There appears to be professional consensus that pharmacotherapy in PTSD is a critical and important treatment component for PTSD (Friedman et al., 2000a) for a number of reasons: research supported biological abnormalities in PTSD; overlap with other disorders that are very responsive to drug treatment, such as depression and Panic Disorder; and its general acceptance by patients despite side effects and often prohibitive costs. The National Center for Post-Traumatic Stress Disorder proposes the use of pharmacological treatment for individuals who have already been through debriefing or brief crisis-oriented psychotherapy.
Without being facetious, alcohol is probably the oldest form of medicinal treatment for PTSD. Heroin abuse and dependence was not uncommon in Vietnam and in those who returned home with addictions. In essence, any medicine, drug, or substance that could calm one's nerves might be sought out as a medicinal remedy to the distress of PTSD. Barbiturates, powerful central nervous system depressants, have been used in the past, but their strong addictive properties and drugging effects have resulted in their falling out of favor. As medicine and pharmacology progressed in both research and practice, newer, more efficacious drugs that could produce the desired effects without the unde-sired consequences of side effects and nontarget effects came into use. The pharmacological treatment of PTSD involves the use of the following classes of drugs: anxiolytics, antidepressants, anticonvulsants, antiadrenergic drugs, antipsychotic agents, and various other, more atypical drugs.
Pharmacotherapy of PTSD should logically focus on reducing the core symptoms of the disorder of reexperiencing, avoidance and numbing, and hyperarousal. Also, increased resilience and coping, improved quality of life, reducing comorbidity, and limiting the degree of disability are important target goals for treatment (Davidson & Connor, 1999). Foa, Keane, and Friedman (2000) suggest that the course of drug treatment for PTSD carry on for 8 to 12 weeks, keeping in mind, however, that symptom reduction has been observed as soon as within 2 to 5 weeks.
Friedman (2001) recommends working from an allostatic load perspective in the pharmacological treatment of PTSD. From this perspective, it is important to keep in mind that "a system can overshoot, undershoot, fail to recover, or become otherwise dysregulated because it is incapable of accurately titrating its adaptive repertoire to environmental demands" (Friedman, 2001, p. 94). This implies that there is a broad range of psychobiological processes implicated in the disorder and, as such, each component of the disorder may respond to a different medication or a different form of treatment. I think the lesson Friedman is teaching us is that although it is prudent to be flexible and open-minded in all treatment, it may be absolutely essential with PTSD.
Anxiolytics are the large class of drugs used to treat anxiety. Gitlin (1996) cites that anxiolytic literally means "loosening of anxiety" (p. 349). Early treatments of Anxiety Disorders as a broad class were dominated by sedating hypnotic drugs and barbiturates. These, however, had significant complications, such as interfering with someone's ability to think clearly, physical responsiveness, and sleepiness, which interfered with everyday functioning and even contributed to dangerous-ness. These drugs and agents were also highly addictive. Gitlin (1996) identifies that there has been a progressive search to find the perfect tranquilizer. Eventually, benzodiazepines replaced these drugs and were more widely used. Librium and Valium made their way onto the scene in 1960 and 1963, respectively.
Benzodiazepines work primarily by enhancing GABA-induced inhibition in the brain, inhibiting glutamate's ability to produce postsynaptic excitation in select and implicated brain areas. Benzodiazepines achieve their effect by functionally increasing the firing threshold of the amygdala in response to either external or internal stimuli by affecting GABA cells. Ultimately, benzodiazepines work to reduce arousal and reactivity by increasing inhibition. Fear is suppressed by setting the system at a higher threshold for responding and inhibiting subsequent reactions.
Research and practice guidelines suggest that benzodiazepines be used as an adjunctive treatment in PTSD for treating sleep difficulties and for quick relief of global anxiety and immediate treatment of impending panic attacks. It is not recommended as a monotherapy.
Antidepressants and PTSD Selective Serotonin Reuptake Inhibitors, Monoamine Oxidase Inhibitors
Tricyclic Antidepressants, and
Selective serotonin reuptake inhibitors (SSRIs) are currently considered first-line therapies for PTSD and are considered a treatment of choice (Friedman, 2004). Treatment guidelines from the International Society for the Treatment of Traumatic Stress (ISTSS) state that SSRIs are the most effective medication for PTSD. Improvement and symptom reduction has been shown as early as 1 to 2 weeks after the drugs are first administered. Remission has been associated with treatment lasting at least 15 months. Fluoxetine has been found to significantly reduce overall PTSD symptoms, including intrusive symptoms and arousal. Sertraline has been found efficacious in both short-term and long-term therapy and has shown specific effects on anger and irritability. Further, the United States Food and Drug Administration recently designated sertraline as a specific treatment for PTSD. This finding is of note according to Friedman (2001) because the effectiveness of sertraline for PTSD appears to be unrelated to its efficacy as an antidepressant as research has revealed that when subjects with PTSD and a history of Major Depressive Disorder were compared to subjects with just PTSD, there was no difference. Paroxetine and flovoxamine both have been effective as well. A bonus feature of this class of drugs is that SSRIs are also very effective in treating common comorbid conditions, such as depression, Panic Disorder, and Social Phobia.
The effectiveness of SSRIs for treatment of PTSD is not a completed picture, however, with no questions remaining. For instance, research has shown that flu-oxetine may be less effective with Vietnam veterans, perhaps due to the severity and chronicity of their symptoms (van der Kolk et al., 1994; Friedman, 1997).
Tricyclic antidepressants (TCAs) have been found effective for short-term treatment of PTSD. Perhaps the most commonly used and most popular TCA is imipramine, which first made its way onto the scene for treatment of depression in the late 1950s. Tricyclic antidepressants have been used as effective treatments for depression and were considered first-line treatments until the advent of the SSRIs. Tricyclic antidepressants have both serotonergic and noradrenergic effects, essentially leading to blocking of reuptake of serotonin and norepinephrine. After initial reuptake is blocked, serotonin levels rise in response to feedback from the hence inhibited presynaptic neuron. Ultimately, serotonin transmission is enhanced, and postsynaptic reception and sensitivity of serotonin is increased. Noradrenergic functioning is altered by inhibiting reuptake as well. Although TCAs have been shown to be effective in treating both depression and PTSD to some extent, once the SSRIs came along, they fell out of favor as comparatively they are more difficult to use, have more side effects, are slightly less effective for the same range of disorders, have a narrower range of disorders for which they are effective, and are less preferred by patients. However, Gitlin (1996) cites that imipramine is still the standard by which all newer antidepressants are held up against in the treatment of depression. He states, "after thirty-five years of research, we still do not have an antidepressant that treats major depression more successfully than imipramine" (p. 279).
Research on the use of monoamine oxidase inhibitors (MAOIs) in the treatment of PTSD has shown some effectiveness, but few studies have been done. Three controlled studies reviewed by Davidson and Connor (1999) demonstrated improvement in intrusion and, to a lesser degree, in avoidance or numbing as well as global or generalized improvement. Monoamine oxidase inhibitors work by inhibiting an enzyme that metabolizes serotonin, norepinephrine, and a number of other neurotransmitters. This has the functional effect of increasing their levels within the synapse. Monoamine oxidase inhibitors are considered third-line antidepressants due at least in part to dietary restrictions for individuals taking MAOIs and with interaction complications with other drugs. It must be stated, however, that research and practice have shown that they are considered just as effective in treating Major Depressive Disorder and may even be more effective than the TCAs in treating atypical depression. Their use with PTSD, however, remains to be fully supported by research and ongoing practice.
What is the mechanism of the antidepressant drugs in PTSD pathophysiology? More research needs to be done, but a gross understanding reveals that this class of antidepressant drugs has the effect of functionally increasing the levels of serotonin available within particular brain systems, and, as was discussed in Chapter 6, serotonin is implicated in the human stress response and in fear responding. Increased levels of serotonin may have the effect of keeping the amygdala in check, for example.
Although more research and clinical experience is needed, a few other anti-depressant drugs have been implicated for use with PTSD. Nefazadone both blocks serotonin reuptake and engages in postsynaptic blockade. Practitioners have endorsed it as a second-choice drug after SSRIs despite a lack of research (Friedman, 2004). Trazadone is a similar drug to nefazadone and has been shown to be modestly effective in one small study (Hertzberg, Feldman, Beckham, & Davidson, 1996).
Although SSRIs are leading the proverbial way in pharmacological treatment for PTSD, still other drugs have been used, are still used, and have shown effectiveness. The anticonvulsant carbamazepine has been effective in treating intrusion and arousal symptoms and another, valproate, has been shown to reduce avoidant or numbing and arousal symptoms. Antiadrenergic drugs such as cloni-dine and propranolol have shown to be effective in reducing arousal, reexperi-encing, and dissociative symptoms (Friedman, 2001). Finally, a note about antipsychotic drugs needs to be made. Certainly, individuals with PTSD may suffer from comorbid psychotic disorders and have flashbacks of a severe nature that may warrant separate clinical attention. However, research and clinical prac tice have yet to yield suggestions or recommendations for use of antipsychotic medication, although Friedman (2001) acknowledges they are currently being used despite adequate guidelines or empirical support for such.
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