Hormonal response during a fenfluramine-associated panic attack

Abstract

Secretion curves for prolactin, cortisol, TSH, and GH from a 37-year old woman with dysthymia and panic disorder with agoraphobia were determined one day prior to (day I), and during a panic attack (day II) associated with an oral dose of 60 mg dl-fenfluramine, a drug known to increase anticipatory anxiety. The increased cortisol secretion observed is discussed in relation to the hormonal correlates of anxiety and the possible role of depression, dl-fenfluramine, and serotonergic receptor sensitivity. Key wordsSeveral lines of evidence implicate serotonin (5-HT) in the pathophysiology of panic disorder. Serotonergic antidepressants such as clomipramine (1,2) and fluvoxamine (3) seem to be more potent in panic suppression than drugs acting mainly on noradrenergic neurotransmission such as imipramine and maprotiline. The occurrence of initial worsening in about 30% of panic patients treated with clomipramine (4) suggests that abnormalities in 5-HT receptor sensitivity may be the pathophysiologic condition underlying the serotonergic dysfunction in panic disorder (5,6). Since serotonin is also involved in the releasing mechanisms of prolactin and cortisol, challenge secretion tests with these hormones have been systematically used to assess the 5-HT receptor status in panic disorder (7,8).Challenge tests with dl-fenfluramine (FEN), a phenylethylamine derivative that releases presynaptic 5-HT and inhibits 5-HT reuptake, are frequently used to assess the responsiveness of the serotonergic system in several psychiatric disorders such as depression (9), bulimia nervosa (10), obsessivecompulsive disorder (11), schizophrenia (12), and social phobia (11).Targum and Marshall (7) administered 60 mg FEN to 9 women with panic disorder, 9 with major depressive disorder, and 9 controls. Panic patients showed significantly greater anxiety response and prolactin and cortisol secretion compared to patients with major depression or control subjects. High anxiety levels were observed for several hours after FEN administration but the occurrence of panic attacks was not adequately described. Targum (8) suggests that FEN can induce a slow rising anxiety state that can persist for several hours contrasting with the acute panic attacks observed with lactate.We report the acute hormonal changes that occurred during a well-documented panic