) antagonists in development which may prove to be very effective for a range of anxiety and depressive disorders and may have a very favorable side effect profile.