Summary
Post-traumatic stress disorder (PTSD) is a syndrome of psychophysiological sequelae occurring in the aftermath of severe emotional trauma. Phenomenologically, symptoms occur in 3 clusters: re-experiencing, avoidance and hyperarousal. Other psychiatric disorders such as depression, panic disorder and substance abuse frequently co-occur with PTSD.
Treatment strategies for PTSD are often multimodal and attempt to integrate biological, behavioural, cognitive, psychodynamic and social formulations. Pharmacotherapy must target specific symptoms in all 3 clusters, and address the presence of comorbid psychiatric disorders. Psychotropic medication can facilitate psychotherapeutic work, or serve as the primary modality in a biologically based approach to treatment.
Specific medications used in the treatment of PTSD span a broad spectrum of pharmacological agents. The most empirically studied agents, tricyclic antidepressants and monoamine oxidase inhibitors, demonstrate a definite but limited impact on specific PTSD symptoms. For the patient who presents in an acute symptomatic state, benzodiazepine anxiolytics may be appropriate. For longer term treatment, selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs), particularly fluoxetine, appear to have broader spectrum therapeutic effects on specific PTSD symptom clusters. Both antidepressants and anxiolytics have, in some studies, shown beneficial effects on depressive symptoms and anxiety, without measurable impact on the symptoms more specific to PTSD.
Maintenance pharmacotherapy frequently requires a multidrug regimen; an SSRI may serve as the primary agent, with adjunctive agents targeting residual hyperarousal and re-experiencing symptoms. Benzodiazepines, sedating tricyclic or antihistamine compounds, and the noradrenergic drugs Clonidine and propranolol are used in this way. Buspirone, a serotonergic anxiolytic, may serve a similar role for some patients, and cyproheptadine in particular appears to be helpful for nightmares. The antikindling agents carbamazepine and valproic acid (sodium valproate) have also been reported to be beneficial, and may provide an alternative for patients with persistent hyper-reactivity and explosiveness that have not responded to other treatments.
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References
Shay J. Achilles in Vietnam. New York: Atheneum, 1994
Gersons BPR, Carlier IVE. Post-traumatic stress disorder: the history of a recent concept. Br J Psychiatry 1992; 161: 742–8
Davidson JRT, Foa EB, editors. Posttraumatic stress disorder: DSM IV and beyond. Washington, DC: American Psychiatric Press, 1993: ix–xiii
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed. Washington, DC: American Psychiatrie Association, 1980
American Psychiatrie Association. Diagnostic and statistical manual of mental disorders. 3rd rev. ed. Washington, DC: American Psychiatrie Association, 1987
American Psychiatrie Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatrie Association, 1994
Breslau N, Davis GC, Andreski P. Traumatic events and posttraumatic stress disorder in an urban population of young adults. Arch Gen Psychiatry 1991; 48: 216–22
Davidson JRT, Fairbank JA. The epidemiology of post-traumatic stress disorder. In: Davidson JRT, Foa EB, editors. Posttraumatic stress disorder: DSM IV and beyond. Washington, DC: American Psychiatrie Press, 1993: 147–69
Rothbaum BO, Foa EB. Subtypes of posttraumatic stress disorder and duration of symptoms. In: Davidson JRT, Foa EB, editors. Posttraumatic stress disorder: DSM IV and beyond. Washington, DC: American Psychiatrie Press, 1993: 23–35
Blank Jr AS. The longitudinal course of posttraumatic stress disorder. In: Davidson JRT, Foa EB, editors. Posttraumatic stress disorder: DSM IV and beyond. Washington, DC: American Psychiatrie Press, 1993: 3–22
Shalev AY, Bonne O, Eth S. Treatment of posttraumatic stress disorder: a review. Psychosom Med 1996; 58: 165–82
Giller Jr EL. Pharmacotherapy of PTSD. In: Miller DJ, editor. Handbook of post-traumatic stress disorders. New York: Plenum Publishing Co. In press
Friedman MJ, Yehuda R. Post-traumatic stress disorder and comorbidity: psychobiological approaches to differential diagnosis. In: Friedman MJ, Charney DS, Deutch AY, editors. Neurobiological and clinical consequences of stress: from normal adaptation to post-traumatic stress disorder. Philadelphia: Lippincott-Raven, 1995: 429–45
Sargant WW, Slater E. Acute war neuroses. Lancet 1940; 140: 1–2
Davidson J. Drug therapy of post-traumatic stress disorder. Br J Psychiatry 1992; 160: 309–14
Sargant WW, Slater E. The use of drugs in psychotherapy. In: Sargant WW, Slater E, editors. An introduction to physical methods of treatment in psychiatry. New York: Science House, 1972: 142–62
van der Kolk BA. The drug treatment of post-traumatic stress disorder. J Affect Dis 1987; 13: 203–13
Solomon SD, Gerrity ET, Muff AM. Efficacy of treatments for posttraumatic stress disorder: an empirical review. JAMA 1992; 268: 633–8
Grinker RR, Spiegel JJ. Men under stress. New York: McGraw-Hill, 1945
Kardiner A. The traumatic neuroses of war. New York: P Hoeber, 1941
Bremner JD, Krystal JH, Southwick SM, et al. Functional neuroanatomical correlates of the effects of stress on memory. J Trauma Stress 1995; 8: 527–53
Charney DS, Deutch AY, Krystal JH, et al. Psychobiologic mechanisms of posttraumatic stress disorder. Arch Gen Psychiatry 1993; 50: 294–305
Friedman MJ. Interrelationships between biological mechanisms and pharmacotherapy of posttraumatic stress disorder. In: Wolf ME, Mosnaim AD, editors. Posttraumatic stress disorder: etiology, phenomenology, and treatment. Washington, DC: American Psychiatric Press Inc., 1990: 204–25
Friedman MJ. Biological approaches to the diagnosis and treatment of post-traumatic stress disorder. J Trauma Stress 1991; 4: 67–91
Friedman MJ, Charney DS, Deutch AY, editors. Neurobiological and clinical consequences of stress: from normal adaptation to post-traumatic stress disorder. Philadelphia: Lippincott-Raven, 1995
Giller Jr EL, editor. Biological assessment and treatment of posttraumatic stress disorder. Washington, DC: American Psychiatric Press Inc., 1990
Kolb LC. A neuropsychological hypothesis explaining posttraumatic stress disorders. Am J Psychiatry 1987; 144: 989–95
Krystal JH, Kosten TR, Southwick S, et al. Neurobiological aspects of PTSD: review of clinical and preclinical studies. Behav Ther 1989; 20: 177–98
Murburg MM, editor. Catecholamine function in posttraumatic stress disorder. Washington, DC: American Psychiatric Press Inc., 1994
Pitman RK. Biological findings in posttraumatic stress disorder: implications for DSM-IV classification. In: Davidson JRT, Foa EB, editors. Posttraumatic stress disorder: DSM-IV and beyond. Washington, DC: American Psychiatrie Press Inc., 1993
Shalev A. Post-traumatic stress disorder: a biopsychological perspective. Isr J Psychiatry Relat Sci 1993; 30: 102–9
Southwick SM, Bremner D, Krystal JH, et al. Psychobiologic research in post-traumatic stress disorder. Psychiatr Clin North Am 1994; 17: 251–64
van der Kolk B, Greenberg M, Boyd H, et al. Inescapable shock, neurotransmitters, and addiction to trauma: toward a psychobiology of post traumatic stress. Biol Psychiatry 1985; 20: 314–25
van der Kolk BA. Psychological trauma. Washington, DC: American Psychiatrie Press Inc., 1987
van der Kolk BA, Saporta J. The biological response to psychic trauma: mechanisms and treatment of intrusion and numbing. Anxiety Res 1991; 4: 199–212
Yehuda R, Giller EL, Southwick SM, et al. Hypothalamic-pituitary-adrenal dysfunction in posttraumatic stress disorder. Biol Psychiatry 1991; 30: 1031–48
Yehuda R, Resnick H, Boaz K, et al. Long-lasting hormonal alterations to extreme stress in humans: normative or maladaptive? Psychosom Med 1993; 55: 287–97
Blanchard EB, Kolb LC, Pallmeyer TP, et al. Psychophysiological study of posttraumatic stress disorder in Vietnam veterans. Psychiatr Q 1982; 54: 220–9
Blanchard EB, Kolb LC, Gerardi RJ, et al. Cardiac response to relevant stimuli as an adjunctive tool for diagnosing posttraumatic stress disorder in Vietnam veterans. Behav Ther 1986; 17: 592–606
Blanchard EB, Kolb LC, Prins A, et al. Psychophysiological responses in the diagnosis of posttraumatic stress disorder in Vietnam veterans. J Nerv Ment Dis 1991; 179: 371–3
Gerardi RJ, Blanchard EB, Kolb LC. Ability of Vietnam veterans to dissimulate a psychophysiological assessment for post-traumatic stress disorder. Behav Ther 1989; 20: 229–43
Malloy PF, Fairbank JA, Keane TM. Validation of a multimethod assessment of post-traumatic stress disorders in Vietnam veterans. J Consult Clin Psychol 1983; 51: 488–94
Pallmeyer TP, Blanchard EB, Kolb LC. The psychophysiology of combat-induced post-traumatic stress disorder in Vietnam veterans. Behav Res Ther 1986; 24: 645–52
Pitman RK, Orr SP, Forgue DF, et al. Psychophysiologic assessment of post-traumatic stress disorder imagery in Vietnam combat veterans. Arch Gen Psychiatry 1987; 44: 970–5
Pitman RK, Orr SP, Forgue DF, et al. Psychophysiologic response to combat imagery of Vietnam veterans with posttraumatic stress disorder versus other anxiety disorders. J Abnorm Psychol 1990; 99: 49–54
McFall ME, Murburg MM. Psychophysiological studies of combat-related PTSD: an integrative review. In: Murburg MM, editor. Catecholamine function in posttraumatic stress disorder. Washington, DC: American Psychiatrie Press Inc., 1994: 161–74
Murburg MM, McFall ME, Veith RC. Basal sympathoadrenal function in patients with PTSD and depression. In: Murburg MM, editor. Catecholamine function in posttraumatic stress disorder. Washington, DC: American Psychiatrie Press Inc., 1994: 175–88
McFall ME, Murburg MM, Roszell DK, et al. Psychophysiologic and neuroendocrine findings in posttraumatic stress disorder: a review of theory and research. J Anxiety Dis 1989; 3: 243–57
McFall ME, Veith RC, Murburg MM. Basal sympathoadrenal function in posttraumatic stress disorder. Biol Psychiatry 1992; 31: 1050–6
Boudewyns PA, Hyer L. Physiological response to combat memories and preliminary treatment outcome in Vietnam veteran PTSD patients treated with direct therapeutic exposure. Behav Ther 1990; 21: 63–87
Dobbs D, Wilson WP. Observations on persistence of war neurosis. Dis Nerv Syst 1960; 21: 686–91
McFall ME, Murburg MM, Ko GN, et al. Autonomie responses to stress in Vietnam combat veterans with posttraumatic stress disorder. Biol Psychiatry 1990; 27: 1165–75
Attias J, Bleich A, Furman V, et al. Event-related potentials in post-traumatic stress disorder of combat origin. Biol Psychiatry 1996; 40: 373–81
Butler RW, Braff DL, Rausch JL, et al. Physiological evidence of exaggerated startle response in a subgroup of Vietnam veterans with combat-related PTSD. Am J Psychiatry 1990; 147: 1309–12
Ross RJ, Ball WA, Cohen ME, et al. Habituation of the startle reflex in posttraumatic stress disorder. J Neuropsychiatry Clin Neurosci 1989; 1: 305–7
Shalev AY, Orr SP, Peri T, et al. Physiologie responses to loud tones in Israeli patients with posttraumatic stress disorder. Arch Gen Psychiatry 1992; 49: 870–5
Morgan III CA, Grillon C, Southwick SM, et al. Fear-potentiated startle in posttraumatic stress disorder. Biol Psychiatry 1995; 38: 378–85
McFarlane A, Weber D, Clark C. Abnormal stimulus processing in posttraumatic stress disorder. Biol Psychiatry 1993; 34: 311–20
Paige SR, Reid GM, Allen MG, et al. Psychophysiological correlates of posttraumatic stress disorder in Vietnam veterans. Biol Psychiatry 1990; 27: 419–30
Pitman RK, van der Kolk BA, Orr SP, et al. Nalaxone-reversible analgesic response to combat-related stimuli in post traumatic stress disorder. Arch Gen Psychiatry 1990; 47: 541–4
Orr SP, Claiborn JM, Altman B, et al. Psychometric profile of PTSD, anxious and healthy Vietnam veterans: correlations with psychophysiological response. J Consult Clin Psychol 1990; 58: 329–35
Ross RJ, Ball WA, Sullivan KA, et al. Sleep disturbance as the hallmark of posttraumatic stress disorder. Am J Psychiatry 1989; 146: 697–707
Dow BM, Kelsoe Jr JR, Gillin JC. Sleep and dreams in Vietnam PTSD and depression. Biol Psychiatry 1996; 39: 42–50
Kosten TR, Mason JW, Giller Jr EL, et al. Sustained urinary norepinephrine and epinephrine elevation in post-traumatic stress disorder. Psychoneuroendocrinology 1987; 12: 13–20
Mason JW, Giller Jr EL, Kosten TR, et al. Psychoendocrine approaches to the diagnosis and pathogenesis of posttraumatic stress disorder. In: Giller Jr EL, editor. Biological assessment and treatment of posttraumatic stress disorder. Washington, DC: American Psychiatric Press Inc., 1990: 65–86
Mason JW, Giller EL, Kosten TR, et al. Elevation of urinary norepinephrine/cortisol ratio in posttraumatic stress disorder. J Nerv Ment Dis 1988; 176: 498–502
Yehuda R, Southwick S, Giller EL, et al. Urinary catecholamine excretion and severity of PTSD symptoms in Vietnam combat veterans. J Nerv Ment Dis 1992; 180: 321–5
Yehuda R, Giller Jr EL, Southwick SM, et al. Relationship between catecholamine excretion and PTSD symptoms in Vietnam combat veterans and Holocaust survivors. In: Murburg MM, editor. Catecholamine function in posttraumatic stress disorder. Washington, DC: American Psychiatric Press Inc., 1994: 203–19
Pitman R, Orr S. Twenty-four hour urinary Cortisol and catecholamine excretion in combat-related post-traumatic stress disorder. Biol Psychiatry 1990; 27: 245–7
Blanchard EB, Kolb LC, Prins A, et al. Changes in plasma norepinephrine to combat-related stimuli among Vietnam veterans with post traumatic stress disorder. J Nerv Ment Dis 1991; 179: 371–3
Murburg MM, McFall ME, Ko GN, et al. Stress-induced alterations in plasma catecholamines and sympathetic nervous system function in PTSD. In: Murburg MM, editor. Catecholamine function in posttraumatic stress disorder. Washington, DC: American Psychiatrie Press Inc., 1994: 189–202
Murburg MM, McFall ME, Lewis N, et al. Plasma norepinephrine kinetics in patients with posttraumatic stress disorder. Biol Psychiatry 1995; 38: 819–25
Hamner MB, Diamond BI. Elevated plasma dopamine in posttraumatic stress disorder: a preliminary report. Biol Psychiatry 1993; 33: 304–6
Perry BD, Giller EL, Southwick SM. Altered platelet alpha-2-adrenergic binding sites in posttraumatic stress disorder. Am J Psychiatry 1987; 144: 1511–2
Perry BD. Neurobiological sequelae of childhood trauma: PTSD in children. In: Murburg MM, editor. Catecholamine function in posttraumatic stress disorder. Washington, DC: American Psychiatrie Press Inc., 1994: 233–55
Lerer B, Ebstein RP, Shestatsky M, et al. Cyclic AMP signal transduction in posttraumatic stress disorder. Am J Psychiatry 1987; 144: 1324–7
Lerer B, Bleich A, Bennett ER, et al. Platelet adenylate cyclase and phospholipase C activity in posttraumatic stress disorder. Biol Psychiatry 1990; 27: 735–40
Lerer B, Bleich A, Solomon Z, et al. Platelet adenylate cyclase activity as a possible biologie marker for posttraumatic stress disorder. In: Wolf ME, Mosnaim AD, editors. Posttraumatic stress disorder: etiology, phenomenology, and treatment. Washington, DC: American Psychiatrie Press Inc., 1990: 148–56
Kohn Y, Newman ME, Lerer B, et al. Absence of reduced platelet adenylate cyclase activity in Vietnam veterans with PTSD. Biol Psychiatry 1995; 37: 205–8
Haier RJ, Buchsbaum MS, Murphy DL, et al. Psychiatrie vulnerability, monoamine oxidase, and the average evoked potential. Arch Gen Psychiatry 1980; 37: 340–5
Wyatt RJ, Murphy DL, Belmaker RH, et al. Reduced monoamine oxidase activity in platelets: a possible genetic marker for vulnerability to schizophrenia. Science 1973; 197: 916–8
Buchsbaum MS, Coursey RD, Murphy DL. The biochemical high-risk paradigm: behavioral and familial correlates of low platelet monoamine oxidase activity. Science 1976; 194: 339–41
Davidson J, Lipper S, Kilts CD, et al. Platelet MAO activity in posttraumatic stress disorder. Am J Psychiatry 1985; 142: 1341–3
Southwick SM, Krystal JH, Morgan CA, et al. Abnormal noradrenergic function in posttraumatic stress disorder. Arch Gen Psychiatry 1993; 50: 266–74
Charney DS, Deutch AY, Southwick SM, et al. Neural circuits and mechanisms of post-traumatic stress disorder. In: Friedman MJ, Charney DS, Deutch AY, editors. Neurobiological and clinical consequences of stress: from normal adaptation to post-traumatic stress disorder. Philadelphia: Lippincott-Raven, 1995: 271–87
Bourne PB, Rose RM, Mason JW. Urinary 17-OHCS levels: data on seven helicopter medics in combat. Arch Gen Psychiatry 1967; 17: 104–10
Bourne PB, Rose RM, Mason JW. 17-OHCS levels in combat: special forces ‘A’ team under threat of attack. Arch Gen Psychiatry 1968; 19: 135–40
Rose RM, Poe RO, Mason JW. Psychological state and body size as determinants of 17-OHCS excretion. Arch Intern Med 1968; 121: 406–13
Mason JW, Giller EL, Kosten TR, et al. Urinary-free Cortisol levels in post-traumatic stress disorder patients. J Nerv Ment Dis 1986; 174: 145–59
Yehuda R, Boisoneau D, Mason JW, et al. Relationship between lymphocyte glucocorticoid receptor number and urinary-free Cortisol excretion in mood, anxiety and psychotic disorder. Biol Psychiatry 1993; 34: 18–25
Yehuda R, Southwick SM, Nussbaum G, et al. Low urinary Cortisol excretion in PTSD. J Nerv Ment Dis 1991; 178: 366–9
Yehuda R, Kahana B, Binder-Brynes K, et al. Low urinary Cortisol excretion in Holocaust survivors with posttraumatic stress disorder. Am J Psychiatry 1995; 152: 982–6
Yehuda R, Lowy MT, Southwick SM, et al. Lymphocyte glucocorticoid receptor number in post traumatic stress disorder. Am J Psychiatry 1991; 148: 499–504
Yehuda R, Giller Jr EL, Levengood RA, et al. Hypothalamicpituitary-adrenal functioning in post-traumatic stress disorder: expanding the concept of the stress response spectrum. In: Friedman MJ, Charney DS, Deutch AY, editors. Neuro-biological and clinical consequences of stress: from normal adaptation to post-traumatic stress disorder. Philadelphia: Lippincott-Raven, 1995: 351–65
Kudler H, Davidson J, Meador K, et al. The DST and posttraumatic stress disorder. Am J Psychiatry 1987; 144: 1068–71
Olivera AA, Fero D. Affective disorders, DST, and treatment in PTSD patients: clinical observations. J Trauma Stress 1990; 3: 407–14
Halbreich U, Olympia J, Carson S, et al. Hypothalamo-pituitary-adrenal activity in endogenously depressed post-traumatic stress disorder patients. Psychoneuroendocrinology 1989; 14: 365–70
Kosten TR, Wahby V, Giller Jr E, et al. The dexamethasone suppression test and thyrotropin-releasing hormone stimulation test in posttraumatic stress disorder. Biol Psychiatry 1990; 28: 657–64
Yehuda R, Southwick SM, Krystal JH, et al. Enhanced suppression of Cortisol following dexamethasone administration in posttraumatic stress disorder. Am J Psychiatry 1993; 150: 83–6
Yehuda R, Teicher MH, Trestman RL, et al. Cortisol regulation in posttraumatic stress disorder: a chronobiological analysis. Biol Psychiatry 1996; 40: 79–88
Segal M. Serotonergic innervation of the locus coeruleus from the dorsal raphe and its action on responses to noxious stimuli. J Physiol 1979; 286: 401–15
Gonzalez-Heydrich J, Peroutka SJ. Serotonin receptor and reuptake sites: pharmacologic significance. J Clin Psychiatry 1990; 51(4 Suppl.): 5–12
Kahn RS, Van Praag HM, Wetzler S, et al. Serotonin and anxiety revisited. Biol Psychiatry 1988; 23: 189–208
Coplan JD, Gorman JM, Klein DF. Serotonin related functions in panic-anxiety: a critical overview. Neuropsychopharmacology 1992; 6: 189–200
Risch SC, Nemeroff CB. Neurochemical alterations in serotonergic neuronal systems in depression. J Clin Psychiatry 1992; 53(10 Suppl.): 3–7
Sandler M, Coppen A, Harnett S, editors. 5-Hydroxytryptamine in psychiatry: a spectrum of ideas. Oxford: Oxford University Press, 1991
Friedman MJ. Interrelationships between biological mechanisms and pharmacotherapy of posttraumatic stress disorder. In: Wolf M, Mosnaim A, editors. Posttraumatic stress disorder: etiology, phenomenology and treatment. Washington, DC: American Psychiatric Press Inc., 1990: 204–25
Friedman MJ, Southwick SM. Towards pharmacotherapy for post-traumatic stress disorder. In: Friedman MJ, Charney DS, Deutch AY, editors. Neurobiological and clinical consequences of stress: from normal adaptation to post-traumatic stress disorder. Philadelphia: Lippincott-Raven, 1995: 465–81
Sierles FS, Chen J-J, McFarland RE, et al. Post traumatic stress disorder and concurrent psychiatric illness: a preliminary report. Am J Psychiatry 1983; 140: 1177–9
Sierles FS, Chen JJ, Messing ML, et al. Concurrent psychiatrie illness in non-Hispanic outpatients diagnosed as having post traumatic stress disorder. J Nerv Ment Dis 1986; 174: 171–3
Faustman WO, White PA. Diagnostic and psychopharmacological treatment characteristics of 536 inpatients with posttraumatic stress disorder. J Nerv Ment Dis 1989; 177: 154–9
Davidson JRT, Kudler HS, Saunders WB, et al. Symptom and comorbidity patterns in World War II and Vietnam veterans with post traumatic stress disorder. Compr Psychiatry 1990; 31: 162–70
Brady KT, Sonne SC, Roberts JM. Sertraline treatment of comorbid posttraumatic stress disorder and alcohol dependence. J Clin Psychiatry 1995; 56: 502–5
Davidson J, Roth S, Newman E. Fluoxetine in post-traumatic stress disorder. J Trauma Stress 1991; 4: 419–23
de Boer M, Op den Velde W, Falger PJR, et al. Fluvoxamine treatment for chronic PTSD: a pilot study. Psychother Psychosom 1992; 57: 158–63
Fichtner CG, Arora RC, O’Connor FL, et al. Platelet paroxetine binding and fluoxetine pharmacotherapy in posttraumatic stress disorder: preliminary observations on a possible predictor of clinical treatment response. Life Sci 1994; 54: PL39–44
Kline NA, Dow BM, Brown SA, et al. Sertraline efficacy in depressed combat veterans with post-traumatic stress disorder [letter]. Am J Psychiatry 1994; 151: 621
March JS. Fluoxetine and fluvoxamine in PTSD [letter]. Am J Psychiatry 1992; 149: 413
Marmar CR, Schoenfeld F, Weiss DS, et al. Open trial of fluvoxamine treatment for combat-related posttraumatic stress disorder. J Clin Psychiatry 1996; 57 Suppl. 8: 66–72
McDougle CJ, Southwick SM, Charney DS, et al. On open trial of fluoxetine in the treatment of posttraumatic stress disorder. J Clin Psychopharmacol 1991; 11: 325–7
Nagy LM, Morgan CA, Southwick SM, et al. Open prospective trial of fluoxetine for posttraumatic stress disorder. J Clin Psychopharmacol 1993; 13: 107–13
Rothbaum BO, Ninan PT, Thomas L. Sertraline in the treatment of rape victims with posttraumatic stress disorder. J Trauma Stress 1996; 9: 865–71
Shay J. Fluoxetine reduces explosiveness and elevates mood of Vietnam combat vets with PTSD. J Trauma Stress 1992; 5: 97–101
van der Kolk BA, Dreyfuss D, Michaels M, et al. Fluoxetine in posttraumatic stress disorder. J Clin Psychiatry 1994; 55: 517–22
Arora RC, Fichtner CG, O’Connor F, et al. Paroxetine binding in the blood platelets of post-traumatic stress disorder patients. Life Sci 1993; 53: 919–28
Fichtner CG, O’Connor FL, Yeoh HC, et al. Hypodensity of platelet serotonin uptake sites in posttraumatic stress disorder: associated clinical features. Life Sci 1995; 57: PL37–44
Prange Jr AJ, Wilson IC, Lynn CW, et al. L-tryptophan in mania: contribution to a permissive hypothesis of affective disorders. Arch Gen Psychiatry 1974; 30: 56–62
Southwick SM, Krystal JH, Morgan CA, et al. Yohimbine and m-chloro-phenyl-piperazine in PTSD. New research abstracts of the American Psychiatrie Association 144th Annual Meeting: 1991 May 11–16; New Orleans, 131–2
Southwick SM, Yehuda R, Morgan III CA. Clinical studies of neurotransmitter alterations in post-traumatic stress disorder. In: Friedman MJ, Charney DS, Deutch AY, editors. Neurobiological and clinical consequences of stress: from normal adaptation to post-traumatic stress disorder. Philadelphia: Lippincott-Raven, 1995: 335–49
Zigmond MJ, Finlay JM, Sved AF. Neurochemical studies of central noradrenergic responses to acute and chronic stress: implications for normal and abnormal behavior. In: Friedman MJ, Charney DS, Deutch AY, editors. Neurobiological and clinical consequences of stress: from normal adaptation to post-traumatic stress disorder. Philadelphia: Lippincott-Raven, 1995: 45–60
Horger BA, Roth RH. Stress and central amino acid systems. In: Friedman MJ, Charney DS, Deutch AY, editors. Neurobiological and clinical consequences of stress: from normal adaptation to post-traumatic stress disorder. Philadelphia: Lippincott-Raven, 1995: 61–81
Sorg BA, Kalivas PW. Stress and neuronal sensitization. In: Friedman MJ, Charney DS, Deutch AY, editors. Neurobiological and clinical consequences of stress: from normal adaptation to post-traumatic stress disorder. Philadelphia: Lippincott-Raven, 1995: 83–102
Stout SC, Kilts CD, Nemeroff CB. Neuropeptides and stress: preclinical findings and implications for pathophysiology. In: Friedman MJ, Charney DS, Deutch AY, editors. Neurobiological and clinical consequences of stress: from normal adaptation to post-traumatic stress disorder. Philadelphia: Lippincott-Raven, 1995: 103–23
van der Kolk BA, Greenberg MS, Orr SP, et al. Endogenous opioids, stress induced analgesia, and posttraumatic stress disorder. Psychopharmacol Bull 1989; 25: 417–21
Glover H. Emotional numbing: a possible endorphin-mediated phenomenon associated with post-traumatic stress disorders and other allied Psychopathologic states. J Trauma Stress 1992; 5: 643–75
Hoffman L, Watson PB, Wilson G, et al. Low plasma betaendorphin in post-traumatic stress disorder. Aust NZ J Psychiatry 1989; 23: 269–73
Hoffman L, Watson PB, Wilson G, et al. ‘Low plasma beta-en-dorphin in post-traumatic stress disorder’: correction. Aust NZ J Psychiatry 1989; 23: 442
Hamner MB, Hitri A. Plasma beta-endorphin levels in post-traumatic stress disorder: a preliminary report on response to exercise-induced stress. J Neuropsychiatry Clin Neurosci 1992; 4: 59–63
Wolf ME, Mosnaim AD, Puente J, et al. Plasma methionine-enkephalin in PTSD. Biol Psychiatry 1991; 29: 305–7
Tallman JF, Paul SM, Skolnick P, et al. Receptors for the age of anxiety: pharmacology of the benzodiazepines. Science 1980; 207: 274–81
Nutt DJ, Glue P, Lawson C, et al. Flumazenil provocation of panic attacks. Arch Gen Psychiatry 1990; 47: 917–25
Woods SW, Charney DS, Silver JM, et al. Behavioral, biochemical, and cardiovascular responses to the benzodiazepine receptor antagonist flumazenil in panic disorder. Psychiatry Res 1991; 36: 115–27
Randall PK, Bremner JD, Krystal JH, et al. Effects of the benzodiazepine antagonist flumazenil in PTSD. Biol Psychiatry 1995; 38: 319–24
Shalev AY, Rogel-Fuchs Y. Auditory startle reflex in posttraumatic stress disorder patients treated with clonazepam. Isr J Psychiatry Relat Sci 1992; 29: 1–6
Mason JW, Giller EL, Kosten TR, et al. Serum testosterone levels in post-traumatic stress disorder inpatients. J Trauma Stress 1990; 3: 449–57
Mason JW, Wang S, Yehuda R, et al. Some approaches to the study of clinical implications of thyroid alterations in posttraumatic stress disorder. In: Friedman MJ, Charney DS, Deutch AY, editors. Neurobiological and clinical consequences of stress: from normal adaptation to post-traumatic stress disorder. Philadelphia: Lippincott-Raven, 1995: 367–79
Rainey JM, Aleem A, Ortiz A, et al. A laboratory procedure for the induction of flashbacks. Am J Psychiatry 1987; 144: 1317–9
Jensen CF, Keller TW, Peskind ER, et al. Behavioral and neuroendocrine responses to sodium lactate infusion in subjects with posttraumatic stress disorder. Am J Psychiatry 1997; 154: 266–8
Bremner JD, Randall P, Scott TM, et al. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry 1995; 152: 973–81
Swayze IIVW, Andreasen NC, Alliger RJ, et al. Subcortical and temporal structures in affective disorder and schizophrenia: a magnetic resonance imaging study. Biol Psychiatry 1992; 31: 221–40
Gur RE, Pearlson GD. Neuroimaging in schizophrenia research. Schizophr Bull 1993; 19: 337–53
Myslobodsky MS, Glicksohn J, Singer J, et al. Changes of brain anatomy in patients with posttraumatic stress disorder: a pilot magnetic resonance imaging study. Psychiatry Res 1995; 58: 259–64
Shin LM, Kosslyn SM, McNally RJ, et al. Visual imagery and perception in posttraumatic stress disorder: a positron emission tomographic investigation. Arch Gen Psychiatry 1997; 54: 233–41
True WR, Rice J, Eisen SE, et al. A twin study of genetic and environmental contributions to liability for posttraumatic stress symptoms. Arch Gen Psychiatry 1993; 50: 257–64
Comings DE, Muhleman D, Gysin R. Dopamine D2 receptor (DRD2) gene and susceptibility to posttraumatic stress disorder: a study and replication. Biol Psychiatry 1996; 40: 368–72
Frank JB, Kosten TR, Giller Jr EL, et al. A randomized clinical trial of phenelzine and imipramine for posttraumatic stress disorder. Am J Psychiatry 1988; 145: 1289–91
Shestatzky M, Greenberg D, Lerer B. A controlled trial of phenelzine in posttraumatic stress disorder. Psychiatry Res 1988; 24: 149–55
Davidson J, Kudler H, Smith R, et al. Treatment of posttraumatic stress disorder with amitriptyline and placebo. Arch Gen Psychiatry 1990; 47: 259–66
Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23: 56–62
Reist C, Kauffman CD, Haier RJ, et al. A controlled trial of desipramine in 18 men with post-traumatic stress disorder. Am J Psychiatry 1989; 146: 513–6
Braun P, Greenberg D, Dasberg H, et al. Core symptoms of posttraumatic stress disorder unimproved by alprazolam treatment. J Clin Psychiatry 1990; 51: 236–8
Blake DD, Weathers FW, Nagy LM, et al. A clinician rating scale for assessing current and lifetime PTSD: the CAPS-1. Behav Ther 1990; 13: 187–8
Katz RJ, Lott MH, Arbus P, et al. Pharmacotherapy of posttraumatic stress disorder with a novel psychotropic. Anxiety 1995; 1: 169–74
Baker DG, Diamond BI, Gillette G, et al. A double-blind, randomized, placebo-controlled, multicenter study of brofaromine in the treatment of post-traumatic stress disorder. Psychopharmacology 1995; 122: 386–9
Davidson JRT, Nemeroff CB. Pharmacotherapy in posttraumatic stress disorder: historical and clinical considerations and future directions. Psychopharmacol Bull 1989; 25: 422–5
Friedman MJ. Toward rational pharmacotherapy for posttraumatic stress disorder: an interim report. Am J Psychiatry 1988; 145: 281–4
Marshall RD, Klein DF. Pharmacotherapy in the treatment of posttraumatic stress disorder. Psychiatric Ann 1995; 25: 588–97
Silver JM, Sandberg DP, Hales RE. New approaches in the pharmacotherapy of posttraumatic stress disorder. J Clin Psychiatry 1990; 51 Suppl.: 33–8
Southwick SM, Yehuda R, Giller EL, et al. Use of tricyclics and monoamine oxidase inhibitors in the treatment of PTSD: a quantitative review. In: Murburg MM, editor. Catecholamine function in post-traumatic stress disorder: emerging concepts. Washington, DC: American Psychiatric Press Inc., 1994: 293–305
Sutherland SM, Davidson JRT. Pharmacotherapy for post-traumatic stress disorder. Psychiatr Clin North Am 1994; 17: 409–23
van der Kolk BA. Psychopharmacological issues in posttraumatic stress disorder. Hosp Community Psychiatry 1983; 34: 683–91
Vargas MA, Davidson J. Post-traumatic stress disorder. Psychiatr Clin North Am 1993; 16: 737–48
Katz L, Fleisher W, Kjernisted K, et al. A review of the psychobiology and pharmacotherapy of posttraumatic stress disorder. Can J Psychiatry 1996; 41: 233–8
Frank JB, Kosten TR, Giller Jr EL, et al. Antidepressants in the treatment of posttraumatic stress disorder. In: Wolf ME, Mosnaim AD, editors. Posttraumatic stress disorder: etiology, phenomenology, and treatment. Washington, DC: American Psychiatric Press Inc., 1990: 170–83
Birkheimer LJ, De Vane CL, Muniz CE. Posttraumatic stress disorder: characteristics and pharmacological response in the veteran population. Compr Psychiatry 1985; 26: 304–10
Davidson JRT, Walker JI, Kilts C. A pilot study of phenelzine in the treatment of post-traumatic stress disorder. Br J Psychiatry 1988; 150: 252–5
Hogben GL, Cornfield RB. Treatment of traumatic war neuroses with phenelzine. Arch Gen Psychiatry 1981; 38: 440–5
Milanes FJ, Mack CN, Dennison J, et al. Phenelzine treatment of post-Vietnam stress syndrome. VA Practitioner 1984; Jun: 40-9
Shen WW, Park S. The use of monoamine oxidase inhibitors in the treatment of traumatic war neurosis. Mil Med 1983; 148: 430–1
Walker JI. Chemotherapy of traumatic war stress. Mil Med 1982; 147: 1029–33
Levenson H, Lanman R, Rankin M. Traumatic war neurosis and phenelzine [letter]. Arch Gen Psychiatry 1982; 39: 1345
Bleich A, Siegel B, Garb R, et al. Post-traumatic stress disorder following combat exposure: clinical features and psychopharmacological treatment. Br J Psychiatry 1986; 149: 365–9
Lerer B, Bleich A, Kotler M, et al. Posttraumatic stress disorder in Israeli combat veterans: effects of phenelzine treatment. Arch Gen Psychiatry 1987; 44: 976–81
Blake DJ. Treatment of acute posttraumatic stress disorder with tricyclic antidepressants. South Med J 1986; 79: 201–4
Burstein A. Treatment of flashbacks by imipramine. Psychosomatics 1984; 25: 683–7
Marshall JR. The treatment of night-terrors associated with posttraumatic stress syndrome. Am J Psychiatry 1975; 132: 293–5
Falcon S, Ryan C, Chamberlain K, et al. Tricyclics: possible treatment for posttraumatic stress disorder. J Clin Psychiatry 1985; 46: 385–8
White NS. Post-traumatic stress disorder [letter]. Hosp Community Psychiatry 1983; 34: 1061–2
Chen C-J. The obsessive quality and clomipramine treatment in PTSD. Am J Psychiatry 1991; 148: 1087–8
Liebowitz NR, El-Mallakh RS. Trazodone for the treatment of anxiety symptoms in substance abusers. J Clin Psycho-pharmacol 1989; 9: 449–51
Hertzberg MA, Feldman ME, Beckham JC, et al. Trial of trazodone for posttraumatic stress disorder using a multiple baseline group design. J Clin Psychopharmacol 1996; 16: 294–8
Southwick SM, Yehuda R, Giller Jr EL, et al. Use of tricyclics and monamine oxidase inhibitors in the treatment of PTSD: a quantitative review. In: Murburg MM, editor. Catecholamine function in posttraumatic stress disorder. Washington, DC: American Psychiatrie Press Inc., 1994: 293–305
Horowitz M, Wilner N, Alvarez N. Impact of events scale: a measure of subjective stress. Psychosom Med 1979; 41: 209–18
Beck AT, Ward CH, Mendelson M, et al. An inventory for measuring depression. Arch Gen Psychiatry 1961; 4: 561–71
Spielberger CD. State-trait anxiety inventory. Palo Alto (CA): Consulting Psychologists Press, 1985
Guy W. ECDEU assessment manual for psychopharmacology. Rev. Rockville (MD): National Institute of Mental Health, 1976
Falsetti SA, Resnick HS, Resick PA, et al. The modified PTSD symptom scale: a brief self-report measure of posttraumatic stress disorder. Behavior Therapist 1993; 16: 161–2
Davidson J, Weisler R. Nefazodone in post traumatic stress disorder [abstract]. Proceedings of the American College of Neuropsychopharmacology: 1996 Oct; Puerto Rico, 177
Wells BG, Chu C-C, Johnson R, et al. Buspirone in the treatment of posttraumatic stress disorder. Pharmacotherapy 1991; 11: 340–3
Fichtner CG, Crayton JW. Buspirone in combat-related posttraumatic stress disorder. J Clin Psychopharmacol 1994; 14: 79–81
LaPorta LD, Ware MR. Buspirone in the treatment of posttraumatic stress disorder. J Clin Psychopharmacol 1992; 12: 133–4
Schwartz LS. A biopsychosocial treatment approach to posttraumatic stress disorder. J Trauma Stress 1990; 3: 221–38
Simpson MA. Buspirone, benzodiazepines, and post-traumatic stress disorder. J Trauma Stress 1991; 4: 305–8
Harsch HH. Cyproheptadine for recurrent nightmares. Am J Psychiatry 1986; 143: 1491–2
Brophy MH. Cyproheptadine for combat nightmares in posttraumatic stress disorder and dream anxiety disorder. Mil Med 1991; 156: 100–1
Kolb LC, Burris BC, Griffiths S. Propranolol and Clonidine in the treatment of post traumatic disorders of war. In: van der Kolk BA, editor. Post traumatic stress disorder: psychological and biological sequelae. Washington, DC: American Psychiatric Press Inc., 1984: 97–107
Kinzie JD, Leung P. Clonidine in Cambodian patients with posttraumatic stress disorder. J Nerv Ment Dis 1989; 177: 546–50
Perry BD. Neurobiological sequelae of childhood trauma: PTSD in children. In: Murburg MM, editor. Catecholamine function in posttraumatic stress disorder. Washington, DC: American Psychiatrie Press Inc., 1994: 233–55
Famularo R, Kinscherff R, Fenton T. Propranolol treatment for childhood posttraumatic stress disorder, acute type. Am J Dis Child 1988; 142: 1244–7
Braun BG. Unusual medication regimen in the treatment of dissociative disorder patients: part I: noradrenergic agents. Dissociation 1990; 3: 144–50
Hollister LE, Muller-Oerlinghausen B, Rickeis K, et al. Clinical uses of benzodiazepines. J Clin Psychopharmacol 1993; 13 Suppl. 1: 1–169S
Feldman TB. Alprazolam in the treatment of posttraumatic stress disorder. J Clin Psychiatry 1987; 48: 216–7
Giller Jr EL, Kosten RT, Yehuda R, et al. Psychoendocrinology and pharmacotherapy of PTSD. Clin Neuropharmacol 1990; 13 Suppl. 2: 329–30
Dunner FJ, Edwards WP, Copeland PC. Clinical efficacy of alprazolam in PTSD patients. New research abstracts of the American Psychiatrie Association 138th Annual Meeting 1985
Loewenstein RJ, Hornstein N, Farber B. Open trial of clonazepam in the treatment of posttraumatic stress symptoms in MPD. Dissociation 1988; 1: 3–12
Risse SC, Whitters A, Burke J, et al. Severe withdrawal symptoms after discontinuation of alprazolam in eight patients with combat-induced posttraumatic stress disorder. J Clin Psychiatry 1990; 51: 206–9
Patterson JF. Withdrawal from alprazolam dependency using clonazepam: clinical observations. J Clin Psychiatry 1990; 51(5 Suppl.): 47–9
Post RM, Kopanda RT. Cocaine, kindling, and psychosis. Am J Psychiatry 1976; 133: 627–34
Post RM. Clinical implications of a cocaine-kindling model of psychosis. Clin Neuropharmacol 1977; 2: 25–42
Post RM, Contel NR. Human and animal studies of cocaine: implications for development of behavioral pathology. In: Creese I, editor. Stimulants: neurochemical, behavioral, and clinical perspective. New York: Raven Press, 1983: 169–203
Post RM, Weiss SRB, Smith MA. Sensitization and kindling: implications for the evolving neural substrates of post-traumatic stress disorder. In: Friedman MJ, Charney DS, Deutch AY, editors. Neurobiological and clinical consequences of stress: from normal adaptation to post-traumatic stress disorder. Philadelphia: Lippincott-Raven, 1995: 203–24
Lipper S. Carbamazepine in the treatment of posttraumatic stress disorder: implications for the kindling hypothesis. In: Wolf ME, Mosnaim AD, editors. Posttraumatic stress disorder: etiology, phenomenology, and treatment. Washington, DC: American Psychiatric Press Inc., 1990: 184–203
Lipper S, Davidson JRT, Grady TA, et al. Preliminary study of carbamazepine in post-traumatic stress disorder. Psychosomatics 1986; 27: 849–54
Wolf ME, Alavi A, Mosnaim AD. Posttraumatic stress disorder in Vietnam veterans: clinical and EEG findings; possible therapeutic effects of carbamazepine. Biol Psychiatry 1988; 23: 642–4
Looff D, Grimley P, Kuller F, et al. Carbamazepine for PTSD. J Am Acad Child Adolesc Psychiatry 1995; 34: 703–4
Bennett TL, Curiel MR Complex partial seizures presenting as a psychiatric illness. Int J Clin Neuropsych 1988; 10: 41–4
Brodsky L, Doerman AL, Palmar LS, et al. Post-traumatic stress disorder: a tri-modal approach. Psychiatr J Univ Ott 1987; 12: 41–6
Stewart JR, Bartucci RJ. Post-traumatic stress disorder and partial complex seizures. Am J Psychiatry 1986; 143: 113–4
Szymanski HV, Herman V, Olympia J. Divalproex in posttraumatic stress disorder. Am J Psychiatry 1991; 148: 1086–7
Brodsky L, Doerman AL, Palmar LS, et al. Post-traumatic stress disorder: an eclectic approach. Int J Psychosom 1990; 37: 89–95
Fesler FA. Valproate in combat-related posttraumatic stress disorder. J Clin Psychiatry 1991; 52: 361–4
Kitchner I, Greenstein R. Low dose lithium carbonate in the treatment of posttraumatic stress disorder: brief communication. Mil Med 1985; 150: 378–81
van der Kolk BA. Psychopharmacological issues in posttraumatic stress disorder. Hosp Community Psychiatry 1983; 34: 683–91
Irwin M, Van Putten T, Guze B, et al. Pharmacologie treatment of veterans with posttraumatic stress disorder and concomitant affective disorder. Ann Clin Psychiatry 1989; 1: 127–30
Lucking RG. Bipolar disorder in post-traumatic stress disorder: a difficult diagnosis: case reports. Mil Med 1986; 151: 282–4
Macleod AD. Vigabatrin and posttraumatic stress disorder. J Clin Psychopharmacol 1996; 16: 190–1
Meuser KT, Butler RW. Auditory hallucinations in combat-related chronic post-traumatic stress disorder. Am J Psychiatry 1987; 144: 299–302
Glover H. A preliminary trial of nalmefene for the treatment of emotional numbing in combat veterans with post-traumatic stress disorder. Isr J Psychiatry Relat Sci 1993; 30: 255–63
Bills LJ, Kreisler K. Treatment of flashbacks with naltrexone [letter]. Am J Psychiatry 1993; 150: 1430
Braun BG. The use of naltrexone in the treatment of dissociative disorder patients [abstract]. Braun BG, Carlson EB, editors. Proceedings of the 7th International Conference on Multiple Personality/Dissociative States: 1990 Nov 9–11; Chicago, 20
Davidson JRT, Kudler HS, Smith RD. Assessment and pharmacotherapy of posttraumatic stress disorder. In: Giller Jr EL, editor. Biological assessment and treatment of posttraumatic stress disorder. Washington DC: American Psychiatrie Press Inc., 1990: 203–33
Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol 1959; 32: 50–5
Nierenberg AA, Cole JO, Glass L. Possible trazodone potentiation of fluoxetine: a case series. J Clin Psychiatry 1992; 53: 83–5
Kudler HS, Davidson JRT, Stein R, et al. Measuring results of treatment of PTSD. Am J Psychiatry 1989; 146: 1645–6
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Fichtner, C.G., Poddig, B.E. & de Vito, R.A. Post-Traumatic Stress Disorder. CNS Drugs 8, 293–322 (1997). https://doi.org/10.2165/00023210-199708040-00004
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DOI: https://doi.org/10.2165/00023210-199708040-00004