Anxiogenic effects of Sumatriptan in panic disorder: A double-blind, placebo-controlled study Daniella Amital a , Leah Fostick a , Yehuda Sasson a , Seth Kindler a , Howard Amital b , Joseph Zohar a, T a Department of Psychiatry, Chaim Sheba Medical Center, Tel-Hashomer, Israel b Department of Medicine B, Chaim Sheba Medical Center, Tel-Hashomer, Israel Received 10 February 2004; accepted 2 December 2004 Both daT and dbT above are affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel Abstract Background: Several lines of evidence point to serotonergic abnormalities in patients with panic disorder (PD). Our goal was to further examine central serotonergic function in panic patients using autonomic and subjective responses to the postsynaptic serotonin 5-HT 1D receptor agonist Sumatriptan. Method: Using a double-blind, randomized, placebo-controlled design, we assessed autonomic and subjective responses to oral Sumatriptan (100 mg) and placebo in 15 patients with PD, free of medication. Subjective responses were measured using the Hamilton Anxiety Rating Scale (HAM-A), National Institute of Mental Health Anxiety Scale (NIMHA), a modified version of the Panic Symptom Inventory (PI), Hamilton Depression Rating Scale (HAM-D), and Montgomery–Asberg Depression Rating Scale (MADRS). Results: PD patients exhibited significantly enhanced autonomic and subjective responses following challenge with Sumatriptan. We observed an increased pulse rate and augmentation of various parameters measured on different anxiety scales. A constant inclination of aggravation of the measured parameters was detected during the hour post challenge. Conclusion: Oral administration of Sumatriptan, a 5-HT 1D agonist, has been associated with an anxiogenic effect in PD patients. D 2004 Elsevier B.V. and ECNP. All rights reserved. Keywords: PD; Sumatripan; Anxiety; Challenge test; Serotonin 1. Introduction Panic disorder (PD) is a severe syndrome associated with significant impairment of the patients’ quality of life as well as their social life function. Comorbidity with depressive and addictive disorders is frequent, and it is considered by numerous authors as a risk factor for suicide (Richter et al., 2003; Kahn et al., 1988b; Klein and Klein, 1989; den Boer and Westenberg, 1990b). A number of clinical studies have attempted to assess the role of serotonin abnormalities in PD. These studies are also based on the use of challenge tests with pani- cogenic agents. Administration of such agents to PD pa- tients allows the induction of panic attacks under labo- ratory conditions. Klein and Klein (1989) investigated the behavioral and neuroendocrine effects of metachlorophe- nylpiperazine (mCPP), a serotonergic agonist, in PD patients and demonstrated that mCPP had significantly greater anxiogenic and panic inducing effects than placebo. In the present study we investigated the potential role of other 5-hydroxytriptophan (5-HT) receptor subtypes, in particular the 5-HT 1D receptor, using the 5-HT 1D specific agonist, Sumatriptan. Sumatriptan is effective in the treat- ment of acute migraine. Its antimigraine activity is derived most likely from the selective vasoconstriction of cranial 0924-977X/$ - see front matter D 2004 Elsevier B.V. and ECNP. All rights reserved. doi:10.1016/j.euroneuro.2004.12.002 T Corresponding author. Tel.: +972 3 5303300; fax: +972 3 5352788. E-mail address: jzohar@post.tau.ac.il (J. Zohar). European Neuropsychopharmacology 15 (2005) 279 – 282 www.elsevier.com/locate/euroneuro