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Anxiety comes in many varieties. There is rational worry about real issues that need decisions to be made. If there is a lack of mental clarity due to a concentration problem or conflicting goals anxiety may increase and lead to indecisiveness. Some worry is totally irrational based upon false premises or superstitious notions. “Step on the crack and you’ll break your mother’s back.” In obsessive-compulsive disorder, the patient seems to be lacking a sense of completeness. “Did I do that? Maybe not, let me check. Did I check it right? Maybe not, let me check again.” Irrational worries usually take the form, if I don’t do this, something bad will happen.

Panic is the most extreme and concentrated form of anxiety with many symptoms flooding at once. It occurs when a person feels life or limb is in jeopardy. It is the activation of our bodies’ alarm system or fight or flight response. A primitive reminder of our jungle origins when man had to face danger at every turn. It too had an adaptive function. All of its symptoms have some function or relate to a preparation to fight or flee.

Panic attacks come on quickly and have peak symptoms within ten minutes or less. The heart rate and breathing rates go up bringing in more oxygen and pumping more blood to large muscle groups in our arms and legs. The adrenaline rush gives a sense of warmth leading to sweating to reduce overheating. Blood volume shifts from areas that can wait to where it is needed in case of our need to run or fight. Blood leaving the gut gives a sense of nausea from slowing digestion of food. Blood leaving the fingers, toes and lips results in a numb and tingling sensation. The pupils dilate to change focus to distance causing blurred vision for anything close up. The rapidly shifting blood supply may cause a sense of wooziness or faintness. In preparation for battle with potential of physical pain, the mind goes into a dissociated state of detachment that may outlast the other physiological symptoms described. This helps us to ignore pain sensations that may result from battle.

What if this reaction occurs when there is no apparent danger or cause? The body is telling you there is something seriously wrong but you don’t know what it is. You panic. You worry that you might be dying or “going crazy.” Patients often go to the emergency room with these symptoms and after an extensive work-up they are told nothing is wrong. But their body has told them something is seriously wrong. They have to explain it in some way. The explanation usually takes the form of an association with whatever is happening externally or with a contemporaneous stream of thoughts. Maybe it occurred while driving on the highway, so the highway is avoided. Maybe in the store, so stores are avoided. Eventually, the individual is constricted from going many places developing agoraphobia. If the panic occurred while having a bad thought, any bad thought might trigger anxiety.

In our jungle days if we encountered a tiger peeking out of the woods near a particular clearing, we might avoid that area in the future. In behavioral terms seeing the tiger was our stimulus for our panic response. The particular clearing became paired with this stimulus such that seeing the clearing elicited the same response as seeing the tiger. This is called classical conditioning as described in Pavlov’s famous dog experiment. Pavlov rang a bell while presenting the dogs with meat. The dog’s normal response to the meat was to salivate. After several presentations the dogs salivated in response to hearing the bell even when no meat was present. In the jungle example, the person became conditioned to have a panic response when they saw the clearing even in the absence of seeing a tiger. In classical conditioning a physiologic response such as fight or flight response becomes paired with an external unrelated stimulus, in this case the clearing.

The dogs took several tries to learn this response. Humans are “smarter” and learn to make the connection in one exposure. In addition, we readily do stimulus generalization. This means we learn so well from a particular experience that we generalize to any similar circumstance. So if we have a panic attack in a particular store, we might avoid all stores. Worse yet we have a hard time forgetting or breaking these connections. So one can see that people who develop agoraphobia in response to panic attacks are actually our best learners and not “crazy” or “stupid” as many others might accuse them of being. Their problem is that they learned the wrong lesson in response to a false alarm. Just as the Department of Homeland security sometimes heightens its warnings on false “chatter,” after a patient’s panic alarm goes off it becomes more sensitive increasing the likelihood of subsequent false alarms. Patients with panic have to reset the alarm to be less sensitive and be retrained to extinguish this inappropriate response.

Undoing a conditioned response is very difficult. While one exposure to a situation during a panic attack conditions our avoidance, it takes multiple exposures to the same situation without having a panic attack to extinguish the pairing. There are two opposing camps on treatment for panic disorder. One advocates for heavy use of medication to rapidly squelch the attacks and the other argues that exposure without medication but using cognitive behavioral therapy can be more effective. In studies comparing these treatments, the group that advocated their form of treatment showed that they performed better. I advocate for both interventions done together. If you try to expose a patient to the avoided situation and they panic, you can actually reinforce the avoidance. If you give them too much medication they lack the drive and motivation to challenge themselves to do what they have learned to avoid. Sedating medications might stop the panic attacks, but you might not have helped the patient much since they are still disabled by the agoraphobia and too drugged to initiate efforts to overcome avoidance behaviors.

Sherri was a 54 year old married woman who had panic attacks and severe agoraphobia most of her life. She limited herself to local traveling and still experienced panic attacks despite treatment with high doses of benzodiazepines initially prescribed by a psychiatrist but continued by her primary care doctor. Her husband was thinking of retiring soon and was upset that Sherri would not travel. She avoided high bridges and wouldn’t go on a plane or train. She finally presented to me after her husband decided to separate from her feeling she was dragging him down. I explained the nature of panic attacks and agoraphobia to her. I added an antidepressant and switched her benzodiazepine to Klonopin. I slowly reduced her Klonopin down to just 0.5mg and referred her to a therapist. She improved rapidly. Although separated, she continued to see her husband who felt skeptical of her changes. She wanted to go out now and do things that she was restricted from doing in the past. After several months she realized that she didn’t need her husband and his skepticism about her progress was bringing her down. Enjoying her new freedom, she planned and took plane flights to visit her children in Europe and the West Coast.

Klonopin is a medication commonly used to treat panic attacks. So is Xanax. Both have been FDA approved to treat panic disorder. Xanax or alprazolam is a fairly short acting medication, which if not given 3 to 4 times per day can cause inter-dosing withdrawal symptoms. As the medication is wearing off the patient is likely to be more prone to panic attacks. This is especially evident when a patient wakes up with panic, which I rarely see in un-medicated patients. Patients try to compensate by using more than is needed only exacerbating these peaks and valleys of medication effect. I have helped more patients by taking them off their Xanax than by putting them on it. Klonopin or clonazepam is a much longer acting benzodiazepine which means twice daily dosing is all that is needed to prevent panic attacks. Previously used as an anti-seizure medication, it was approved to treat panic attacks only just before it went generic and knowledge of its appropriate use was not widely disseminated. The PDR (Physician’s Desk Reference) that has the FDA approved information reports two studies of Klonopin in panic disorder which very few physicians seem to be aware of. In one study patients were given either a placebo or 5 different dosages of Klonopin, 0.5, 1, 2, 3 or 4 mg per day. Interestingly only the group receiving 1mg per day did better than placebo with 74% being panic free compared to 54% on placebo. In the second study doctors were able to titrate the dose of Klonopin as needed. Klonopin did better than placebo but the average dose taken was 2.3 mg and the response rate was lower than in the study with Klonopin 1mg. These studies may seem contradictory but my clinical experience reinforces the findings. Patient do better on a lower dose of Klonopin than a higher dose. Why would this be?

Patients with panic want immediate relief for their panic attacks. But panic attacks are brief and time limited. If allowed to self medicate they take more than they need. Once a panic attack starts the medication doesn’t abort it but may prevent the next attack. So if a patient takes too much medication during a panic attack they are just going to feel over medicated and sedated. This wooziness feels like a symptom of the attack. Being overmedicated they can’t think clearly which is necessary to overcome their irrational fears. Finally, after being over medicated they are more likely to experience withdrawal symptoms from the medication leading to more panic just as in the case of Xanax. How do you convince a patient not to use too much of the medication when they are still symptomatic?

Not all patients with panic attacks will respond to a low dose of Klonopin. This doesn’t mean they should have more. I advocate for using alternative medications to add on to get a more complete response. Panic patients have irrational worries very similar to what is seen in obsessive-compulsive disorder. More than half of patients with panic disorder will have depression at some time in their life. If a low dose of benzodiazepine is not adequate a serotonin antidepressant (SSRI) should be added. If this strategy fails patients should be re-evaluated for either attention deficit disorder (ADHD) or bipolar disorder. Panic attacks are a common complaint in patients with bipolar disorder and occur in both manic and depressed phases. (See chapters 9 and 10).

Jeff was a 36-year-old married man who was struggling with panic attacks for several years. He was a tough guy who did body building and felt he should be able to control this without medications. He went to several different therapists and spent hundreds of dollars on an advertised treatment program on audiotapes. He listened to the tapes religiously and did all of the exercises but still felt terrible with panic attacks. He forced himself to resist impulses to avoid situations yet he still felt trapped by panic. I explained the value of medication to reset his panic alarm to be less sensitive. He began on a low dose of Klonopin to which I added Zoloft. Within a couple of months he was cured. Once on the medication, all that he had learned with the tapes and therapy fell into place. Over the course of a year he came off the Klonopin and weaned off the Zoloft. Within a few months off of the medications the panic returned. Disappointed and despairing it took higher dosages of medication and longer to improve. He did improve and again was able to come off the Klonopin but chose to stay on a low dose of Zoloft to prevent relapse.

Agoraphobia is like gangrene. If you let one avoidance fester untreated it spreads and leads to other avoidances. Gangrene many start in the toes but eventually the whole leg is infected and must be removed restricting ambulation. I have had patients who let their agoraphobia go untreated so long that they can’t leave their neighborhood or even their house. Ironically, the situations avoided often make no sense. One elderly patient of mine loves to travel but won’t fly. She will take a Titanic-like boat across to Europe at great expense but won’t fly. She has taken Amtrak across the country and has been in two train wrecks and will continue to use the train but not fly. She feels she is too old to change. Therefore I strongly encourage tackling all fears systematically when one is young. Also the earlier one gets treatment the better since fewer avoidances have developed and maladaptive relationships have not become ingrained.

Medication alone is never adequate to treat panic disorder. Some form of cognitive behavioral therapy with exposure needs to be given in addition. For some highly motivated patients just reading self-help books or tapes (bibliotherapy) may be enough when added on to medications. But most patients need an active therapist to guide and motivate them to overcome their fears. For some couples the dependency needs of the agoraphobic partner match the nurturing needs of the spouse. Steve presented with fairly new onset panic attacks after an incident at work. He responded quickly to medications and counseling. His dramatic improvement was incentive for him to refer his wife who had life long panic and agoraphobia. She took longer to improve but as she did she needed her husband less and less. She eventually decided to leave her husband as she felt she had missed out on a good part of her life and didn’t want to be trapped in a relationship. When she was agoraphobic she needed her husband to do things for her. This enabling came at the expense of him making decisions for her. She came to see this original support of her as controlling behavior. He had a hard time letting go of his parental role. Steve eventually remarried. I don’t know what happened to his wife.

It is evident that while anxiety can be a normal part of life, excess anxiety can lead to many negative consequences. These can greatly limit an individual’s potential in life. It can also affect their interpersonal lives and may lead to inappropriate choices in relationships. Fortunately there are very good treatments that involve both judicious use of medications and psychotherapy.