Disease relevance of citalopram

• Citalopram toxicity [1].
• Symptoms and signs of severe citalopram overdose [2].
• The selective serotonin reuptake inhibitors, zimelidine and paroxetine, have shown little effectiveness in neuropathic pain, but small studies in diabetic neuropathy have shown that paroxetine and citalopram have modest effects [3].
• RESULTS: After three and six weeks of treatment, citalopram significantly improved abdominal pain, bloating, impact of symptoms on daily life, and overall well being compared with placebo [4].
• A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome [4].

Psychiatry related information on citalopram

• Common changes in cerebral blood flow in patients with social phobia treated with citalopram or cognitive-behavioral therapy [5].
• INTERVENTION: Combined psychotherapy (8 sessions of cognitive behavior therapy) plus pharmacotherapy (citalopram) [6].
• Patients were matched for sex, age, and phobia severity, based on social anxiety questionnaire data, and randomized to citalopram medication, cognitive-behavioral group therapy, or a waiting-list control group [5].
• These results support the efficacy of citalopram in late-life anxiety disorders [7].
• A proton MRSI study of brain N-acetylaspartate level after 12 weeks of citalopram treatment in drug-naive patients with obsessive-compulsive disorder [8].

High impact information on citalopram

• We investigated the effect of the selective serotonin reuptake inhibitor citalopram on uncontrolled crying in stroke patients in a double-blind placebo-controlled crossover study [9].
• CONCLUSIONS: Common sites of action for citalopram and cognitive-behavioral treatment of social anxiety were observed in the amygdala, hippocampus, and neighboring cortical areas, ie, brain regions subserving bodily defense reactions to threat [5].
• HTR2A encodes the serotonin 2A receptor, which is downregulated by citalopram [10].
• We searched for genetic predictors of treatment outcome in 1,953 patients with major depressive disorder who were treated with the antidepressant citalopram in the Sequenced Treatment Alternatives for Depression (STAR*D) study and were prospectively assessed [10].
• The order of affinities of these drugs was identical in the locus coeruleus and dorsal and median raphe and was characteristic of binding to NETs (desipramine > imipramine > citalopram) [11].

Chemical compound and disease context of citalopram

• OBJECTIVE: Open-label trials with the selective serotonin reuptake inhibitor citalopram suggest that this agent is effective and safe for the treatment of depressive symptoms in children and adolescents [12].
• METHOD: Eighty-five hospitalized patients with at least one moderate to severe target symptom (aggression, agitation, hostility, suspiciousness, hallucinations, or delusions) were randomly assigned to receive either citalopram, perphenazine, or placebo under double-blind conditions for up to 17 days [13].
• Mice treated with the 5-HTT inhibitors showed less right ventricle hypertrophy (ratio of right ventricle/left ventricle + septum = 36.7 +/- 2.0% and 35.8 +/- 1.3% in citalopram- and fluoxetine-treated mice, respectively, vs. 41.5 +/- 1.5% in vehicle-treated mice) and less pulmonary vessel muscularization (p < 0.01) than those receiving the vehicle [14].
• The PTSD subjects participated in a 10-week, double-blind treatment with citalopram (n = 19), sertraline (n = 18), or placebo (n = 7) [15].
• Effects of diazepam, citalopram, methadone and naloxone on PCP-induced stereotyped behaviour and social isolation in the rat social interaction test [16].

Biological context of citalopram

• Citalopram relative to placebo also suppressed differences in heart rate associated with the viewing of pleasant and unpleasant images, but did not alter subject's subjective responses to emotional images [17].
• High affinity recognition of serotonin transporter antagonists defined by species-scanning mutagenesis. An aromatic residue in transmembrane domain I dictates species-selective recognition of citalopram and mazindol [18].
• In contrast, 2-week infusion of the SSRI, citalopram, produced a widespread downregulation of SERT-binding sites, independent of any alterations at the mRNA level [19].
• In vitro biotransformation of the selective serotonin reuptake inhibitor citalopram, its enantiomers and demethylated metabolites by monoamine oxidase in rat and human brain preparations [20].
• Sertraline and citalopram show linear and fluoxetine, fluvoxamine, and paroxetine nonlinear pharmacokinetics [21].

Anatomical context of citalopram

• Significant increases in N-acetylaspartate level were detected in the prefrontal cortex and frontal white matter in OCD patients after 12 weeks of citalopram treatment [8].
• The metabolism of citalopram, of its enantiomers and demethylated metabolites was investigated in rat brain microsomes and in rat and human brain mitochondria [20].
• Citalopram also reduced responses within the hippocampus and medial prefrontal cortex (mPFC) specifically during the fear-relevant stimuli [22].
• CONCLUSION: The amount of citalopram and other selective serotonin inhibitors (SSRIs) passed to breast milk and delivered to the child correlates to the serum concentration of the mother [23].
• 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 [24].

Associations of citalopram with other chemical compounds

• Despite a pronounced increase in plasma prolactin and two subjects reporting hot flushes compatible with an 5-HT-induced adverse effect, cortical [18F]altanserin binding was insensitive to the citalopram challenge, even after pindolol pretreatment [25].
• At baseline, all patients met the criteria for a major depressive episode according to DSM-IV and had received citalopram or paroxetine during a minimum of 4 weeks without responding to the treatment [26].
• These results suggest that the time course of the gradual return of presumed 5-HT neuronal firing activity, which was reported to account for the delayed effect of SSRI on 5-HT transmission, is congruent with the earlier onset of action of escitalopram vs citalopram in validated animal models of depression and anxiety [27].
• Receipt of amitriptyline or sertraline as initial medication was associated with a per capita increase (p < or = 0.05) in health service utilization (17% and 9%, respectively) relative to citalopram [28].
• In total, 357 outpatients with MDD were randomized to treatment with reboxetine 8-10 mg or citalopram 20-40 mg per day during 24 weeks [29].

Gene context of citalopram

• Citalopram produces mild inhibition of CYP2D6 [30].
• Here, we report the inhibitory effects of various antidepressants: imipramine, desipramine, amitriptyline, nortriptyline, clomipramine, maprotiline, and citalopram, on GIRK channels [31].
• In contrast, citalopram (10 mg/kg i.p., twice daily for 28 days) caused a 100% increase in (125)I-PYY binding in CA, CA3 and DG while levels of preproNPY mRNA and extracellular NPY in the hippocampus were unaffected [32].
• We had previously reported an association between variation on the SERT gene (SLC6A4) and clinical remission after citalopram treatment [33].
• Metabolism of citalopram enantiomers in CYP2C19/CYP2D6 phenotyped panels of healthy Swedes [34].

Analytical, diagnostic and therapeutic context of citalopram

• METHOD: Unmedicated euthymic women with a history of major depression and matched comparison subjects with no history of depression were given a facial expression recognition task following intravenous infusion of saline or citalopram (10 mg) in a double-blind, between-group design [35].
• OBJECTIVE: The present study aimed to 1) assess facial expression recognition in subjects with a previous history of major depressive disorder relative to subjects with no history of depression and 2) characterize the effects of acute citalopram infusion on recognition performance for both groups [35].
• METHODS: Citalopram in breast milk and in the serum of a nursing mother and her infant was determined by high-performance liquid chromatography [23].
• Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo [36].
• However, maternal therapeutic drug monitoring of citalopram should be recommended to minimize fetal exposure [37].

References