Fixed-Dose Trial of the Single Isomer SSRI Escitalopram in Depressed Outpatients

Burke, William J.; Gergel, I.; Bose, Anjana

doi:10.4088/jcp.v63n0410

Cited by 302 publications

(278 citation statements)

References 0 publications

Supporting

Mentioning

256

Contrasting

Unclassified

Order By: Relevance

“…7 In clinical trials, both racemic (R,S)-citalopram (marketed as Celexa) and (S)-citalopram (marketed as Lexapro) were significantly better than placebo for improving depression. [8][9][10][11] The early data suggest that (S)-citalopram has greater efficacy than (R,S)-citalopram at doses predicted to be equivalent as well as equal efficacy to (R,S)-citalopram at a dose that produces fewer side effects. 12,13 Overall, (S)-citalopram appears to have advantages over racemic citalopram and is a good example of the potential benefits of single-enantiomer drugs.…”

Section: The Hypothetical Interaction Between the 2 Enantiomers Of mentioning

confidence: 99%

Stereochemistry in Drug Action

McConathy

Owens²

2003

Prim. Care Companion CNS Disord.

236

213

View full text Add to dashboard Cite

Section: The Hypothetical Interaction Between the 2 Enantiomers Of mentioning

confidence: 99%

Stereochemistry in Drug Action

McConathy

Owens²

2003

Prim. Care Companion CNS Disord.

236

213

View full text Add to dashboard Cite

“…The SSRI activity of citalopram resides in S-citalopram, whereas R-citalopram is practically devoid of serotonin reuptake inhibitory potency (Burke et al, 2002;Hyttel et al, 1992;Lepola et al, 2004;Montgomery et al, 2001;Owens et al, 2001;Wade et al, 2002). Due to this fact, Scitalopram has been developed as a single enantiomer drug (escitalopram).…”

Section: Introductionmentioning

confidence: 99%

Altered brain concentrations of citalopram and escitalopram in P-glycoprotein deficient mice after acute and chronic treatment

Karlsson¹,

Carlsson²,

Hiemke³

et al. 2013

European Neuropsychopharmacology

View full text Add to dashboard Cite

According to both in vitro and in vivo data P-glycoprotein (P-gp) may restrict the uptake of several antidepressants into the brain, thus contributing to the poor success rate of current antidepressant therapies. The therapeutic activity of citalopram resides in the S-enantiomer, whereas the R-enantiomer is practically devoid of serotonin reuptake potency. To date, no in vivo data are available that address whether the enantiomers of citalopram and its metabolites are substrates of P-gp. P-gp knockout (abcb1ab (-/-)) and wild-type (abcb1ab (+/+)) mice underwent acute (single-dose) and chronic (two daily doses for 10 days) treatment with citalopram (10 mg/kg) or escitalopram (5 mg/kg). Serum and brain samples were collected 1-6 h after the first or last i.p. injection for subsequent drug analysis by an enantioselective HPLC method. In brain, 3-fold higher concentrations of S-and R-citalopram, and its metabolites, were found in abcb1ab (-/-) mice than in abcb1ab (+/+) mice after both acute and chronic citalopram treatments. After escitalopram treatment, the S-citalopram brain concentration was 3-5 times higher in the knockout mice than in controls. The results provide novel evidence that the enantiomers of citalopram are substrates of P-gp. Possible clinical and toxicological implications of this finding need to be further elucidated.

show abstract

“…Clinical and preclinical studies have shown that the citalopram effects on 5-HT reuptake inhibition and its antidepressant activity resides in the S-enantiomer (Hyttel et al, 1992;Montgomery et al, 2001;Burke et al, 2002;Wade et al, 2002;Lepola et al, 2004). In addition, using a variety of behavioral paradigms for depression/anxiety, it has been shown that escitalopram showed a more rapid and efficacious effect than citalopram, and that R-citalopram counteracted these effects in vivo and in vitro (M rk et al, 2003;Sánchez et al, 2003a, b;Sánchez and Kreilgaard, 2004).…”

Section: Introductionmentioning

confidence: 99%

Effects of Acute and Long-Term Administration of Escitalopram and Citalopram on Serotonin Neurotransmission: an In Vivo Electrophysiological Study in Rat Brain

Mansari

Sanchéz

Chouvet

et al. 2005

Neuropsychopharmacol

179

102

View full text Add to dashboard Cite

The present study was undertaken to compare the acute and long-term effects of escitalopram and citalopram on rat brain 5-HT neurotransmission, using electrophysiological techniques. In hippocampus, after 2 weeks of treatment with escitalopram (10 mg/kg/day, s.c.) or citalopram (20 mg/kg/day, s.c.), the administration of the selective 5-HT 1A receptor antagonist WAY-100,635 (20-100 mg/kg, i.v.) dose-dependently induced a similar increase in the firing activity of dorsal hippocampus CA 3 pyramidal neurons, thus revealing direct functional evidence of an enhanced tonic activation of postsynaptic 5-HT 1A receptors. In dorsal raphe nucleus, escitalopram was four times more potent than citalopram in suppressing the firing activity of presumed 5-HT neurons (ED 50 ¼ 58 and 254 mg/kg, i.v., respectively). Interestingly, the suppressant effect of escitalopram (100 mg/kg, i.v.) was significantly prevented, but not reversed by R-citalopram (250 mg/kg, i.v.). Sustained administration of escitalopram and citalopram significantly decreased the spontaneous firing activity of presumed 5-HT neurons. This firing activity returned to control rate after 2 weeks in rats treated with escitalopram, but only after 3 weeks using citalopram, and was associated with a desensitization of somatodendritic 5-HT 1A autoreceptors. These results suggest that the time course of the gradual return of presumed 5-HT neuronal firing activity, which was reported to account for the delayed effect of SSRI on 5-HT transmission, is congruent with the earlier onset of action of escitalopram vs citalopram in validated animal models of depression and anxiety.

show abstract

Fixed-Dose Trial of the Single Isomer SSRI Escitalopram in Depressed Outpatients

Cited by 302 publications

References 0 publications

Stereochemistry in Drug Action

Stereochemistry in Drug Action

Altered brain concentrations of citalopram and escitalopram in P-glycoprotein deficient mice after acute and chronic treatment

Effects of Acute and Long-Term Administration of Escitalopram and Citalopram on Serotonin Neurotransmission: an In Vivo Electrophysiological Study in Rat Brain

Contact Info

Product

Resources

About