d-Fenfluramine in panic disorder: a dual role for 5-hydroxytryptamine

Abstract 

Rationale: 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. Objectives: 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.