When a combat veteran presents to a military behavioral health clinic, it is usually because he or she is desperate. After three or four deployments to a war zone and spending more time in the theater of battle than at home, these soldiers find themselves no longer able to function as husbands, wives, fathers, mothers and co-workers. It is because of men and women like these that many of the dedicated Department of Defense behavioral healthcare professionals remain in the field of military psychiatry.
The most rewarding part of the job is seeing the smiling face of a patient when he or she returns for a follow-up appointment and reports with jubilation that he or she slept without a nightmare. Of all the symptoms reported by soldiers affected by post-traumatic stress disorder (PTSD), insomnia and terror-type nightmares are perhaps the most debilitating. It has been said that restorative sleep is fuel to the brain. Without it, the brain has little chance of functioning optimally. And that is what most sufferers long for: simple functionality.
According to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revised (DSM-IV-TR) a person is affected by PTSD if he or she experiences:1
an immediate, fearful response to a traumatic event and then manifests at least one repeated symptom (i.e., vivid, intrusive memories or nightmares)
at least two symptoms of hyperarousal (i.e., insomnia, irritability or anger, poor concentration, hypervigilance, or exaggerated startle response to loud noises)
at least three avoidance symptoms (i.e., anhedonia, detachment, a sense of a foreshortened future, avoiding crowds or social events that were once enjoyable, or avoiding war movies or novels that were once pleasurable activities).
If these symptoms are present for 1 month or longer, the person is diagnosed with PTSD. If the symptoms have been present for less than a month, the diagnosis is acute stress reaction. If the presenting picture involves some of the above criteria but does not quite fulfill the requisite number of symptoms, the diagnosis is anxiety disorder not otherwise specified (NOS).1
In a busy military behavioral health clinic, either in garrison or in a combat zone, it may not be possible to confirm a soldier's account that he or she was involved in a traumatizing incident. Therefore, fulfilling the first criterion of PTSD is not always possible. Unfortunately the soldier's veracity is sometimes in question, primarily due to the potential of secondary gain in obtaining a diagnosis of PTSD. Soldiers who obtain this diagnosis become eligible for separation from the military with a lifetime pension. Therefore, it is often necessary to utilize the diagnosis of anxiety disorder NOS until corroborating evidence is available. Regardless of what the disorder is called, the paramount issue is the treatment of the debilitating symptoms.
Approaches to Treatment
In people who have experienced a traumatic event, nightmares often arise soon afterward. Vivid daytime intrusive memories can also occur and may be debilitating, but the nighttime dreams tend to affect patients during the brain's most vulnerable period, when it is asleep. Poor sleep, initial and middle-of-the-night insomnia are a major symptom cluster in PTSD. This begs the question of which came first, the nightmare or the insomnia. Many people who experience post-traumatic symptoms develop a fear of going to sleep due to the night terrors that occur. If this symptom alone were eradicated, victims of this anxiety disorder would fare much better.
This is exactly what was discovered with the resurrection of an unlikely older medication, the alpha-1 blocker prazosin (Minipress). The Veteran Affairs Department (VA) was conducting studies of prazosin in Vietnam War veterans to assess the efficacy of treating their hypertension and benign prostatic hypertrophy (established indications) when an unexpected finding was discovered. Many of the veterans reported that their nightmares were going away and their overall anxiety levels were markedly reduced.2 This discovery ushered in a revolution for the treatment of anxiety disorders. After the VA released its findings, further studies investigated the prospective treatment of anxiety symptoms.
The use of prazosin to treat PTSD is an off-label use. Low-dose prazosin, with its antagonistic action at the alpha-1 noradrenergic receptor, seems to ameliorate and often eliminate nightmares. When used as an adjunct to an antihistaminic sleeping agent, such as trazodone (Oleptro) or mirtazapine (Remeron), doses of prazosin as low as 1 mg to 3 mg per night work well.2 The studies conducted by the VA reported that the average effective dose for nightmare suppression was 13 mg per night, but empirically it has been found that a dose of 1 mg to 3 mg per night seems is therapeutically effective.2 A typical regimen is to have the patient start at 1 mg per night for 2 to 3 nights. If a nightmare occurs, the provider can titrate by 1 mg every 2 to 3 nights until nightmare suppression is achieved. Whatever dose induces adequate sleep is considered the maintenance dose. In many cases when sleep is not a significant problem but the patient wakes up often as a result of nightmares, prazosin alone with no sleeping agent can be effective. It is important to emphasize the potential for orthostatic hypotension while using prazosin. This side effect is usually self-limiting at low doses and typically happens during the first dose or two, if it happens at all. So, a reminder to have the patient sit up for a few seconds before standing abruptly in the middle of the night should avert this potential side effect.
Because PTSD is an anxiety disorder and the hallmark symptoms are driven primarily by a disordered limbic system, the underlying anxiety disorder requires attention. Clinical research using brain scans has demonstrated that patients with anxiety and depression have hippocampi that are much smaller than control subjects with no symptoms.3 Since the hippocampus is rich in serotonin receptors, it only makes sense to nourish the apparent diseased part of the brain with more serotonin. When this happens, the overall anxiety symptoms improve. If all symptoms are being treated adequately, the odds of reaching remission are good.3 Remission is the absence of symptoms, not mere improvement or response to treatment.
No single medication will treat all symptoms of PTSD; in most cases it takes a combination of medications. Patients can be tapered off the medications about 12 months after remission is achieved. This approach reduces the risk of relapse.3
A typical medication regimen for treating PTSD includes a selective serotonin reuptake inhibitor (SSRI), a histaminic sleeping agent and prazosin. Much debate exists among psychopharmacotherapists as to whether one SSRI is better for PTSD. Only sertraline (Zoloft) and paroxetine (Paxil) have official indications for treating PTSD.4 Serotonin and norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (Effexor) and duloxetine (Cymbalta) have been utilized with good effect as well.
Many providers have a favorite serotonergic agent for various reasons. I happen to favor sertraline, since empirically I see a more positive response with fewer side effects compared to other agents. Sertraline tends to be weight neutral and its risk of causing sexual dysfunction tends to be lower than what is seen with other SSRIs. A typical dosing regimen with sertraline is 25 mg daily, titrating by 25 mg every week up to 100 mg daily. It is dosed at bedtime with a snack to augment potential drowsiness and offset gastrointestinal upset. With its 26-hour half-life, sertraline tends to be therapeutic no matter the time of the day it is taken. However, nighttime dosing helps avoid noticeable side effects and offers a better chance at adherence if the patient is taking all medications once daily at night.
Whichever antidepressant agent used, it should be the base of the treatment. Since the goal is to get the patient back to a functional level and achieve lifelong remission, it is helpful to "bathe" the limbic structures in the enhanced serotonergic state for the recommended 12 months of treatment.3
An SSRI does not do much to improve poor sleep. Sertraline can cause some sedation, but the likelihood that this side effect will treat the insomnia by itself is not very good. This symptom should be treated on its own. It is prudent to use a medication that antagonizes histamine, such as trazodone (Oleptro), mirtazapine (Remeron), low-dose doxepin (Silenor) or hydroxyzine (Atarax). Drugs that affect the benzodiazepine site on the gamma-aminobutyric acid (GABA) receptors, either benzodiazepines themselves or the "Z" drugs, zolpidem (Ambien), zaleplon (Sonata) or eszoplicone (Lunesta), are generally not recommended. There is evidence to suggest that benzodiazepines should not be used with PTSD due to the masking effect they give when trying to engage patients in desensitization therapies.5 Also, the risk of encountering the addictive and tolerance-building properties of these drugs is generally not worth it.
The "Z" drugs affect GABA receptors at a benzodiazepine omega site on GABA-A receptors. Reportedly, the addictive properties of these agents are not as great as those of the benzodiazepines; however, empirically this report has been found to be without merit.6 The risk of the patient experiencing a parasomnia (widely reported with these agents) in a population that at times commits amnestic, aggressive acts toward bed partners while coming out of a combat related nightmare could prove to be problematic.5
Trazodone tends to be a good choice due to its empiric efficacy in combination with SSRIs. Because trazodone has some serotonergic properties itself, it works synergistically with SSRIs in treating the anxiety. It also has a bit of an alpha-1 noradrenergic antagonism that can decrease nightmares. It does not seem to achieve this action as robustly as prazosin, but it can help with the bad dreams. It is dosed at 50 mg 1 to 2 hours before bedtime with instructions to titrate by 50 mg every 3 nights up to 150 mg if needed. It is important to advise men about the rare risk of priapism with trazodone.4
Patients with PTSD should not drink alcohol or use illicit substances while receiving treatment. This population is at high risk for substance abuse and this must be mitigated before psychotropic agents are considered.
Treatment should be initiated with the SSRI. If insomnia is present in follow-up a week or two later, a sleeping agent can be added. If nightmares continue after this, prazosin should be added. This paradigm is not absolute. Depending on the presentation, it might be more beneficial to start with one of the other agents first. If the insomnia is the worst presenting symptom, start with the sleeping agent and add the SSRI later. Due to the risk of drug-drug interactions or intolerance to one or the other medication, it is advisable to wait at least a week in between start-up times in order to allow the person's body to adjust to a new medication before adding another agent.
As symptoms abate and the patient achieves remission, it is possible to taper off the sleeping agent if desired.
The period of time needed to achieve remission varies, but two to three months seem to a realistic time frame.3 Whether or not the prazosin for dream suppression can be discontinued may be tested, but if the patient is tolerating it well with no untoward side effects, it is reasonable to continue this medicine with the serotonergic agent. The challenge is to convince the patient to remain on the regimen for 12 months. People tend to stop taking the medications once they are symptom free. The natural tendency is to think that the previous symptoms plaguing them at the onset were not quite as bad as they thought, and perhaps it was all a coincidence and the medications had nothing to do with the symptomatic relief. This is the crucial time in treatment when the neurons are healing, and if given the proper treatment duration, they are apt to regain their healthy neurologic state.5
The purpose of this overview is to detail some empirical guidelines for treating PTSD with psychopharmacology. However, this is merely a small piece of the puzzle in treating the myriad symptoms of this disorder. Remember that the primary reason these symptoms exist is because the brain has failed to properly process the patient's experiences. While medications can help the neurons symptomologically, the real healing takes place when the person can process the experiences in a healthy manner. This is accomplished through various therapeutic measures, but the crux of the intervention is to allow the brain to desensitize itself to the experiences through controlled sessions of in-vitro re-exposure. In many cases this is achieved with no medications at all. In some instances this should take place simultaneously with medication treatment, but often the therapy is most successful after a person's symptoms have been stabilized on a good medication regimen.
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., TR. American Psychiatric Association: Washington DC; 2000.
2. Calohan J, et al. Prazosin treatment of trauma nightmares and sleep disturbance in soldiers deployed in Iraq. J Trauma Stress. 2010;23(5):645-648.
3. Figley CR, Nash WP. In: Combat Stress in Injury: Theory, Research and Management. New York, NY: Routledge Taylor & Francis Group; 2007: 86, 206, 226.
4. Stahl SM. In: Essential Psychopharmacology: The Prescriber's Guide. Canada: Cambridge University Press; 2007: 377, 465, 513.
5. VA/DoD Clinical Practice Guideline for Management of Post-Traumatic Stress.
Department of Veterans Affairs, Department of Defense. http://www.healthquality.va.gov/Post_Traumatic_Stress_Disorder_PTSD.asp
Rick Sonnier is a nurse practitioner at Fort Hood Department of Behavioral Health in Fort Hood, Texas, where he specializes in the treatment of psychiatric disorders including post traumatic stress disorder. The views expressed in the article are those of the author and do not reflect the official policy or position of the Department of the Army, Department of Defense or the U.S. Government.