ACUTE STRESS DISORDER (ASD) PHARMACOTHERAPY

R = level of recommendation (see appendix A)

Although the effectiveness of SSRI has been demonstrated for PTSD – it has not been tested in ASD and therefore can not be recommended.

OBJECTIVE

To lessen the physical, psychological, and behavioral morbidity associated with acute stress reaction, hasten the return to full function (duty, work, social role function), and diminish the likelihood of chronicity.

BACKGROUND

Stress reactions produce biologic, psychological, and behavioral changes. Biologic alterations include disruptions in nerurochemicals, sleep patterns, hyper-arousal, and somatic symptoms (e.g., pain, gastrointestinal symptoms, etc). Psychological changes include: mood disturbances (e.g., labiality, irritability, blunting, numbing) anxiety (e.g., increased worry, ruminations) and cognitive disturbances (e.g., memory impairment, confusion, and impaired task completion. Different types of trauma can lead to ASD, from interpersonal assaultive violence to accidents to combat related trauma. For example, as many as ninety percent of individuals whom experience sexual assault will have acute stress symptoms ( Breslau, 1996).

Empiric studies in ASD pharmacotherapy are lacking. To facilitate provision of physical needs, normalization, and psycho-education, it may be prudent to wait 24 to 48 hours before beginning medications . Pharmacotherapy may be aided by determining whether the patient suffers from excessive adrenergic arousal or symptoms of psychomotor withdrawal. If non-pharmacological treatments fail to improve symptomatology, and potential medical causes of neuropsychiatric impairment are ruled out, then medications may be considered.
The use of medications for short-term treatment of targeted symptoms may be beneficial (e.g. Insomnia).

RECOMMENDATIONS

1. Provide for physical needs, sleep, normalization, and other non-pharmacological modalities.
2. Consider the use of medication for individuals that do not respond to non-pharmacological treatment.
3. Consider the use of imipramine to ameliorate the symptoms of ASD
4. Consider a short course of medication targeted for specific symptoms.
   • Sleep disturbance/insomnia
   • Benzodiazepines (up to 5 days)
   • Chloral hydrate (up to 5 days)
   • Hyperarousal/excessive arousal/panic attacks
   • Propranolol and other anti-adrenergic agents (up to 10 days)
   • Imipramine (up to 7 days)
   • Benzodiazepines (up to 5 days) avoid short acting agent [e,g, alprazolam])
5. There is insufficient evidence to support a recommendation for preventative use of a pharmacological agent to prevent the development of PTSD
6. There is insufficient evidence to support a recommendation for PTSD pharmacotherapies for patient presenting symptoms for less than 4 weeks.

DISCUSSION

Few studies have examined the effectiveness of pharmacological treatment for acute symptom management and PTSD prevention during the first four weeks following a traumatic event. There are no double-blind, placebo-controlled trials investigating the utility of benzodiazepines to prevent PTSD. Some descriptive studies do exist, however. The evidence for the use of benzodiazepines is mixed. In an open-label trial short-term use of benzodiazepine for sleep was associated with acute reduction in posttraumatic symptoms (Mellman et al., 1998). Four patients with acute stress symptoms that included disturbed sleep were treated within 1 to 3 weeks of trauma exposure with temazepam. The drug was administered for 5 nights, tapered for 2 nights, then discontinued. Evaluations 1 week after the last dose of medication revealed improved sleep and reduced stress symptoms.

Another open-label study found that early, more prolonged benzodiazepine use was associated with a higher rate of subsequent PTSD (Gelpin et al., 1996). This open study followed 13 patients that received clonazepam 2.7 mg/d + 0.8 mg/d or alprazolam 2.5 mg/d within 6.7 + 5.8 days of a traumatic event and 13 pair-matched trauma survivors for 6 months. Nine (69%) of the benzodiazepine-treated patients compared to only 3 (23%) of the control patients met criteria for PTSD (p = NS).

Propranolol may be considered for treatment of post-event hyperarousal. One study suggests that treatment with a beta-adrenergic blocker following an acute psychologically traumatic event may reduce subsequent posttraumatic stress disorder (PTSD) symptoms (Pitman et al., 2002). Within 6 hours of a traumatic event patients were randomized to a 10-day course of propranolol (n = 18) versus placebo (n = 23) 40 mg four times daily. The mean (SD) 1-month Clinician-Administered PTSD Scale (CAPS) score of 11 propranolol completers was 27.6 (15.7) compared to 20 placebo completer’s average score of 35.5 (21.5) (t = 1.1, df = 29, p = 0.15). Two propranolol-treated patients' scores fell above, and nine below, the placebo group's median (p = 0.03,sign test). None of the eight propranolol-, but six of 14 placebo-treated patients were physiologic responders during script-driven imagery of the traumatic event when tested 3 months afterward (p = 0.04, one-tailed t-test). These pilot results suggest that acute, post-trauma propranolol may have a preventive effect on subsequent PTSD.

A prospective, randomized, double blind study of pediatric (mean age 8, range 2 – 29) burn patients determined the effect of imipramine (n=12) and chloral hydrate (n=13) on ASD symptoms for 7 days (Robert et al., 2000). These children had a mean total burn area of 45% and received a structured interview 3 times over the study period. Five of 13 (38%) patients that received chloral hydrate compared to 10 of 12 (83%) imipramine-treated patients (p<0.02) was considered improved.

There are no controlled trials of the usefulness of antihistamines or antidepressants for the management of ASD (Cochrane Database Pharmacotherapy Review 2002). Open trials and clinical experience with clonidine, guanfacine, and prazosin suggest they maybe useful for ASR; however, they have not been systematically studied.

There is insufficient research to support a recommendation for preventative use of a pharmacological agent to prevent the development of PTSD (Cochrane Systematic Review of PTSD 2002).

Future research should included additional studies of prevention and comparative trials between agents. Research questions that remain include the timing of non-pharmacological and pharmacological intervention(s), the type of trauma and between drug class and within drug class response, dose-response trials, the relationship between treatment trial duration and outcome, the effects of demographics (e.g., age, gender, culture) on treatment outcomes, pharmacotherapy and psychosocial therapy interactions, the effect of co-morbid diagnoses on treatment response, and the psychobiologic correlates of treatment response. Also, the effect of clinical setting (e.g., military versus civilian), treatment-compensation interactions, and the effect of PTSD severity on outcome should be investigated. Standardization of assessment measures should be addressed that would include scales for individual symptoms, global assessment, and quality of life, as well as the psycholobiological correlates of treatment response.