New SSRI touts fewer side effects

September 16, 2002

Forest Laboratories' Lexapro hits the market

 

Rx CARE

New SSRI touts fewer side effects

Low prices and heavy promotion, plus a solid clinical profile, will make escitalopram oxalate (Lexapro) a blockbuster for Forest Laboratories, according to several financial analysts. Health professionals say escitalopram's early onset of antidepressant action (starting at one to two weeks) could be advantageous, if clinical experience shows such onset commonly occurs.

The Food & Drug Administration first approved escitalopram for the treatment of major depression in mid-August. Two weeks later, it OK'd another indication—as maintenance treatment for major depression. The selective serotonin reuptake inhibitor (SSRI) already has approval in several European countries to treat panic disorder with or without agoraphobia. Studies show escitalopram also works for social anxiety disorder and general anxiety disorder.

Forest seems intent on ensuring that people give up escitalopram's parent drug, racemic citalopram (Celexa), and switch to escitalopram, the active isomer of citalopram, before citalopram's U.S. patent expires in January 2004. A company spokesman said escitalopram would cost slightly less than citalopram, which Forest will continue to manufacture but will not promote.

However, the British edition of Yahoo.com reported in mid-August that Forest and the Danish company H. Lundbeck (the original developer) "recently have been [marketing] Celexa in pediatrics and now compulsive shopping sufferers. The strategy is to extend the patent of Celexa while still differentiating it from Lexapro." Forest needs a big success with escitalopram and/or continuing income from citalopram because the $1 billion in citalopram sales is almost 70% of Forest's revenues.

"Lexapro is a welcomed treatment option because it offers many patients relief from depression symptoms quickly, with few side effects and a low risk of drug interactions," said Jack Gorman, M.D., professor and vice chair for research of the Department of Psychiatry, College of Physicians and Surgeons, Columbia University.

"Almost every new antidepressant has claimed the same thing [e.g., fewer side effects, earlier efficacy]. But they actually have different, not fewer, side effects," said Dan Still, clinical pharmacologist at the San Antonio State Hospital and clinical professor of pharmacy at the University of Texas Health Science Center. As for early onset, it simply takes time for SSRIs to downregulate receptors. The early-onset effects in studies often are anxiolytic or sedative, he said.

Voicing the wait-and-see attitude common among clinicians when a new drug appears, Still added that escitalopram is not revolutionary. But there will be a honeymoon period with very positive reports from stock analysts and others.

Citalopram studies influenced the FDA approval process, as did escitalopram studies involving more than 1,100 patients, including men and women ages 18-65 with moderate or severe depression.

With a 10-mg dose of escitalopram, the most common side effects were nausea (15% for escitalopram patients and 7% for placebo patients), insomnia (9% and 4%, respectively), ejaculation disorder (9% and < 1%), somnolence (6%, 2%), increased sweating (5%, 2%), and fatigue (5%, 2%). The recommended starting dose is 10 mg once daily. Studies show a 20-mg dose produces no greater clinical benefit than the 10-mg dose. So the drug's labeling recommends prescribers wait at least a week before increasing the dose. For elderly or hepatically impaired patients, the recommended dose is 10 mg/day.

The tablets are white to off-white, round, scored, and film-coated. The imprint on the scored side has "F" on the left side and "L" on the right side. The nonscored side has the dosage: 5 (mg), 10, or 20.

Escitalopram started appearing on pharmacy shelves early this month.

Steve Carrell

The author is a clinical writer based in Texas.

TIPS TO REMEMBER: Lexapro

  • Celexa (40 mg/day) did not impair psychomotor performance. However, psychoactive drugs can impair judgment, thinking, or motor skills, so patients should not operate autos or other hazardous machinery until they are reasonably sure Lexapro causes no psychomotor impairment.

  • There is no evidence showing Celexa or Lexapro increases the effects of alcohol, but concomitantly using the two substances is not advised.

  • Do not take both drugs at the same time because they are closely related.

  • Improvement may occur within one to four weeks. However, continue taking Lexapro as directed.

  • Patients should tell their physician if they are pregnant or plan to become pregnant, are taking or plan to take any other prescription drugs, or are breast-feeding an infant.

  • Lexapro should not be used in combination with monoamine oxidase inhibitors or within 14 days of discontinuing MAOI treatment. Similarly, at least 14 days should elapse between stopping Lexapro and starting an MAOI. Lexapro may also interact with cimetidine, sumatriptan, metoprolol, lithium, alcohol, and other central nervous system drugs.

 

Steve Carrell. New SSRI touts fewer side effects. Drug Topics 2002;18:23.