citalopram Celexa
Studies on acute toxicity and drug levels of citalopram in the dog.

Boeck V, Overo KF, Svendsen O.

Electrocardiographic and haemodynamic changes have been studied in conscious dogs after a sublethal oral dose (20 mg . kg-1) of citalopram. Furthermore, the effects of continuous intravenous infusion of citalopram (10 mg . kg-1 per hour) have been studied in conscious and anesthetized dogs. The findings have been related to plasma levels of citalopram. Severe convulsive attacks occurred in conscious dogs after infusion of 21.3 or 26.5 mg . kg-1 and after the oral dose. The convulsions were successfully treated with diazepam. In contrast convulsions were not seen in the anesthetized dogs. They died from respiratory arrest after infusion of 42.2 or 61.3 mg . kg-1. Atrioventricular and intraventricular conduction was unchanged and electrocardiographic changes were negligible. Sinus tachycardia which could be reversed by diazepam and moderate haemodynamic changes were seen. Since no electrocardiographic changes were seen in conscious dogs even during pauses in the convulsive seizure it is concluded that citalopram does not exert cardiotoxic effects in the dog. Good correlation was found between general clinical findings and citalopram levels in plasma. Conscious dogs were exposed to drug levels exceeding those of the average patient by a factor of about 20, while anesthetized dogs had considerable higher concentrations.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6953747&dopt=Abstract citalopram Celexa



citalopram Celexa
Kinetics of citalopram in test animals; drug exposure in safety studies.

Fredricson Overo K.

1. Plasma levels of citalopram and its metabolites were assayed after single oral and intravenous doses to baboons (4 mg/kg), dogs (1, 4, 5, and 10 mg/kg), rats (8 mg/kg), and mice (24 mg/kg). Kinetic parameters were estimated. 2. Half-lives were short (estimate for baboon 3, dog 3 1/2-8, rat 3, and mouse 1 1/2 hours) and systemic plasma clearance high (baboon 39, dog 37-14, male rat 82, female rat 103, male mouse 87, and female mouse 116 ml/min/kg body weight). Considerable first-pass metabolism was demonstrated. 3. Drug level data were obtained in long-term safety studies in dogs (1, 3, and 8 mg/kg), rats (32 and 320 mg/kg), and mice (640 mg/kg). The high-dose citalopram level in dogs and rats exceeded that of patients by a factor of 10; the factor for mice was 40.

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citalopram Celexa
Kinetics of citalopram in man; plasma levels in patients.

Fredricson Overo K.

1. Citalopram is rapidly absorbed and slowly eliminated in man. The kinetics is linear and characterized by systemic and apparent oral clearance values of 0.4 l/min, a theoretical distribution volume of 14 l/kg and a half-life of 1 1/2 days. 2. The steady state plasma levels in 70 patients range from 95 to 720 nM at doses of 30 to 60 mg and agree well with predicted values. The mean level is 245 nM at the standard dose of 40 mg daily. 3. Inter-individual variation is 7-fold and independent of sex and age (21-65 years). The average intra-individual variation is about 15%. Estimates of apparent oral clearance vary from 0.15 to 1.02 l/min. 4. The average concentration ratio between citalopram and its demethylated metabolite is 2.7. The levels of di-demethylated metabolite are negligible.

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citalopram Celexa
Preliminary studies with citalopram (LU 10-171), a specific 5-HT-reuptake inhibitor, as antidepressant.

Gastpar M, Gastpar G.

1. Ten hospitalized, depressive, female patients above the age of 50 have been treated in a 3 week open trial with citalopram, a specific 5-HT-uptake inhibitor. 2. Six full and two partial responders demonstrate a recovery rate within the well known range for tricyclic antidepressant drugs. 3. Early onset of clinical effect and minimal side effects indicate that citalopram is possible a new effective antidepressant.

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citalopram Celexa
Citalopram--a specific 5-HT-reuptake inhibitor--as an antidepressant drug: a phase II multicentre trail.

Ofsti E.

1. Twenty-nine inpatients with a long history of rather severe, affective psychosis were admitted for a 4 weeks treatment with citalopram, a very specific 5-Ht-reuptake inhibitor. 2. Twenty-six patients (15 men and 11 women) completed the study and among these 15 had been depressed for more than 10 years and 19 showed an entry total score of more than 25 points on the Hamilton Rating Scale for Depression (17 items). 3. When treated with a dose of 40-60 mg once daily, approximately one third of the patients showed a marked response and another third a moderate response to treatment. Fifteen of the patients showed a marked or moderate response already within the first two weeks of treatment. 4. Only a few and transient side effects (nausea and increased sweating) were recorded and, in particular, no anticholinergic or cardiovascular side effect were observed. 5. Taking into consideration the severity of illness as well as the long and serious anamneses, these results of treatment with citalopram must be considered most satisfactory.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6959197&dopt=Abstract citalopram Celexa



citalopram Celexa
Preliminary studies of the kinetics of citalopram in man.

Overo KF.

The plasma concentrations of citalopram, a potent serotonin reuptake inhibitor, and its demethylated metabolite have been determined by a specific fluorescence coupling technique during single dose experiments in volunteers and in clinical tests. Citalopram was found to have linear kinetics within the dose range investigated, which were characterized by fairly rapid absorption and slow elimination (biological half-life 1--21/2 days). Steady state levels in the range 120--340 nM (i.e. slightly above those associated with pharmacodynamic activity in animals) were attained within a week. A drug/metabolite ratio of 2--3 was recorded.

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citalopram Celexa
Comparison of managed care charges among patients treated with selective serotonin reuptake inhibitors for premenstrual dysphoric disorder.

Endicott J, McLaughlin TP, Grudzinski AN.

New York State Psychiatric Institute, New York, NY, USA.

OBJECTIVE: To determine the impact on managed care charges of selecting citalopram, fluoxetine, paroxetine, or sertraline as first-line pharmacotherapy for newly diagnosed premenstrual dysphoric disorder (PMDD). METHOD: This retrospective study analyzed administrative claims data from 14 managed care plans in the United States. The study population was identified from an integrated outcomes database for the period Jan. 1, 1998, to Dec. 31, 1999. Patients aged 18 years or older, newly diagnosed with PMDD, and initiating therapy with a selective serotonin reuptake inhibitor (SSRI) within 30 days of the diagnosis were eligible for analysis. To date, there is no specific ICD-9 diagnosis code for PMDD; thus, patients were required to have an ICD-9 diagnosis of premenstrual tension syndrome (ICD-9 625.4). Patients with documented previous psychiatric disorders/treatment were excluded. All inpatient, outpatient, and pharmacy claims incurred by each patient during the study period were included in the analysis. PMDD-related treatment charges for the 6-month period following treatment initiation were compared using multivariate regression. RESULTS: A total of 1413 patients met the study criteria. Fluoxetine and sertraline were the most common agents selected as first-line therapy. After differences in age, managed care plan, pretreatment resource utilization, physician specialty, index prescription year, treatment charges, presence of mental health and nonmental health comorbid conditions, and changes in medication were controlled for, patients taking paroxetine and citalopram had significantly higher PMDD-related treatment charges than sertraline patients (paroxetine, p =.0430; citalopram, p =.0226). Fluoxetine patients also had higher treatment charges than sertraline patients, though statistical significance was not reached. CONCLUSIONS: Sertraline, as first-line therapy for PMDD, was associated with lower PMDD-related treatment charges compared with other SSRIs during the first 6 months after treatment initiation.

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citalopram Celexa
Fluoxetine, but not sertraline or citalopram, potentiates the locomotor stimulant effect of cocaine: possible pharmacokinetic effects.

Fletcher PJ, Sinyard J, Salsali M, Baker GB.

Section of Biopsychology, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada. Paul_Fletcher camh.net

RATIONALE: The selective serotonin reuptake inhibitor (SSRI) fluoxetine enhances some of the behavioural effects of cocaine, including locomotor stimulation. While this effect has often been interpreted as evidence for a serotonergic component to the behavioural effects of cocaine, direct evidence for this hypothesis is lacking. One alternative explanation is that fluoxetine, by inhibiting cytochrome P450 (CYP) enzymes, interferes with the metabolism of cocaine. OBJECTIVES: These experiments were undertaken to: 1) compare the effects of fluoxetine with those of two other SSRIs, sertraline and citalopram, on cocaine-induced locomotor activity, 2) examine the effects of fluoxetine on cocaine-stimulated locomotion in rats depleted of serotonin (5-hydroxytryptamine; 5-HT), and 3) determine the effect of fluoxetine on cocaine levels in the brain. METHODS: Locomotor activity was measured, using photocell based activity monitors, in rats habituated to those monitors. Depletion of 5-HT was achieved by injecting 5,7-dihydroxytryptamine (5,7-DHT) into the dorsal and median raphe nuclei. Cocaine levels in whole brain were measured using high-performance liquid chromatography with ultraviolet detection. RESULTS: In experiment 1, 5 mg/kg fluoxetine enhanced the ability of 10 and 15 mg/kg cocaine to increase locomotor activity. Neither citalopram nor sertraline (5 and 10 mg/kg) altered the stimulant effect of 10 mg/kg cocaine. Experiment 2 showed that this effect of fluoxetine was also apparent in rats with large and widespread depletion of brain 5-HT levels. The 5-HT depletion also failed to alter the response to cocaine itself. In experiment 3, brain levels of cocaine were elevated in rats pretreated with fluoxetine compared with rats that received cocaine alone. CONCLUSION: Fluoxetine enhanced the ability of cocaine to increase locomotor activity. This effect appears not to depend upon increasing 5-HT function since fluoxetine was also effective in rats with substantial 5-HT depletions, and two other SSRIs did not alter the effects of cocaine. Fluoxetine-treated rats had higher brain levels of cocaine than rats treated with cocaine alone. This effect suggests that fluoxetine slows the metabolism of cocaine, perhaps by inhibition of CYP enzymes involved in metabolizing cocaine. The results also indicate that 5-HT reuptake inhibition may not play a prominent role in mediating the stimulant effects of cocaine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14740149&dopt=Abstract citalopram Celexa