citalopram Celexa
Citalopram for Social Anxiety Disorder: An Open-label Pilot Study in Refractory and Nonrefractory Patients.

Simon NM, Korbly NB, Worthington JJ, Kinrys G, Pollack MH.

Department of Psychiatry, Harvard Medical School, Boston, MA, USA.

There is limited systematic data assessing alternate pharmacotherapy of social anxiety disorder in patients failing to tolerate or fully respond to initial treatment; no data specifically address the efficacy of citalopram in this scenario. We present a prospective open-label trial of citalopram in 10 patients with generalized social anxiety disorder, 6 of 10 of whom had not responded to or not tolerated a prior treatment intervention for the disorder. Citalopram, at a mean dose of 55 mg (SD+/-12.7 mg) was well tolerated, and patients improved significantly on all outcome measures. Results of this study suggest that citalopram may be a safe and effective treatment for generalized social anxiety disorder, including patients who have failed to tolerate or respond to a prior treatment trial.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15097929&dopt=Abstract citalopram Celexa



citalopram Celexa
Cost-effectiveness of escitalopram versus citalopram in the treatment of severe depression.

Hemels ME, Kasper S, Walter E, Einarson TR.

International Department of Health Economics and Epidemiology, H. Lundbeck A/S, 37 Avenue Pierre 1er de Serbie, 75008 Paris, France. MEHH Lundbeck.com

BACKGROUND: Severe depression is associated with an extensive economic burden on both the patient and society. OBJECTIVE: To estimate the cost-effectiveness in Austria of escitalopram compared with citalopram in the management of severe depression (Montgomery-Asberg Depression Rating Scale score > or =30). METHODS: A decision model incorporated treatment paths and associated direct resource use (psychiatric hospitalization, medications, general practitioner and psychiatrist visits, treatment discontinuation, suicide attempts) associated with managing severe depression and the indirect cost of work absenteeism over a 6-month period. Main outcomes were clinical success (remission at 6 mo) and cost (2002 Euros equals approximately 1.25 US) of treatment. The analysis was performed from the Austrian societal and Social Healthcare Insurance System (SHIS) perspectives. Clinical input data were derived from a meta-analysis of 8-week randomized clinical trials. Costs were derived from standard Austrian price lists or from the literature. RESULTS: Six months after the start of treatment, the overall clinical success remission rate was higher for escitalopram (53.7%) than for citalopram (48.7%). From the SHIS perspective, the total expected cost per successfully treated severely depressed patient was 924 (32.1%) lower for escitalopram (2879) compared with citalopram (3803). From the societal perspective, the total expected cost per successfully treated severely depressed patient was 1369 (24.4%) lower for escitalopram (5610) than for citalopram (6979). Sensitivity analyses demonstrated that the model was robust and that, even if citalopram had no acquisition cost, escitalopram remained the dominant strategy for both perspectives. CONCLUSIONS: Treatment with escitalopram was the dominant strategy. These data suggest that escitalopram is a cost-effective antidepressant compared with citalopram in the management of severe depression in Austria.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15113989&dopt=Abstract citalopram Celexa



citalopram Celexa
Stereoselective metabolism of citalopram in plasma and cerebrospinal fluid of depressive patients: relationship with 5-HIAA in CSF and clinical response.

Nikisch G, Mathe AA, Czernik A, Eap CB, Jimenez-Vasquez P, Brawand-Amey M, Baumann P.

Department of Psychiatry and Psychotherapy, Box 2364, Klinikum Fulda, D-36013 Fulda, Germany. Georg.Nikisch.Psychiatrie klinikum-fulda.de

Plasma and cerebrospinal fluid (CSF) concentrations of the enantiomers of citalopram (CIT), its N-demethylated metabolite demethylcitalopram (DCIT) and its deaminated metabolite citalopram propionic acid derivative (CIT-PROP) were measured in plasma and CSF in 22 depressed patients after a 4-week treatment with 40 mg/d citalopram, which was preceded by a 1-week washout period. CSF 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured at baseline and after the 4-week CIT medication period. Patients were assessed clinically, using the Hamilton Depression Rating Scale (21-item HAM-D): at baseline and then at weekly intervals. CSF concentrations of S-CIT and R-CIT were 10.6 +/- 4.3 and 20.9 +/- 6 ng/mL, respectively, and their CSF/plasma ratios were 52% +/- 9% and 48% +/- 6%, respectively. The CIT treatment resulted in a significant decrease (28%) of 5-HIAA (P < 0.0001) and a significant increase (41%) of HVA in the CSF. Multiple linear regression analyses were performed to identify the impact of plasma and CSF CIT enantiomers and its metabolites on CSF monoamine metabolites and clinical response. There were 10 responders as defined by a > or =50% decrease of the HAM-D score (DeltaHAM-D) after the 4-week treatment. DeltaHAM-D correlated (Spearman) significantly with CSF S-CIT (r = - 0.483, P < 0.05), CSF S-CIT-PROP (r = -0.543, P = 0.01) (a metabolite formed from CIT by monoamine oxidase [MAO]) and 5-HIAA decrease (Delta5-HIAA) (r = 0.572, P = 0.01). The demonstrated correlations between pharmacokinetic parameters and the clinical outcome as well as 5-HIAA changes indicate that monitoring of plasma S-CIT, CSF S-CIT and CSF S-CIT-PROP may be of clinical relevance.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15118482&dopt=Abstract citalopram Celexa



citalopram Celexa
Great expectations in stereochemistry: focus on antidepressants.

DeVane CL, Boulton DW.

Department of Psychiatry, Medical University of South Carolina, Charleston, South Carolina, USA.

Chirality has become an increasingly important consideration in the development of psychoactive drugs because enantiomers often show major differences in their pharmacokinetic and pharmacologic properties. This review illustrates the implications of stereochemistry in clinical psychopharmacology using the antidepressant class of drugs as a focus. In many cases, a better understanding of stereochemistry can improve therapeutic outcomes. For example, with citalopram, the racemic formulation is effective for depression as well as panic and obsessive-compulsive disorders. However, the S-enantiomer, escitalopram, is at least twice as potent as racemic citalopram as an inhibitor of serotonin reuptake, implying that it can be used at lower doses, while offering an improved therapeutic index as well as an improved safety profile and reduced drug interaction liability. Clinical trial data support these advantages. Continuing research on the stereochemical properties of psychoactive drugs should simplify the characterization of dose-response relationships, and clarify the effects of disease states, genetic polymorphisms, pregnancy, age, and gender on stereoselective pharmacokinetics and pharmacodynamics. Better understanding of the fate of chiral psychotropic agents and the factors that influence their stereoselective disposition and actions will provide a rational basis for their expanded use in various patient populations.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15131490&dopt=Abstract citalopram Celexa



citalopram Celexa
Escitalopram: A Second-Generation SSRI.

Owens MJ, Rosenbaum JF.

Department of Psychiatry and Behavioral Science, Emory University School of Medicine, Atlanta, Georgia, USA.

Serotonin (5-hydroxytryptamine, 5-HT) has long been suspected to play a role in the etiology of depression, and modern neurochemical techniques have confirmed this suspicion. Furthermore, all drugs known to be selective (a relative term) serotonin transporter (SERT) inhibitors are effective antidepressants. Of the selective serotonin reuptake inhibitors (SSRIs) approved in a number of countries for use in depression, panic disorder, and obsessive-compulsive disorder, citalopram is the most selective. Citalopram has been used worldwide to treat an estimated 35 million patients, with an excellent safety record. Citalopram is a racemic drug, and its effects on serotonin transport are thought to reside in the S-enantiomer, known as (S)-citalopram or escitalopram. Escitalopram is the most selective SSRI yet developed. Its receptor binding properties and activity in preclinical animal models of depression predict that escitalopram would be effective in the treatment of depression, with approximately twice the potency of the racemate. The pivotal clinical trials of escitalopram not only support this conclusion, but also suggest escitalopram possesses advantages over citalopram in terms of both efficacy and safety. In conclusion, escitalopram is a promising candidate for use as a first-line antidepressant.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15131491&dopt=Abstract citalopram Celexa



citalopram Celexa
Efficacy comparison of escitalopram and citalopram in the treatment of major depressive disorder: pooled analysis of placebo-controlled trials.

Gorman JM, Korotzer A, Su G.

Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Background: Citalopram is a racemic selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of depression. Citalopram is a racemate and its serotonin reuptake inhibitory activity resides primarily in the single S-isomer, escitalopram, which is now being evaluated for its potential usefulness in the treatment of depression and other psychiatric disorders. Results from placebo-controlled studies that also included citalopram as an active control have shown that escitalopram is effective in treating depression and associated symptoms of anxiety. However, none of these studies was powered sufficiently to detect differences between active treatment groups. The goal of the present analysis is to evaluate the efficacy of escitalopram compared with citalopram in the treatment of major depressive disorder. Method: Data were pooled from three similarly designed, randomized, double-blind, placebo-controlled trials of escitalopram (10-20 mg/day) and citalopram (20-40 mg/day). Patients were male or female, greater than or equal to 18 years of age, who met criteria for a major depressive episode with a Montgomery Asberg Depression Rating Scale (MADRS) score greater than or equal to 22 at baseline. Efficacy measures included change from baseline in MADRS score and the Clinical Global Impression of Improvement (CGI-I) scale. Improvement in associated symptoms of anxiety was measured using the change from baseline in the MADRS inner tension item. Results: Both escitalopram and citalopram significantly improved depression and anxiety symptoms compared with placebo, and there were significantly more MADRS responders (defined as >/=50% improvement in MADRS scores at end point) in the escitalopram and citalopram treatment groups. Escitalopram treatment was associated with statistically significant improvements in all efficacy measures relative to placebo after 1 week of treatment, whereas citalopram treatment statistically separated from placebo at the end of week 4 (CGI-I and MADRS inner tension) or week 6 (MADRS). Escitalopram treatment also was statistically significantly superior to citalopram treatment at a number of time points. Conclusion: These data support the effectiveness of escitalopram and citalopram in the treatment of major depressive disorder, and suggest escitalopram may have a faster onset and greater overall magnitude of effect than citalopram in improving symptoms of depression and anxiety in patients with major depressive disorder.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15131492&dopt=Abstract citalopram Celexa



citalopram Celexa
Effects of chronic treatment with escitalopram or citalopram on extracellular 5-HT in the prefrontal cortex of rats: role of 5-HT1A receptors.

Ceglia I, Acconcia S, Fracasso C, Colovic M, Caccia S, Invernizzi RW.

Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milano, Italy.

1 Microdialysis was used to study the acute and chronic effects of escitalopram (S-citalopram; ESCIT) and chronic citalopram (CIT), together with the 5-HT1A receptor antagonist WAY100,635 (N-[2-[methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide trihydrochloride) and the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on extracellular 5-hydroxytryptamine (5-HT) levels in the rat prefrontal cortex. 2 Extracellular 5-HT rose to 234 and 298% of basal values after subcutaneous (s.c.) acute doses of 0.15 and 0.63 mg kg(-1) ESCIT. No further increase was observed at 2.5 mg kg(-1) ESCIT (290%). 3 The effect of 13-day s.c. infusion of 10 mg kg(-1) day(-1) ESCIT on extracellular 5-HT (422% of baseline) was greater than after 2 days (257% of baseline), whereas exposure to ESCIT was similar. In contrast, the increase in extracellular 5-HT induced by the infusion of CIT for 2 (306%) and 13 days (302%) was similar. However, brain and plasma levels of S-citalopram in rats infused with CIT for 13 days were lower than after 2 days. 4 Acute treatment with 2.5 mg kg(-1) ESCIT or 5 mg kg(-1) CIT raised extracellular 5-HT by 243 and 276%, respectively, in rats given chronic vehicle but had no effect in rats given ESCIT (10 mg kg(-1) day(-1)) or CIT (20 mg kg(-1) day(-1)) for 2 or 13 days, suggesting that the infused doses had maximally increased extracellular 5-HT. WAY100,635 (0.1 mg kg(-1) s.c.) increased extracellular 5-HT levels by 168, 174 and 169% of prechallenge values in rats infused with vehicle or ESCIT for 2 or 13 days, respectively. WAY100,635 enhanced extracellular 5-HT levels to 226, 153 and 164% of prechallenge values in rats infused with vehicle or CIT for 2 and 13 days, respectively. 5 8-OH-DPAT (0.025 mg kg(-1)) reduced extracellular 5-HT by 54% in control rats, but had no effect in those given ESCIT and CIT for 13 days. 6 This series of experiments led to the conclusion that chronic treatment with ESCIT desensitizes the 5-HT1A receptors, regulating the release of 5-HT in the prefrontal cortex and enhances the effect of the drug on extracellular 5-HT. They also indicate that chronic treatment with ESCIT and CIT did not prevent WAY100,635 from raising extracellular 5-HT.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15148253&dopt=Abstract citalopram Celexa



citalopram Celexa
Inhibition of P-glycoprotein by newer antidepressants.

Weiss J, Dormann SM, Martin-Facklam M, Kerpen CJ, Ketabi-Kiyanvash N, Haefeli WE.

Department of Internal Medicine VI, Clinical Pharmacology, and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany. Johanna_weiss med.uni-heidelberg.de

Pharmacokinetic drug-drug interactions often occur at the level of P-glycoprotein (Pgp). To study possible interactions caused by the newer antidepressants we investigated citalopram, fluoxetine, fluvoxamine, paroxetine, reboxetine, sertraline, and venlafaxine and their major metabolites desmethylcitalopram, norfluoxetine, paroxetine-metabolite (paroxetine-M), desmethylsertraline, N-desmethylvenlafaxine, and O-desmethylvenlafaxine for their ability to inhibit Pgp. Pgp inhibition was studied by a fluorometric assay using calcein-acetoxymethylester as Pgp substrate and two different cell systems: L-MDR1 cells (model for human Pgp) and primary porcine brain capillary endothelial cells (pBCECs, model for the blood-brain barrier). Both cell systems proved to be suitable for the evaluation of Pgp inhibitory potency of drugs. All antidepressants tested except O-desmethylvenlafaxine showed Pgp inhibitory activity with sertraline, desmethylsertraline, and paroxetine being the most potent, comparable with the well known Pgp inhibitor quinidine. In L-MDR1 cells fluoxetine, norfluoxetine, fluvoxamine, reboxetine, and paroxetine-M revealed intermediate Pgp inhibition and citalopram, desmethylcitalopram, venlafaxine, and N-desmethylvenlafaxine were only weak inhibitors. The ranking order was similar in pBCECs. The fact that some of the compounds tested exert Pgp inhibitor effects at similar concentrations as quinidine suggests that pharmacokinetic drug-drug interactions between the newer antidepressants and Pgp substrates should now be thoroughly studied in vivo.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12649369&dopt=Abstract citalopram Celexa