Placebo-controlled trial of the CCK-B antagonist, CI-988, in panic disorder.

Abstract

BACKGROUND:

Based on the induction of panic-like symptoms by infusion of cholecystokinin (CCK) peptide in normals and panic disorder patients, it has been proposed that CCK may play a role in the disease mechanisms underlying anxiety disorders. Selective antagonists of CCK-B receptors can block the challenge-induced symptoms in a dose-dependent manner, leading to the hypothesis that these compounds may have anxiolytic effects.

METHODS:

A randomized, double-blind study was carried out to compare the effects of placebo with CI-988, a selective antagonist of the CCK-B receptors. Following a one-week placebo lead-in, patients with Panic Disorder with or without Agoraphobia received either placebo or CI-988 100 mg TID for six weeks. Panic attacks were recorded by a daily diary method.

RESULTS:

A total sample of 88 patients was planned but and interim analysis was carried out when about half the patients had been enrolled (n = 41). All patients improved during treatment and no difference in the weekly rate of panic attacks was seen between the treatment groups. The study was terminated at this point due to the remote likelihood of showing a treatment difference.

CONCLUSIONS:

CI-988 was not superior to placebo in reducing panic attacks. Several explanations are possible, including the poor pharmacokinetic characteristics of CI-988 which may make it unsuitable to test the CCK hypothesis of anxiety.

• Authors: A C Pande, M Greiner, J B Adams, R B Lydiard, M W Pierce
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 46 Issue 6 Pg. 860-2 (Sep 15 1999) ISSN: 0006-3223 [Print] United States
• PMID: 10494457 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Anxiety Agents
• Indoles
• Receptors, Cholecystokinin
• PD 134308
• Meglumine

Topics

• Adolescent
• Adult
• Aged
• Anti-Anxiety Agents (pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Humans
• Indoles (pharmacology, therapeutic use)
• Meglumine (analogs & derivatives, pharmacology, therapeutic use)
• Middle Aged
• Panic Disorder (drug therapy)
• Receptors, Cholecystokinin (antagonists & inhibitors)