Pharmacology Update

Escitalopram Oxalate Tablets (Lexapro— Forest Laboratories)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The FDA has approved the active (S-enantiomer) of citalopram for the treatment of depression.

Citalopram, a SSRI that is currently available as "Celexa," is the racemic mixture containing S and R enantiomers. Antidepressant activity for escitalopram (S-enantiomer) is about 100 times more potent than the R-enantiomer and twice as potent as racemic citalopram. Escitalopram is marketed by Forest Laboratories as Lexapro.

Indications

Escitalopram is indicated for the treatment of major depression.1

Dosage

The recommended starting dose is 10 mg once daily. It may be taken in the morning or evening without regard to meals. A 10 mg dose is also recommended for most elderly and those with hepatic dysfunction. No dose adjustment is required for those with mild or moderate renal dysfunction.1

Escitalopram is available as 10 mg and 20 mg tablets.

Potential Advantages

Escitalopram does not appear to provide any significant clinical advantage over the racemic citalopram. Greater potency or more rapid onset of action of the active enantiomer over the racemic mixture has not been clearly established. Like citalopram, escitalopram may have a lower incidence of drug/drug interactions compared to other SSRIs.

Potential Disadvantages

Escitalopram does not appear to have any significant disadvantage over the racemic citalopram.

Comments

Escitalopram was approved based on extrapolation of efficacy from racemic citalopram and an 8-week fixed-dose study.2 In this study, 491 patients with DSM-IV major depression were randomized to placebo, escitalopram 10 mg, 20 mg, or citalopram 40 mg. The Montgomery-Asberg Depression Rating Scale (MADRS), the 24-item Hamilton Rating Scale for Depression (HAM-D), the Clinical Gobal Impressions (CGI) scales, the Hamilton Rating Scale for Anxiety (HAM-A), and patient-rated quality of life scales, assessed efficacy. Burke and colleagues concluded that escitalopram 10 mg was significantly better than placebo, and there was no significant difference among escitalopram 10 mg, 20 mg, or citalopram 40 mg. In addition, the incidence of discontinuation due to adverse events was not different among the treatment arms. Another study compared escitalopram 10 mg, citalopram 20 mg, and placebo in 469 patients. Montgomery and associates reported that at 4 weeks escitalopram 10 mg was more effective than placebo, while 20 mg citalopram was not.3 A third study also found escitalopram 10 mg to be effective compared to placebo.4 Unpublished studies presented at the XII World Congress of Psychiatry (Yokohama, Japan, August 2002) suggested that escitalopram may have greater efficacy and more rapid onset than citalopram.5 The wholesale cost of escitalopram 10 mg is $1.78 compared to $1.93 for citalopram 20 mg.

Clinical Implications

Citalopram is well established as a safe and effective antidepressant. Its efficacy is similar to other SSRIs.7 Its primary advantage over other SSRIs is a low potential for drug interactions involving the cytochrome P450 isoform.6 For example, fluoxetine and paroxetine are considered as potent inhibitors of, and sertraline as a moderate inhibitor of, CYP2D6, while citalopram has little effect. Currently there are inadequate published data to clearly distinguish whether the single enantiomer is more potent or more rapid acting that racemic citalopram. Forest is expected to cease promoting citalopram in favor escitalopram as the former is scheduled to lose patent protection in January 2004.7

Dr. Elliott is Northern California Kaiser Permanente; Asst. Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.

References

1. Lexapro Product Information. Forest Pharmaceutical, Inc. August 2002.

2. Burke WJ, et al. J Clin Psychiatry. 2002;63(4):331-336.

3. Montgomery SA, et al. Pharmacol Toxicol. 2001;88: 282-286.

4. Wade A, et al. Int Clin Psychopharmacol. 2002;17(3): 95-102.

5. Poole R. Inpharma Weekly. 2002;1357:13-14.

6. Hemeryck A, Belpaire FM. Curr Drug Metab. 2002; 3(1):13-37.

7. FDC Report. The Pink Sheet. 2002;64(33)3.