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PTSD: The Soldier’s Private War-TMS as a Treatment Option

Thursday, January 17th, 2013

Samuel Pepys was a member of parliament and a high-ranking figure in the Admiralty, where he was instrumental in strengthening the Royal Navy, but he is best remembered as a diarist. His account of the Great Fire of London, which razed the area where the city – the financial nexus of the United Kingdom – now stands, is perhaps the definitive eyewitness narrative of the tragedy. Fully six months after Pepys saw the Great Fire devour people and buildings, his sleep was broken by nightmares of the horror.

Today we would say that Pepys was probably suffering from post-traumatic stress disorder (PTSD), the mental state that we associate with the broken military dribbling back from 12 years of war in the Middle East.

PTSD denotes a psychiatric illness that follows a physical or psychological trauma, like seeing your buddy’s legs blown of by a roadside bomb. But PTSD is older even than warfare; it is probably as old as anxiety itself. However, wars have been a propitious time for studying PTSD, not least because physicians encounter so many more cases of it.

The term PTSD entered the official lexicon of psychiatric diseases in the 1980 edition of the American Psychiatric Association’s Diagnostic and Statistical Manual (DSM-III) and underwent revision in the subsequent edition of the manual; today, clinical psychiatrists, many researchers, disability evaluators, the courts and, for better or worse, anyone else who requires a standardized set of criteria, rely on DSM-IV.

Like other diseases, psychiatric illnesses are recognized by their symptoms, and the clusters of symptoms define a syndrome. PTSD has three important symptoms:
1.hyper-arousal – a state of persistent mental and physical excitation that may endure for months or years;
2.avoidance and numbing – psychological defense mechanisms to block out memories of the trauma, or even life situations that resemble the trauma;
3.re-experiencing the trauma in nightmares like Pepys’, or experiencing “flashbacks,” defined as vivid, waking remembrances of the traumatic event.

In its current incarnation, DSM classifies PTSD as an anxiety disorder, along with free-floating anxiety and panic disorder. One skeptic among many with respect to this classification is co-author James L. Knoll IV MD, associate professor of psychiatry and director of the division of forensic psychiatry at the State University of New York Upstate Medical University in Syracuse. Knoll contends there is strong overlap with other anxiety disorders, but with PTSD, there is very likely a different biological mechanism going on. As a forensic psychiatrist, Knoll is no stranger to PTSD, for he works with crime victims who may have been traumatized for protracted periods of time, if not for life.

Almost every major war in modern times has been accompanied by a different synonym for PTSD, each perhaps with a unique tweak. The first scientifically rigorous investigations of this condition were carried out by Civil War military surgeon J.M. Da Costa. Though the label “Da Costa’s Syndrome” is still used in medical histories, Da Costa himself chose the term “irritable heart” because of the severe, frightening pounding of the heart that prevented soldiers from taking to the field. And the treatment for irritable heart? The only sedative-hypnotic of the day: rum.

In the serene Victorian years that followed the Civil War, ladies of means took to their beds with symptoms of palpitations, shortness of breath, tremulousness and perspiration. Their physicians gave them the diagnosis of neurasthenia, a misleading expression which means “nervous exhaustion.” These women – and many men of the day – had most if not all of the symptoms of Da Costa’s Syndrome. By today’s diagnostic criteria, men and women previously designated as suffering from “neurasthenia” would meet the criteria for PTSD.

With the onset of World War I, British military physicians (and their counterparts in the German trenches) soon observed a cluster of symptoms that they attributed to a kind of concussion from the explosion of artillery shells. The condition was dubbed “shell shock,” but when these soldiers were examined more closely, 60-80 percent were deemed “neurasthenic” and 10 percent suffered from what was then called “a fugue state” and which we now recognize as numbing.

And so it went from war to war. Da Costa’s Syndrome became whatever psychiatric or physiological symptom seemed the most prominent: effort syndrome, neurocirculatory asthenia, combat fatigue, post-Vietnam Syndrome, and finally PTSD. As new drugs became available, physicians tried them, graduating from alcohol to laudanum (a tincture of opium) to chloral hydrate and barbiturates to benzodiazepines and Thorazine-like compounds to antidepressants.

Just as DaCosta’s Syndrome, effort syndrome, neurasthenia and PTSD have a common profile on the symptomatic level, so too do they have a common denominator on the physiological level. This was first shown by two British investigators in 1946 (M. Jones and V. Mellersh, Psychosomatics). The scientists were studying the “effort syndrome.” When these patients are exercised, it turns out that their blood lactate, a normal product of muscular exertion, is significantly higher than controls without the effort syndrome. This finding, which still has psychiatrists scratching their heads, was confirmed by several other investigators in the next few years.

There the matter lay until 1967, when two Washington University psychiatrists conducted an ingenious experiment: they infused lactate into an arm vein of normal controls and patients suffering from chronic anxiety. The lactate had no effect on controls, but the patients with anxiety “neurosis” (to use a term that was prevalent at the time) experienced full-blown panic attacks from the lactate infusion; in some instances the reaction was so violent that the infusion had to be stopped prematurely.

So, exercise abnormally raises the level of blood lactate in patients with “effort syndrome,” while conversely, infusion of lactate into patients with a history of anxiety provokes panic attacks. Research with lactate continues; of particular interest is that several teams (i.e., Am J Psychiat 1987 Oct;1317-9) have administered lactate infusions to patients with PTSD; the infusions were found to provoke flashbacks of the traumatic event.

The word “panicogenic” was coined for a diverse group of chemicals that trigger panic attacks. Besides lactate, they include carbon dioxide and cholecystokinin. It’s not known whether these chemicals are impacting on the physiological substrate of anxiety, or whether their effects are parenthetical. Evidence from the science of pharmacology suggests that they really do mobilize the physiological mechanism of anxiety. The reasoning goes like this: it’s not known whether the diverse panicogens all act on the same underlying, natural cause or causes of anxiety. As we’ll see, drugs that block anxiety attacks (namely antidepressants) also block the action of panicogens, suggesting that panicogens hit on the underlying cause of anxiety, but this is only an educated guess.

It is well established that most antidepressants block panic attacks, but they do not work like the benzodiazepines (Klonopin, Valium, Xanax, other peer drugs). Antidepressants usually take at least two weeks to kick in, because this is thought to be the time required to boost neurotransmission of serotonin in the brain. On the other hand, benzodiazepines often calm the patient in a couple of hours by inhibiting the central nervous system through their effect on releasing the neurotransmitter GABA (gamma-amino-butyric -acid). Anti-depressants prevent the attacks from “happening.” One such antidepressant is the drug imipramine (Tofranil). It has been shown that imipramine blocks the panic attacks artificially induced by panicogens, just as it blocks “natural” panic attacks.

It is especially interesting, therefore, that antidepressants constitute front-line therapy for patients with PTSD. These days, psychiatrists generally use specific serotonin reuptake inhibitors (SSRIs) such as Zoloft, Prozac or Paxil, or a specific serotonin/noradrenaline reuptake inhibitor, notably the drug Effexor. To these, in his clinical practice, co-author Knoll may add low doses of a second generation antipsychotic, of which the most familiar are Abilify, Seroquel or Zyprexa. Antipsychotics are not curative in themselves, but they enhance the effectiveness of antidepressants. A third drug in Knoll’s armamentarium is Prazosin. Though marketed as an antihypertensive, practitioners and patients have found Prazosin effective at blocking nightmares. Of particular interest is a study by Michael H. Mithoefer, MD that MDMA (a k a ecstasy) was found to be highly effective for treating PTSD in combination with psychotherapy. And at the University of Arizona, Sue Sisley MD, a psychiatrist and internist, is awaiting delivery of a supply of marijuana from the National Institute on Drug Abuse (NIDA) to begin a trial approved by the Food and Drug Administration (FDA). There has been some interest in propranolol (Inderal) for “erasing” PTSD-type memories, but this is based on anecdotal accounts and small-scale studies. On the other hand, propranolol can cause vivid nightmares – the last thing you’d want in a patient with PTSD.

Besides drugs, psychiatrists are studying other approaches to treating PTSD. Thus, retired Lt. Gen. Stephen N. Xenakis MD is using hyperbaric oxygen therapy. In this procedure, the patient breathes in oxygen at very high pressure. This ties in neatly with what we know about lactate; high levels of oxygen would be predicted to speed up cellular metabolism, burning off lactate in the process.

A second approach for which there are a number of positive claims is transcranial magnetic stimulation (TMS). Briefly, TMS uses an oscillating magnetic field to release neurotransmitters over the course of a month of daily outpatient treatments; it bears no resemblance whatever to shock therapy. We were informed by the manufacturer of the NeuroStar TMS instrument that the military is interested in TMS and has purchased a number of instruments.

Tags: Anxiety, depression, Mental Health, Military, psychiatrist, psychiatry, PTSD, Soldiers, tms, transcranial magnetic stimulation
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