Modulation of noradrenergic neuronal firing by selective serotonin reuptake blockers. (1/558)

Using in vivo extracellular unitary recording, the effect of short term (2-day) and long-term (21-day) administration of the selective 5-HT reuptake inhibitor (SSRI) paroxetine (10 mg kg(-1) day(-1), s.c. using osmotic minipumps) was examined on the spontaneous firing activity of locus coeruleus noradrenergic neurons. Long-term but not short-term treatment significantly decreased firing activity. Thus, it appears that enhancing 5-HT neurotransmission by sustained SSRI administration leads to a reduction of the firing rate of noradrenergic neurons. The SSRI paroxetine therefore alters the activity of noradrenergic neurons with a delay that is consistent with its therapeutic action in depression and panic disorder.  (+info)

Effect of activated charcoal alone or given after gastric lavage in reducing the absorption of diazepam, ibuprofen and citalopram. (2/558)

AIMS: The efficacy of activated charcoal alone, and gastric lavage followed by charcoal in reducing the absorption of diazepam, ibuprofen and citalopram was studied in healthy volunteers. METHODS: In a randomized cross-over study with three phases, nine healthy volunteers were administered single oral doses of 5 mg diazepam, 400 mg ibuprofen and 20 mg citalopram, taken simultaneously after an overnight fast. Thirty minutes later, the subjects were assigned to one of the following treatments: 200 ml water (control), 25 g activated charcoal as a suspension in 200 ml water or gastric lavage followed by 25 g charcoal in suspension given through the lavage tube. Plasma concentrations of diazepam, ibuprofen and citalopram were determined up to 10 h. RESULTS: The AUC(0,10 h) of diazepam was reduced by 27% (P<0.05) by both charcoal alone and charcoal combined with lavage. The increase in plasma diazepam concentration from 0.5 h onwards was prevented by both interventions (P+info)

Serotonin reuptake inhibition by citalopram in rat strains differing for their emotionality. (3/558)

Acute administration of the selective serotonin (5-HT) reuptake inhibitor (SSRI), citalopram (1-10 mg/kg, i.p. 1 h before an elevated plus-maze test), to Spontaneously Hypertensive rats (SHRs), Lewis (LEW) rats, and Wistar-Kyoto (WKY) rats, i.e., rat strains differing for their emotionality, promoted anxiety, and/or hypoactivity, except in WKY rats. In the three strains, such a pretreatment increased central 5-HT levels and/or decreased 5-hydroxyindoleacetic acid levels. Hippocampal, but not midbrain or striatal, [3H]citalopram binding at 5-HT transporters was lower in WKY rats than in SHRs. However, neither [3H]5-HT reuptake kinetics nor the potencies of citalopram (1-1000 nM) to inhibit [3H]5-HT reuptake into hippocampal and striatal synaptosomes differed between strains. This was confirmed in vivo by means of microdialysis in the hippocampus of freely moving rats. Thus, although LEW rats displayed a 3-4 fold higher baseline level of extracellular 5-HT in the hippocampus, compared with SHRs and WKY rats, local perfusion with 1 microM citalopram promoted relative increases in extracellular 5-HT levels over baseline that were similar in all strains. Lastly, acute i.p. administration of 3.3 mg/kg citalopram (1 h beforehand) decreased to similar extents [3H]5-HT reuptake into hippocampal synaptosomes from SHRs and WKY rats. This study indicates that genetic differences in the behavioural responses to SSRIs may involve 5-HT transporter-independent mechanisms.  (+info)

The activity of rat brain nitric oxide synthase following chronic antidepressant treatment. (4/558)

Nitric oxide synthase (NOS) is an enzyme involved in the activation of the glutamate/NMDA receptor-induced cascade of events. In this study we investigated the NOS activity in different rat brain regions after chronic electroconvulsive, imipramine and citalopram treatments. Chronic electroconvulsive treatment significantly increased the NOS activity (by 49%) in the cerebral cortex. However, chronic treatment with imipramine or citalopram did not alter the activity of NOS in all examined brain regions (cortex, hippocampus or cerebellum). The increased NOS activity after electroconvulsive but not pharmacologic (imipramine or citalopram) treatment may well reflect the differences between the adaptive changes of the NMDA receptor complex induced by these treatments.  (+info)

Citalopram controls phobic symptoms in patients with panic disorder: randomized controlled trial. (5/558)

OBJECTIVE: To examine the effects of long-term treatment with citalopram or clomipramine on subjective phobic symptoms in patients with panic disorder. DESIGN: Double-blind, parallel-group, five-arm study. PATIENTS: Patients aged 18 to 65 years with panic disorder (DMS-III-R diagnosis) and with no major depressive symptoms. INTERVENTIONS: Four hundred and seventy-five patients were randomized to 8 weeks of treatment with either citalopram (10 to 15 mg per day; 20 to 30 mg per day; or 40 to 60 mg per day), clomipramine (60 to 90 mg per day) or placebo. Two hundred and seventy-nine patients continued treatment after the 8-week acute phase. OUTCOME MEASURES: Phobic symptoms were assessed using the Phobia Scale and the Symptom Checklist's (SCL-90) phobia-related factors. RESULTS: At all dosages, citalopram was more efficacious than placebo, with 20 to 30 mg generally being the most effective dosage. Citalopram (20 to 30 mg) generally decreased phobic symptoms significantly more than placebo after Month 3. Interpersonal sensitivity decreased when measured on the respective SCL-90 sub-scale. Alleviation of phobic symptoms generally continued to increase towards the end of the treatment. The effect of clomipramine was not as consistent. CONCLUSIONS: All active treatment groups, especially the group receiving 20 to 30 mg per day of citalopram, effectively controlled phobic symptoms in patients with panic disorder. Long-term treatment with citalopram further decreased phobic symptoms.  (+info)

Acute psychological effects of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") are attenuated by the serotonin uptake inhibitor citalopram. (6/558)

3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a recreational drug that has been shown to release serotonin (5-HT) and dopamine (DA) in animals. The effect of MDMA on 5-HT release can be blocked by 5-HT uptake inhibitors such as citalopram, suggesting that MDMA interacts with the 5-HT uptake site. It is unknown whether this mechanism is also responsible for the psychological effects of MDMA in humans. We investigated the effect of citalopram pretreatment (40 mg iv) on the psychological effects of MDMA (1.5 mg/kg po) in a double-blind placebo-controlled psychometric study in 16 healthy human volunteers. MDMA produced an emotional state with heightened mood, increased self-confidence and extroversion, moderate derealization, and an intensification of sensory perception. Most of these effects were markedly reduced by citalopram. This finding suggests that the psychological effects of MDMA are mediated via action at the 5-HT uptake site to increase 5-HT release through the carrier, as expected from animal studies.  (+info)

Citalopram--a review of pharmacological and clinical effects. (7/558)

OBJECTIVE: To provide clinicians with a critical evaluation of citalopram, a selective serotonin reuptake inhibitor (SSRI) that has been available in Canada since March 1999. DATA SOURCES: Commercial searches (MEDLINE and BiblioTech) and an "in-house" search (InfoDrug) were used to find published English-language references for clinical and preclinical publications. There was no restriction of publication dates. Primary index terms used were: pharmacological properties, receptors, pharmacological selectivity, pharmacokinetics, age-related pharmacokinetics, sex-related pharmacokinetics, renal dysfunction, hepatic dysfunction, cytochrome activity, drug interactions, adverse reactions, antidepressant switching, precautions, overdose, drug discontinuation, children, geriatric, depression, combination therapy, placebo control, refractory depression, anxiety disorders and medical disorders. STUDY SELECTION: A total of 74 studies were reviewed. Twenty-one of these studies specifically examined the clinical efficacy and tolerability of citalopram in depressive disorders as well as other disorders. In depressive disorders, clinical studies were required to have either placebo or active comparison controls for a minimum of 3 weeks. For other disorders, in the absence of double-blind trials, open-label studies were included. Pharmacological studies were limited to animal studies focusing on citalopram's selectivity and receptor specificity, and positron emission tomography studies were incorporated to include human pharmacological data. Pharmacokinetic studies focused on the metabolism, safety and tolerability of citalopram, specifically with reference to adverse reactions, drug interactions and overdose in addition to citalopram's effect on vulnerable populations, such as children, the elderly and patients with metabolic diseases. DATA EXTRACTION: Data on clinical studies were summarized according to test measures, study duration and outcome of study. Pharmacokinetic and pharmacodynamic studies were summarized according to properties and interactions. Adverse reactions were extracted to outline citalopram's safety profile. DATA SYNTHESIS: Citalopram is an SSRI antidepressant with a more specific and selective pharmacological profile than other antidepressants of its class. It is well tolerated, and drug interactions are not a significant concern. It is also reasonably safe for populations vulnerable to pharmacokinetic effects, such as the elderly and patients with metabolic diseases. In addition to its tolerability, citalopram is effective in the treatment of major depression, other depressive disorders and panic disorder. It has the potential to effectively treat other anxiety disorders and substance-use disorders; in addition, it may be useful in several medical conditions. CONCLUSIONS: There is evidence to support the role of citalopram as a well-tolerated and effective SSRI antidepressant. There is a need for further evaluation of its role in psychiatric disorders other than major depressive disorder.  (+info)

Variations in response to citalopram in men and women with alcohol dependence. (8/558)

OBJECTIVE: To examine the differential effects of citalopram on alcohol consumption in nondepressed women and men with mild to moderate alcohol dependence. DESIGN: Prospective, placebo-controlled study. PARTICIPANTS: Sixty-one subjects (34 men and 27 women). INTERVENTIONS: After a 2-week baseline, subjects were randomly assigned to 12 weeks of citalopram (40 mg per day) (n = 15 women, 16 men) or placebo (n = 12 women, 18 men). All received brief standard psychosocial interventions. OUTCOME MEASURES: Alcohol Dependence Scale, Montgomery-Asberg Depression Scale, Michigan Alcohol Screening Test, State-Trait Anxiety Inventory and daily alcohol intake. RESULTS: Pretreatment sex differences were evident in alcohol consumption, alcohol dependence, alcohol-related problems and on anxiety and depression measures. After treatment, analyses of covariance with depression and anxiety scores as covariates revealed a differential benefit of citalopram for men. Men receiving citalopram reduced average drinks per day by 44%, whereas women exhibited a 27% decrease (p < 0.05). CONCLUSIONS: Men may benefit more than women from citalopram in the treatment of alcohol dependence. These findings highlight the importance of examining sex as a significant variable in evaluating response to pharmacotherapy.  (+info)

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