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)

Maternal separation in non-human primates has been proposed as a model of early adversity. The symptoms of separation anxiety were studied in vervet monkeys, during the weaning period, when psychotropic medications were administered. The control group received a normal diet and treatment groups received citalopram, reboxetine or lamotrigine in their food daily. Treatment was given for 7 weeks starting 1 month prior to weaning. Behavior was recorded twice weekly for 8 weeks, and was rated for anxiety and depression. Cerebrospinal fluid was collected at the beginning and end of the trial and analyzed for monoamines and metabolites using High Performance Liquid Chromatography. Citalopram pretreatment prevented the reduction of affiliation behavior and reduced stereotypies after weaning, and both citalopram and reboxetine abolished the increase in activity seen in control monkeys after weaning, but no statistically significant differences were found between groups. Citalopram pretreatment also significantly increased noradrenaline and 5-hydroxyindolacetic acid (5-HIAA) levels and reboxetine significantly decreased dopamine levels over time. The 5-HIAA levels of reboxetine and lamotrigine treated monkeys were significantly lower than that of the control group at the end of the trial. Although limited by a small sample size, this study demonstrates the possibility of investigating the psychopharmacology of early adversity in a non-human primate model.
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PMID:Psychopharmacology of maternal separation anxiety in vervet monkeys. 1685 Feb 60

Intravenous (iv) administration of an antidepressant is a common practice in some European countries, particularly in France, Spain, and Italy in the initial treatment phase of hospitalised, severe depressed patients. After a beneficial response is observed, patients are switched to an oral formulation. The approved treatment period of the iv form of citalopram is limited to 8-10 days. The high bioavailability of citalopram permits the use of identical iv and oral doses. Citalopram is a racemate, consisting of a 1:1 mixture of the S- and R-enantiomers. The therapeutically active component is the S-enantiomer (escitalopram). Pharmacokinetic single dose administration studies in healthy subjects have demonstrated that daily oral administration of 20 mg of escitalopram or 40 mg citalopram results in similar plasma concentrations of the S-enantiomer of citalopram. This open-label multicentre French prospective study investigated the tolerability and efficacy of oral escitalopram 10 and 20 mg/day, administered for a 6-week period as continuation treatment of citalopram (20 mg or 40 mg daily) intravenous (iv), in patients with Major Depressive Disorder. A total of 171 patients were enrolled, of whom 147 (85%) completed the study. The mean MADRS score at inclusion (last citalopram dose) was 31.6 +/- 9.9. The total MADRS score decreased after 3 days of oral treatment with escitalopram. Escitalopram demonstrated a continuous effect in treating depressive symptoms throughout the study. The decrease in MADRS mean total score from baseline was statistically significant to each visit (day 3, 15; p < 0.0001). At final visit (J42), the decrease was - 18.9 +/- 11.7 (p < 0.0001) and the MADRS mean total score was 12.7 +/- 9.3. There were no differences seen in the patient response comparing gender, age, and the single or recurrent episodes. The changes of Clinical Global Impression scores (CGI-S, CGI-I, PGE-Patient Global Evaluation) were also indicative of an improvement of the patients' depression. The CGI-I and PGE scores were significantly correlated indicating good agreement between investigator and patient in rating the degree of improvement. At the end of the study, 67% of patients were classified as responders (decrease of MADRS score from baseline > or = 50%), and the majority of them were considered remitters (final MADRS score < or = 12). Overall, the switch from intravenous citalopram to oral escitalopram was well tolerated in the study population. In all, 57 patients (33%) reported at least one adverse event (AE) during the study (21 patients in the 10 mg group and 36 patients in the 20 mg group); of these, 7 patients (4%) withdrew from the study. The most frequently reported AEs were suggestive of residual symptoms of depression (anxiety, 9%; insomnia, 5% of patients). In conclusion, in this study oral escitalopram (10 mg or 20 mg) was well tolerated as continuation treatment after switching from intravenous citalopram (20 mg or 40 mg). From the efficacy and safety data of this study, it can be concluded that the switch from citalopram iv to oral escitalopram (10 and 20 mg/day) is effective in decreasing depressive symptoms, and could be safely proposed in patients with major depressive disorder.
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PMID:[Safety and efficacy of oral escitalopram as continuation treatment of intravenous citalopram, in patients with major depressive disorder--the navigade switch study]. 1691 Jun 29

The most studied and most frequently used pharmacologic treatments in bulimia nervosa are the selective serotonin reuptake inhibitors (SSRIs), in particular, fluoxetine. Less is known about the efficacy of the other SSRIs. To compare fluoxetine with citalopram in the treatment of bulimic patients, 37 bulimic patients were randomized to receive fluoxetine (n=18) or citalopram (n=19); these patients were assessed with regard to clinical (ie, body mass index, pathologic behaviors), psychopathologic (Eating Disorder Inventory-2, Body Shape Questionnaire, Binge-Eating Scale, Beck Depression Inventory), personality (Temperament and Character Inventory), and clinical global impression measures. These measures were compared between the 2 treatment groups at baseline and at the end of treatment. Dropout rates were similar in the 2 groups. Both groups showed significant improvement in eating psychopathology, angry feelings, and clinical global impression. Patients in the fluoxetine group displayed a greater reduction in introjected anger, whereas those in the citalopram group displayed a greater reduction in depressive feelings. Both treatments showed some effect on outcome measures, but efficacy profiles did not overlap. Citalopram may be useful in depressed patients with bulimia, whereas fluoxetine is more specific for those with introjected anger and bulimia.
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PMID:Citalopram versus fluoxetine for the treatment of patients with bulimia nervosa: a single-blind randomized controlled trial. 1691 31

The authors report an improvement in delusions and hallucinations after antidepressant treatment (Clomipramine) in a parkinsonian patient with psychosis and comorbid depression. Their findings, which support a previous case treated with Citalopram, highlight the possible effectiveness of antidepressant therapy on psychotic symptoms in parkinsonian patients.
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PMID:Antidepressant use in treatment of psychosis with comorbid depression in Parkinson's disease. 1691 77

Most patients with depression have symptoms of anxiety associated with their illness. Our aim in this study was to investigate the efficacy of escitalopram, a proven antidepressant, on symptoms of anxiety in patients with major depressive disorder (MDD). Data from five placebo-controlled escitalopram studies in MDD were analyzed. Three of the studies also included a comparison with citalopram. In all studies, anxiety was assessed using the Inner Tension item (item 3) of the Montgomery-Asberg Depression Rating Scale (MADRS). In three studies, anxiety symptoms were also specifically assessed, either continuously over time or at baseline and end point, by using the Hamilton Rating Scale for Anxiety (HAM-A), the Anxious Mood item of the HAM-A (item 1), the Psychic Anxiety subscale of the HAM-A (items 1-6 and 14), the Anxiety Psychic item (item 10) of the Hamilton Rating Scale for Depression (HAM-D-24), and the Anxiety/Somatization subfactor (items 10-13, 15, and 17) of the HAM-D-24. Escitalopram was significantly superior to placebo in all comparisons. Citalopram was also consistently better than placebo in all comparisons, except in the HAM-D-24 Anxiety/Somatization subfactor. In some comparisons with placebo, escitalopram showed a significantly earlier onset of action or an earlier separation. Escitalopram was significantly more effective compared to placebo in treating both anxiety symptoms and the entire depression in the total depressive population, as well as in depressive patients with a high degree of anxiety.
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PMID:Escitalopram in the treatment of anxiety symptoms associated with depression. 1693 93

Tryptophan hydroxylase-1 (TPH1) is the rate-limiting enzyme in serotonin biosynthesis, and selective serotonin reuptake inhibitors (SSRIs) exert their activity enhancing the general serotonergic tone. Citalopram is the most selective SSRI, with little or no affinity for a variety of receptor types. The goal of this study was to investigate whether the A218C polymorphism of the TPH1 gene is associated with the citalopram antidepressant response in subjects with major depressive disorder (MDD). All of the patients were evaluated using the 21-item Hamilton Depression Rating Scale before beginning and after 8 weeks of citalopram treatment. Genotyping was performed with the polymerase chain reaction. The remission rate to citalopram treatment was worse in MDD subjects with the TPH1 A/A and A/C genotypes than in those with the TPH1 C/C genotype. Our results suggest that the A218C polymorphism of the TPH1 gene serves as a modulator of antidepressant activity, especially in terms of treatment remission.
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PMID:Association between the tryptophan hydroxylase-1 gene A218C polymorphism and citalopram antidepressant response in a Korean population. 1697 75

The suicide-related data on citalopram from controlled clinical trials in depression and anxiety disorders were analysed. Safety data from placebo-controlled and relapse prevention citalopram trials in depression/major depressive disorder (MDD) and anxiety were searched for specific events relating to fatal suicide, non-fatal self-harm or suicidal thoughts. Efficacy data (item 10, suicidal thoughts, on the Montgomery-Asberg Depression Rating Scale [MADRS]) were also analysed. In the clinical trial database, the number of adverse events (fatal suicide, non-fatal self-harm or suicidal thoughts) was low, both during the first 2 weeks of treatment and during the full treatment period, with no statistically significant differences between citalopram and placebo. There was one fatal suicide during treatment (after 12 weeks of double-blind treatment in a relapse-prevention trial) for a patient treated with citalopram (incidence: 0.4%; rate: 0.010) and none on placebo. Citalopram was significantly more efficacious than placebo in lowering suicidal thoughts, based on efficacy rating (MADRS, item 10). There was no indication from this review of clinical trial data that citalopram may increase the risk of suicide in patients with MDD or anxiety. However, the patients in these clinical trials represent a selected group, as those patients with a significant risk of suicide were excluded at trial onset.
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PMID:Citalopram and suicidality in adult major depression and anxiety disorders. 1703 5

Using a model of depression in which chronic social stress induces depressive-like symptoms, we investigated effects of the selective serotonin-reuptake inhibitor (SSRI) citalopram on gene expression in the dorsal raphe nucleus of male rats. Expression of tryptophan hydroxylase (TPH) protein was found to be upregulated by the stress and normalized by citalopram, while mRNAs for genes TPH 1 and 2 were differentially affected. Citalopram had no effect on serotonin transporter mRNA but reduced serotonin-1A autoreceptor mRNA in stressed animals. The SSRI prevented the stress-induced upregulation of mRNA for CREB binding protein, synaptic vesicle glycoprotein 2b and the glial N-myc downstream-regulated gene 2, but increased mRNA for neuron-specific enolase (NSE) in both stressed and unstressed animals having no effect on stress-induced upregulation of NSE protein. These findings demonstrate that in the dorsal raphe nucleus of chronically stressed rats, citalopram normalizes TPH expression and blocks stress effects on distinct genes related to neurotransmitter release and neuroplasticity.
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PMID:Effect of chronic citalopram on serotonin-related and stress-regulated genes in the dorsal raphe nucleus of the rat. 1718 23

Deficits in serotonergic (5-HT-ergic) neurotransmission and stressful life events have been implicated in affective disorders, and chronic variable stress (CVS) can elicit behavioral changes reminiscent of increased emotionality, anxiety and atypical depression after partial 5-HT depletion. This study examined the effect of chronic citalopram treatment (10 mg/kg daily) on these changes. Parachloroamphetamine (PCA) (2 mg/kg) reduced the levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the frontal cortex, increased anxiety in the social interaction test, and increased activity in the open field. CVS reduced social activity in the social interaction test and immobility time in the forced swimming test. Reduction of excrements left during immobilization indicated partial adaptation with the CVS. Specific stressors had different effects on body weight gain, shorter lasting stressors having a smaller effect in general than those that lasted longer. Combination of CVS and PCA increased sucrose intake after two weeks of stress. In addition, combination of the two treatments reduced diving in the forced swimming test. Citalopram prevented the increase in sucrose consumption in the PCA+CVS rats, and in 5-HT-depleted animals blocked the increase in struggling and reduced the number of defecations in the forced swim test. In conclusion, citalopram treatment prevented several effects of either 5-HT depletion or combined PCA+CVS treatment, suggesting that these behavioral changes could be used in studies on the neural mechanisms underlying emotional behavior that may have relevance to the neurobiology of depression.
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PMID:Rat behavior after chronic variable stress and partial lesioning of 5-HT-ergic neurotransmission: effects of citalopram. 1782 80

Psychiatric symptoms were retrospectively assessed in a clinic population of 241 children and adults with tuberous sclerosis complex (TSC). Sixty-six (27%) patients had a history of mood disorder symptoms, 66 (27%) had a history of anxiety disorder symptoms, 73 (30%) had a history of attention-deficit hyperactivity disorder (ADHD) symptoms, and 68 (28%) had a history of aggressive/disruptive behavior disorder symptoms. Significant relationships were found between these symptoms and patient age, gender, genetic mutation, seizure history, surgical history, cognitive impairment, features of autism or pervasive developmental disorder, and neurological manifestations of TSC. In 43 patients seen by at least one of two affiliated psychiatrists, the most common formal diagnoses were anxiety disorders (28%), mood disorders (26%), adjustment disorders (21%), ADHD (21%), and mental disorders not otherwise specified due to general medical condition (42%). Citalopram demonstrated efficacy in treating anxiety and depression, and risperidone, in treating problematic behaviors.
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PMID:Psychiatric comorbid conditions in a clinic population of 241 patients with tuberous sclerosis complex. 1793 87


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