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Authors: Charles W. Hoge M.D.

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B) Other Antidepressants

Several newer antidepressants are likely to be useful in PTSD, and studies
are now being conducted to confirm their effectiveness. These include venlafaxine (Effexor), duloxetine (Cymbalta), desvenlafaxine (Pristiq), and
mirtazapine (Remeron). All of these affect nerve transmission of norepinephrine (related to adrenaline) in addition to serotonin, although mirtazapine works by a different mechanism than the other three. They are
likely to be useful in part because of their effect on serotonin (similar to the
SSRIs), and they appear to be less likely to cause sexual side effects. However, they do have some additional side effects, which usually make them a
second choice after trying an SSRI. Venlafaxine (Effexor), duloxetine (Gymbalta), and desvenlafazine (Pristiq) have a modest effect on elevating blood
pressure and heart rate, and it's necessary to monitor these while taking
them. Like SSRIs, they can cause increased anxiety when first started. Mirtazapine (Remeron) can cause drowsiness, constipation, and weight gain.

Again, it's wise to talk with your doctor and review the package insert
so you're fully informed of the risks, side effects, and precautions. In addition to these medications, there are a number of older antidepressants in
the "tricyclic" class that can be tried if there hasn't been response from the
newer agents; however, these have more side effects and risks.

C) Blood Pressure Medicine Prazosin (Minipress) for Nightmares

For warriors, nightmares are often associated with increased blood pressure, pounding heart rate, and feeling revved up. Prazosin helps to reduce
these physiological reactions, which in turn can help with the nightmares.
See chapter 4 (skill 4) for a more complete discussion of this medicine.

D) Atypical Antipsychotics and Mood Stabilizers

There are several new medicines approved by the FDA for treatment of
schizophrenia and bipolar (manic depressive) disorder that are now being
combined with an SSRI or other antidepressant to try to improve results in PTSD treatment (particularly sleep problems and nightmares). The most
common medication that is being used in this way is quetiapine (Sero-
quel). Other medicines in the same category as quetiapine (called "atypical
antipsychotics") include risperidone (Risperdal), olanzapine (Zyprexa),
ziprasidone (Geodon), and aripiprazole (Abilify). Mood stabilizers (anticonvulsants) are a class of medicine used in bipolar (manic depressive)
illness, and include lithium, valproic acid/divalproex sodium (Depakote),
carbamazepine (Tegretol), oxcarbazepine (Trileptal), and lamotrigine
(Lamictal). All of these medicines have significant side effects and risks,
which are beyond the scope of this chapter to review. They should be considered only after exhausting other options, and should be prescribed in
consultation with a psychiatrist (i.e., a primary care doctor should not be
initiating these medicines without input from a psychiatrist).

Quetiapine (Seroquel), in particular, has gained popularity in recent
years because of its apparent safety, its antidepressant effects, and its usefulness
in improving sleep and reducing nightmares. However, there are emerging
concerns about this medicine contributing to diabetes, heart problems, and
weight gain, as well as other risks. There needs to be very careful assessment
to ensure that the potential benefits outweigh the risks for this medicine, and
it should be used cautiously, only after exhausting other options. Monitoring
weight, glucose, and lipids before and during treatment are required.

E) Benzodiazepine Antianxiety Medicines

Benzodiazepines include alprazolam (Xanax), clonazepam (Klonopin),
lorazepam (Ativan), and diazepam (Valium). These medicines are marketed
to alleviate anxiety, and unfortunately are prescribed all too frequently to
warriors with PTSD to help reduce anxiety and improve sleep. However,
benzodiazepines have not been shown to be effective in alleviating PTSD
symptoms, and have very detrimental side effects; most important, they
carry a high risk of becoming addictive. Benzodiazepines are sometimes a
warrior's favorite medicine because they act like taking a drink of alcohol.
They are positively my least favorite medication to prescribe, because they
almost always make things worse. Please see the sleep section in chapter 4
for a much more detailed description of this class of medicine.

F) Medicines to Help with Sleep

This topic is covered in chapter 4, skill 4.

Complementary and Alternative Medicines (CAM) and other
Potential Treatments

There are numerous new modalities of treatment being promoted for
PTSD (and mTBI), and treatments du jour seem to be constantly springing up as the latest "answer" to the PTSD (or mTBI) problem for returning combat veterans. A lot of interest has been generated by increased
government funding for research for both of these conditions since the
start of the wars in Iraq and Afghanistan, particularly in complementary
and alternative medicines (CAM). CAM is a fancy term used to describe
the large amount of nontraditional approaches that are widely available.
Some of these have been promoted in news stories, and many veterans
have questioned why the DoD and VA have not adopted them for regular
use. The reason is that these modalities have not been proven to be effective in rigorous research studies.

This is only a sample of some of the approaches being promoted as
effective for PTSD: virtual reality therapy, herbal supplements, megavitamins, acupuncture, yoga, biofeedback, tai chi, qigong, Reiki, massage, heart
rate variability monitoring, low-voltage electrical stimulation (e.g., Alpha-
Stim), bio-energy work, hyperbaric oxygen, experiential Outward Bound
programs, dance therapy, art therapy, Emotional Freedom Techniques
(EFT), neurofeedback/EEG feedback, pet therapy, blue light therapy,
transcranial magnetic stimulation, and MDMA (the party drug Ecstasy).

Given this lengthy (and incomplete) list, how do you make sense of
all this? One simple way is to first group all of the modalities that involve
any sort of bodywork or physiological feedback (e.g., acupuncture, yoga,
biofeedback, tai chi, qigong, Reiki, massage, heart rate variability monitoring, neurofeedback/EEG feedback, bio-energy, and maybe EFT). These
may be of benefit for some PTSD symptoms because they likely have a biological basis in reducing the physiological stress response. In essence, they
are likely to be complementary with standard stress inoculation and stress
reduction techniques that have been studied scientifically, such as dia phragmatic breathing, meditation, and relaxation exercises that reduce
anxiety and the physiological processes involved in being revved up. It's
doubtful that they are any better than the standard stress reduction techniques, but they do offer alternatives that might appeal to some people.
Whatever approaches you find most helpful to relax and reduce your own
physiological reactions are definitely going to be useful. Outward Bound,
dance therapy, and maybe pet therapy similarly mobilizes the body and
mind. It's not likely that any of these modalities can be sufficient for alleviating PTSD without the narration and cognitive components found in
other therapies, or the close connection to someone you're sharing your
story with.

While herbal supplements and megavitamins are readily available,
they haven't been proven to be effective in PTSD, and they carry risks,
including negative interactions with prescription medicines. Low-voltage
electrical stimulation (e.g., Alpha-Stim), blue light therapy, transcranial
magnetic stimulation, and hyperbaric oxygen are experimental, and have
a limited theoretical basis to think that they will be particularly useful for
the full spectrum of PTSD symptoms. The idea of using MDMA (Ecstasy)
is particularly worrisome because this drug can cause irreversible changes
in serotonin nerve transmission, as distinct from SSRIs, which have effects
on neurons that wear off quickly. We just don't know enough about how
any of this works in the brain to take that kind of risk.

Virtual reality simulation for treating PTSD has received high public
attention in news stories. Virtual reality is a method designed to expose
warriors to traumatic wartime images similar to those from their own experiences in an effort to desensitize or habituate them to these experiences,
thereby reducing their level of anxiety. Essentially, virtual reality is another
way to deliver exposure therapy, and involves an interactive process
between the warrior and the therapist related to the combat experiences.
To date, there has been no definitive head-to-head comparison between
virtual reality and standard exposure therapy. My assessment of the current evidence is that there is nothing that beats talking with someone faceto-face without any other distractions, and it's unlikely that virtual reality
will play a prominent role in PTSD treatment after thorough evaluation. Where virtual reality will probably be most useful is in helping to prepare
warriors before deployment through combat simulation. Tough realistic
training can improve preparation and may offer the possibility of improving resilience and preventing PTSD in the future.

The discussion of CAM and other modalities highlights the critical
need for high-quality research of all new PTSD treatments. Many of these
are being actively promoted to veterans and health professionals as cures
for PTSD, without adequate research data to support these claims. Initial
reports of effectiveness, even for many conventional treatments, often do
not meet expectations when rigorous research is conducted, and sometimes treatments that show high promise initially are ultimately found to
be harmful. The bottom line is that there is no "magic bullet" for PTSD,
and claims to the contrary should be taken with more than a grain of salt.

How do you evaluate if a new treatment has adequate evidence for
effectiveness? Although there is no simple answer to this question, the most
direct answer is that the treatment has been shown to be effective (evidencebased) in one or more controlled scientific studies in which the proposed/
experimental treatment is directly compared with a standard treatment or
no treatment, as described above under the "treatment effectiveness" section. To do these types of research studies, patients with PTSD are invited to
participate and provided with a detailed explanation of potential risks and
benefits (informed consent). They are then randomly assigned to either
the treatment group or the control group, and both groups are followed
for an equal duration of time. The evidence is stronger if the control group
includes a standard treatment (or at least a sham treatment); if there are
several studies that show the same results; and if studies involve "blinded"
methods, where the researchers evaluating the outcomes don't know which
groups study participants are assigned to. These types of studies are difficult
to do, expensive, and require a high level of ethical and scientific oversight.
Obviously, it's a lot easier to just claim that a treatment is effective without
doing the research, which is why there's a glut of snake oil salesmen in this
business now. For this reason, it's critical that both medical professionals
and veterans advocate strongly for evaluation through rigorous scientific
methods, and not accept claims at face value.

DISABILITY AND TREATMENT

One final topic that I hesitate to bring up, but needs to be discussed, is the
relationship between treatment effectiveness and receiving disability compensation for the condition that is being treated-in this case, PTSD. This
is a particularly important topic if you have gone through (or are going
through) the disability evaluation processes in the DoD, VA, or both. (The
topic of mTBI disability was covered in chapter 2.)

PTSD can be a severely disabling condition, and it's appropriate
and necessary for warriors who have severe PTSD symptoms to receive
compensation up to the level that matches their functional impairment,
which may be as high as 100 percent. If they can no longer function in
an operational setting, hold a job, or have a meaningful relationship as a
result of wartime traumatic events incurred while serving their country,
then they need all the assistance and support that this country can offer.
Unfortunately, however, when warriors embark on the journey of seeking
disability compensation for their wartime experiences, they find themselves in the most peculiar of catch-22s, more insane even than some
battlefield scenarios that they may have encountered, and akin to the
situation that the main character in Catch-22, Yossarian, found himself in
(see chapter 7, skill 2).

This peculiar situation, generated by the ponderous and almost incomprehensible DoD and VA disability regulations (contained in the Code of
Federal Regulations) is as follows: A warrior who is in legitimate need of
assistance with wartime trauma must be sufficiently ill with the disorder for
a long-enough period of time to qualify for PTSD disability. However, in
order to accomplish this, he has to be well enough to navigate the slow, cumbersome, frustrating, and bureaucratic disability application process, which
if successful likely means that: 1) He wasn't able to find an impossible-to-get
job that would have permitted him to spend innumerable hours away from
work dealing with the application and treatment process, thereby making
it more likely that he is jobless; 2) His interpersonal skills were severely
tested on a daily basis by the situation, thereby making it more likely that
he was deemed to have "interpersonal problems"; 3) He was able to show
up for all of his therapy appointments, as required, but the time in these many sessions was only sufficient to focus on improving his ability to cope
with his "occupational" and "interpersonal problems" and not kill anyone;
and 4) There wasn't sufficient time in the many therapy sessions to focus
on the real issues of treating his PTSD, which turns out to be a "blessing in
disguise," because if there had been time to really address his PTSD symptoms, this may have resulted in his disability application being denied or his
disability rating lowered. Welcome home, warrior!

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