citalopram Celexa
Transplacental transfer of citalopram, fluoxetine and their primary demethylated metabolites in isolated perfused human placenta.

Heikkine T, Ekblad U, Laine K.

Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.

OBJECTIVE: To investigate the transplacental transfer and the effects of protein binding on the transfer of citalopram, desmethylcitalopram, fluoxetine and desmethylfluoxetine in the isolated perfused human placenta model. DESIGN: Prospective observational study. METHODS: Fifteen term human placentas were obtained immediately after delivery with maternal consent and a 2-hour non-recirculating perfusion cycle of a single placental cotyledon was set up. Citalopram (1230 nmol/L) and desmethylcitalopram (600 nmol/L) or fluoxetine (1455 nmol/L) and desmethylfluoxetine (1525 nmol/L) were added to the maternal reservoir and their appearance to the fetal circulation was followed by repeated measurements. To investigate the effect of protein binding on the transfer of citalopram and fluoxetine, nine additional perfusions were performed without albumin in the perfusion medium. Citalopram and desmethylcitalopram concentrations were measured by reversed-phase high performance liquid chromatography. Fluoxetine and desmethylfluoxetine concentrations was measured by gas chromatography and antipyrine (used as a reference compound) concentrations spectrophotometrically. RESULTS: The mean (SD) steady-state transplacental transfer (TPT(SS)%) for citalopram, desmethylcitalopram, fluoxetine and desmethylfluoxetine was 9.1%, 5.6% (P = 0.017 compared with citalopram), 8.7% and 9.1%, respectively, calculated as the ratio between the steady-state concentrations in fetal venous and maternal arterial sides. The TPT(SS)%s of citalopram, desmethylcitalopram, fluoxetine and desmethylfluoxetine were 86%, 50%, 88% and 91% of that of freely diffusable antipyrine. The absence of albumin significantly reduced the transfer of citalopram and fluoxetine (TPT(SS)% 1.1% and 4.8%, respectively) but not the transfer of antipyrine. CONCLUSION: Citalopram, fluoxetine and desmethylfluoxetine all cross the human placenta, and may, therefore, affect the perinatal outcome of infants exposed to these drugs during pregnancy. The transfer of desmethylcitalopram was significantly lower, which in the clinical setting may suggest lower fetal exposure of serotonin re-uptake inhibition by citalopram compared with fluoxetine. The presence of albumin was necessary for the transplacental transfer of both citalopram and fluoxetine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12269673&dopt=Abstract citalopram Celexa



citalopram Celexa
The effects of acute and subchronic treatment with fluoxetine and citalopram on stimulus control by DOM.

Winter JC, Eckler JR, Doat MM, Rabin RA.

Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, 102 Farber Hall, Buffalo, NY 14214-3000, USA. jcwinter acsu.buffalo.edu

Previous reports from our laboratory have provided evidence that acute, i.e., concurrent, treatment with selective serotonin reuptake inhibitors (SSRIs) augments the stimulus effects of indoleamine and phenethylamine hallucinogens in the rat. In the present investigation, the acute effects of fluoxetine and citalopram on stimulus control induced by (-)-2,5-dimethoxy-4-methylamphetamine (DOM) were compared with those following subchronic, i.e., 10-day treatment with the SSRIs. Stimulus control was established using DOM (0.56 mg/kg; 75-min pretreatment time) in a group of 11 rats. A two-lever, fixed ratio 10, positively reinforced task with saline controls was employed. The effects of a range of doses of DOM when given alone were compared with those following both acute and subchronic pretreatment with fluoxetine and citalopram in combination with DOM. It was found that acute administration of fluoxetine and citalopram potentiated the stimulus effects of DOM. Furthermore, it was observed that the degree of potentiation was not diminished by treatment with either fluoxetine or citalopram for a period of 10 days. It is concluded that whatever adaptive changes may take place in response to a 10-day period of treatment with either citalopram or fluoxetine, these adaptations are independent of the mechanisms responsible for the potentiation of the stimulus effects of DOM by the SSRIs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12376156&dopt=Abstract citalopram Celexa



citalopram Celexa
Citalopram in children and adolescents with depression or anxiety.

Baumgartner JL, Emslie GJ, Crismon ML.

College of Pharmacy, University of Texas, Texas Department of Mental Health and Mental Retardation, Austin, USA.

OBJECTIVE: To investigate the efficacy and tolerability of citalopram in children and adolescents. METHOD: Retrospective chart review of 17 outpatients treated with citalopram at a tertiary care center. Subjects were diagnosed with a depressive or anxiety disorder with or without comorbidities and may have received concurrent medications. The primary outcome measure was the Clinical Global Impression Improvement Scale (CGI-I). Secondary outcome measures were the Children's Depression Rating Scale-Revised (CDRS-R), Inventory of Depressive Symptomatology, and Screen for Child Anxiety-Related Emotional Disorders (SCARED). Adverse effects were assessed via chart documentation. RESULTS: Patients were treated with a mean citalopram dose of 22.4 +/- 7.3 mg for 12 weeks. Thirteen patients (76%) had CGI-I scores </=2: 8 of 12 patients with depression and 5 of 5 patients with an anxiety disorder. The mean time to response was 7.6 +/- 3.6 weeks. Additionally, 6 of 8 patients had >/=50% reduction from baseline CDRS-R score, with 3 patients (38%) meeting criteria for remission. Three of 4 patients had a >50% reduction for baseline SCARED-parent score. Overall, adverse effects appeared minor and transient. One patient discontinued citalopram due to intolerable adverse effects, and 1 patient required dose reduction. CONCLUSIONS: Citalopram appears to be effective and well tolerated in this group of children and adolescents with depressive or anxiety disorders and a high degree of comorbidity. Controlled studies in this patient population are indicated.

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citalopram Celexa
Effects of chronic citalopram treatment on central and peripheral spontaneous open-field behaviours in rats.

Kugelberg FC, Apelqvist G, Bengtsson F.

Division of Clinical Pharmacology, Department of Medicine and Care, Faculty of Health Sciences, Linkoping University, Sweden.

The spontaneous open-field behavioural effects of 10 days of chronic treatment with two clinical doses (10 and 20 mg/kg daily) and one high/toxic dose (100 mg/kg daily) of the selective serotonin reuptake inhibitor citalopram (delivered subcutaneously by implanted osmotic pumps) were examined in rats. Central and peripheral arena locomotor and rearing activities were recorded simultaneously, and the data were assessed during the first hour as well as during the following 24 hr (the latter for effects on the diurnal rhythm). Rats treated with 100 mg/kg daily exhibited lower peripheral locomotor and rearing activities than the other groups during the first test hour. The ratio between central and peripheral activity increased in a dose-dependent non-proportional manner during the first test hour, indicating a general increase in the central arena activity exerted by the rats when treated with citalopram. No major differences were observed between any of the four groups in overall behavioural activities over the 24-hr period. This study indicated that the open-field locomotor and rearing behaviours in normal rats were affected by increasing doses of racemic citalopram, particularly during the first hour of adaptation.

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citalopram Celexa
Relationship between clinical effects, serum drug concentration, and concurrent drug interactions in depressed patients treated with citalopram, fluoxetine, clomipramine, paroxetine or venlafaxine.

Charlier C, Pinto E, Ansseau M, Plomteux G.

University of Liege, Toxicology Laboratory, CHU Sart Tilman, B-4000 Liege, Belgium.

The relationship between clinical effects and plasma concentrations of citalopram, fluoxetine, clomipramine, paroxetine and venlafaxine was studied in 119 cases of major depression. Clinical effects were evaluated using the Clinical Global Impression (CGI) improvement scale. Antidepressants were quantified by a separative chromatographic methodology. Plasma concentrations in responder patients were compared with the plasma concentrations proposed in literature as effective values. We found that the usual therapeutic window is convenient for citalopram and clomipramine, but could be reduced for fluoxetine and increased for venlafaxine and paroxetine. Concurrent drug interactions were also evaluated and clomipramine or citalopram plasma levels were found to be influenced by the presence of associated drugs. A larger study is needed, taking into account not only plasma concentrations and clinical effects, but also some pharmacokinetic data, especially the metabolic activity characterising the patient, and the presence or not of associated drugs. Copyright 2000 John Wiley & Sons, Ltd.

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citalopram Celexa
Which neuroreceptors mediate the subjective effects of MDMA in humans? A summary of mechanistic studies.

Liechti ME, Vollenweider FX.

Clinical Research Unit, University Hospital of Psychiatry, Zurich, Switzerland.

In preclinical studies, 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') has been shown to release serotonin (5-HT), dopamine and norepinephrine. However, the role of these neurotransmitters and their corresponding receptor sites in mediating the subjective effects of MDMA has not yet been studied in humans. Therefore, we investigated the effects of three different neuroreceptor pretreatments on the subjective, cardiovascular and adverse effects of MDMA (1.5 mg/kg orally) in 44 healthy human volunteers. Pretreatments were: the selective serotonin reuptake inhibitor citalopram (40 mg intravenously) in 16 subjects, the 5-HT(2) antagonist ketanserin (50 mg orally) in 14 subjects, and the D(2) antagonist haloperidol (1.4 mg intravenously) in 14 subjects. Each of these studies used a double-blind placebo-controlled within-subject design and all subjects were examined under placebo, pretreatment, MDMA and pretreatment plus MDMA conditions. Citalopram markedly reduced most of the subjective effects of MDMA, including positive mood, increased extraversion and self-confidence. Cardiovascular and adverse effects of MDMA were also attenuated by citalopram. Haloperidol selectively reduced MDMA-induced positive mood but had no effect on other subjective effects of MDMA or the cardiovascular or adverse responses to MDMA. Ketanserin selectively reduced MDMA-induced perceptual changes and emotional excitation. These results indicate that the overall psychological effects of MDMA largely depend on carrier-mediated 5-HT release, while the more stimulant-like euphoric mood effects of MDMA appear to relate, at least in part, to dopamine D(2) receptor stimulation. The mild hallucinogen-like perceptual effects of MDMA appear to be due to serotonergic 5-HT(2) receptor stimulation. Copyright 2001 John Wiley & Sons, Ltd.

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citalopram Celexa
A retrospective assessment of citalopram in children and adolescents with pervasive developmental disorders.

Couturier JL, Nicolson R.

Department of Psychiatry, University of Western Ontario, London, Ontario, Canada.

Although selective serotonin reuptake inhibitors have been used to treat symptoms of aggression and anxiety in children and adolescents with pervasive developmental disorders (PDDs), there are no published reports of the use of citalopram in this population. The purpose of this study was to examine the benefits and adverse effects of citalopram in a group of children and adolescents with PDDs. Target behaviors included aggression, anxiety, stereotypies, and preoccupations. Seventeen patients with PDDs (14 with autistic disorder, three with Asperger's disorder) (mean age = 9.4 +/- 2.9 years; range 4-15 years) were treated with citalopram for at least 2 months (mean duration of treatment = 7.4 +/- 5.3 months; range 1-15 months). Treatment was initiated at a low dose (5 mg daily) and was increased by 5 mg weekly as tolerated and as necessary. The mean final dose was 19.7 +/- 7.8 mg (range 5-40 mg). Outcome was based on a consensus between clinician and parents, using the Improvement item of the Clinical Global Impressions Scale as a guide. Ten (59%) children were judged to be much improved or very much improved regarding target behaviors. Core symptoms of PDDs (social interactions, communication) did not show clinically significant improvement. Citalopram was generally well tolerated, although four patients developed treatment-limiting adverse effects: two with increased agitation, one with insomnia, and one with possible tics. The results of this case series suggest that citalopram has beneficial effects on some interfering behaviors associated with PDDs with few adverse effects. Controlled trials are warranted.

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citalopram Celexa
Acute and chronic effects of citalopram on cerebral glucose metabolism in geriatric depression.

Smith GS, Kramer E, Hermann CR, Goldberg S, Ma Y, Dhawan V, Barnes A, Chaly T, Belakhleff A, Laghrissi-Thode F, Greenwald B, Eidelberg D, Pollock BG.

Department of Psychiatry Research, Hillside Hospital and the Neuroscience Institute of the North Shore-Long Island Jewish Health System, Glen Oaks, NY 11004, USA. gsmith lij.edu

OBJECTIVE: In vivo studies of serotonin function have been limited by the lack of safe and selective pharmacologic agents and availability of suitable radiotracers. In the present study, the authors evaluated the cerebral metabolic effects of acute and continued administration of the selective serotonin reuptake inhibitor citalopram in patients with geriatric depression as a potential marker of serotonin dysfunction. METHODS: Six patients with geriatric depression and five comparison subjects underwent two resting positron emission tomography (PET) studies, performed after administration of a placebo infusion (Day 1) and a citalopram infusion (40 mg, Day 2). The patients were re-scanned after 8 weeks of treatment with the oral medication. RESULTS: The elderly comparison subjects demonstrated greater right-hemisphere cortical decreases than the patients. The depressed patients demonstrated greater left-hemisphere cortical decreases than comparison subjects. The depressed patients demonstrated greater increases in the right putamen and left occipital cortex. After 8 weeks of citalopram treatment, regional decreases and increases in metabolism were observed. CONCLUSION: These findings suggest regional deficits and also compensatory responses in the acute metabolic response to citalopram in the patients. These preliminary results suggest that the cerebral metabolic response to citalopram may be a useful marker of the pathophysiology of serotonin function in geriatric depression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12427580&dopt=Abstract citalopram Celexa