DOCTOR'S VIEW ARCHIVE
The US Food and Drug Administration (FDA) approved sertraline (Zoloft), a drug commonly used to manage depression, as the first medication specifically for the treatment of post-traumatic stress disorder.
Post-traumatic stress disorder is a pattern of behavior that develops after a traumatic event. A traumatic event in this context is defined as one that may bring serious injury or death to oneself or to another person. Traumatic events capable of causing post- traumatic stress disorder include kidnapping, natural disasters (hurricanes, earthquakes, tornadoes, floods, etc), physical and sexual abuse, combat, drug abuse, and near-death experiences.
Historically referred to as "soldier's heart" and "shell shock" because the behavior characteristic of post-traumatic stress disorder was seen in men after wartime combat, the symptoms and behaviors of post-traumatic stress disorder have been shown to occur in children, adolescents, and adults.
Constellation of changes in post-traumatic stress
Post-traumatic stress disorder is a constellation of changes in personality and behavior that begin after a traumatic event and persist for more than a month. Following the traumatic event, individuals who develop post-traumatic stress disorder may feel like the everyday world is no longer real and that they are in a dream- like state. They may feel that their minds are detached from their emotions as well as from their physical bodies, a condition referred to as dissociation.
Persons with post-traumatic stress disorder may continuously experience flashbacks. During these flashbacks they relive the traumatic event and reexperience feelings of intense fear and of inability to escape from the traumatic event. Every effort is taken to avoid actions or thoughts associated with the traumatic event in order to prevent these flashbacks.
Ultimately, behavior becomes erratic and hyperactive, as if the individual were constantly defending himself. For example, the person may develop anxiety, have disturbed sleep, and be easily startled. Over the long run this behavior can lead to complete dysfunction with a sense of hopelessness, a total lack of self- esteem, and overwhelming fear of people. There also may be substance abuse (use of alcohol or narcotics, for example) and difficulty maintaining existing relationships.
Variable duration of the disorder
In about half of the individuals with post-traumatic stress disorder, the condition resolves within six months while the other half continue to suffer for years. Post-traumatic stress disorder is considered to be acute if symptoms and behaviors last less than three months, chronic if symptoms and behaviors persist for more than three months, and delayed in onset if symptoms and behaviors begin at least six months after the traumatic event.
About 4% of the general population or approximately 10 million people develop post-traumatic stress disorder each year. It is twice as common in women as in men. In one study it was found to occur in 15% of war veterans up to19 years after combat. Several factors including psychological traits, genetics factors and life experiences may contribute to the likelihood of developing post-traumatic stress disorder.
For most patients with post-traumatic stress disorder, treatment has consisted of counseling, psychotherapy, or drugs. A combination of these approaches is sometimes employed. We will focus here on the drugs used for post-traumatic stress disorder.
Drug treatment of post-traumatic stress disorder
The erratic, hyperactive behavior, anxiety, and sleep disturbance associated with post-traumatic stress disorder were first thought due to over-activity of the sympathetic nervous system, the part of the nervous system that is active when there is fear. For this reason, children were treated with propranolol (Inderol) which blocks the sympathetic nervous system. However, propranolol proved to provide little benefit.
New research has revealed how severe trauma can produce long-term changes in the nerves in the brain. In particular, it is now believed that the problem is caused by alterations in the chemical substances that nerves in the brain use to communicate with each other, substances referred to as neurotransmitters. These alterations in neurotransmitters may be responsible for the symptoms and behaviors.
Treatment of post-traumatic stress disorder has therefore shifted to drugs that target these chemical substances. For example, antidepressants including imipramine and phenelzine (Nardil) that alter neurotransmitters such as serotonin, norepinephrine, dopamine, and acetylcholine have been found do more to reduce flashbacks and the feelings of helplessness more than placebo (a dummy pill). Unfortunately, however, side effects interfered with the long-term use of these drugs.
Trials with sertraline (Zoloft)
A trend that emerged from these studies was that greater improvement was seen with drugs that altered serotonin more than other neurotransmitters. This finding led to studies with sertraline (Zoloft) which alters serotonin in the brain. In two 12 week-long trials involving 385 patients -- mainly women who developed post- traumatic stress disorder after sexual or physical assault - sertraline (Zoloft) was compared with placebo. Sertraline (Zoloft) reduced both the number and intensity of symptoms by 50% compared with 30% for placebo. A third similar study found no difference in the response between sertraline (Zoloft) and placebo. A fourth study in war veterans with post-traumatic stress disorder also found no difference in response.
In sum, sertraline (Zoloft) may be effective in reducing symptoms in at least some but by no means all patients with post-traumatic stress disorder. In particular, sertraline (Zoloft) may be useful for women with post-traumatic stress disorder as a result of sexual or physical assaults. Nevertheless, the response to sertraline (Zoloft) was not much greater than the response to placebo, suggesting that the drug's effectiveness is limited.
Issues raised by the studies but not answered are whether men respond as well as women, whether post-traumatic stress disorder caused by different types of traumatic events will respond similarly, and whether patients with other psychological problems in addition to post-traumatic stress disorder also will respond to sertraline (Zoloft). None of the studies to date have addressed the issue of how effective sertraline (Zoloft) will be with long-term treatment or what happens if treatment is discontinued.
Newer drugs in development
For now, treatment of post-traumatic stress disorder is likely to remain focused upon drugs that alter serotonin but are less likely to cause side effects. Nefazodone (Serzone) and mirtazapine (Remeron) are already being tested. It is likely that fluoxetine (Prozac), paroxetine (Paxil), and citalopram (Celexa) will soon be studied for the treatment of post-traumatic stress disorder.
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