Panic attacks associated with citalopram.

ABSTRACT

Citalopram is the newest selective serotonin reuptake inhibitor (SSRI) available in the United States. It is currently approved by the Food and Drug Administration for the treatment of major depression. However, a number of studies have found it to be effective in the treatment of panic disorder as well. While there have been no previous case reports of citalopram inducing panic attacks in patients, this phenomenon has been reported with other members of the SSRI class of antidepressants. We present the case of a 61-year-old woman who had frank panic attacks after her citalopram dose was increased. She had had no history of anxiety symptoms. Anxiety abated completely upon discontinuance of citalopram therapy.

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CITALOPRAM HYDROBROMIDE (Celexa) is a selective serotonin reuptake inhibitor (SSRI) with established safety and efficacy in the treatment of depression. (1) Some citalopram studies have shown promising results in the treatment of panic disorder. (2) The most common side effects seen with citalopram use are nausea (21%), dry mouth (20%), somnolence (18%), insomnia (14%), and increased sweating (11%). (3)

In a review of SSRI side-effect reports in Sweden, psychiatric symptoms were the second leading adverse reaction reported, occurring in 19.5% of patients. (4) The most common psychiatric side effect reported was "anxiety," which began, on average, 4 days after institution of treatment. (4) The development of anxiety and panic attacks during treatment with SSRIs has been well documented in the literature. Increased anxiety or the onset of panic attacks has been associated with sertraline, (5-7) fluoxetine, (8-12) paroxetin, (13,14) and fluvoxamine, (15) despite the fact that they all have some efficacy in the treatment of panic disorder. (6)

No case reports of increased anxiety or panic associated with citalopram treatment were found on MEDLINE. We now report the first known case of panic attacks induced by citalopram.

CASE REPORT

The patient was a 61-year-old white woman hospitalized for revision of a popliteal bypass. Her medical history included major depression for 20 years, a myocardial infarction, peripheral vascular disease, three cerebrovascular accidents, type 2 diabetes mellitus, urinary incontinence, and a duodenal ulcer, which were all stable on admission. Her usual medications were clopidogrel (75 mg daily), enalapril (5 mg bid), digoxin (0.25 mg/day), warfarin (5 mg/day), metformin (1,000 mg bid), glipizide (10 mg orally tid), tolterodine (2 mg orally qd), metoprolol (50 mg orally bid), and enoxaparin (30 mg subcutaneously bid). Six weeks before admission, her antidepressant medication was changed from imiparamine to citalopram (20 mg daily) without any anxiety symptoms or adverse effects. She denied any history of substance abuse. There was no family history of anxiety disorders.

During her hospitalization, the patient complained of worsening depressive symptoms, including sleep difficulties, decreased interest, "a horribly depressed" mood and poor concentration. She denied anxiety symptoms, delusions, hallucinations, or suicidal ideations. Serum electrolyte values, complete blood count, thyrotropin level, and folate levels were within normal limits. Vitamin [B.sub.12] level was low at 158.8 pg/mL, and she was given 1,000 [micro]g of vitamin [B.sub.12] intramuscularly that evening. Three days later, the citalopram dose was increased to 40 mg each morning. As needed, doses of zaleplon (5 mg qhs) were added for insomnia.

Four days after the citalopram dose increase, the patient reported worsening anxiety symptoms, and a day later, she began having panic attacks. These attacks were characterized by a feeling of "going crazy" with a "fear of losing control." She had bouts of shortness of breath, heart palpitations, accelerated heart rate, nausea, and perioral numbness. The attacks began abruptly, lasted between 3 and 5 minutes and continued for the next 2 days (approximately 5 attacks per day). Her cardiac and respiratory status were evaluated for any appreciable contribution to these symptoms, but none was identified. The increased dose of citalopram was believed to be the cause of the panic attacks, and it was withdrawn. She continued to report some anxiety but no accompanying physical symptoms for the first 24 hours after discontinuing citalopram therapy. After that, no further anxiety or panic was noted.

DISCUSSION

The SSRIs have been found to be useful in the treatment of panic disorder. (16) However, SSRJ therapy can give rise to a variety of adverse reactions, including generalized anxiety and panic attacks. The growing abundance of case reports of SSRI-induced panic attacks continues to implicate serotonergic neuronal overactivity in their origin. (17)

Although increased anxiety and panic attacks have been associated with all SSRIs, we believe our report is the first documented account of citalopram-associated panic attacks. The anxiety and panic attacks appeared only after increasing the patient's initial citalopram dose, and they subsided quickly after the drug was withdrawn. All other medications remained unchanged except for the addition of zaleplon, which is not known to be a cause of anxiety or known to have an interaction with citalopram. Premarketing clinical trials found that zaleplon in short-term use was not associated with any significant adverse effects. (3) The patient continued to use zaleplon after discontinuance of citalopram therapy, without further panic attacks.

Our patient had nonspecific anxiety on day 4 and panic attacks on day 5 after increasing the dose of citalopram from 20 mg to 40 mg daily. Most anxiety reactions reported among patients receiving SSRIs occurred at a median time interval of 4 days. (4) When citalopram therapy was discontinued, our patient had no further panic attacks, likely because of citalopram's relatively short half-life of 33 hours. (18) This rapid disappearance of panic symptoms is also seen in patients taking other SSRIs with a relatively short half-life. In the previously reported cases of panic attacks associated with sertraline treatment, (5-7) the panic symptoms all abated quickly after the medication was discontinued. This is in stark contrast to fluoxetine and its active metabolite norfluoxe tine, which have half-lives of 24 to 72 hours and 168 to 360 hours, respectively. (18) In two of the previously reported cases of panic attacks associated with fluoxetine therapy, the panic symptoms continued for more than 4 months after treat ment was discontinued. (12)

In cases involving other SSRI-induced panic attacks, the use of benzodiazepines has been reported to relieve anxiety symptoms until the adverse effect of the SSRI wears off. This adjunctive therapy has been particularly useful with the SSRIs that have longer half-lives (such as fluoxetine/norfluoxetine), which take a considerable amount of time for complete excretion.

In conclusion, even though citalopram has been shown to be an effective agent in the treatment of panic disorder, (16) it may precipitate or worsen anxiety symptoms in some patients. Initiation of citalopram therapy should begin at a low dose and be increased at a slow rate to reduce the risk of exacerbation of anxiety or of inducing the onset of panic attacks.

References

(1.) Feighner J. Overo K: Multicenter, placebo-controlled, fixed close study of citalopram in moderate-to-severe depression. J Clin Psychiatry 1999; 60:824-830

(2.) Wade AG, Lepola U, Koponen HJ, et al: The effect of citalopram in panic disorder. Br J Psychiatry 1997; 170:549-553

(3.) Physicians' Desk Reference. Montvale, NJ, Medical Economics Co, 54th Ed, 2000

(4.) Spigset O: Adverse reactions of selective serotonin reuptake inhibitors, reports from spontaneous reporting system. Drug Saf 1999; 20:277-287

(5.) Zinner SH: Panic attacks precipitated by sertraline. Am J Psychiatry 1994; 151:147-148

(6.) Varon J, Lechin AE, Taylor TV: "Impending death" and sertraline. J Emerg Med 1995; 13:246

(7.) Catalano G, Hakala SM, Catalano Mc: Sertraline-induced panic attacks. Clin Neuropharmacol 2000; 23:164-168

(8.) Saran A, Halaris A: Panic attack precipitated by fluoxetine. J Neuropsychiatry Clin Neurosci 1989; 1:219-220

(9.) Marshall RD, Printz D, Cardena D, et al: Adverse events in PTSD patients taking fluoxetine. Am J Psychiatry 1995; 152:1238-1239

(10.) Louie AK, Lewis TB, Lannon RA: Use of low-dose fluoxetine in major depression and panic disorder. J Clin Psychiatry 1993; 54:435-438

(11.) Cookson J, Duffert R: Fluoxetine: therapeutic and undesirable effects. Hosp Med 1998; 59:622-626

(12.) Altshuler LL: Fluoxetine-associated panic attacks. J Clin Psychopharmacol 1994; 14:433-434

(13.) Lecrubier Y, Bakker A, Dunber C, et al: A comparison of paroxetine, clomipramine and placebo in the treatment of panic disorder. Acta Psychiatr Scant 1997; 95:145-152

(14.) Ballenger JC, Wheadon DE, Steiner M, et al: Double-blind, fixed-dose, placebo-controlled study of paroxetine in the treatment of panic disorder. Am J Psychiatry 1998; 155:3642

(15.) Sandmann J, Lorch B, Bandelow B, et al: Fluvoxamine or placebo in the treatment of panic disorder and relationship to blood concentrations of fluvoxamine. Pharmacopsychiatry 1998; 31:117-121

(16.) Sheehan DV: Current concepts in the treatment of panic disorder. J Clin Psychiatry 1999; 60(suppl 18): 16-21

(17.) Nutt D, Lawson C: Panic attacks: a neurochemical overview of models and mechanisms. Br J Psychiatry 1992; 160:165-178

(18.) Nutt D: Antidepressants in panic disorder: clinical and preclinical mechanisms. J Clin Psychiatry 1998; 59(suppl 8):24-28

RELATED ARTICLE: KEY POINTS

* The selective serotonin reuptake inhibitors (fluoxetine, fluvoxamine, paroxetine, sertraline, and citalopram) are now commonly used in the treatment of anxiety disorders.

* Fluoxetine, fluvoxamine, paroxetine, and sertraline have previously been associated with treatment emergent anxiety symptoms.

* We describe the first reported case of the development of frank panic attacks during treatment with citalopram.

From the Department of Psychiatry and Behavioral Medicine, University of South Florida College of Medicine, Tampa.

Reprint requests to Glenn Catalano, MD, University of South Florida Psychiatry Center, 3515 E Fletcher Ave, Tampa, FL 33613.