Could proton pump inhibitors cause increased anxiety and panic attacks? found this article on the internet
Rabeprazole-Induced Panic Attacks
Rabeprazole is an anti-ulcer drug in the class of proton pump inhibitors (PPIs). Psychiatric adverse effects reported for rabeprazole during controlled trials and postmarketing experience are rare and include insomnia, anxiety, depression, somnolence, abnormal dreams, decreased libido, agitation, amnesia, and confusion.1 The following is a published report in which a patient developed marked anxiety and panic attacks in association with use of rabeprazole.2
A 55-year-old white woman was prescribed rabeprazole 20 mg/day administered in the morning for persistent symptoms of dyspepsia. Her history was notable for a depressive episode 8 years earlier, which resolved and did not recur after 4 months of treatment with an (unspecified) antidepressant. She was not taking any other medications, including over-the-counter drugs or herbal remedies. She had no known allergies or history of alcohol abuse or illicit drug use. She smoked 15 cigarettes a day. She denied any stressful or traumatic change in her lifestyle during the prior 6 months.
Ten days after initiation of rabeprazole, she presented with a 7-day history of marked anxiety associated with panic attacks, night terror (pavor nocturnus), episodic mental confusion, and attention deficit. The panic attacks lasted from a few minutes to approximately 1 hour and consisted of intense apprehension, dyspnea, palpitations, fear, and a feeling of impending disaster. Within 2 days of discontinuing rabeprazole, all of her symptoms completely resolved. Later work-up revealed the presence of gastroesophageal reflux disease with erosive gastro-duodenitis positive for Heliobacter pylori. Subsequent treatment with esomeprazole for a period of 4 weeks did not result in any psychiatric adverse effects.
It appears that rabeprazole induced this patient’s anxiety and panic symptoms. Among PPI, rabeprazole has the highest capacity to induce increased secretion of gastrin.3,4 PPI-induced secretion of gastrin is mediated by the release of gastrin-releasing peptide (GRP).5 GRP and its receptor are found in the dorsal hippocampus and amygdala, where they are involved in regulating synaptic plasticity and aspects of behavior that might be altered in disorders such as anxiety, depression, and dementia.6 It is known that pentagastrin, a synthetic pentapeptide derived from gastrin, when administered to healthy volunteers, leads to increases in anxiety, heart rate, and physical symptoms of panic in a dose-related manner.7,8 Furthermore, the highly selective gastrin receptor antagonist PD-136,450 has anxiolytic activity in rats and rabbits.9
Regardless of mechanism of action, rabeprazole may be anxiogenic in certain vulnerable patient populations. Further studies are needed to confirm these preliminary observations. PP
1. Aciphex [package insert]. Tokyo: Eisai Co., Ltd; 2003.
2. Polimeni G, Cutroneo P, Gallo A, Gallo S, Spina E, Caputi AP. Rabeprazole and psychiatric symptoms. Ann Pharmacother. 2007;41(7):1315-1317.
3. Williams MP, Sercombe J, Hamilton MI, Pounder RE. A placebo-controlled trial to assess the effects of 8 days of dosing with rabeprazole versus omeprazole on 24-h intragastric acidity and serum gastrin concentrations in young healthy male subjects. Aliment Pharmacol Ther. 1998;12(11):1079-1089.
4. Warrington S, Baisley K, Boyce M, Tejura B, Morocutti A, Miller N. Effects of rabeprazole, 20 mg, or esomeprazole, 20 mg, on 24-h intragastric pH and serum gastrin in healthy subjects. Aliment Pharmacol Ther. 2002;16(7):1301-1307.
5. Takehara Y, Sumii K, Tari A, et al. Evidence that endogenous GRP in rat stomach mediates omeprazole-induced hypergastrinemia. Am J Physiol. 1996;271(5 Pt 1):G799-804.
6. Roesler R, Henriques JA, Schwartsmann G. Gastrin-releasing peptide receptor as a molecular target for psychiatric and neurologic disorders. CNS Neurol Disord Drug Targets. 2006;5(2):197-204.
7. McCann UD, Slate SO, Geraci M, Uhde TW. Peptides and anxiety: a dose-response evaluation of pentagastrin in healthy volunteers. Anxiety. 1994-1995;1(6):258-267.
8. Geraci M, Anderson TS, Slate-Cothren S, Post RM, McCann UD. Pentagastrin-induced sleep panic attacks: panic in the absence of elevated baseline arousal. Biol Psychiatry. 2002;52(12):1183-1189.
9. Bastaki SM, Hasan MY, Chandranath SI, Schmassmann A, Garner A. PD-136,450: a CCK2 (gastrin) receptor antagonist with antisecretory, anxiolytic and antiulcer activity. Mol Cell Biochem. 2003;252(1-2):83-90.