Recommendations for Pharmacological Treatment of Acute Stress Reactions

Clinicians are understandably reluctant to utilize pharmacotherapy during the immediate aftermath of exposure to a traumatic event. Although most people will be distressed during the acute post-impact phase, the great majority will recover during the following weeks. As a result, clinicians are hesitant to "pathologize" such normal reactions to traumatic stress by utilizing medications.

However, the use of medications may be necessary when the survivor is dangerous, extremely agitated, or psychotic. In such circumstances, the individual should be taken to an emergency room. In the emergency room, short-acting benzodiazepines (e.g. lorazepam) or high potency neuroleptics (e.g. haldol) with minimal sedative, anticholinergic, and orthostatic side effects may prove effective. Atypical neuroleptics (e.g. risperidone), at relatively low doses, may also be useful in treating impulsive aggression.

Pharmacological treatment may also be warranted during the first month after trauma because some trauma survivors experience extreme and persistent arousal in the form of anxiety, panic, hypervigilance, irritability, and insomnia. Empirical research has shown that hyperarousal during the first few weeks following trauma is a risk factor for the development of posttraumatic stress disorder (PTSD). Behavioral techniques to reduce arousal include psychotherapy, relaxation and breathing exercises, and utilization of social supports. (For more information on behavioral treatment during the acute phase following trauma, please see our Psychological First Aid Manual.) If such behavioral treatments are ineffective, clinicians should consider pharmacotherapy.

Generally, the trauma survivor should have a thorough psychiatric and medical examination prior to receiving medication. Ongoing medical conditions, psychiatric diagnoses, current medications, and possible drug allergies should be assessed. In addition, clinicians should ask questions regarding alcohol, marijuana, stimulants, and other drugs since these substances may interact with prescribed medications and may complicate an individual's psychological and physiological response to the trauma. For individuals with medical and/or surgical concerns, a clinician may need to take special precautions when prescribing psychotropic medications. It is also extremely important to consider possible drug interactions for individuals who are taking other prescribed or over-the-counter medications.

Which medication decisions are empirically supported?

Unfortunately, we still know relatively little about the potential of pharmacotherapy as an acute posttraumatic intervention. Only a few medications have been tested rigorously, mostly in small clinical trials. Some relevant empirical research is summarized below:

Propanolol. Results of studies with propanolol are promising, suggesting that acute propranolol treatment may have prophylactic benefits (1-3). More research is needed with propranolol and other antiadrenergic agents such as clonidine, guanfacine, and prazosin.

Clinicians should prescribe propranolol, clonidine, and guanfacine judiciously for survivors with cardiovascular disease. This is because these medications may reduce blood pressure. In addition, clonidine may induce rebound hypertension if the client's blood levels fall due to infrequent dosing or a sudden discontinuation. Furthermore, these agents should not be prescribed to persons with diabetes as they may interfere with counterregulatory hormone responses to hypoglycemia.

Hydrocortisone. As with the propranolol studies, the hydrocortisone findings are promising (4-5). Understanding the rationale for acute glucocorticoid administration, however, is less clear than with propranolol. All of the mechanisms that have been proposed, however, involve key target sites that mediate the human stress response.

Imipramine. Imipramine is a tricyclic antidepressant that blocks presynaptic reuptake of both serotonin and norepinephrine. A prospective randomized controlled trial with tricyclics showed that imipramine treatment was significantly superior in reducing acute stress disorder symptoms among hospitalized child and adolescent burn victims (6). Unfortunately, these investigators did not carry out a long-term follow-up to assess how effectively this treatment prevented the later development of PTSD. These findings certainly indicate the need for additional studies with tricyclic antidepressants.

Benzodiazepines. Benzodiazepines are useful because they are effective and fast acting. However, research suggests that acute benzodiazepine-mediated activation of GABA receptors is not sufficient to prevent the later development of PTSD (7-8). It is recommended that benzodiazepines be used to treat extreme arousal, insomnia, and anxiety, but their use should be time-limited.

What other factors need to be considered?

Recent trauma survivors may also suffer from debilitating symptoms of depression, with or without PTSD. Since selective serotonin reuptake inhibitors (SSRI's) and the selective serotonin norepinephrine reuptake inhibitor (SNRI), venlafaxine, effectively ameliorate both depression and PTSD symptoms, it is recommended that SSRI's and SNRI's be considered for persistent posttraumatic depression. In addition, SSRI's may be useful for controlling anxiety and irritability. SSRI's, SNRI's, and other antidepressants should be administered in a "start low and go slow" dosing regimen because some individuals may develop increased anxiety, agitation, or other side effects in response to them.

Some individuals have preexisting psychiatric disorders, including preexisting PTSD, at the time that they experience trauma. The most recent trauma may exacerbate these preexisting conditions, making it essential to carefully assess the individual's psychotherapeutic and pharmacological needs. It is imperative that a clinician contact any other current providers and maintain continuity of care.

It is also possible that trauma will precipitate disorders other than depression, traumatic grief, acute stress disorder, or PTSD. In such cases, careful assessment and diagnosis should inform appropriate treatment.

Finally, it is essential that providers educate patients about their medication's interactions with alcohol, other medications, or substances of abuse. Providers also need to inform their patients of the medication's potential side effects, and remain in close touch with their patients after initiating the use of these and other psychotropic agents. This will allow providers to gauge the severity of any side effects, encourage compliance, and forestall complications that might arise as a result of extreme or otherwise idiosyncratic reactions to these medications. In addition, the added therapeutic support can help relieve the psychological burden from which people with posttraumatic distress suffer.

For more information, see: Friedman, M. J. (2008). The role of pharmacotherapy in early interventions. In M. Blumenfield & R. Ursano (Eds.), Intervention and resilience after mass trauma (pp. 107-125). Cambridge, UK; New York: Cambridge University Press.

References

1. Pitman, R.K., Sanders, K.M., Zusman, R.M., Healy, A.R., Cheema, F., Lasko, N.B., Cahill, L., & Orr, S.P. (2002): Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry, 51, 189-192.
2. Vaiva, G., Ducrocq, F., Jezequel, K., Averland, B., Lestavel, P., Brunet, A., & Marmar, C.R. (2003). Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma. Biological Psychiatry, 54, 947-949.
3. Taylor, F.B., & Cahill, L. (2002). Propranolol for reemergent posttraumatic stress disorder following an event of retraumatization: A case study. J Trauma Stress, 15, 433-437.
4. Schelling, G., Kilger, E., Roozendaal, B., de Quervain, D.J.F., Briegel, J., Dagge, A., Rothenhausler, H-B, Krauseneck, T., Nollert, G. & Kapfhammer, H-P. (2004): Stress doses of hydrocortisone, traumatic memories, and symptoms of posttraumatic stress disorder in patients after cardiac surgery: A randomized study.
5. Schelling, G., Stoll, C., Kapfhammer, H.P., Rothenhausler, H.B., Krauseneck, T., Durst, K., Halle, M., & Briegel, J. (1999). The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder and health-related quality of life in survivors. Critical Care Medicine, 27: 2678-2683.
6. Robert R, Blakeney PE, Villarreal C, Rosenberg L, Meyer WJ 3rd (1999). Imipramine treatment in pediatric burn patients with symptoms of acute stress disorder: a pilot study. J Am Acad Child Adolesc Psychiatry 38:873-882.
7. Gelpin, E., Bonne, O., Peri, T., Brandes, D., & Shalev, A.Y. (1996). Treatment of recent trauma survivors with benzodiazepines: A prospective study. J Clin Psychiatry, 57, 390-394.
8. Mellman, T.A., Bustamante, V., David, D., & Fins, A.I. (2002). Hypnotic medication in the aftermath of trauma (letter). J Clin Psychiatry, 63, 1183-1184.