A preliminary study of tricyclic antidepressant (TCA) ovine FAB for TCA toxicity.
BACKGROUND
Animal studies suggest that tricyclic antidepressant antibody fragments (TCA Fab) may be a useful therapy for tricyclic antidepressant poisoning. The objective of this study is to determine if TCA Fab increases total serum TCA levels without raising free serum TCA levels in human overdose patients, indicating that TCA Fab effectively binds TCA.


METHODS
This was a prospective, dose escalation study of patients with mild to moderate TCA poisoning. Patients were treated with an escalating intravenous infusion totaling 7 or 14 gm of TCA Fab. The outcomes of interest were serum TCA levels (total and free), worsening of TCA toxicity, and adverse effects.


RESULTS
Seven patients were treated with Fab. Infusion of TCA Fab was associated with a dramatic increase in total serum TCA levels, while free TCA levels fell in both dosing groups. There were no significant changes in QRS duration, heart rate or mean arterial pressure associated with the Fab Infusion. Worsening of TCA toxicity did not occur despite marked elevation of total serum TCA concentrations. The two patients with the greatest prolongation of QRS showed a prompt shortening in their QRS duration temporally associated with the Fab infusion. Mild wheezing was observed in one asthmatic patient.


CONCLUSIONS
1) TCA Fab raises total serum TCA levels while lowering free levels in TCA poisoned patients; 2) no toxic effects were associated with the increase in TCA levels and no severe adverse effects were observed during the hospital course following Fab infusion.
Heard
Kennon
K
University of Colorado Health Sciences Center Section of Medical Toxicology, Division of Emergency Medicine, Department of Surgery, Denver 80231, USA. Kennon.Heard@uchsc.edu
Dart
Richard C
RC
Bogdan
Gregory
G
O'Malley
Gerald F
GF
Burkhart
Keith K
KK
Donovan
J Ward
JW
Ward
Suzanne B
SB
D000328:Adult; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000276:immunology / Q000506:poisoning*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011041:Poisoning / Q000188:drug therapy; D011446:Prospective Studies; D012756:Sheep; D016896:Treatment Outcome
D000929:Antidepressive Agents, Tricyclic; D007140:Immunoglobulin Fab Fragments; D007155:Immunologic Factors