Antidepressants have a role in clinical practice but they are grossly over-utilized. As a certified psychopharmacologist, practitioner of Whole  Psychiatry(Functional Medicine and  traditional psychiatry), and Clinical Professor of Psychiatry at Georgetown School of Medicine, I prescribe antidepressants but  only after a thorough multi-faceted  evaluation of the patient.

 We rely on drugs as a solution rather than deal with root causes of illness, and the pills generally are not as effective as we would be led to believe by the  pharmaceutical companies (publically acknowledged as distorted in peer reviewed journals such as New England Journal of Medicine, Eric Turner, 2008). Nor are  these drugs without financial costs and side effects. I suggest that the solution is to develop better assessments of the metabolic factors leading to the syndrome  of depression. The psycho-social-spiritual risk factors are reasonably well spelled out, and we have excellent targeted psychotherapeutic techniques available  now.

 The fact that the head and brain are connected to the body by something called the neck may be relevant. In fact, there is a great deal of basic science and a good deal of clinical science indicating the very significant role played in subjective and objective mental health by at least six metabolic systems: nutrition, gastrointestinal physiology, immune/inflammatory/infectious processes, methylation processes, oxidative stress, and all hormonal systems. This list excludes other factors such as circulatory problems, physical-structural problems, age, gender, and lifestyle factors.

Assessing these metabolic systems, and their mediators in a careful comprehensive manner, and re-establishing multi-system reserves not only helps depression with less medication, but at the same time reduces the side effect burden imposed by medication, and reduces the incidence of known co-morbidities such as diabetes, cardiovascular disease, osteoporosis, sexual dysfunction. Psychopharmacology is only one small tool in our toolbox. As Confucius once said, “To do good work, one must first have good tools.” Anti-depressants are somewhat useful tools; they are just not the best or the only ones. We have other tools at our disposal. Why not use them?

Vitamin B12 deficiency and its detection have been in the news lately from the New York Times and The Dr. Oz Show.

B12 Deficiency Effects Widespread
The effects of vitamin B12 deficiency are widespread.  Vitamin B12 has a major influence on the function of neurons and also on the ability of the bone marrow to make red blood cells.

B12 Causes Psychiatric Symptoms
B12 deficiency can cause almost any psychiatric symptom—from anxiety, and panic to depression and hallucinations.  This is because B12 deficiencies trigger symptoms in the nervous system and red blood cells.

Diagnosing B12 Deficiency
While it is not possible to go into the details of the diagnosis and how to interpret these tests, it is important to understand that assessing vitamin B status involves understanding A DYNAMIC (moving & interacting changes in these parameters) not static assessment of the metabolic systems involved.  And because it is a dynamic system, a static measurement (e.g., B12 level) does not suffice.

As an example of the interactive dynamics, a low iron level makes red blood cells smaller; and, low vitamin B12 makes red blood cells larger. Thus, normal red blood cell size can present a false normal because low iron and low b12 counterbalance each other. If one assesses the size of the red blood cells alone once would miss this fact. However if one also looks at the iron and homocysteine, one would not miss it.  Similarly, a homocysteine level is the result of B12, folate, and mercury levels and therefore a normal homocysteine does not necessarily mean an absence of of B12 or folic acid deficiency.  In turn, all must be assessed to understand the homocysteine.

Early Detection Is Critical
It is critical that a vitamin B12 deficiency be detected as early as possible in order to prevent permanent damage to the nervous system.

The Best Way to Assess for B12 Deficiency
Unfortunately a simple B12 blood level is NOT a sensitive test for detection of B12 deficiency.  A variety of studies have shown that a simple B12 blood level misses vitamin B12 deficiency over 80% of time.  There is no one perfect test for the diagnosis of vitamin B12 deficiency.  Therefore, to determine a vitamin B12 deficiency a thorough assessment involves the following tests and other factors:

Tests

1.    Homocysteine level

2.    Red blood cell count

3.    MCV which (mean corpuscular volume)

4.    Iron & ferritin

5.   MTHFR - a genetic test

Other Factors

1.         One’s age and dietary history (the elderly and vegetarians most often have B 12 deficiencies)

2.        Medications used (people on Glucophage/Metformin, and proton pump inhibitors are often deficient)  

3.        Findings from a physical examination

(Methylmalonic acid testing is commonly thought to be useful, however a little known fact is that less than 20% of the variation in the blood or urine level is accounted for by B12 metabolism, so this test is not useful.)

If you think you have a B12 deficiency, get yourself assessed and treated right away.  

I was wandering around the internet last night, looking for scholarly articles on something called ‘methylation pathways’, when I came across a very disturbing article on the potentially quite toxic interaction between nitrous oxide (NO2) and certain states of B12 deficiency. Before getting into the nitty gritty, bottom line, let me give you some background.

Nitrous Oxide (NO2)-commonly referred to as ‘laughing gas’ was used for years in the practice of dentistry.  It is used currently as part of general anesthesia, and recently has been gaining popularity as a ‘recreational drug’.  An article in Popular Science in the late 1940’s demonstrates how easy it is to make NO2 with an at ‘home laboratory’.

The methylation pathway I refer to above is a fundamental biochemical pathway occurring billions of times per second in the human body.  It’s like the dollar bill of our economy-it keeps things moving.  Methylation plays a key role in the building up and breaking down of molecules.  For example, methylation helps make and break down neurotransmitters (serotonin, dopamine, norepinephrine), estrogens, and histamine (think allergy); methylation helps turn certain genes on and others off, and methylation is involved in protecting nerve cells, making blood cells, strengthening collagen (fewer wrinkles), etc.

The methylation pathways work well when we get enough B12 in our diet (vegans are very vulnerable to B12 deficiencies), enough folic acid (spinach, kale, Swiss chard), and B6.  Additionally selenium (nuts), vitamin B2 (riboflavin), magnesium (Brazil nuts and almonds), and some amino acids (methionine, cysteine, serine, glycine, taurine) are needed to keep the methylation cycle running smoothly.

In addition to these nutrients, we must have genes that can make the enzymes that ‘grease the wheels’ of these pathways.  These enzymes allow things to flow smoothly, and allow methylation to meet the demands of the body and environment.  There are several genes involved in the methylation pathways, and abnormalities of one or more of these genes are quite common (e.g., MTHFR C677T).  These abnormalities slow down the methylation pathways, and connected detoxification and free-radical pathways.

So here is the punch line:

Laughing gas (N02)―nitrous oxide―stops the methylation pathway in its tracks by deactivating B12, and stopping the activity of a certain enzyme for days to weeks. When someone is already deficient in B12/folate (e.g., due to diet, medications such as proton pump inhibitors or Metformin),  or has genes that are not functioning properly, the B12 deficiency is suddenly worsened, and weeks later neurological and psychiatric problems develop. They can be subtle (e.g., trouble with balance) or they can be severe (cognitive problems); any psychiatric syndrome (e.g., panic, depression) can develop.  It is unlikely that anyone will make a correlation of cause and effect between the NO2 and the symptoms, because of the delayed toxicity, and the fact that not every one is effected. Symptoms can be subtle.

NO2 is a very serious danger to your health. The risk is unappreciated by college students who are using NO2 as a recreational drug, and the risk needs to be assessed before use of anesthesia (by testing homocysteine and methionine in the blood, looking for risk factors for B12 deficiency such as a vegan diet or the use of certain medications, as well as the genetic MTHFR test) when possible.  Please raise people awareness of this risk by passing this information along.

Your Biologic Clock

Your Biologic Clock keeps our body rhythms and sleep –wake cycles in synch with the light-day cycle of the earth. It is located in the suprachiasmatic nucleus (SCN) in the hormone control center of the brain, the hypothalamus.  When light enters the eye, it activates this part of the brain and reduces production of the sleep hormone (melatonin) produced in the pineal gland of the brain.  The light also acts to the release of a variety of other hormones and affects body temperature. 

Interestingly, we are programmed to cycle every 24.2 hours―but our exposure to light on a regular basis keeps us linked closely to the earth’s rhythms.  Four neurotransmitters (dopamine, norepinephrine, glutamate, and GABA) have roles in controlling the biological clock.  Importantly, melatonin cannot be produced if thyroid hormone levels are not adequate.  So, if you have sleeping problems, in addition to noting the amount of light you get each day, have your thyroid hormone levels checked.
 
Generally, the more bright light one gets during the day (especially earlier in the day), the more likely one is to make more melatonin (sleep hormone) during the night, and the less sensitive one is to minor light exposure in the evening or night time.

Light Therapy

Light therapy uses specialized artificial light to treat mood disorders, shift one’s biological clock, or synchronize one’s sleep-wake cycle with the day/light cycle.  
It may also be useful in normalizing sleep and behavior in people with dementia, although more research is needed.

The artificial light consists of either a light box which emits up to 10,000 lux  of light, much brighter than a customary incandescent lamp, or a lower intensity of specific wavelengths of light from the blue (470 nm ) to the green (525 nm) areas of the visible spectrum.

Application and Timing of Light Therapy

Synchronizing and/or Shifting Sleep/Wake Cycle
If one wants to delay sleep onset, it is best to give light therapy in the hours before bedtime, when core body temperature is beginning to go down.  On the other hand if one wants to move sleep earlier in the day/night cycle, it is best to administer light therapy in the second half of the night.
 
For Mood Disorders
Seasonal Affective Disorder [SAD] is strictly defined as present when a person has a mood disorder which occurs during a particular time/season of the year, and then clears completely at other times of the year. Current criteria require that this occur for 2 years, consecutively.  In practice, most people have a seasonal component to their depression, but do not fit strict criteria.  Nevertheless, people with a seasonal component do benefit from light therapy.  Light therapy is not a substitute for other treatments in non-seasonal depression, and is probably only an adjunct in those who only have a seasonal component to their mood disorder.  People with a tendency to oversleep and overeat are more likely to respond to light therapy than others.

If one is treating a mood disorder, light therapy is best given for duration of 30 minutes for every hour one sleeps beyond 6 hours.  So for example, if one sleeps 8 hours, they would require one hour of light therapy given one hour before they would normally wake.  Since this is unlikely to be done by people who already feel the need for more sleep, it is best to use a dawn simulator light.
 
Light therapy for mood disorders should usually begin about one week before depressive symptoms tend to begin (based on your past experience), or as soon as they begin.  It should be tapered as the day lengthens.  The transition dates are around the spring and fall equinox (March 20/21 and September 22/23 each year.)

For Dementia
It is possible that bright light between 7-9 PM may help people with dementia sleep better, have fewer nighttime awakenings, reduce the decrease cognitive functioning and orientation (called ‘sun-downing’) which occurs at night.

What Kind of Light Is Best?

Early studies used 10,000 lux (a measure of light intensity) broad spectrum light, kept one to two feet from the eyes. However, newer data indicates that low lux light (500 lux―which is about 1/10 as strong as the light at dawn) may be just as effective.  Short wavelength light (blue part of the light spectrum) seems to be the most active part of the light spectrum, in terms of shifting sleep/wake cycles.  Nevertheless most lights available for SAD are 5,000 - 10,000 lux.

Placement of Light [Dawn Simulator]

A dawn simulator is placed above the head (on a headboard), with the light facing the pillow.  It is set to go on very gradually–starting about three hours before the normal waking time, and peaking in intensity at the normal waking time.  It then shuts off within 10-15 minutes.  The advantage of the dawn simulator is that the treatment is administered while you are asleep, and simulates conditions on a normal spring day.

Are There Side Effects of Light Therapy?

 
Light therapy is similar to drug therapy in that the response depends on dose, timing of dose, and duration of use.  There can be mild side effects as well (agitation, insomnia, and rarely nausea or headache).  If side effects do occur it is usually best to reduce the amount of light therapy, after discussion with your doctor.  One need not look directly into the light to obtain benefits.  If you have an eye condition, you should consult your ophthalmologist before using light therapy.

Yes!  Over the last 20 years, ample evidence has accumulated to prove that inflammation in the body causes changes in the brain that lead to depression, anxiety, sleep problems, and memory problems. Inflammation comes from the Latin  ‘inflammare’ -- to set on fire.  Our brain is ‘on fire’ when it is inflamed, or when our body is inflamed.

What sets your brain on fire?

Your body experiences inflammation the way your skin reacts to a cut:  The area becomes swollen, warmer, and it may hurt.  (This happens because there is increased blood flow, increased immune activity, and a change in the chemistry in the area.)

When there is inflammation any where in the body, signals are sent to the brain via various cytokines. The cytokines send signals to the brain via the vagus nerve and other pathways.  These cytokine signals then block the brain from making serotonin.

What does the fire do to your brain?

Inflammation affects hormones and other neurotransmitters in your brain. Inflammation drives down the level of serotonin, which can lead to feelings of depression or anxiety, and problems with memory.  It prevents melatonin from being produced, which causes insomnia.  It causes dopamine levels to rise, which contributes to insomnia, and feelings of anxiety and agitation.  The excitatory neurotransmitter, glutamate, goes up. Over time or with excessive levels of glutamate, anxiety can result. In extreme amounts, glutamate can be toxic to brain cells.

In fact, in depression, a certain type of brain cell-called an astrocyte, actually deteriorates under these circumstance, which permits the inflammation to continue. Now you have a brain that is, if not on fire, at least smoldering.

You too can prevent brain fires!

It’s not as complicated as you might think!  Try these suggestions (with your doctors approval of course.)

A) Clean up your diet by eliminating food common allergies –

¨    breads

¨    gluten

¨    milk and dairy products

¨    eggs 

¨    sugar

B) Balance your diet

¨    Try the Barry Sear’s “Zone” diet, or one of the diets in my book-“The Anti-depressant Survival Guide”

C) Keep exercise moderate,

D) Make sure your air is clean

¨    No mold, or things you are allergic to-such as dust mites

E) Reduce your stress so your adrenal glands can recover their anti-inflammatory function

F) Clear up all gut issues

¨    70% of inflammation comes from the gut-such as bloating, gassiness, diarrhea, constipation and reflux.

G) Be sure you do not have any hidden infections.

H) Drink lots of water

I) Eat lots of anti-oxidant rich foods

¨    Lots of organic colorful veggies, with a bit of fruit

Many people would be surprised that the immune system, the gastro-intestinal tract and stress interact, but that is what the most recent of a number of studies shows. In this study on mice, (Brain, Behavior, and Immunity Volume 25, Issue 3, March 2011, Pages 397-407. http://www.ncbi.nlm.nih.gov/pubmed/21040780)  researchers demonstrated that  psychological stress causes almost immediate changes to the gut bacterial population, and that some of these affected sub-populations strongly influence the effect that stress has on immunity. In the study, the researchers exposed mice to social disruption, which is known to cause increases in circulating cytokines ('hormones of the immune system), which themselves induce enhanced reactivity in the immune system.  The researchers found that social disruption altered bacterial counts of some gut bacteria sub-populations, particularly when the bacteria were assessed immediately after stress exposure. Stress exposure  increased the relative abundance of bacteria in the genus Clostridium, which often causes prolonged and severe diarrhea (generally after antibiotc use). The stressor also increased circulating levels of IL-6  which was significantly correlated with stressor-induced changes to certain other sub-populations. In a second experiment, these researchers found that a combination of antbiotics prevented the stress induced increase IL-6. This means that certain gut bacteria are necessary for stressor-induced increases in circulating cytokines.So, not only does stress affect the gut bacterial population, but these organisms are also required for  activation of the immune system.

This information becomes even more relevant for psychiatric disorders such as OCD, and depression, as activation of IL-6 has clearly been associated with depression. In fact blockers of IL-6 (eg etanercept) have been shown to reduce depression scores. Furthermore, we can now see, that stress, via its effect on gut bacteria, and hence the immune system (IL-6) can change brain function. We know this because IL-6 activates a certain enzyme (IDO), which actually 'steals' or syphons-off  tryptophan from its normal metabolic pathway ( ie conversion into serotonin and then melatonin) and instead converts it into chemicals that increase activity of glutamate (in depression) at an excitatory-and some times toxic- receptor (NMDA) in the brain. The result of all of this is increased depression, anxiety, and reduced memory. In mice this effect can take moths to reverse. The upshot of all of this, is that stress, the gut, the brain and the immune system are really intimately linked, and inseparable. While this might be news to most psychiatrists, it is not news when one understands the Whole Psychiatry model.

With the ongoing release of radiation into the atmosphere from the damaged Japanese nuclear facilities, many people are wondering whether they should protect themselves as well as what they can do to protect themselves and their families.  Some authorities expect the radiation to spread from Japan in an easterly direction, to the west coast of the United States, while others state that the thousands of miles between Japan and the west coast, will protect the US population from any harmful effects. It seems very likely, that the thousands of miles will in fact dilute the radiation significantly.  

In the United States the Three Mile Island nuclear accident was the worst nuclear disaster we have experienced.  To determine the effect of this radiation exposure on the population a 2002 study conducted by the University of Pittsburgh determined that the average radiation dose to individuals was less than the average annual radiation people receive on a routine basis. Twenty-five years after the accident, the researchers concluded that there was no increase in cancer deaths.  However, another analysis conducted by the Radiation and Health Project has found that death rates for infants, children, and the elderly rose significantly in the two years after the accident.

Based on the above and other conflicting opinions, there remains a question about the real effects of nuclear accidents in the short and long term.  In Japan, the accident has involved five nuclear reactors.  So, it is worth educating oneself about the potential risks.  There is no question that large amounts of radiation over time can increase one's risk of cancer.  Acute release of radiation can cause radiation sickness, which affects the most rapidly dividing cells in the body-the gut, hair, the thyroid, the blood system, the reproductive system and the heart.  The most vulnerable are infants, young children, young adults, pregnant women, and the elderly.

One of the measures recommended to protect oneself from radiation's negative effects, is the use of potassium iodide.  This will protect one from thyroid cancer, when taken quickly after exposure.  This is most likely to benefit those who are in the immediate and surrounding areas of the nuclear event. The further away from the exposure the lower one's risk, and therefore the "cost benefit ratio" shifts against using the potassium iodide. Excessive doses of potassium iodide can cause severe illness, and people who are allergic to iodine should not take it.  People with some skin conditions can be harmed by it, and should consult their doctors regarding the safety of use.  Check out the FDA website (under emergency preparedness) for more information.

According to a new study discussed on Health.com "about 2.4% of people around the world have had a diagnosis of bipolar disorder at some point in their lifetime, according to the first comprehensive international figures on the topic.The United States has the highest lifetime rate of bipolar disorder at 4.4%, and India the lowest, with 0.1%". 

Bipolar disorder has a strong genetic component. Depending on which studies you look at, the  gentics acount for anywhere from 40-60% of the vulnerability. While that seems like a high number it also means 40-60% of the risk of developing the disorder  despite having the same genes comes from the environment. Only 40-60% of  every set of identical twins will develop the disorder. So what is it that could be triggering this high rate of bipolar disorder in the US?

Let's look at this problem from the 'macro' to the micro' levels. On a socio-economic macro level, the US, as the largest and most industrialized Western society, has a somewhat exagerated culture. First, we have the largest gap between rich and poor, so the economic stresses on a large part of thepopulation are greater than in other western societies. This translates into psychological stress, more substance abuse, poorer quality nutrition, and fragmentation of the family. Early child hood rearing is more likely to be by a day care center -which is inherently unstable (people change centers or caregivers change in a center) and impersonal. There is a higher likelihood of bullying and reduced supervision.

The result of all this is impaired social bonding in those who are particularly vulnerable. The poor nutrition results in imparied metabolic functioning (now we are into the micro level), trouble making or breaking down neurotransmitters, more likely infection and inflammation (which change brain chemistry). This is a simple overview, and many books could easily be written about this subject (in fact I have written three books myself on these factors). Suffice it to say that the most vulnerable amoung us pay the price for our imbalanced society. Included in that group are the young, the ill, the genetically vulnerable, and the elderly.

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).

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 agoraphobia, 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 behavioral 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.