citalopram Celexa
Effects of repeated fluoxetine and citalopram administration on cytokine release in C57BL/6 mice.

Kubera M, Simbirtsev A, Mathison R, Maes M.

Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.

This study examines the effects of repeated administration of the selective serotonin reuptake inhibitors (SSRIs), fluoxetine and citalopram (10 mg/kg, i.p.), on immunoreactivity in C57BL/6 mice. Immune functions were evaluated by the ability of splenocytes to reduce a tetrazolium salt to formazan (MTT test), to proliferate, and to produce cytokines, including interleukin (IL)-1, IL-2, IL-4, IL-6, IL-10 and interferon gamma (IFN gamma). Citalopram administered for 1, 2 and 4 weeks stimulates the proliferative activity of splenocytes and suppresses their ability to secrete the anti-inflammatory cytokine IL-4. Fluoxetine administration for 1 and 2 weeks, but not 4 weeks, stimulates the proliferative activity of splenocytes, whereas a 4-week administration of fluoxetine suppresses the secretion of IL-4. Four weeks of prolonged administration of citalopram and fluoxetine induces a significant increase in the production of IL-6 and IL-10, a cytokine with immunosuppressive and anti-inflammatory activities. The results show that, in C57BL/6 mice, the immunomodulatory effects of SSRIs depend on the SSRI used and the duration of administration.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11084221&dopt=Abstract citalopram Celexa



citalopram Celexa
Treatment of Interictal Depression with Citalopram in Patients with Epilepsy.

Hovorka J, Herman E, Nemcova I I.

Neurology and Neuropsychiatry Department, The Na Frantisku Hospital, Prague 1, Czech Republic

The purpose of this study is to assess the efficacy and safety of the selective serotonin-reuptake inhibitor (SSRI) citalopram in depressed epileptic patients. We evaluated 43 epileptic patients who suffered from depression and whose total score on the 21 items of the Hamilton Scale for Depression (HAMD 21) exceeded 15 points. These patients were examined by the psychiatrist and scaled before treatment and after 4 and 8 weeks of treatment with citalopram. The dose of citalopram was flexible, related to the actual condition of the patient. In each patient and in the whole group of patients we compared the monthly seizure frequency (total, partial seizures, generalized tonic-clonic seizures) recorded during treatment with citalopram with that recorded during the 2 months preceding the start of citalopram. During treatment we observed a decrease in the total score on the HAMD 21 from a mean initial value of 21.5 +/- 2.9 (range, 17-26) prior to therapy 14.5 +/- 2.9 (range, 10-19) (P < 0.001) after 4 weeks of treatment and to 9.9 +/- 3.1 (range, 4-19) (P < 0.001) after 8 weeks of treatment. There were 9 (20.9%) responders after 4 weeks of treatment and 28 responders (65.1%) after 8 weeks, all of them with decrease on the HAMD 21 greater than 50%. Nausea was the most common adverse event in 7 patients (16.3%) during the first month of treatment and in 3 patients (6.9%) during the second month of treatment. Sexual dysfunction (decrease of libido) was reported in 2 (4.7%) male patients during the entire course of treatment. No seizure worsening was observed in our patients. Monthly seizure frequency did not change significantly: 2.24 (+/-0.76) seizures before treatment with citalopram, 2.29 (+/-0.81) seizures in the first month of treatment, 2.21 (+/-1.00) seizures in the second month of treatment. No occurrence of de novo generalized tonic-clonic seizures was recorded in individual patients. Citalopram is a safe and effective antidepressant in the treatment of depressed epileptic patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12737834&dopt=Abstract citalopram Celexa



citalopram Celexa
Catalepsy induced by the 5-HT(1A) receptor antagonist WAY 100635 in rats pretreated with the selective serotonin reuptake inhibitor citalopram.

Eltayb A, Svensson TH, Ahlenius S.

Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77, Stockholm, Sweden.

Neither a high dose of the selective serotonin reuptake inhibitor citalopram (100 micromol kg(-1) s.c.), nor the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide 3HCl (WAY 100635) (0.1--0.4 micromol kg(-1) s.c.) produced any evidence of catalepsy in adult male rats. When combined with citalopram, however, WAY 100635 produced a dose-dependent, and statistically significant, catalepsy in the inclined grid test.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11164384&dopt=Abstract citalopram Celexa



citalopram Celexa
Effects of MDMA (ecstasy) on prepulse inhibition and habituation of startle in humans after pretreatment with citalopram, haloperidol, or ketanserin.

Liechti ME, Geyer MA, Hell D, Vollenweider FX.

Psychiatric University Hospital Zurich, Zurich, Switzerland.

Prepulse inhibition (PPI) of the acoustic startle response is an operational measure of sensorimotor gating that can be assessed in animals and in humans. Serotonin releasers such as MDMA disrupt PPI and reduce startle habituation in rodents. These effects are prevented by pretreatment with selective serotonin uptake inhibitors, indicating that the effect of MDMA on startle plasticity is largely due to carrier-mediated release of serotonin from presynaptic terminals. In contrast, MDMA has been shown to increase PPI in humans. It is unclear, however, whether the MDMA-induced increase in PPI in humans is also dependent on carrier-mediated serotonin release and which postsynaptic receptors are involved. We investigated the effects of three different pretreatments on the MDMA-induced effects on PPI and habituation in humans. Pretreatments were: (1) the highly selective serotonin uptake inhibitor citalopram (40 mg IV) in 16 subjects, (2) the D(2) antagonist haloperidol (1.4 mg IV) in 14 subjects, and (3) the 5-HT(2A/C) antagonist ketanserin (50 mg PO) in 14 subjects. Each of the three studies used a double-blind placebo-controlled design. All healthy volunteers were examined four times at 2-4-week intervals after placebo, pretreatment, MDMA (1.5 mg/kg PO), and pretreatment plus MDMA. MDMA increased PPI. Habituation was not altered by MDMA, although MDMA-induced individual differences on habituation and psychological symptoms were inversely correlated. Citalopram attenuated the MDMA-induced increase in PPI and most of the psychological effects of MDMA. Neither haloperidol nor ketanserin had any effect on PPI increases produced by MDMA, although each partially attenuated some MDMA-induced psychological effects. Results are consistent with the view that MDMA increases PPI of the acoustic startle reflex in humans via release of presynaptic serotonin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11166515&dopt=Abstract citalopram Celexa



citalopram Celexa
The effect of combined administration of ethanol and sertraline, fluoxetine and citalopram on rabbit EEG.

Pietrzak B, Czarnecka E.

Department of Pharmacodynamics, Medical University of Lodz, Muszynskiego 1, 90-151, Lodz, Poland. bpietrzak pharm.am.lodz.pl

In this study we have decided to examine acute interaction of ethanol with some drugs that belong to selective serotonin inhibitor (SSRI) group. Therefore, the influence of sertraline, fluoxetine and citalopram on the effect of ethanol on EEG of rabbits (frontal cortex, hippocampus, MRF) was tested. Sertraline (10mg/kg i.p.), fluoxetine (10mg/kg i.p.) and citalopram (5mg/kg i.p.) were given 30min before ethanol injection in a dose 0.8g/kg i.v. Ethanol caused the increase of the slow frequencies (0.5-4cps) in the recording, as well as a marked decrease of the fastest frequencies (13-30 and 30-45cps). Sertraline, fluoxetine and citalopram (given before ethanol) prevented the increase in the slow frequencies (0.5-4cps) in the recordings from the frontal cortex and hippocampus, which indicates on antagonism inhibitory action of ethanol. These drugs administered together with ethanol may increase its influence on fast frequencies. This effect depends on brain structure and drug.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12742007&dopt=Abstract citalopram Celexa



citalopram Celexa
[Anxiolytic effects of serotonin reuptake inhibitors and their mechanism of action]

[Article in Japanese]

Hashimoto S.

Department of Psychiatry, Neural Function, Division of Neurological Science, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.

The purpose of this study was to examine the anxiolytic effects of serotonin (5-HT) reuptake inhibitors and to clarify their action mechanisms and roles in the brain serotonergic system in the psychopathology of anxiety. It has been proposed that conditioned fear stress (CFS)-induced freezing behavior in rats could be used as a model of anxiety. In the experiment using this model, acute treatment with the 5-HT reuptake inhibitors reduced CFS-induced freezing behavior, while acute treatment with the noradrenaline or dopamine reuptake inhibitors failed to alter CFS-induced freezing. CFS elevated extracellular 5-HT levels in the medial prefrontal cortex, and this elevations of 5-HT level was followed by a resolution of the freezing. A dose of 10 mg/kg of a selective 5-HT reuptake inhibitor (SSRI), citalopram, administered 60 min before exposure to CFS increased extracellular 5-HT concentrations immediately and potently, and reduced freezing. The 5-HT1A receptor antagonists, particularly at low doses, enhanced the antifreezing effect of citalopram. While the antifreezing effect of citalopram (10 mg/kg) disappeared by prolongation of the period between conditioning and exposure to CFS, acute challenge of citalopram (10 mg/kg) reduced freezing in the rats into which citalopram (10 mg/kg) had been injected twice daily for 7 days. From these findings, it is indicated that 1) 5-HT reuptake inhibitors decrease anxiety, 2) 5-HT release is increased at the nerve terminal under anxiety conditions, 3) the elevation of 5-HT levels in the terminal has an anxiolytic action which is closely related to the pharmacological effects of SSRI-class of anxiolytics, and 4) 5-HT1A receptor antagonist enhances the antifreezing effect of SSRI by blocking the autoreceptor-mediated negative feedback mechanisms of 5-HT neurons. By prolonging the period between conditioning and exposure to CFS, the author recognized the feasibility to establish an animal model which reflects the psychopathology of anxiety disorder more precisely. Presynaptic 5-HT1A receptor desensitization may account for the mechanism of action of repeated treatment with SSRI.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11193934&dopt=Abstract citalopram Celexa



citalopram Celexa
An open trial of citalopram in adolescents with post-traumatic stress disorder.

Seedat S, Lockhat R, Kaminer D, Zungu-Dirwayi N, Stein DJ.

Department of Psychiatry, University of Stellenbosch, Tygerberg, Cape Town, South Africa.

In this preliminary, 12-week open-label study, eight adolescents with moderate to severe post-traumatic stress disorder (PTSD) were treated with citalopram (the most selective of the selective serotonin reuptake inhibitors) in a fixed daily dose of 20 mg, and rated at 2-week intervals. The Clinician-Administered PTSD Scale (Child and Adolescent Version) was the primary measure used to assess treatment outcome. Core PTSD symptoms (re-experiencing, avoidance, and hyperarousal symptoms) showed statistically significant improvement at week 12 on the Clinician-Administered PTSD Scale (Child and Adolescent Version) (CAPS-CA), with a 38% reduction in total CAPS scores between baseline and endpoint. Citalopram failed to effect improvement on self-reported depressive symptoms. All seven adolescent completers were rated as much improved or very much improved on Clinical Global Impression Improvement scores. Citalopram was well-tolerated overall with reported adverse experiences being relatively benign. However, larger, controlled trials are needed to consolidate these preliminary results.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11195256&dopt=Abstract citalopram Celexa



citalopram Celexa
Chronic pharmacological treatment with certain antidepressants alters the expression and DNA-binding activity of transcription factor AP-2.

Damberg M, Ekblom J, Oreland L.

Department of Neuroscience, Section of Pharmacology, Uppsala University, Sweden.

Several of the genes in the serotonergic and the dopaminergic systems have consensus binding sites for the AP-2 transcription factor family in their regulatory regions. Imbalances in these systems have been implicated in many psychiatric disorders, including depression and bipolar affective disorder. We have made an effort to further elucidate the molecular mechanisms of drugs used for affective disorders. Recently, we analyzed the effects of chronic treatment with certain antidepressants on AP-2 in rat brain. The present study demonstrates that chronic administration of three different classes of antidepressants modulates the DNA-binding activity of AP-2 in the rat brain. Chronic administration of citalopram (10 mg/kg), imipramin (10 mg/kg) and lithium-chloride (40 mg/kg) significantly decreased DNA-binding activity of AP-2. Furthermore, citalopram (10 mg/kg) and imipramin (10 mg/kg) significantly decreased the amount of AP-2alpha protein as determined by ELISA. In addition, citalopram (10 mg/kg) significantly decreased the amount of AP-2beta protein. In contrast, chronic administration of lithium-chloride (40 mg/kg) did not affect the amount of the two AP-2 isoforms. An increased understanding of the function of transcription factors and their involvement in human disease, such as depression, could make it possible in the future to selectively modulate relevant target genes directly.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11205881&dopt=Abstract citalopram Celexa