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.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Biological Psychiatry
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Pentagastrin infusion in patients with panic disorder. I. Symptoms and cardiovascular responses.Biol Psychiatry. 1994; 36: 73-83
- Double-blind, placebo-controlled study of a CCK-B receptor antagonist, CI-988, in patients with Generalized Anxiety Disorder.J Clin Psychopharmacol. 1995; 15: 428-434
- Cholecystokinin dipeptoid antagonists.J Med Chem. 1993; 36: 552-565
- The cholecystokinin hypothesis of anxiety and panic disorder.Ann NY Acad Sci. 1994; 713: 273-282
- Imipramine antagonism of the panicogenic effects of CCK-4 in panic disorder patients.Am J Psychiatry. 1994; 49: 318-323
- The panicogenic effects of cholecystokinin tetrapeptide are antagonized by L-365,260, a central cholecystokinin receptor antagonist, in patients with panic disorder.Arch Gen Psychiatry. 1994; 51: 486-493
- Effect of CI-988 on cholecystokinin tetrapeptide-induced panic symptoms in healthy volunteers.Biol Psychiatry. 1995; 38: 742-746
- Lymphocyte cholecystokinin concentrations in panic disorder.Am J Psychiatry. 1993; 150: 1111-1113
- Failure of CCK receptor ligands to modify anxiety-related behavioural suppression in an operant conflict paradigm in rats.Psychopharmacology. 1995; 121: 127-134
- Lack of effect of CCKB receptor antagonists in ethological and conditioned animal screens for anxiolytic drugs.Psychopharmacology. 1995; 121: 109-117
- A placebo-controlled trial of L-365,260, a CCK-B antagonist, in panic disorder.Biol Psychiatry. 1995; 37: 462-466
- CSF cholecystokinin concentrations in patients with panic disorder and in normal comparison subjects.Am J Psychiatry. 1992; 149: 691-693
- The CCK-B antagonist LY288513 blocks effects of diazepam withdrawal on auditory startle.Neuroreport. 1993; 5: 154-156
- Evidence for an involvement of the brain cholecystokinin B receptor in anxiety.Proc Natl Acad Sci USA. 1991; 88: 1130-1133
- Effect of the cholecystokinin-B receptor antagonist L-365,260 on lactate-induced panic attacks in panic disorder patients.Biol Psychiatry. 1996; 40: 804-806
- Pentagastrin induced panic attacks.Psychopharmacology. 1994; 114: 449-455
- Effect of the selective serotonin reuptake inhibitor (SSI) fluvoxamine on CCK-4 induced panic attacks.Psychopharmacology. 1994; 10: 270
- The cholecystokinin-B receptor antagonist CI-988 failed to affect CCK-4 induced symptoms in panic disorder patients.Psychopharmacology. 1997; 129: 243-248
Accepted: April 6, 1999
Received in revised form: March 22, 1999
Received: September 10, 1997
© 1999 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.