Citalopram (Celexa) in Children & Adolescents

A Treatment for Depression

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Citalopram (Celexa), analogous to paroxetine (Paxil) and the Study 329 story [1], for the management of major depressive disorder (MDD) in children and adolescents is an additional example of promotion trumping the evidence that this drug should not be used in younger populations of patients.

What We Knew and When

What was known and in plain sight for prescribers since July 1998 when citalopram was first approved by the Food and Drug Administration (FDA) was information contained in the drug's professional product label and other agency documents warning prescribers not to use citalopram in children and adolescents.

Original Product Label

The original professional product label for citalopram from July 1998 contained the following statement in the Pediatric Use section of the label:

Safety and effectiveness in pediatric patients have not been established.[2]

Under the Best Pharmaceuticals for Children Act the sponsor submitted two studies in 2002 seeking additional marketing exclusivity for citalopram. The decision was:

Only one of two clinical studies is positive and this supplement is not approvable.[3]

Exclusivity was granted based on the completion of these two studies.

Both of these studies were published. The positive study in June 2004 and the other that found in the treatment of adolescent depression a therapeutic effect for citalopram as compared to placebo could not be found.[4,5]

Amended in 2005

The professional product labeling for citalopram was amended in February 2005. A box warning, the strongest type of caution the FDA can require, was added to the professional product label and contains the following statement:

Celexa is not approved for use in pediatric patients.

The following description of the 2 clinical trials submitted to obtain pediatric exclusivity was added to the Pediatric Use section of the professional product label in 2005:

Two placebo-controlled trials in 407 pediatric patients with MDD have been conducted with Celexa, and the data were not sufficient to support a claim for use in pediatric patients.

Warned in 1998 and 2002

The FDA warned prescribers about citalopram and its use in children and adolescents in 1998 and in 2002 found the review of 2 pediatric exclusivity studies did not support the use of the drug in this population of patients for MDD. The FDA concluded its pediatric assessment of citalopram 8 months after the publication of the first citalopram study in 2004 that was positive. Citalopram's label was revised in 2005 to strengthen the warning about the use of the drug in younger populations. [6] The second study, which was negative, appeared in the literature in 2006.

Promotion and the circulation of Wagner's [4] 2004 positive paper appear to be the spark for citalopram's market place success. The prescribing of drugs may largely be a function of promotion and not the quality of available objective useful scientific information.

Recommendations

Resources would be better utilized in improving prescribing that directly impacts patient safety and wasteful drug budgets.

Professional product labeling changes; continuing education programs for prescribers; re-analyses confirming old FDA decisions; and calling for journal article retractions have appeared to be uniformly unproductive.

An intervention that has not been fully attempted is directly promoting FDA approved professional product labels and documents and how to use them directly to patients and their families.

Reference

1. Sasich LD. Paroxetine and Study 329: what we already knew and when. BMJ. Oct 14 2015; 351:h5411 [Letter].

2. Forest Pharmaceuticals, Inc. Celexa (citalopram) Professional Product Label, July 17, 1998. At https://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20822lbl.pdf. Accessed May 2, 2017.

3. Hearst ED, US Food and Drug Administration. Pediatric Supplement Celexa (citalopram), April 2002. At https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM162562.pdf. Accessed May 2, 2017.

4. Wagner KD, Robb AS, Findling RL, et al. A randomized, placebo-controlled trial of citalopram for the treatment of major depression in children and adolescents. Am J Psychiatry. 2004; 161(6):1079-1083.

5. Von Knorring AL, Olsson GI, Thomsen PH, et al. A randomized, double-blind, placebo-controlled study of citalopram in adolescents with major depressive disorder. J Clin Psychopharmacol. 2006; 26(3): 311-315.

6. Forest Pharmaceuticals, Inc. Celexa (citalopram) Professional Product Label, February 2, 2005. At https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/020822s29lbl.pdf. Accessed May 2, 2017.

Background by Larry Sasich. Posted with permission.

Related Article

See the related article, Canadian children prescribed potent psychiatric drugs, written by a Social Worker in a Canadian school.

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