Panic Disorders

[David Baxter PhD]

Panic Disorders: Part 1
by Robert J. Hedaya, M.D. , Psychology Today
February 11, 2011

The spectrum of disorders associated with panic
Panic attacks are among the most terrifying experiences a person can have. Panic disorders include panic with and without [goraphobia, simple phobia, posttraumatic stress disorder, and perhaps social phobias. The controversy over whether these disorders are closely related, and in what way is not addressed, since the research in this area is inconsistent and inconclusive. The focus here is on the current understanding of the biological underpinnings of the panic attack itself, as well as the psychosocial aspects of panic disorder.

Diagnostic Considerations
Symptoms of panic disorder, according to the DSM IV, include two broad categories. First, a subjective sense of terror, going crazy, losing control, or dying must be present. Second, accompanying the subjective criteria, are a host of symptoms of hyperarousal of various body systems including cardiovascular (rapid pulse, palpitations, lightheadedness), respiratory (sighing, hyperventilation, shortness of breath, subjective sense of difficulty breathing or breathlessness), gastrointestinal (dry mouth, nausea, vomiting, diarrhea) urogenital (urge to urinate), cognitive (trouble thinking clearly), dermatologic (sweating, clamminess, flushing) and neurological (tremulousness, tingling, trouble with speech, dizziness, dissociation). Panic attacks may be spontaneous (ie without provocation of a situation or thought) or triggered.

Associated Features of Panic Disorders
Once a person has developed panic attacks a series of consequences may follow. He or she is likely to try to avoid situations that either would trigger panic (as in phobic panic) or place themselves in a situation where help might not be available. Since the patients with spontaneous panic would feel shortness of breath and suffocation feelings as a first symptom, they would be fearful of being in any situation that would impair their ability to either get help (if they felt they were suffocating) or to get fresh air. Eventually, perhaps thru a kindling mechanism caused by repetitive firing of the involved nuclei, a sense of anticipatory anxiety (fear of the possibility of a panic attack) would lead to constant over activity of parts of the brain involved in anticipatory fear (the raphe nucleus in the brain stem). This anticipatory anxiety component is not treatable by older medications such as imipramine (which was one of the first medications effective for panic). It requires other medications such as buspirone (Buspar) which act on the serotonin receptors of raphe nucleus neurons, or benzodiazepines, such as clonazepam (Klonopin) which act on other brain regions that mediate general levels of anxiety via the GABA (inhibitory) neurons and receptors. Some people with a triggered panic attack take a counter-phobic response, so for example, someone who has a panic attack when speaking in public, joins Toastmasters. In my case, when I was young (around 19) I needed to earn some money, so I took a job that involved climbing up 20 foot ladders (they seemed like they were 50 feet tall). At first I felt panicky (not a full panic), and so I desensitized myself by slowly going up the ladder, bit by bit. By the end of the first day, I was able to climb the ladder in a relaxed state of mind. Desensitization works only when there is a sense of control, ie, that one way or another, if you need to, you can terminate the panic.

Medical Conditions Associated with Panic Disorder
Patients with panic disorder have a higher likelihood of having mitral valve prolapse (MVP). MVP is a weakness of one of the valves of the heart. It is relatively benign, but does occasionally produce abnormal sensations including pounding heart, rapid heart rate, lightheadedness, dizziness, fainting, fatigue, difficulty breathing and chest pain. In one study, 34% of panic disorder patients had MVP. One of my first patients had a panic disorder which did not respond at all to any of the usual treatments (cognitive behavior therapy, and various medication trials) and it turned out that she had a severe B12 deficiency. Her panic cleared completely with the first B12 injection. Other patients may have an underlying have seizure disorder (e.g., temporal lobe syndrome), adrenal or thyroid dysfunctions, with PMS, post-partum, post -menopausal, and with significant inflammation or infection (which alters brain production of serotonin, dopamine, and glutamate). I recall one woman who had chronic inflammation as a result of both a chronic sinus condition and work in a very moldy environment.

Patients with bipolar disorder have a 20% chance of having a panic disorder and panic disorder is associated with increased risk of suicide, major depression and other anxiety disorders. Patients with panic disorder have a significantly higher rate of gastrointestinal complaints, such as irritable bowel syndrome . In general most panic disorder patients tend to describe themselves as always having been fearful and shy as children, have discomfort with aggression, and low self esteem. This description is reminiscent of the discussion on temperament.

 

[David Baxter PhD]

Panic Disorders: Part 2
by Robert J. Hedaya, M.D.
fEBRUARY 16, 2011

Biological Theory of Panic Disorder (Recurrent Panic Attacks)
The prevailing theory of panic disorder states that there are two types of panic attacks, non-phobic spontaneous panic and triggered panic attacks. Nonphobic panic attacks are thought to be the result of abnormal, over- sensitivity of a brain alarm system whose function is to detect early signs of suffocation. This theory is called the suffocation alarm theory. The cardinal symptoms of nonphobic panic are respiratory: shortness of breath, chest discomfort, palpitations and choking or suffocation sensations.

Normally, carbon dioxide, the waste product of respiration, is exhaled from the lungs. In the event of suffocation, the theory suggests that levels of CO2 in the blood, and particularly the brain, rise. Neurons in the solitary nucleus of the brain stem, which are constantly sampling the blood in the brain for levels of carbon dioxide (CO2), become activated about two minutes after an actual or misperceived drop in CO2. This causes a deep sigh, and sensations of smothering (respiratory distress: 'Hey, you're not breathing big fella!'). About one and one half minutes following activation of this phase of the alarm, signals are sent to the locus coeruleus. This nucleus is the "on-switch" for almost all of the norepinephrine containing neurons of the brain. As a result of the activation of this nucleus via the solitary nucleus, the second wave of symptoms of panic occur, involving the non-respiratory systems listed above (fight/flight response:'You better act now if you want to live!') as well as compensation mechanisms in the respiratory system itself (hyperventilation: 'Pick up the breathing pace, big guy!'). Thus the panic itself is a time limited episode of short (about 4 minutes) duration. Nonphobic panic will occur whenever CO2 levels build up. This usually occurs when respiration slows or CO2 builds up due to exercise. Thus spontaneous nonphobic panic will occur during sleep, as one falls asleep, or during relaxation training, because respiration has slowed allowing CO2 levels to rise. This triggers the overly sensitive suffocation alarm system (solitary nucleus). Patients with this type of panic chronically hyperventilate and sigh, keeping the levels of CO2 low, as a way of preventing sensations of respiratory distress and suffocation. Interestingly, women are more vulnerable to panic attacks premenstrually and just after childbirth. These are both times when the levels of progesterone drop suddenly. Since progesterone decreases the levels of CO2 in the brain by increasing respiratory rate, the loss of progesterone at these points in time would lead to increased CO2, and more vulnerability to panic.

The second type of panic, trigger induced or phobic panic, is the more common type, and is fear induced. It is manifested primarily by symptoms of pounding heart (palpitations), sweating, and trembling (remember that nonphobic panic starts with a subjective sense of suffocation or breathlessness). In this type of panic the locus ceruleus is activated by a real situation of perceived (thought) threat of death or separation. Sometimes it can be triggered by an unconscious awareness of a cue that is linked to a previously dangerous situation. For example, a person who was raped at a young age may have repressed the memory. When a cue which was noticed and associated with the rape activates the amygdala (rage/fear/sex) nucleus of the brain, it activates the locus ceruleus before the person even is conscious of why she/he is feeling that way! The locus ceruleus can be activated by the threat of separation from the group, an individual one is emotionally or physically dependent on, or life itself. This separation alarm triggers the flight or fight response with release of noradrenalin (more commonly called nor epinephrine) in the brain and adrenalin (epinephrine) in the body. According to Donald Klein, fear induced panic activates the stress response system (the hypothalamic pituitary hormonal axis) immediately.

Clinical Differentiation of Panic Subtypes
In treating patients with panic attacks, the clinician should ask questions aimed at differentiating the type of panic attacks which the patient suffers from. The table will assist you in that process. Ask about the cognitions associated with the panic. Is it phobic? Does the panic wake you from sleep? Does it occur as you are falling asleep or relaxing? When it started, were you premenstrual, post-partum, or just weaning your child, (when progesterone levels are falling)? Have their been recent separations, losses which might activate the separation alarm? If a very careful history indicates that there are no triggers (thoughts or situations) just before the episode panic itself, or associated with the onset of the panics, and if the early symptoms seem associated with relaxation and respiratory symptoms, then it is biologically based and the cause should be investigated thoroughly.

Clinical Implications
The possibility of two types of panic attacks implies that treatment must be tailored to the type of panic. Also, the phase of the disorder must be considered since over time complications such as anticipatory anxiety, agoraphobia, substance abuse, or depression may have developed.
Spontaneous, nonphobic panic attacks, marked by respiratory distress respond better to SSRI's (e.g., fluoxetine [Prozac[), SNRI's (e.g., venlafaxine [Effexor]), imipramine (Tofranil) than benzodiazepines such as alprazolam (Xanax). It is thought that imipramine as well as the SSRI's (selective serotonin reuptake inhibitors) such as fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil) fluvoxamine (Luvox) decrease the sensitivity of the suffocation alarm (the solitary nucleus), and perhaps the locus ceruleus. [

Cognitive therapy should be of limited value in this group, since the panic is unrelated to cognitions, but education about the lack of danger, a search for cause, and the treatable nature of the disorder can be very helpful. Relaxation training would be harmful, since it would slow respiration and increase CO2. This would lead to panic. Exercise, and the premenstrual and post partum period would also increase vulnerability to these panic attacks.

Phobia induced panic responds preferentially to alprazolam (Xanax), and benzodiazepines such as clonazepam (Klonpin), since these medications work on the anxiety (raphe nucleus), GABA and glutamate receptors, and the norepinephrine induced terror (locus coeruleus). Beta Blockers (eg propranolol [Inderal] block the physical symptomns of panic very quickly, but have no effect on the cognitive experinece. They can be very useful for specific situations (e.g., public speaking), or with other forms of panic. Cognitive therapy and behavioral exposure should be effective in this group. Buspirone (Buspar) works on the serotonin neurons in the raphe nucleus to reduce anticipatory anxiety, but does not have any effect on the norepinephrine induced terror (locus coeruleus).

Treatment and Long Term Outcome
As with other disorders, after subtyping and any indicated medical and psycho-social-spiritual-work-up, a combination approach of appropriate medication and therapy are most effective. In a recent study Luvox (a serotonin reuptake inhibitor) when used in combination with exposure to the panic-ogenic situation was twice as effective in reducing self reported avoidance behavior, depression, and anxiety.

The cognitive model of panic assumes that the panic attack develops as a result of misinterpretation of bodily sensations (such as palpitations) as dangerous. Cognitive therapy aims at correction of the misinterpretation and catastrophic thinking. One study compared the effectiveness of cognitive therapy and Luvox, and found 81% of medication treated patients were panic free at 8 weeks, versus 53 % of the cognitive therapy patients. However relapse rates upon discontinuation of medication are high and are reported as being between 20% to 90%. This indicates that, as in the mood disorders, there may be a need for maintenance medication, if there are no physioloc=gical, metabolic underpinnings. Despite the sense that panic disorder can be chronic, there is evidence that a large number of panic disorder patients are significantly improved on long term follow up. It should be noted that in none of the studies cited, were the panic attacks subtyped according to the dichotomy discussed above (phobic vs. spontaneous panic).