To review the literature on certain psychobiologic elements of posttraumatic stress disorder (PTSD) as they pertain to possible pharmacotherapeutic interventions.
Method:
The literature pertaining to the neuroanatomical, neurochemical, and cellular elements was reviewed. As well, both controlled and uncontrolled studies of pharmacotherapy in PTSD were analyzed.
Results:
The literature suggests that the stress response triggers certain neuromodulators with subsequent psychoneurological restructuring; that various antidepressants have been demonstrated to be effective for treatment of criterion B symptoms; that, to date, a single antidepressant has been demonstrated to be effective in a controlled trial for criterion C symptoms; and that, to date, in controlled trials, antidepressants and a benzodiazepine have proved effective for criterion D symptoms.
Conclusion:
Currently, a comprehensive approach requires multimodel understanding and multimodal treatment.
BreslauNDavisGCAndreskiPPetersonE. Traumatic events and posttraumatic stress disorder in an urban population of young adults. Arch Gen Psychiatry1991;48:216–22.
2.
DavidsonJRTHughesDBlazerDGGeorgeLK. Posttraumatic stress disorder in the community: An epidemiological study. Psychol Med1991;21:713–21.
3.
CharneyDDeutchAKrystalJSouthwickSMDavisM. Psychobiologic mechanisms of posttraumatic stress disorder. Arch Gen Psychiatry1993;50:295–305.
4.
YehudaRResnickHKahanaBGillerEL. Longlasting hormonal alterations in extreme stress in humans normative or maladaptive?Psychosom Med1993;55:287–97.
5.
YehudaRGillerEL, Levengood RA, and others. Hypothalamic-pituitary-adrenal functioning in PTSD: Expanding the concept of the stress response spectrum. In: FriedmanMJCharneyDSDeutchAW, editors. Neurobiological and clinical consequences of stress: From normal adaptation to PTSD. New York: Raven Press; (in press).
6.
YehudaRMcFarlaneA. Conflict between current knowledge about posttraumatic stress disorder and its original conceptual basis. Am J Psychiatry1995;152:1705–13.
7.
Van der KolkBA. The drug treatment of posttraumatic stress disorder. J Affect Dis1987;13:203–13.
8.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed.Washington (DC): American Psychiatric Association; 1994.
9.
FoaERiggsDGershunyB. Arousal, numbing, and intrusion: Symptom structure of PTSD following assault. Am J Psychiatry1995;152:116–20.
10.
DavidsonJRT. Drug therapy of posttraumatic stress disorder. Br J Psychiatry1992;160:309–14.
11.
MesulamM. Large-scale neurocognitive networks and distributed processing for attention, language, and memory. Ann Neurol1990;28:597–613.
12.
LiDSpiegelD. A neural network model of dissociative disorders. Psychiatric Annals1992;22:144–7.
13.
Van der KolkB. The body keeps the score: Memory and the evolving psychobiology of post traumatic stress. Harvard Review of Psychiatry1994;1:253–65.
14.
SchwarzEDPerryBD. The posttraumatic stress response in children and adolescents. Psychiatr Clin North Am1994;17:311–26.
15.
DelaneyRTussiDGoldPE. Long-term potentiation as a neurophysiological analog of memory. Pharmacol Biochem Behav1983;18:137–9.
16.
McGaughJL. Involvement of hormonal and neuromodulatory systems in the regulation of memory storage. Annu Rev Neurosci1989;2:255–87.
17.
GrayJ. The neuropsychology of anxiety: An inquiry into the functions of the septo-hippocampal system. London: Oxford University Press; 1982.
18.
BillsLKreislerK. Treatment of flashbacks with naltrexone [letter]. Am J Psychiatry1993;150:1430.
19.
GloverH. A preliminary trial of nalmefene for the treatment of emotional numbing in combat veterans with post-traumatic stress disorder. Isr J Psychiatry Relat Sci1993;30:255–63.
20.
Van der KolkBADreyfussDMichaelsMSheraDBerkowitzR, Fisler R, and others. Fluoxetine in posttraumatic stress disorder. J Clin Psychiatry1994;55:517–22.
21.
SutherlandSMDavidsonJRT. Pharmacotherapy for posttraumatic stress disorder. Psychiatr Clin North Am1994;17:409–23.
22.
FrankJBKostenTRGillerELDanE. A randomized clinical trial of phenelzine and imipramine for posttraumatic stress disorder. Am J Psychiatry1988;145:1289–91.
23.
ReistCKauffmanCDHaierRJSangdahlCDeMetEM, Chicz-DeMet A, and others. A controlled trial of desipramine in 18 men with posttraumatic stress disorder. Am J Psychiatry1989;146:513–6.
24.
DavidsonJRTKudlerHSSmithRMahorneySLLipperS, Hammett E, and others. Treatment of posttraumatic stress disorder with amitriptyline and placebo. Arch Gen Psychiatry1990;47:259–66.
25.
ShestatzkyMGreenbergDLererB. A controlled trial of phenelzine in posttraumatic stress disorder. Psychiatry Res1988;24:149–55.
26.
KudlerHSDavidsonJRTSteinREricksonL. Measuring results of treatment of PTSD [letter]. Am J Psychiatry1989;146:1645–6.
27.
BraunPGreenbergD, Dasberg H, and others. Core symptoms of posttraumatic stress disorder unimproved by alprazolam treatment. J Clin Psychiatry1990;15:236–8.
28.
LipperSDavidsonJRTGradyTAEdingerJDHammettEB, Mahorney SL, and others. Preliminary study of carbamazepine in posttraumatic stress disorders. Psychosomatics1986;27:849–54.
29.
De BoerMOp den VeldeWFalgerPRJHovensJEDe GroenJHMDuijnHV. Fluvoxamine treatment for chronic PTSD: A pilot study. Psychother Psychosom1992;57:158–63.
30.
KlineNADowBMBrownSAMatloffJL. Sertraline efficacy in depressed combat veterans with posttraumatic stress disorder [letter]. Am J Psychiatry1994;151:621.
31.
Van der KolkBAGreenbergMOrrSPPitmanRK. Endogenous opioids, stress induced analgesia, and posttraumatic stress disorder. Psychopharmacol Bull1989;25:417–21.
32.
PutnamFW. Dissociation as a response to extreme trauma. In: KluftRP, editor. The childhood antecedents of multiple personality. Washington (DC): American Psychiatric Press; 1985. p 65–97.
33.
AroraRCFichtnerCG, O'Connor F, and others. Paroxetine binding in the blood platelets of post-traumatic stress disorder patients. Life Sci1993;53:919–28.
34.
HensmanRGuimaraesFS, Wang M, and others. Effects of ritanserin on aversive classical conditioning in humans. Psychopharmacology1991;104:220–4.
35.
DeakinJFW. Roles of serotonergic systems in escape, avoidance, and other behaviours. In: CooperSJ, editor. Theory of psychopharmacology. London: Academic Press; 1983. p 149–93.
36.
KostenTRFrankJBDanEMcDougleCJGillerEL. Pharmacotherapy for posttraumatic stress disorder using phenelzine or imipramine. J Ner Ment Dis1991;179:366–70.
37.
NagyLMMorganCAIIISouthwickSMCharneyDS. Open prospective trial of fluoxetine for posttraumatic stress disorder. J Clin Psychopharmacol1993;13:107–13.
38.
DavidsonJRTWalkerJIKiltsCD. A pilot study of phenelzine in posttraumatic stress disorder. Br J Psychiatry1987;150:252–5.
39.
KolbLC. Neurophysiological hypothesis explaining posttraumatic stress disorder. Am J Psychiatry1987;144:989–95.
40.
ButlerRWBraffDLRauschJL. Physiological evidence of exaggerated startle response in a subgroup of Vietnam veterans with combat-related PTSD. Am J Psychiatry1990;147:1308–12.
41.
ShalevAYOrrSPPeriTSchreiberSPitmanRK. Physiologic responses to loud tones in Israeli patients with post traumatic stress disorder. Arch Gen Psychiatry1993;49:870–5.
42.
AsbergMSchallingD, Traksman-Bendz L, and others. Psychobiology of suicide, impulsivity, and related phenomena. In: MeltzerHY, editor. Psychopharmacology: The third generation of progress. New York: Raven Press; 1987.
43.
AkilHWatsonSJYoungE. Endogenous opioids: Biology and function. Annu Rev Neurosci1983;7:223–55.
44.
KolbLCBurrisBGriffithS. Propranolol and Clonidine in treatment of the chronic posttraumatic stress disorders of war. In: Van der KolkBA, editor. Posttraumatic stress disorder: Psychological and biological sequelae. Washington (DC): American Psychiatric Association; 1984. p 97–107.
45.
FriedmanMJ. Toward rational pharmacotherapy for posttraumatic stress disorder: An interim report. Am J Psychiatry1988;145:281–5.
46.
AndreasenNC. Posttraumatic stress disorder: Psychology, biology, and the Manichaean warfare between false dichotomies. Am J Psychiatry1995;152:963–5.
