citalopram Celexa
[The transfer of selective serotonin reuptake inhibitors to human milk]

[Article in Norwegian]

Nordeng H, Bergsholm YK, Bohler E, Spigset O.

Institutt for farmakoterapi Postboks 1065 Blindern 0316 Oslo. h.m.e.nordeng farmasi.uio.no

BACKGROUND: This article presents an overview of the excretion of the SSRIs citalopram, paroxetine, fluoxetine, fluvoxamine and sertraline in breast milk. MATERIAL AND METHODS: Published articles on selective serotonin reuptake inhibitors and excretion in breast milk were identified and reviewed. In addition, drug concentrations were measured in milk from eight women using paroxetine (n = 4), citalopram (n = 3) or fluvoxamine (n = 1). RESULTS: Data from the literature indicate that the relative dose to the infant is lowest for fluvoxamine and sertraline, somewhat higher for paroxetine and highest for citalopram and fluoxetine. Adverse effects were reported in three of the 119 breastfed infants. Our own results show minimal excretion of fluvoxamine, small excretion of paroxetine and higher excretion of citalopram into breast milk. INTERPRETATION: If treatment with a selective serotonin reuptake inhibitor is started during the postpartum period, fluoxetine should not be the first alternative. High doses of citalopram should also be used with caution. However, when the use of an SSRI is clearly indicated in a breastfeeding woman, available data generally indicate that the positive effects of breast-feeding outweigh the risks for pharmacological effects in the infant.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11475200&dopt=Abstract citalopram Celexa



citalopram Celexa
Serotonin reuptake inhibitors fluoxetine and citalopram relax intestinal smooth muscle.

Pacher P, Ungvari Z, Kecskemeti V, Friedmann T, Furst S.

Institute of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary. ppacher hotmail.com

Selective serotonin reuptake inhibitor antidepressants (SSRIs) exert depressant effects on cardiac myocytes and vascular smooth muscle cells by inhibiting Ca2+ channels. We hypothesized that the SSRIs fluoxetine and citalopram affect the contractile activity of intestinal smooth muscle by interfering with Ca2+ entry and (or) signaling pathways. The effects of fluoxetine and citalopram on contractions of guinea-pig ileum longitudinal muscle-myenteric plexus preparations (LMMP) were compared with the effects of the voltage-operated Ca2+ channel inhibitors nifedipine and diltiazem. In a concentration-dependent manner, nifedipine, diltiazem, fluoxetine, and citalopram elicited relaxation of LMMPs contracted by electrical field stimulation (EC50 values of 4 x 10(-7) M, 1.4 x 10(-6) M, 1.4 x 10(-5), and 6.8 x 10(-6) M, respectively). Nifedipine, diltiazem, fluoxetine, and citalopram also relaxed LMMPs contracted with a depolarizing concentration of KCl (48 mM; EC50 values of 1.8 x 10(-8) M, 1.4 x 10(-7) M, 3.7 x 10(-6) M, and 6.3 x 10(-6), respectively), a response that could be reversed by increasing the extracellular Ca2+ concentration (2.5-30 mM). These data suggest that fluoxetine and citalopram elicit relaxation of intestinal smooth muscle, likely by inhibiting Ca2+ channel(s). This effect may be of clinical importance.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11478591&dopt=Abstract citalopram Celexa



citalopram Celexa
Methylphenidate augmentation of citalopram in elderly depressed patients.

Lavretsky H, Kumar A.

Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, Los Angeles, CA, USA.

The authors followed 10 elderly depressed patients (mean age=79.8 years; in an open trial of methylphenidate (MPH) augmentation of citalopram used to accelerate and enhance their antidepressant response. Eight of the 10 patients demonstrated clinically significant improvement by Week 8. Four of the seven patients with augmentation initiated during the first week of treatment with citalopram met the criteria for rapid response at Week 2. No patient discontinued treatment. These preliminary observations suggest that a combination of MPH and citalopram may be an effective, relatively well tolerated treatment in this patient population and may accelerate onset of action. However, patients may require dosage adjustment for tolerability of this combination.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11481139&dopt=Abstract citalopram Celexa



citalopram Celexa
Citalopram for social phobia: a clinical case series.

Simon NM, Sharma SG, Worthington JJ, Marzol PC, Pollack MH.

Anxiety Disorders Program, Massachusetts General Hospital, Boston 02114, USA. nsimon partners.org

Social anxiety disorder is a common illness with significant associated disability. Serotonin selective reuptake inhibitors (SSRIs) have become first-line treatment given their improved tolerability; however, there are few reports on the use of citalopram. Nine consecutive patients with a primary diagnosis of DSM-IV generalized social phobia were prospectively treated with citalopram. Citalopram was generally well-tolerated, and seven patients achieved responder status. This series of patients improved significantly on all measures. Results suggest that citalopram may be a safe and effective treatment for social anxiety disorder.

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citalopram Celexa
Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine.

Owens MJ, Knight DL, Nemeroff CB.

Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA.

BACKGROUND: Single isomers of the selective serotonin reuptake inhibitors citalopram (escitalopram, S-citalopram) and fluoxetine (R-fluoxetine) are currently under development for the treatment of depression and other psychiatric disorders. Previous studies conducted in laboratory animals have revealed that the biological effects on serotonin reuptake for citalopram reside in the S enantiomer. In contrast, both enantiomers of fluoxetine contribute to its biological activity. METHODS: In the present study, the potency and selectivity of escitalopram, R-fluoxetine, and all of the other currently available selective serotonin reuptake inhibitors were compared for binding affinity at the human serotonin, norepinephrine, and dopamine transporters and several select neurotransmitter receptors using radioligand binding assays. RESULTS: Both escitalopram and R-fluoxetine were potent inhibitors of the serotonin transporter (K(i) = 1.1 and 1.4 nmol/L, respectively). Escitalopram was the most serotonin transporter-selective compound tested and was approximately 30-fold more potent than R-citalopram. CONCLUSIONS: As noted previously, paroxetine and sertraline possess moderate affinity (<50 nmol/L) for the human norepinephrine transporter and dopamine transporter, respectively. R-Fluoxetine, unlike the other selective serotonin reuptake inhibitors, possesses moderate affinity (K(i) = 64 nmol/L) for the serotonin 2C receptor. Potential clinical correlates of these unique attributes of escitalopram and R-fluoxetine are discussed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11543737&dopt=Abstract citalopram Celexa



citalopram Celexa
High-performance liquid chromatographic method to screen and quantitate seven selective serotonin reuptake inhibitors in human serum.

Tournel G, Houdret N, Hedouin V, Deveau M, Gosset D, Lhermitte M.

Institut de Medecine Legale de Lille, Faculte de Medecine, Universite de Lille II, France.

A high-performance liquid chromatographic screening method (HPLC) is described for the determination of seven selective serotonin reuptake inhibitors (SSRIs) (fluvoxamine, milnacipran, paroxetine, sertraline, fluoxetine, citalopram, venlafaxine) and for three pharmacologically active N-demethylated metabolites (desmethylcitalopram, didesmethylcitalopram and norfluoxetine). A tricyclic antidepressant, clomipramine, was used as an internal standard. The method consists of liquid extraction of serum after alcalinisation at pH 9.50, followed by chromatography on a Beckman C18 reversed-phase column. Compounds were detected at 200.4 nm. The standard curves were linear over a working range of 50-1,000 ng/ml for fluvoxamine, 15-1,000 ng/ml for fluoxetine, 25-500 ng/ml for norfluoxetine, 50-500 ng/ml for sertraline, 20-500 ng/ml for paroxetine, 25-550 ng/ml for citalopram, 25-750 ng/ml for desmethylcitalopram, 25-800 ng/ml for didesmethylcitalopram, 25-650 ng/ml for milnacipran, and 25-500 ng/ml for venlafaxine. The quantitation limits of the method were 15 ng/ml for fluoxetine, 20 ng/ml for paroxetine, 25 ng/ml for venlafaxine, norfluoxetine and citalopram, and its metabolites, 40 ng/ml for sertraline and 50 ng/ml for fluvoxamine. No interferences were noted with this sensitive and specific method which can be used for therapeutic drug monitoring.

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citalopram Celexa
Action of selective serotonin reuptake inhibitor on aggressive behavior in adult rat submitted to the neonatal malnutrition.

Medeiros JM, Silva CM, Sougey EB, Costa JA, Castro CM, Castro RM.

Departamento de Nutricao, Universidade Federal de Pernambuco, Recife, PE, Brasil.

The effect of the malnutrition during suckling on the aggressiveness was investigated in adult rats treated or not with citalopram, a selective serotonin reuptake inhibitor (SSRI). The animals were divided into two groups according to the diet used: nourished group - the rats received the control diet with 23% protein during the life; and malnourished group - the rats had its mothers submitted to diet with 7.8% protein during suckling. At 120 days of age, each group was sub-divided according to the treatment: acute - consisting a single i.p. injection of saline solution or 20-mg/Kg citalopram; chronic - consisting the single injections (1 per day during 14 days) of saline or 20 mg/Kg citalopram. The acute or chronic treatment with SSRI reduces aggressive response in nourished rats, but not in malnourished ones. Thus, the malnutrition during the critical period of brain development seems to induce durable alterations in the function of the serotoninergic neurotransmission

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citalopram Celexa
Effects of acute citalopram treatment on the methamphetamine-induced locomotor activity.

Kameda K, Tanaka T, Miura J, Kusumi I, Koyama T.

Department of Psychiatry, Hokkaido University School of Medicine, Sapporo, Japan. kenkamed med.hokudai.ac.jp

1. Previously the authors have shown that acute citalopram treatment increased the dopamine D2 receptor expression in rat brain striatum (Kameda et al., 2000). In the present study, the authors attempted to determine whether these effects of citalopram influence the methamphetamine-induced locomotor activity. 2. The pretreatment with a single administration of citalopram (10 mg/kg, i.p.) resulted in the significant enhancement of the locomoter activity induced by methamphetamine treatment (1 mg/kg, i.p.). The enhancement was observed 30 min, 12 hours, 24 hours, but not 7 days after withdrawal of citalopram administration. 3. Then the authors determined the methamphetamine concentration in rat brain striatum by gas chromatography-mass spectrometry (GC-MS) The results showed that the concentration of methamphetamine wars significantly higher in the rats 24 hours, and also 7 days after withdrawal of citalopram administration, compared to the control rats. 4. These results emphasized the involvement of the high methamphetamine concentration, caused by the pretreatment with citalopram, in the enhancement of the methamphetamine-induced locomotor activity. However high methamphetamine concentration alone could not account for this enhancement, since the high concentration of methamphetamine observed 7 days after withdrawal of citalopram administration did not appear to enhance the methamphetamine-induced locomotor activity. Another mechanism through which the pretreatment with citalopram enhanced the methamphetamine-induced locomotor activity, such as the increased expression of the dopamine D2 receptors, could not be excluded.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11642656&dopt=Abstract citalopram Celexa