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Provocation of a Posttraumatic Flashback by Cholecystokinin Tetrapeptide?

To the Editor: Among the intrusive symptoms of posttraumatic stress disorder (PTSD), flashbacks represent a still poorly understood phenomenon. Some symptomatic aspects of flashbacks closely resemble panic attacks; experimental paradigms of panic provocation, such as sodium lactate (1, 2) and yohimbine (3), have also been reported to provoke flashbacks in PTSD patients, even without comorbid panic disorder. We report our observation of the first PTSD patient to receive an intravenous bolus of 50 mg of the potent panicogen cholecystokinin tetrapeptide (CCK-4) (4) in a double-blind, placebo-controlled randomized trial. Written informed consent was obtained from the patient, and the protocol was approved by the institutional review board.

Mr. A, a 35-year-old African American, has been suffering from chronic PTSD (DSM-IV) with repetitive flashbacks for 4 years after being shot in the stomach point-blank. The Structured Clinical Interview for DSM-IV showed a remitted alcohol dependence but no other axis I comorbidity. After placebo injection, no significant symptoms emerged. After injection of CCK-4, Mr. A developed a full-blown panic attack (DSM-IV criteria) with nausea and abdominal symptoms. Furthermore, he reported 1) having seen himself, as though in a video, back in the posttrauma emergency room; 2) having smelled blood; and 3) having felt a drainage in his stomach for about 45 seconds, beginning approximately 1 minute after the injection of CCK-4.

This flashback occurring during a CCK-4-induced panic attack, could have been a drug effect mediated by the activation of brainstem CCK-B receptors (4). On the other hand, Mr. A's abdominal symptoms produced by CCK-4 and his contingent memories of the trauma could have acted as conditioned stimuli to trigger his flashback. In addition, the hospital environment's possible facilitating role for a flashback to an emergency room needs to be kept in mind (1). Of course, a spontaneous or factitious flashback cannot be definitely excluded. Further experiments with CCK-4 to assess the role of CCK-B receptors in the pathophysiology of posttraumatic flashbacks and symptoms of anxiety in patients suffering from PTSD are promising.

REFERENCES

1. Rainey JM, Aleem A, Ortiz A, Yeragani V, Pohl R, Berchou R: A laboratory procedure for the induction of flashbacks. Am J Psychiatry 1987; 144:1317–1319 [Abstract/Free Full Text]
2. Jensen CF, Keller TW, Peskind ER, McFall ME, Veith RC, Martin D, Wilkinson CW, Raskind MA: Behavioral and neuroendocrine responses to sodium lactate infusion in subjects with posttraumatic stress disorder. Am J Psychiatry 1997; 154:266–268 [Abstract]
3. Southwick SM, Krystal JH, Morgan CA, Johnson D, Nagy LM, Nicolaou A, Heninger GR, Charney DS: Abnormal noradrenergic function in posttraumatic stress disorder. Arch Gen Psychiatry 1993; 50:266–274[Abstract]
4. Harro J, Vasar E, Bradwejn J: CCK in animal and human research on anxiety. Trends Pharmacol Sci 1993; 14:244–249[Medline]

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