d-Fenfluramine in panic disorder: a dual role for 5-hydroxytryptamine.
BACKGROUND
5-Hydroxytryptamine (5-HT) appears to modulate different forms of anxiety in different ways, but the importance of this in human anxiety disorders is unknown.


OBJECTIVE
To investigate whether the 5-HT releasing agent d-fenfluramine (dFEN) has different effects on resting and panic anxiety in panic disorder.


METHODS
Thirteen drug-free patients with DSM-IIIR panic disorder were tested in a double-blind placebo-controlled crossover design. Carbon dioxide 7% (CO2) was given as a panic challenge 270 min after administration of dFEN or placebo.


RESULTS
Compared to placebo, dFEN increased anxiety and arousal, maximal at 120 min, but tended to reduce CO2-induced anxiety and panic attacks with a significant reduction in Panic Visual Analogue Scale ratings (P=0.040). Anxiety following CO2, but not dFEN, administration resembled panic attacks (compared to Acute Panic Inventory symptom profile during patients' usual attacks). Patients with more severe disorders exhibited enhanced behavioural responses and blunted prolactin responses to dFEN.


CONCLUSIONS
dFEN caused anxiety similar to generalised anxiety in panic disorder patients but reduced anxiety following 7% CO2 challenge, a laboratory analogue of naturally occurring panic attacks. These findings are consistent with a dual role for 5-HT in pathological anxiety. Patients with more severe symptoms differed in 5-HT function compared to more mildly affected individuals.
Mortimore
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Department of Psychiatry, The University of Manchester, Manchester Royal Infirmary, UK.
Anderson
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IM
D000328:Adult; D000704:Analysis of Variance; D001007:Anxiety / Q000139:chemically induced; D002245:Carbon Dioxide / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005277:Fenfluramine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000188:drug therapy* / Q000523:psychology; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*
D002245:Carbon Dioxide; D005277:Fenfluramine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors