Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Citalopram is an antidepressant belonging to a new class of drugs which enhance serotoninergic neurotransmission through potent and selective inhibition of serotonin reuptake. Preliminary trials suggest that its short term therapeutic efficacy is significantly greater than that of placebo and mianserin, and comparable to that of amitriptyline, maprotiline and imipramine. It appears to be a weaker antidepressant agent than clomipramine, but better tolerated. Its elimination half-life of 33 hours permits once daily oral administration. Symptomatic improvement obtained with short term treatment has been maintained when therapy has been extended for up to 1 year; in the few patients studied for this extended period, the relapse rate was lower than with fluvoxamine, fluoxetine or imipramine. Compared to standard antidepressant agents, citalopram is well tolerated. It does not appear to be cardiotoxic, has not been associated with seizures in humans, and is relatively nonsedating. Unlike the tricyclic antidepressants, citalopram has minimal anticholinergic effects. Mild and transient nausea, with or without vomiting, is the most frequent adverse effect--occurring in 20% of patients--and increased perspiration, headache, dry mouth, tremor and insomnia are experienced by 15 to 18% of patients. Citalopram thus offers similar therapeutic efficacy and a more favourable tolerability profile than the tricyclic antidepressants. Preliminary data suggest that it may be particularly useful in patients who cannot tolerate the anticholinergic or cardiovascular side effects of tricyclic antidepressants and in those for whom sedation is not indicated.
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PMID:Citalopram. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness. 171 47

Citalopram, a selective 5-HT uptake inhibitor with antidepressant properties, was assessed in three studies in 12 healthy subjects using a battery of EEG, psychological, subjective and symptomatic measures. Study A involved the administration of citalopram, 20 mg and 40 mg, amitriptyline 50 mg and placebo in single dose using a balanced cross-over design. The test battery was applied before, and 1 and 3 h after each drug. Citalopram decreased slow-wave EEG activity whereas amitriptyline increased power in most EEG wavebands. Citalopram increased tapping rate and symbol copying whereas amitriptyline impaired these and other psychomotor tasks. Subjectively, amitriptyline was much more sedative than citalopram and produced more complaints of dry mouth. Study B comprised the administration of citalopram in the usual clinical dose of 40 mg, amitriptyline in the low clinical dose of 75 mg and placebo, each given for 9 nights using a balanced cross-over design. The test battery was applied on the first morning (pre-drug) and on the morning after the last nightly dose. None of the physiological tests showed any drug effects. Subjectively, citalopram was associated with feelings of shaking, nausea, loss of appetite and physical tiredness; amitriptyline produced feelings of shaking, nausea, loss of appetite, dryness of mouth, irritability, dizziness and indigestion; in general, amitriptyline effects were more marked than those of citalopram. Plasma samples were taken on the last day and plasma concentrations of both drugs and their metabolites were found to be in the expected range for the regimens used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of citalopram in single and repeated doses and with alcohol on physiological and psychological measures in healthy subjects. 346 75

Since citalopram was first approved in 1989, it has been prescribed to an estimated > 600 000 patients. An integrated safety database has been prepared, including data from 3107 patients from 24 clinical trials. In placebo-controlled trials, nausea, dry mouth, somnolence, increased sweating, tremor, diarrhoea, and ejaculation failure, mostly of mild to moderate severity, occurred significantly (p < 0.05) more frequently with citalopram. The excess incidence of these events over placebo was always less than 10%. In pooled comparative studies, citalopram's tolerability profile was similar to that of other selective serotonin reuptake inhibitors (SSRIs) and superior to that of tricyclic antidepressants (TCAs). Spontaneous adverse event reports arising from clinical use have confirmed the safety profile defined during the trials programme. Specific monitoring of all serious adverse events from around 10 000 patients receiving citalopram in clinical trials (including small open studies) has indicated a low potential for convulsions and extrapyramidal effects. There is no evidence of withdrawal phenomena on abrupt discontinuation, no clinically relevant effects on cardiac or laboratory parameters, and little or no effect on psychomotor function. When taken in overdose alone, citalopram appears to have a relatively wide margin of safety. Citalopram has been well tolerated in both short- and long-term use, and the profile seen in trials has been confirmed in the clinic.
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PMID:The safety and tolerability of citalopram. 873 43

The effect of comedication with fluvoxamine on the plasma concentrations of the enantiomers of citalopram and its metabolites in dextromethorphan/mephenytoin phenotyped patients pretreated with citalopram (CIT) was studied: seven female patients (45.1 +/- 13.9 years) suffering from a major depressive episode [ICD-10: F32.2 (n = 3 patients), F33.2 (n = 2), F32.10 (n = 1) or F32.11 (n = 1)], who were non-responders to a 3-week treatment with 40 mg/day CIT (From day-21 to day 0) (day 0: MADRS score > or = 12), were co-medicated for another 3 weeks with fluvoxamine (50 mg/day from day 1-7, 100 mg/day from day 14-21). All patients were extensive metabolizers of mephenytoin (CYP2C19) and dextromethorphan (CYP2D6), except one patient, who had a genetic deficiency of CYP2D6. There was a significant increase of the plasma concentrations of S- and R-citalopram from day 0 (27 +/- 14 micrograms/l and 55 +/- 23 micrograms/l, respectively) to day 21 (83 +/- 38 micrograms/l and 98 +/- 44 micrograms/l, respectively), after addition of fluvoxamine (P < 0.02, for each comparison), and the mean ratio S/R-citalopram increased from 0.48 to 0.84. S-Citalopram inhibits more potently 5-HT uptake than R-citalopram: therefore, fluvoxamine increases the pharmacologically more active S-citalopram with some stereoselectivity. According to a previous in vitro study, this pharmacokinetic interaction occurs on the level of CYP2C19, but also of CYP2D6 and CYP3A4 which, in contrast to CYP1A2, contribute to the N-demethylation of citalopram and which are stereoselectively inhibited by fluvoxamine. All but one patient showed clinical improvement by a decrease of the MADRS score by at least 50% and a final score < or = 13 (mean +/- SD: day 0:30.6 +/- 9.2; day 21:11.0 +/- 6.5). Some patients showed minor symptoms, such as nausea and tremor, but the combined treatment was generally well tolerated.
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PMID:Non-response to citalopram in depressive patients: pharmacokinetic and clinical consequences of a fluvoxamine augmentation. 898 13

A meta-analysis of 20 short term comparative studies of 5 selective serotonin reuptake inhibitors (SSRIs; citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) has shown no difference in efficacy between individual compounds but a slower onset of action of fluoxetine. There were suggestions that fluoxetine caused more agitation, weight loss and dermatological reactions than the other SSRIs. More patients discontinued fluvoxamine and fewer patients stopped sertraline because of adverse effects than their comparator SSRIs. The most common adverse reactions to the SSRIs were gastrointestinal (especially nausea) and neuropsychiatric (particularly headache and tremor). Data from the Committee on Safety of Medicines showed more reports of suspected reactions (including discontinuation reactions) to paroxetine, and of gastrointestinal reactions to fluvoxamine and paroxetine, than the other SSRIs during their first 2 years of marketing. Prescription-event monitoring revealed a higher incidence of adverse events related to fluvoxamine than its comparators. There were higher incidences of gastrointestinal symptoms, malaise, sedation and tremor during treatment with fluvoxamine and of sedation, tremor, sweating, sexual dysfunction and discontinuation reactions with paroxetine. Fluoxetine was not associated with a higher incidence of suicidal, aggressive and related events than the other SSRIs. Patients have survived large overdoses of each of the compounds, but concern has been expressed over 6 fatalities following overdoses of citalopram. Drug interactions mediated by cytochrome P450 enzymes are theoretically less likely to occur during treatment with citalopram and sertraline, but there is a sparsity of clinical data to support this. Methodological difficulties and price changes do not allow choice for recommendations on the choice of SSRI based on pharmacoeconomic data. Taking into account the strengths and weaknesses of the methods used to compare drugs, guidelines to the selection of individual SSRIs in clinical practice are proposed. Citalopram should be avoided in patients likely to take overdoses. Fluoxetine may not be the drug of first choice for patients in whom a rapid antidepressant effect is important or for those who are agitated, but it may have advantages over other SSRIs in patients who are poorly compliant with treatment and those who have previously had troublesome discontinuation symptoms. Fluvoxamine, and possibly paroxetine, should not be used as first choice in patients especially prone to SSRI-related adverse reactions, while paroxetine should be avoided if previous discontinuation of treatment was troublesome. When in doubt about the risks of drug interactions, citalopram or sertraline should be considered given the lower theoretical risk of interactions.
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PMID:Systematic review and guide to selection of selective serotonin reuptake inhibitors. 1065 95

Idiopathic Parkinson's disease (IPD) is characterized by motor signs such as akinesia, rigidity, and often tremor at rest. In addition to these symptoms, depression is a common finding affecting 40% of patients with IPD. This study evaluates the effect of the selective serotonin reuptake inhibitor, citalopram, on motor and nonmotor symptoms of depressed and nondepressed patients with IPD. Forty-six nondemented patients with IPD (24 men, 22 women; mean age 64 +/- 5.3 years; mean +/- SD disease duration, 6.4 +/- 3.2 years; mean +/- SD Hoehn-Yahr stage, 2.8 +/- 1.2) were included in the study. Patients were divided in two subgroups: depressed (n = 18) and nondepressed (n = 28). Citalopram was added in an unblinded manner, starting with 10 mg/d, and, after a week, increased up to 20 mg/d in the depressed subgroup (n = 18) and in half of the nondepressed subgroup (n = 14). Parkinsonian and depressive symptoms were evaluated before and after 1 and 4 months of treatment. Statistical evaluation was made by analysis of variance for repeated measures. Citalopram did not worsen motor performance in IPD, but improved bradykinesia and finger taps after 1 month and 4 months of treatment both in patients with and without depression (p < 0.05 versus baseline). A clear improvement in mood was also observed in 15 of 16 patients with depression. Although case reports indicate that citalopram can potentially worsen the motor symptoms in patients with PD, to date this effect has not been confirmed. Many of the symptoms, typically associated with depression, can be observed in nondepressed patients with IPD, because signs thought to represent depression can be produced by Parkinson's disease. In this study, we observed that when combined with levodopa, citalopram induces an improvement of motor performance, in particular of subscores 23 and 31 of Unified Parkinson's Disease Rating Scale both in depressed and in nondepressed patients with IPD.
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PMID:The SSRI, citalopram, improves bradykinesia in patients with Parkinson's disease treated with L-dopa. 1185 92

Citalopram, a serotonin reuptake inhibitor (SSRI) is one of the widely used antidepressants. Apart from its antidepressant activity citalopram is also used for anxiety, panic disorders, obsessive-compulsive disorder and behavioral disturbances of dementia. Tremor is the second most common neurological adverse effect in patients receiving treatment with SSRIs. Use of these agents in depressed patients with essential tremor has not been studied. The present study was undertaken to investigate the effect of chronic citalopram treatment on harmaline-induced tremors in rats. Female Sprague-Dawley rats weighing 70+/-2 g were given citalopram in doses of 0, 10, 20 and 40 mg/kg by gavage for 2 weeks. On the 15th day, the rats were given harmaline (10 mg/kg, i.p.) 30 min after the last dose of citalopram. The latency of onset, intensity and duration of tremor and EMG were recorded. Serotonin (5HT) and 5-hydroxy indole acetic acid (5HIAA) were measured in brain stem. Citalopram dose dependently exacerbated the duration, intensity and amplitude of EMG of harmaline-induced tremor. A significant decrease in 5HT turnover (5HIAA/5HT ratio) in the brain stem was observed suggesting a possible role of serotoninergic impairment in citalopram-induced augmentation of harmaline-induced tremor. Clinical implications of these observations warrant further investigation.
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PMID:Citalopram, a selective serotonin reuptake inhibitor augments harmaline-induced tremor in rats. 1521 2

The serotonin toxicity (ST) is a potentially life-threatening adverse drug reaction results from therapeutic drug use, intentional self-poisoning, or inadvertent interactions between drugs. ST can be caused by a single or a combination of drugs with serotonergic activity due to excessive serotonergic agonism on central nervous system and peripheral serotonergic receptors (monoamine oxidase inhibitors, tricyclic antidepressants, SSRIs, opiate analgesics, over-the-counter cough medicines, antibiotics, weight-reduction agents, antiemetics, antimigraine agents, drugs of abuse, H2-antagonist and herbal products). The serotonin toxicity is often described as a clinical triad of mental-status changes (agitation and excitement with confusion), autonomic hyperactivity (diaphoresis, fever, tachycardia, and tachypnea), neuromuscular abnormalities (tremor, clonus, myoclonus, and hyperreflexia) and, in the advanced stage, spasticity; not all of these findings are consistently present. In this article, we describe two cases of ST due to interaction between Citalopram and two CYP2D6 inhibitors: Cimetidine and Topiramate and their clinical resolution after treatment discontinuation.
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PMID:Serotonin toxicity: a short review of the literature and two case reports involving citalopram. 2149 Oct 99