Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the central nervous system (CNS) and in the periphery, specific proteins (transporters) are responsible for the regulation of the synaptic concentrations of the major monoamine neurotransmitters, noradrenaline (NE), serotonin (5-HT) and dopamine (DA). Several reports have shown that the expression of these transporters within the CNS may be altered in patients with certain neurodegenerative or neuropsychiatric disorders. Therefore, in the CNS the monoamine transporters are major targets for existing and developmental drugs. The best known drugs targeting these transporters are the selective 5-HT reuptake inhibitors (SSRIs) (e.g. citalopram, Celexa) that are most frequently used in the treatment of clinical depression. Selective NE reuptake inhibitors (NRIs) have also found use for the treatment of depression and other conditions such as attention deficit hyperactivity (ADHD) disorder. Given that the NE transporter (NET) is also a binding site for cocaine and drugs of abuse, there is a great need for a probe to assess the densities of NET in vivo by brain imaging with either positron emission tomography (PET) or single photon emission tomography (SPET). PET in particular has the potential to measure NET densities quantitatively and with high resolution in the human brain in vivo. The quality of a PET image depends crucially on the radioligand used in the emission measurement. Commonly used radionuclides in PET radioligands are carbon 11 (t(1/2) = 20.4 min) and fluorine-18 (t(1/2) = 109.8 min). This review specifically summarizes the present status of the development of (11)C- or (18)F-labeled ligands as tools for imaging NET in brain with PET in support of neuropsychiatric clinical research and drug development.
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PMID:Development of radioligands for imaging of brain norepinephrine transporters in vivo with positron emission tomography. 1797 89

Although a large literature supports the benefits of breastfeeding, this review suggests that breastfeeding is less common among postpartum depressed women, even though their infants benefit from the breastfeeding. Depressed mothers, in part, do not breastfeed because of their concern about potentially negative effects of antidepressants on their infants. Although sertraline (Zoloft) and paroxetine (Paxol) concentrations are not detectable in infants' sera, fluoxetine (Prozac) and citalopram (Celexa) do have detectable levels. Unfortunately these findings are not definitive because they are based on very small sample, uncontrolled studies. As in the literature on prenatal antidepressant effects, the question still remains whether the antidepressants or the untreated depression itself has more negative effects on the infant. It is possible that the positive effects of breastfeeding may outweigh the positive effects of the antidepressants for both the mother and the infant. In addition, some alternative therapies may substitute or attenuate the effects of antidepressants, such as vagal stimulation or massage therapy, both therapies being noted to reduce depression. Further studies of this kind are needed to determine the optimal course of therapy for the benefit of the depressed, breastfeeding mother and the breastfed infant.
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PMID:Breastfeeding and antidepressants. 1827 27

Thirty-six patients with arterial hypertension complicated with disturbances of carbohydrate metabolism (from changes of tolerance to glucose to diabetes mellitus type II), lipid metabolism (obesity of different degree) and depression have been studied. In 23 cases (main group), a combined therapy with somatotropic and psychotropic drugs was used while 13 patients were (control group) treated only with somatotropic medications. Citalopram, a selective inhibitor of serotonin reuptake, was the main psychopharmacological drug used in the treatment of the main group. In some cases other medications (neuroleptics, benzodiazepines) were used. Patient's state was assessed by the results of the somatic and psychopathological examination using psychometric scales and by a number of indices obtained in the instrumental and laboratory (biochemical etc) study. The results suggest the higher efficacy of the combined therapy by all parameters--arterial pressure, indices of carbohydrate and lipid metabolism, severity of affective disorders.
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PMID:[Psychopharmacotherapy of patients with arterial hypertension complicated with metabolic disturbances and depression]. 1837 72

The correlation between depression and cardiovascular pathologies was studied in geriatric age. As a matter of fact, the high comorbidity of depression with the sudden cardiac deaths or other cardiovascular events requires a careful evaluation of these causalities. A total of 110 patients were analyzed, recovered in assisted sanitary residence (from the widely used Italian name: "residenza sanitaria assistita" abbreviated as RSA) during the last 12 months. All patients were above the age of 80 years at the admission (mean age was 83.2+/-2.8 years), and all of them have had a diagnosis of depression according to the DSM IV. All patients were treated with the antidepressive specific serotonin reuptake inhibitor (SSRI) (Citalopram, 20-40mg/day, or Sertraline 50-100mg/day). The patients were divided on the basis of their therapeutic response in two groups: Group A (responders) and Group B (non-responders). After 4, 6 and 12 months of treatment, we observed a reduction of the cardiovascular events (-75%, -83% and -60%, respectively). These findings confirm the existence of a correlation between the level of affectivity and the cardiac functions.
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PMID:Use of specific serotonin reuptake inhibitors (SSRIs) (Sertraline or Citalopram) in the treatment of depression reduces the cardiovascular risk in the elderly: evidence from a Sicilian population >80 years recovered in the assisted sanitary residences (RSA). 1844 Jun 57

Citalopram and escitalopram are highly selective serotonin reuptake inhibitors widely used in the treatment of depression. They exhibit adverse drug reactions and side effects, however, and the development of specific methods for their determination is of great interest in clinical and forensic toxicology. A liquid chromatography-tandem mass spectrometry method has been developed and validated for the assay of citalopram, escitalopram, and their demethylated metabolites in 10-mg hair samples. The analytes were extracted by incubation in methanol and liquid/liquid extraction with diethyl ether/dichloromethane. Gradient elution on a narrow bore C18 column was realized using clomipramine-d3 as an internal standard. Positive ion electrospray ionization and tandem mass spectrometry determination by collision-induced dissociation were performed in an ion trap mass spectrometer. The method exhibited a linear range of 25 to 2000 pg/mg, a quantification limit of 25 pg/mg for all analytes, relative standard deviations in the range of 12.10 to 9.80 (intraassay), and 13.80 to 11.78 (interassay), and accuracies (as percent recovery of the spiked standards) in the range of 90% to 110%; it was applied to the determination of citalopram and escitalopram and their metabolites in hair samples of two newborns to document their in utero exposure to the drugs. The method proved suitable for neonatal hair analysis of citalopram or escitalopram and was applied to two real cases of gestational exposure.
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PMID:Quantification of citalopram or escitalopram and their demethylated metabolites in neonatal hair samples by liquid chromatography-tandem mass spectrometry. 1864 54

Citalopram is marketed as a racemate (50:50) mixture of the S(+)-enantiomer and R(-)-enantiomer and the active S(+)-enantiomer (escitalopram) that possess inhibitory effects. Citalopram was introduced in Sweden in 1992 and is the most frequently used antidepressant to date in Sweden. In 2002, escitalopram was introduced onto the Swedish market for treatment of depression and anxiety disorders. The main objective of this study was to investigate S(+)-citalopram [i.e., the racemic drug (citalopram) or the enantiomer (escitalopram)] present in forensic autopsy cases positive for the presence of citalopram in routine screening using a non-enantioselective bioanalytical method. Fifty out of the 270 samples found positive by gas chromatography-nitrogen-phosphorus detection were further analyzed using enantioselective high-performance liquid chromatography. The 50 cases were genotyped for CYP2D6 and CYP2C19, as these isoenzymes are implicated in the metabolism of citalopram and escitalopram. In samples positive for racemic citalopram using the screening method for forensic autopsy cases, up to 20% would have been misinterpreted in the absence of an enantioselective method. An enantioselective method is thus necessary for correct interpretation of autopsy cases, after the enantiomer has been introduced onto the market. The percentage of poor metabolizers was 6% for CYP2D6 and 8% for CYP2C19.
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PMID:Enantioselective analysis of citalopram and escitalopram in postmortem blood together with genotyping for CYP2D6 and CYP2C19. 1923 31

Area-specific and stimulation-dependent changes of human brain activation by selective serotonin reuptake inhibitors (SSRI) are an important issue for improved understanding of treatment mechanisms, given the frequent prescription of these drugs in depression and anxiety disorders. The aim of this neuroimaging study was to investigate differences in BOLD-signal caused by administration of the SSRIs escitalopram and citalopram using pharmacological functional magnetic resonance imaging (pharmaco-fMRI). Eighteen healthy subjects participated in a placebo-controlled, randomized, double-blind study in cross-over repeated measures design. Each volunteer performed facial emotional discrimination and a sensorimotor control paradigm during three scanning sessions. Citalopram (20 mg/d), escitalopram (10 mg/d) and placebo were administered for 10 days each with a drug-free period of at least 21 days. Significant pharmacological effects on BOLD-signal were found in the amygdala, medial frontal gyrus, parahippocampal, fusiform and middle temporal gyri. Post-hoc t-tests revealed decreased BOLD-signal in the right amygdala and left parahippocampal gyrus in both pharmacological conditions, compared to placebo. Escitalopram, compared to citalopram, induced a decrease of BOLD-signal in the medial frontal gyrus and an increase in the right fusiform and left parahippocampal gyri. Drug effects were concentrated in brain regions with dense serotonergic projections. Both escitalopram and citalopram attenuated BOLD-signal in the amygdala and parahippocampal cortex to emotionally significant stimuli compared to control stimuli. We believe that reduced reactivity in the medial frontal gyrus found for escitalopram compared to citalopram administration might explain the response differences between study drugs as demonstrated in previous clinical trials.
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PMID:Area-specific modulation of neural activation comparing escitalopram and citalopram revealed by pharmaco-fMRI: a randomized cross-over study. 1983 14

Serotonergic and noradrenergic pathways are the main targets of antidepressants. Their differential effects on emotion processing-related brain activation are, however, to be further characterized. We aimed at elucidating the neural sites of action of an acute differential serotonergic and noradrenergic influence on an emotion-processing task, which was earlier shown to be associated with depressiveness. In a single-blind pseudo-randomized crossover study, 21 healthy subjects (16 subjects finally included in the analysis) participated to ingest a single dose at three time points of either 40 mg citalopram, a selective serotonin-reuptake inhibitor, 8 mg reboxetine, a selective noradrenaline-reuptake inhibitor, or placebo 2-3 h before functional magnetic resonance imaging (fMRI). During fMRI, subjects performed a task comprising the anticipation and perception of pictures of either 'known' (positive, negative, neutral) or 'unknown' valence (randomly 50% positive or negative). In direct comparison with citalopram and with placebo, reboxetine increased brain activity in the medial thalamus. Citalopram modulated certain prefrontal and insular areas more prominently. Other frontal and parieto-occipital areas were modulated by both drugs. In conclusion, the functional network involved in emotional information processing could be modulated by the acute application of selective noradrenergic and serotonergic drugs revealing a noradrenergic effect in thalamic and frontal areas, and a prefrontal and insular focus of serotonergic modulation. These findings could have implications for future selection criteria concerning personalized antidepressant medication in depression.
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PMID:Serotonergic and noradrenergic modulation of emotion processing by single dose antidepressants. 1984 60

To assess the effectiveness and tolerability of citalopram for the acute treatment of children and adolescents suffering from depression and/or anxiety disorders. As much as 78 outpatients, aged 7-18 years with a diagnosis of depressive and/or anxiety disorder, completed an 8-week open trial with citalopram (20-40 mg/day). Outcome, side effects and suicidality were assessed weekly to bi-weekly using appropriate rating scales. At endpoint 56% of subjects were found to be responders (Clinical Global Impression-Improvement [CGI-I] Scale <or= 2). Subjects with less severe psychopathology and subjects with anxiety disorders showed a more favorable response. As much as 43% of depressed and 51% of anxious subjects had a 50% or greater reduction in scores on our secondary outcome measures, Children's Depression Rating Scale-Revised (CDRS-R) and Screen for Child Anxiety Related Emotional Disorders (SCARED). Most reported adverse events were mild to moderate and did not affect medication adherence. No increase in suicidality was observed during the study. Citalopram was moderately effective, generally well tolerated and safe for the acute treatment of depressed and anxious children and adolescents.
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PMID:Effectiveness and tolerability of citalopram for the treatment of depression and anxiety disorders in children and adolescents: an open-label study. 1985 5

The aim of this study was to examine the effects of the SSRI antidepressant drug citalopram on anxiety, depression and mental adjustment to cancer in terminally ill cancer patients, considering also the 5-HTTLPR genetic polymorphism. A group of twenty-one consecutive patients admitted to the hospice of the Casa di Cura Pineta del Carso (Trieste, Italy) with different types of advanced cancer, who were clinically judged to require treatment with an antidepressive drug, was treated with citalopram for two weeks. The response was determined and related to 5-HTTLPR. Citalopram significantly reduced the scores on the depression and anxiety subscales of the Hospital Anxiety and Depression Scale (HADS). When the effects of citalopram were analyzed in relation to the 5-HTTLPR polymorphism, the HADS depression score was significantly decreased only in patients with the "l/l" allelic variant of the serotonin transporter conferring high functional activity, while the score of the Mini-MAC fatalism scale was significantly increased in patients carrying at least one "s" allele. These preliminary findings seem to indicate that two weeks of treatment with citalopram are effective in reducing depressive symptoms in terminally ill cancer patients. Moreover, the effects of citalopram on fatalism as a strategy of mental adaptation to cancer, and on depressive symptoms depend on the allelic variants of the 5-HTTLPR genotype of the patients. These results seem to encourage the examination of a larger patient sample and of different treatment schedules, as well as a more thorough characterization of fatalism as a coping strategy in cancer patients.
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PMID:Serotonin transporter 5-HTTLPR polymorphism and response to citalopram in terminally ill cancer patients: report of twenty-one cases. 1985 60


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