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)

To develop a method to measure the dynamic response of the serotonin system in vivo, the effects of intravenously administered citalopram (the most selective of the serotonin reuptake inhibitors) on cerebral glucose metabolism were evaluated. Cerebral glucose metabolism was measured with positron emission tomography (PET) in 14 normal subjects scanned after administration of saline placebo and citalopram administered on 2 separate days. Citalopram administration resulted in a decrease in metabolism in the right anterior cingulate gyrus (BA 24/32), right superior (BA 9) and right middle frontal gyrus (BA 6), right parietal cortex (precuneus), right superior occipital gyrus, left thalamus, and right cerebellum. Increased metabolism was observed in the left superior temporal gyrus and left occipital cortex. Alterations in metabolism by acute citalopram administration involved the heteromodal association cortices that also show metabolic alterations in patients with geriatric depression and overlap with the regions affected by antidepressant treatment. Future studies will evaluate how the acute metabolic response to citalopram relates to the metabolic response after chronic treatment in patients with geriatric depression.
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PMID:Serotonin modulation of cerebral glucose metabolism measured with positron emission tomography (PET) in human subjects. 1211 3

We obtained information on the efficacy and safety of citalopram in settings that resemble actual clinical practice. A total of 1,783 patients participated in this open, uncontrolled, naturalistic Phase IV evaluation of citalopram at 447 U.S. investigative sites. Participants were selected by guidelines in the citalopram package insert using minimal exclusion criteria. Citalopram dosing began at 20 mg/day and could be titrated to 60 mg/day. Outcomes included the Clinical Global Impressions-Improvement scale (CGI-I) and a Patient Global Evaluation. Separate analyses were performed on patients with a primary diagnosis of major depressive disorder (MDD) (76%) who reported intolerance or nonresponse to previous selective serotonin reuptake inhibitors (SSRIs). Patients included tended to have treatment-resistant or intolerant, chronic or recurrent, comorbid depression with a mean duration of illness of 10 years. At study completion, more than 68% of treatment completers were classified as responders (CGI-I score of 1 or 2). Endpoint analyses showed response rates of 54% in all patients, 56% in patients with MDD, 49% in SSRI nonresponsive patients, and 53% in patients with a history of SSRI intolerance. Nausea (9.8%) and headache (7.3%) were the most often reported adverse events. Patients with a history of SSRI intolerance had a discontinuation rate of 21.8%, whereas those without such a history had a discontinuation rate of 13.3%. Citalopram administered at an average dose of 23.6 mg/day was associated with favorable outcomes and was generally well tolerated.
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PMID:Naturalistic study of the early psychiatric use of citalopram in the United States. 1241 37

We assessed the tolerability and antidepressant response to citalopram in a group of patients who could not tolerate a recent trial of paroxetine therapy. Sixty-one outpatients with major depressive disorder and a confirmed history of intolerance to paroxetine (mean final dose: 26.7 mg/day) were switched after at least a 1 week washout to citalopram therapy (20 mg/day). During the 6-week, open label treatment protocol, citalopram could be titrated up to a maximum dose of 40 mg/day. Response was evaluated using the Clinical Global Impressions CGI scale, the 24-item Hamilton Rating Scale for Depression, and several other measures of symptoms and quality of life. Fifty-three patients (87%) completed 6 weeks of citalopram therapy (mean intent-to-treat dose: 23.9 mg/day). The specific side effects that were reported to be intolerable during the earlier paroxetine trial typically recurred only less than 30% of the time during citalopram therapy; only 6 patients (10%) dropped out because of adverse events. The intent-to-treat CGI response rate was 56% at study endpoint; 62% of the completers responded. Significant improvement from pretreatment was observed on various symptom measures after two weeks of citalopram therapy. Citalopram therapy was well tolerated, and more than one half of the patients who began treatment improved significantly. Although further work is necessary to assess the relative merits of this within-class switching strategy (as compared to other options), these data provide further evidence that the various selective serotonin reuptake inhibitors do not have interchangeable tolerability profiles.
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PMID:Citalopram treatment of paroxetine-intolerant depressed patients. 1241 38

Selective serotonin reuptake inhibitors (SSRIs) are extensively used for the treatment of depression. Aside from their antidepressant properties, they provoke a deficit in paradoxical sleep (PS) that is most probably mediated by the transporter blockade-induced increase in serotonin concentration in the extracellular space. Such an effect can be accounted for by the action of serotonin at various types of serotonergic receptors involved in PS regulation, among which the 5-HT(1A) and 5-HT(1B) types are the best candidates. According to this hypothesis, we examined the effects of citalopram, the most selective SSRI available to date, on sleep in the mouse after inactivation of 5-HT(1A) or 5-HT(1B) receptors, either by homologous recombination of their encoding genes, or pharmacological blockade with selective antagonists. For this purpose, sleep parameters of knockout mice that do not express these receptors and their wild-type counterparts were monitored during 8 h after injection of citalopram alone or in association with 5-HT(1A) or 5-HT(1B) receptor antagonists. Citalopram induced mainly a dose-dependent inhibition of PS during 2-6 h after injection, which was observed in wild-type and 5-HT(1B)-/- mice, but not in 5-HT(1A)-/- mutants. This PS inhibition was fully antagonized by pretreatment with the 5-HT(1A) antagonist WAY 100635, but only partially with the 5-HT(1B) antagonist GR 127935. These data indicate that the action of the SSRI citalopram on sleep in the mouse is essentially mediated by 5-HT(1A) receptors. Such a mechanism of action provides further support to the clinical strategy of antidepressant augmentation by 5-HT(1A) antagonists, because the latter would also counteract the direct sleep-inhibitory side-effects of SSRIs.
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PMID:5-HT 1A/1B receptor-mediated effects of the selective serotonin reuptake inhibitor, citalopram, on sleep: studies in 5-HT 1A and 5-HT 1B knockout mice. 1263 54

Some clinical reports suggest that tricyclic antidepressants which block both noradrenaline and serotonin (5-HT) reuptake (SNRIs) are more effective than selective 5-HT reuptake inhibitors (SSRIs) in treating severe depression. Moreover, one neurochemical study reported larger increases in extracellular 5-HT in rat frontal cortex in response to the tricyclic antidepressant imipramine compared to the SSRI fluoxetine. However, imipramine, which blocks both 5-HT and noradrenaline reuptake, also binds with relatively high affinity to receptors for noradrenaline, histamine and acetylcholine. Thus, to test the hypothesis that compounds that inhibit both 5-HT and noradrenaline reuptake produce larger increases in 5-HT efflux, we compared the effects of acute systemic administration of several SNRIs and SSRIs. Extracellular 5-HT was measured using microdialysis probes implanted in the diencephalon and frontal cortex of unanesthetized rats. We tested the SSRIs paroxetine (0.3-10 mg/kg), citalopram (10-20 mg/kg) and fluoxetine (10 mg/kg), the nonselective tricyclic antidepressant imipramine (20 mg/kg) and the more selective SNRIs duloxetine (3-30 mg/kg) and venlafaxine (30-50 mg/kg). During the lights-off period, paroxetine and duloxetine increased 5-HT in the diencephalon approximately 300 and approximately 200%, respectively. During the lights-on period, paroxetine and duloxetine each increased 5-HT approximately 400% in the diencephalon. In the frontal cortex, both paroxetine and duloxetine increased 5-HT approximately 200%. Citalopram and venlafaxine each increased 5-HT in the diencephalon approximately 300%. Fluoxetine and imipramine increased 5-HT in the diencephalon by approximately 125 and approximately 80%, respectively. Thus, these results do not support the hypothesis that compared to SSRIs, compounds which inhibit both 5-HT and noradrenaline reuptake have a larger acute effect on extracellular 5-HT.
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PMID:Effects of selective serotonin and serotonin/noradrenaline reuptake inhibitors on extracellular serotonin in rat diencephalon and frontal cortex. 1264 3

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.
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PMID:Treatment of Interictal Depression with Citalopram in Patients with Epilepsy. 1273 34

Treatment of patients with both social anxiety disorder and major depression has been little studied although social anxiety disorder and depression frequently co-occur. Each disorder has been shown to respond to serotonin reuptake inhibitor treatment. Objectives of this study were to characterize a sample of these comorbid patients and to assess response to treatment with citalopram. Patients with primary DSM-IV generalized subtype of social anxiety disorder and comorbid major depression (N = 21) were assessed for symptoms of each disorder, including atypical depressive features, and functional impairment. Patients were treated with a flexible dose of open label citalopram for 12 weeks. Response rates for the intention-to-treat sample at week 12 were 14/21 (66.7%) for social anxiety disorder and 16/21 (76.2%) for depression. All continuous measures of social anxiety, depression, and functional impairment improved significantly with treatment, but depression symptoms responded more rapidly and more completely than social anxiety symptoms. Mean dose of citalopram at study endpoint was 37.6 mg/day. Only three patients (14.3%) fulfilled DSM-IV criteria for atypical features of depression, although 18 (85.7%) fulfilled the criterion for interpersonal rejection sensitivity. Citalopram treatment may benefit patients with primary social anxiety disorder and comorbid major depression, and it should be further studied in controlled trials. Improvement in social anxiety disorder symptoms lagged behind improvement in depression, and greater than 12 weeks of treatment may be required to assess full social anxiety response in patients with comorbid depression. The overlap of social anxiety disorder with atypical features of depression may primarily be due to the shared feature of rejection sensitivity.
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PMID:Citalopram treatment of social anxiety disorder with comorbid major depression. 1282 Jan 74

Citalopram (20 mg/day for 42 days) was given to 20 patients (mean age 54.4+/-2.5 years) with depression after myocardial infarction. This was associated with substantial antidepressive effect (50% and more lowering of the total score of the Beck depression questionnaire) in 89% of patients, reduction of number and severity of somatic complaints, and improvement of parameters of quality of life. Citalopram did not affect blood pressure and according to Holter ECG monitoring data produced no arrhythmogenic or proischemic effects. Overall tolerability of citalopram was good however 21% of patients experienced slight drowsiness, dizziness or sweating.
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PMID:[Clinical effectiveness and safety of citalopram in patients with depression after myocardial infarction]. 1289 Dec 83

Citalopram is a highly selective serotonin reuptake inhibitor (SSRI) that has been prescribed to >30 million patients in >70 countries. The purpose of this focused overview is to summarize the data from well-controlled clinical trials and published literature relative to the safety of citalopram in patients with depression and depressive symptoms. This overview is based mainly on 3 sources: (1) data from clinical trials sponsored by Forest Laboratories, (2) published clinical studies, and (3) case reports. Both pharmacokinetic and pharmacodynamic interactions were scrutinized, as were data on special populations and safety concerns. The available data suggest that citalopram 20-60 mg once daily is safe for patients with depression. Few drugs appear to interact with citalopram in a clinically meaningful way. Well-designed short- and long-term trials demonstrate an overall safety/side effect profile consistent with other SSRIs. The more frequent adverse events (nausea, somnolence, dry mouth, increased sweating) are mainly transient, mostly mild to moderate in severity, and observed consistently across studies at rates similar to other SSRIs. Analysis of laboratory values, ECG, and vital signs revealed no unusual findings. Only a small, clinically unimportant reduction in heart rate was observed, similar to that seen with other SSRIs. Citalopram treatment did not increase risk of suicide, overdose, seizure, or arrhythmia. Thus, the pharmacodynamic, pharmacokinetic, and safety profiles of citalopram demonstrate that it is safe for use in adults with depression and depressive symptoms, including the elderly and patients with mild to moderate renal and hepatic disease.
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PMID:Overview of the safety of citalopram. 1456 52

Hepatitis C affects an estimated 4 million Americans and 100 million people worldwide. Rates of depression are higher than that seen in the general population. Antidepressant therapy is often initiated at lower doses in patients with liver disease because of concerns about impaired metabolism and clearance. This study assessed plasma levels of citalopram in 15 subjects with hepatitis C and major depression during an 8-week trial. The mean citalopram dose at study completion was 26.67 mg/day. Mean plasma levels of citalopram, compared with levels previously reported, were lower than expected (at 10 mg/day [N = 1]: 21 ng/ml [N = 1]; at 20 mg/day [N = 8]: mean = 42.25 ng/ml, SD = 18.38; at 30 mg/day [N = 1]: 54 ng/ml; at 40 mg/day [N = 5]: mean = 76.2 ng/ml, SD = 35.86). There was a tendency for lower plasma levels to be found in those subjects receiving interferon, although a statistically significant difference was not observed. Citalopram was well tolerated. The results of this study suggest that patients with major depression and hepatitis C, but without evidence of severe liver disease, may be able to tolerate usual recommended doses of citalopram, thus avoiding the potential for undertreatment of the depression.
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PMID:Plasma levels of citalopram in depressed patients with hepatitis C. 1470 58


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