Citalopram Group Research Articles

Comparison of citalopram and fluoxetine sexual side-effects in male patients referred to psychiatric clinic

Introduction: Selective serotonin reuptake inhibitors (SSRIs) are among the selected medication to treat depression, panic disorder and many other psychiatric disorders. The most common undesirable effects of SSRIs are sexual dysfunctions that may lead to discontinuation of treatment in some patients. This study was conducted to compare sexual side-effects of two common drugs, citalopram and fluoxetine in male patients. Methods: This cross-sectional study was carried out on 60 male patients referred to the psychiatric clinics of Tabriz University of Medical Sciences, Iran, in 2013. They were candidates for SSRIs treatment and the clinic physicians prescribed citalopram or fluoxetine for them. The patients were examined in two groups after taking written informed consent and initial completion of the International Index of Erectile Function (IIEF) questionnaire and no history of sexual dysfunction, considering the inclusion and exclusion criteria. Both citalopram and fluoxetine groups completed IIEF questionnaire again at the end of the first and second months after treatment and statistical analysis was done using SPSS. Results: Sexual dysfunction was observed in both groups in the all sexual function indices and its components. Although there was no significant difference in terms of sexual function components between the two groups, general sexual dysfunction was significantly higher in the fluoxetine group. In both groups, age was inversely related to the general sexual function index. Conclusion: Unlike many other studies suggesting no difference on SSRI sexual side-effects, the present study showed a reduction in sexual function of men taking citalopram and fluoxetine and the reduction was more prominent with fluoxetine.

Effects of antidepressant therapy on serotonin and tryptophan hydroxylase 2 in ovariectomized rats with depressive disorder

Obiective To investigate the effects of antidepressant therapy on whole regulating function of serotonin and tryptophan hydroxylase 2 system in ovariectomized(OVX) rats with depressive disorder. Methods seventy-two female Sprague-Dawley rats were used as subjects.The rats were randomly divided into 8 groups as following: Sham operation group (Sn), depression group(Dn), the OVX group(On), OVX with depression group(ODn), OVX with depression+ sertraline group(ODs), OVX with depression+ citalopram group(ODx), OVX with depression+ venlafaxine group(ODw) , OVX with depression+ reboxetine group(ODr). Rats in group OVX and group OVX with depression were ovariectomized.Rats in group with depression were exposed to the chronic unpredictable mild stress (CUMS). Open-field test and sugar consumption experiment were tested on all rats before the experiment and the 28th day of experiment.The expression of TPH2 mRNA was measured with RT-PCR, and the expression of TPH2 protein was detected by Western blot.The concentration of 5-HT was detected by ELISA. Results (1) After exposure of CUMS, the scores of motion and percentage of sugar consumption experiment in Dn group were decreased contrast to the Sn group(P<0.05) , and the scores in ODn group were decreased compared with the on group(P<0.05). (2)The protein and gene expression of THP2 in On and Dn group were decreased contrast to the Sn group (P<0.05). The protein and gene expression of THP2 in ODn were decreased compared with the on group (P<0.05). The protein and gene expression of THP2 in ODs(protein (0.68±0.07); gene (0.87±0.09)), ODx(protein (0.71±0.05); gene (0.84±0.17)), ODw(protein (0.69±0.04); gene (0.88±0.16)) and ODr(protein (0.53±0.07); gene (0.70±0.15)) were increased compared with the ODn(protein (0.31±0.09); gene (0.56±0.16)) group(P<0.05). (3)The concentration of 5-HT of hippocampus and serum in Dn and On group were decreased contrast to the Sn group (P<0.05). The concentration of 5-HT of hippocampus and serum in ODs, ODx, ODw and ODr group was increased compared with the ODn group (P<0.05). Conclusion The antidepressants can up-regulate the expression of THP2 and the concentration of 5-HT in the OVX rats with depressive disorder.Sertralin is stronger however Reboxetine Mesylate is the poorest. Key words: Antidepressant; Depressive disorder rats model; Ovariectomized rats model; Tryptophan hydroxylase 2; 5-hydroxytryptamine

Citalopram attenuates tau hyperphosphorylation of cortex and memory deficits in social isolation-reared rats

Objective To explore the effect of citalopram on tau phosphorylation and memory deficits induced by social isolation (SI) in adult rats. Methods Sixty Sprague-Dawley adult rats (8 months) were grouped or isolation reared for six-weeks. Following the initial two-week period of rearing, citalopram (10 mg/kg, i.p.) was administered for 4 weeks. Novel object recognition test, Western blot and ELISA were used to detect recognitive function, the levels of tau and GSK-3β protein, and melatonin level respectively. Results In the novel object recognition test, compared with the citalopram group(0.71±0.05) and housed group(0.73±0.13), discrimination ratio(0.48±0.15) in SI group was significant decreased (P<0.05). Tau hyperphosphorylation at Tau-1 ((0.88±0.11)), Ser396 (3.94±0.74) episodes were found and almost reversed by citalopram at Tau-1 (1.56±0.17), Ser396 (2.31±0.24) episodes in SI group. Compared with GH group, the total level of GSK-3β(1.12±0.09) was significantly increased, while the level of Ser9-phosphorylated GSK-3β (inactive form) (0.47±0.11) was significantly decreased in the SI group, both of which were reversed by citalopram (GSK-3β (0.87±0.08) and Ser9-phosphorylated GSK-3β (0.80±0.07)). The melatonin level was decreased in SI group ((359.54±18.80)pg/ml), and citalopram could partly restore the level of melatonin (418.15±18.72)pg/ml, P<0.05). Conclusion The results demonstrate that citalopram increases the level of melatonin which negatively regulates GSK-3β and attenuates tau hyperphosphorylation and memory deficits induced by SI in adult rats. Key words: Social isolation; tau protein; Citalopram; Alzheimer's disease; Melatonin

Comparison of citalopram and venlafaxine's role in treating sleep disturbances in menopausal women, a randomized, double-blind, placebo-controlled trial.

Sleep disturbance is a common complaint in postmenopausal women. Few studies compared symptom improvement taking antidepressants versus placebo. This study aims to evaluate the efficacy of venlafaxine and Citalopram compared to placebo in treatment of sleep disturbance in healthy postmenopausal women. This randomized, double-blind, placebo-controlled clinical trial was conducted in three groups of 20 postmenopausal women. The patients took venlafaxine 75 mg/daily (group I) or citalopram 20 mg/d (group II) or placebo (group III). Each patient filled Pittsburgh sleep quality index (PSQI) and Pittsburgh and Beck depression questionnaires. The frequency of hot flashes in a day and its severity were measured through diaries. Somatic symptoms and adverse side effects were evaluated. Follow-up visit was conducted after 3 months. The prior and the later results were compared. The PSQI scores in three placebo, venlafaxine, and citalopram groups before treatment were 14.25 ± 3.85, 11.55 ± 3.96, and 13.50 ± 3.56, respectively (p = 0.076). These values after treatment reached 9.95 ± 5.07, 8 ± 3.06, and 6.95 ± 1.84, respectively. PSQI score in citalopram and venlafaxine group was not significantly different (p = 0.19) but the score in both groups was significantly lower compared with placebo group after treatment (p = 0.01). The frequency of hot flashes in a day was reduced significantly by both citalopram and venlafaxine (p < 0.05), although it was more reduced by citalopram than venlafaxine (p = 0.03). Severity of hot flashes in both venlafaxine and citalopram was significantly lower in comparison with placebo group (p = 0.02), and there was no significant difference between two drugs, though (p = 0.84). Beck score decreased more in venlafaxine group in comparison with other groups but it did not reach significant (p = 0.06). Citalopram and venlafaxine are equally more effective than placebo in reducing sleep disturbance and severity of hot flashes, while citalopram is more effective in reducing frequency of hot flashes than venlafaxine. Meanwhile, venlafaxine is more effective than citalopram in treatment of depression in postmenopausal women. Iranian Registry of Clinical Trials 201210152576N6.

Poorer Drinking Outcomes with Citalopram Treatment for Alcohol Dependence: A Randomized, Double-Blind, Placebo-Controlled Trial.

Previous research on the use of selective serotonin reuptake inhibitors (SSRIs) as a treatment for alcohol dependence has yielded mixed results. Depression has been shown to be a predictor of relapse and poor outcome following treatment, and it has been hypothesized that SSRIs would be beneficial in reducing drinking in depressed alcohol-dependent individuals. This randomized, double-blind, placebo-controlled trial was designed to test the effects of citalopram on treatment outcomes among alcohol-dependent individuals with and without depression. Two hundred and sixty-five patients meeting criteria for a DSM-IV diagnosis of alcohol abuse or dependence were randomly assigned to receive placebo or citalopram 20 mg per day for the first week, followed by 40 mg per day from weeks 2 through 12. All patients received a standard course of treatment consisting of weekly individual and group psychotherapy. Participants were reassessed at 12 weeks, including dropouts from both treatment groups to determine rates of abstinence, changes in alcohol use, addiction severity, depressive symptoms, and psychiatric status. Citalopram provided no advantage over placebo in terms of treatment outcomes, and for some measures, citalopram produced poorer outcomes. Patients in the citalopram group had a higher number of heavy drinking days throughout the trial, and smaller changes in frequency and amount of alcohol consumption at 12 weeks. There was no influence of depression severity on outcomes in either medication group. Survival analyses also indicated no differences between depressed and nondepressed patients in the citalopram group for time to first slip or relapse. A diagnosis of personality disorder was associated with poorer treatment responses overall, regardless of treatment condition. This trial does not support the use of citalopram in the treatment of alcohol dependence. The results suggest that the use of SSRIs among depressed and nondepressed alcohol-dependent individuals early in recovery, prior to the onset of abstinence, may be contraindicated.

Double-Blind Randomized Clinical Trial of the Efficacy of Venlafaxine Versus Citalopram in the Treatment of the Acute Phase of Major Depressive Disorder.

Background:There are many antidepressant medications with different side-effects and efficacy profiles.Objectives:In this study, we compared the efficacy of citalopram and venlafaxine in major depression, which has not yet been studied in Iran.Patients and Methods:In this double-blind, randomized controlled trial study, 39 patients aged 18-54 year old with major depressive disorder were randomly allocated into two groups in Yazd City, Iran, between March 2011 and December 2012. A total of 16 patients were treated with velafaxine and 23 patients were treated with citalopram for 8 weeks. Hamilton Depression Rating Scale (HDRS) questionnaire was used for monitoring depression severity. Data were analyzed by SPSS version 20.0 software using Mann Whitney U test and chi-square statistical tests.Results:The HDRS scores were decreased significantly in each group after 8 weeks of treatment (P = 0.001). However, there was no significant difference considering the score of HDRS (P = 0.110). Ten patients in the venlafaxine group and two patients in the citalopram group stopped using medication, all due to nausea or vomiting, or both, and the rate of these two side-effects was significantly higher in the venlafaxine group (P = 0.010).Conclusions:The efficacy of venlafaxine and citalopram are almost the same, but compliance for the use of medication, such as nausea and vomiting, in patients using venlafaxine is much higher than the citalopram group. Therefore, this implies that citalopram could be a safer antidepressant for patients suffering from major depression.

No difference between citalopram plus naltrexone, naltrexone alone for depression with alcohol use

Adding the selective serotonin reuptake inhibitor (SSRI) citalopram to naltrexone and clinical case management for patients with co‐occurring major depression and alcohol dependence did not result in significant improvement over placebo in a study of 138 adults. Both the citalopram and placebo groups experienced substantial improvements in mood and drinking outcomes in the 12‐week study.

Role of citalopram in the treatment of agitation in Alzheimer's disease.

Neuropsychiatric symptoms (NPS) are common among individuals with Alzheimer's disease (AD), associated with excess morbidity and mortality, greater healthcare use, earlier institutionalization, and caregiver burden. Agitation presents as emotional distress, excessive psychomotor activity, aggressive behaviors, disruptive irritability and dishibition. There is an unmet need to find pharmacologic treatment for agitation in patients with AD that can be safely and effectively used as a concurrent treatment alongside psychosocial interventions. A recent, multicenter, randomized, placebo-controlled trial explored the efficacy of a 30-mg daily dose of citalopram for agitation in patients with AD and showed a significant decrease in agitation for citalopram compared with placebo. Both QTc prolongation and cognitive worsening, as measured by the Mini Mental State Examination, were observed in the citalopram group and present a concern to clinicians. Citalopram at a 20-mg daily dose should be considered as a possible first-line treatment in addition to psychosocial intervention.

Citalopram for pediatric functional abdominal pain: a randomized, placebo-controlled trial.

Antidepressants are effective in adults with pain-related functional gastrointestinal disorders. We investigated the effectiveness of citalopram in the treatment of childhood functional abdominal pain (FAP). Children with FAP, based on the Rome III criteria (n = 115, aged 6-18 years), were randomized to receive either citalopram 20 mg/day or placebo for 4 weeks. Treatment response was defined as ≥ 2 point reduction in the 6-point Faces pain rating scale or 'no pain'. Depression, anxiety, somatization, and physician-rated global severity and improvement were also evaluated. Patients were followed up for 8 weeks after medication period. Eighty-six patients completed the medication (43 in each group). Response rate in the citalopram and placebo groups based on per-protocol (intention-to-treat) analysis was 55.8% (40.6%) and 39.5% (30.3%) at week 4 (p = 0.097 [0.169]) and 72.0% (52.5%) and 53.4% (41.0%) at week 12 (p = 0.059 [0.148]), respectively. In per-protocol analysis, more reduction was observed in pain (F = 3.84, p = 0.024) and global severity scores (F = 4.12, p = 0.021) in the citalopram group compared with the placebo group over the study period. Such differences were not present in the intention-to-treat analysis. No difference was found between the two groups regarding change in depression, anxiety, or somatization score over the study. Overall, we found a trend toward the effectiveness of citalopram in the treatment of children with FAP. Trials with longer treatment duration in larger samples of patients are required in this regard.

A single dose of antidepressant alters eye-gaze patterns across face stimuli in healthy women.

Early neurocognitive changes in emotional processing are seen following SSRI administration, which may be involved in mechanisms of action. However, the perceptual processes underpinning these effects have not been specified. In a double-blind, placebo-controlled eye-tracking study, we assessed the effect of single dose of citalopram (20mg) in 25 healthy females. Face stimuli with direct and averted gaze were presented while visual scan patterns and pupil sizes were monitored. Subjective state was monitored using visual analogue scales. There were no significant effects of citalopram on subjective state. However, the citalopram group displayed increased saccade numbers and shorter fixation duration during face viewing compared to the placebo group. Volunteers receiving citalopram also showed reduced monitoring of the eye region irrespective of the direct or averted eye position of the stimuli. The citalopram group also showed significantly larger pupil sizes than the control group. These results suggest that the SSRI administration affects the perceptual processing of face stimuli. The current pattern of findings is consistent with anxiogenic-like mechanisms early on in SSRI treatment. Eye-tracking provides a novel method to characterise and detect these effects.

Evaluation of the effect of selective serotonin reuptake inhibitors on bone mineral density: an observational cross-sectional study

SummarySixty patients diagnosed with generalized anxiety disorder and treated with either paroxetine, sertraline, or citalopram for at least 12 months were enrolled in this study, and the bone mineral density (BMD) of the patients was compared with that of 40 healthy volunteers. Selective serotonin reuptake inhibitor (SSRI) therapy in generalized anxiety disorder was found to be related with decreased BMD values.IntroductionThe objectives of this study were to evaluate the effect of SSRI therapy on BMD in postmenopausal women diagnosed with generalized anxiety disorder (GAD) and to identify the effects of the duration of disease and treatment on risk factors for osteoporosis.MethodsSixty patients diagnosed with GAD and treated with paroxetine, sertraline, or citalopram from the SSRI group for at least 12 months were enrolled. Social demographic features, the Hamilton Anxiety Scale (HAS) results, and the Hamilton Depression Scale (HDS) scores of all the patients were assessed. The BMD of the patients was measured by dual-energy X-ray absorptiometry (DXA) at the femoral and lumbar regions. The patients were divided into three groups which are the paroxetine, sertraline, and citalopram groups. The BMD of the patients was compared with that of 40 healthy volunteers.ResultsThe L2–L4, total lumbar vertebrae, femoral intertrochanteric, total femoral Z-scores, and femoral Ward’s region T-scores of the treatment group were lower than the median T- and Z-scores of the control group (p < 0.05). Of the treatment groups, the femoral neck, trochanteric and intertrochanteric T- and Z-scores, total femoral T- and Z-scores, and femoral Ward’s T- and Z-scores of the sertraline group were significantly lower than the BMD values measured at the identical regions in the paroxetine and citalopram groups (p < 0.05).There was a significant negative correlation between the duration of treatment and the BMD values.ConclusionSSRI therapy in GAD was found to be related with decreased BMD values. Further randomized controlled studies are warranted to determine whether SSRI use is a risk factor for osteoporosis; such studies should investigate these factors by performing BMD assessments before treatment.

Antidepressant Reduces Amyloid Load, Study Finds

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessAntidepressant Reduces Amyloid Load, Study FindsJoan Arehart-TreichelJoan Arehart-TreichelSearch for more papers by this authorPublished Online:3 Jul 2014https://doi.org/10.1176/appi.pn.2014.7a15AbstractAntidepressants have lowered levels of beta-amyloid in laboratory animals and some human volunteers, but future studies will have to determine whether the drugs can help prevent Alzheimer’s disease.The notion that antidepressants can prevent Alzheimer’s disease sounds almost too good to be true. Yet some animal work and human pilot research suggest that this is a possibility.In research headed by Yvette Sheline, M.D., a professor of psychiatry at the University of Pennsylvania, tiny probes were implanted in the brain memory centers—the hippocampi—of mice modeled to have Alzheimer’s. Some of the mice were given the SSRI antidepressant citalopram in 2.5 mg/kg doses, others in 5 mg/kg doses, and still others in 10 mg/kg doses. Fluid from their hippocampi was drawn before antidepressant administration and 24 hours after to measure the levels of beta-amyloid—a hallmark of Alzheimer’s disease—in that brain region. The results were published May 14 in Science Translational Medicine.Lower levels of beta-amyloid, a hallmark of Alzheimer’s disease, were found after administration of certain doses of the antidepressant citalopram.Molekuul.be/Shutterstock.comThere was no change in the levels of beta-amyloid in the mice that had been given the 2.5 mg/kg doses. But there were significantly lower levels in the mice that had been given the 5 mg/kg or the 10 mg/kg doses. The 10 mg dose is comparable to 50 mg/day in humans—a “common, though high, dose of citalopram prescribed to treat depression,” the researchers noted.The researchers then gave mice modeled to have Alzheimer’s either 10 mg/kg of citalopram or a placebo for 28 days. The animals’ brains were imaged before and after antidepressant or placebo administration to determine the number of beta-amyloid plaques present.Antidepressant treatment reduced the number of newly appearing plaques significantly more than placebo treatment did. Moreover, the rate of growth in existing plaques was significantly less in the antidepressant group than in the placebo group. Finally, the researchers gave 23 human volunteers aged 18 to 50 with no medical disease or history of antidepressant use either a 50 mg dose of citalopram or a placebo, then took cerebrospinal fluid samples from each volunteer before, during, and up to 45 hours after treatment to assess levels of beta-amyloid in the two groups. Beta-amyloid production in the cerebrospinal fluid was slowed by 37 percent in the citalopram group compared with the placebo group. This change was associated with a 38 percent decrease in total cerebrospinal fluid concentration in the antidepressant group.“The ability to decrease central nervous system beta-amyloid concentrations is thus potentially important as a preventive strategy for Alzheimer’s disease,” Sheline and her colleagues said in their report.“It has to be emphasized that these were not clinical studies and that no treatment recommendations can be based on these preliminary reports,” Joel Yager, M.D., a professor of psychiatry at the University of Colorado and chair of the APA Council on Quality Care, said in an interview with Psychiatric News. “Additional studies will be required to see whether reductions in beta-amyloid production in fact persist with long-term SSRI treatment in humans, and whether reduced production might actually result in clinically meaningful reductions in plaque formation and cognitive impairment. In addition, studies will have to consider potential adverse effects of long-term chronic SSRI treatments in the elderly. All that said, these results might suggest preventive strategies for future practice,” particularly in those at high risk for Alzheimer’s disease, he noted.The study was funded by the National Institutes of Health, the Washington University Hope Center for Neurological Diseases, and the Washington University Biomedical Mass Spectrometry Resource. ■An abstract of “An Antidepressant Decreases CSF Beta-Amyloid Production in Healthy Individuals and in Transgenic Alzheimer’s Mice” can be accessed here. ISSUES NewArchived

The effects of the estrus cycle and citalopram on anxiety-like behaviors and c-fos expression in rats

In rats, hormonal fluctuations during the estrus cycle may have numerous behavioral and neurobiological consequences. The aim of this study was to investigate the effects of estrus cycles and citalopram on behavior, ultrasonic vocalizations, anxiety levels, and c-fos expression in rats. With this aim, the rats were grouped into two: (1) a control group (n=16) and (2) a citalopram group (n=16), which received daily intraperitoneal 20mg/kg citalopram from baseline (D0) to the 10th day (D10). Behavioral analysis and ultrasonic vocalization (USV) recordings were made on D0 and D10. Next, the rats were further subgrouped according to estrus phases identified through a vaginal smear (8 proestrus rats and 8 non-proestrus rats, in each group). The rat's anxiety levels were analyzed with an elevated plus maze (EPM), and their c-fos expression was measured at the cingulate cortex, the amygdala, and the paraventricular thalamic nucleus. Our results showed that the citalopram group showed significantly more grooming behaviors on D10 than the control group (p=0.002). USVs on D0, D10 and during the EPM did not show any significant differences between the groups. Proestrus rats in the control group showed significantly less anxiety-like behavior during the EPM than the non-proestrus rats in the control group (p=0.028 for time spent in open arms, and p=0.011 for entries into open arms). There was no significant difference in anxiety-like behavior between the control and citalopram groups, and between the proestrus and non-estrous rats in the citalopram group. C-fos expression at the amygdala (p=0.013) and the paraventricular thalamic nucleus (p=0.014) was significantly inhibited in the citalopram group. We concluded that estrus cycles have a significant effect on anxiety levels in rats, which may be suppressed behaviorally and neurobiologically by citalopram.

Changes in QTc interval in the citalopram for agitation in Alzheimer's disease (CitAD) randomized trial.

BackgroundA Food and Drug Administration (FDA) safety communication in August 2011 warned that citalopram was associated with a dose dependent risk of QT prolongation and recommended dose restriction in patients over the age of 60 but did not provide data for this age group.MethodsCitAD was a randomized, double-masked, placebo-controlled, multicenter clinical trial for agitation in Alzheimer's disease (AD). Participants were assigned to citalopram (target dose of 30 mg/day) or placebo in a 1∶1 ratio. 186 people, 181 of whom were over the age of 60, having probable AD with clinically significant agitation were recruited from September 2009 to January 2013. After the FDA safety communication about citalopram, ECG was added to the required study procedures before enrollment and repeated at week 3 to monitor change in QTc interval. Forty-eight participants were enrolled after enhanced monitoring began.ResultsCitalopram treatment was associated with a larger increase in QTc interval than placebo (difference in week 3 QTc adjusting for baseline QTc: 18.1 ms [95% CI: 6.1, 30.1]; p = 0.004). More participants in the citalopram group had an increase ≥30 ms from baseline to week 3 (7 in citalopram versus 1 in placebo; Fisher's exact p = 0.046), but only slightly more in the citalopram group met a gender-specific threshold for prolonged QTc (450 ms for males; 470 ms for females) at any point during follow-up (3 in citalopram versus 1 in placebo, Fisher's exact p = 0.611). One of the citalopram participants who developed prolonged QTc also displayed ventricular bigeminy. No participants in either group had a cardiovascular-related death.ConclusionCitalopram at 30 mg/day was associated with improvement in agitation in patients with AD but was also associated with QT prolongation.Trial RegistrationClinicalTrials.gov NCT00898807

The Efficacy of Citalopram in the Treatment of Functional Abdominal Pain in Children: A Randomized, Double-Blind, Placebo-Controlled Study

Introduction: Limited data are available on the effectiveness of antidepressants in the treatment of functional gastrointestinal disorders in children. We evaluated the effectiveness of citalopram in the treatment of childhood functional abdominal pain (FAP). Material and Methods: Children with FAP (n=115, aged 6-18 years) received either citalopram 20 mg/day or placebo for 4 weeks. Treatment response was defined as ≥ 2 point reduction in the 6-point pain rating scale or “no pain”. Depression, anxiety, somatization, and physician-assessed global severity and improvement were also evaluated. Patients were followed for 8 weeks after medication period. Results: Eighty six patients completed the trial (43 in each group). Treatment response rate in the citalopram and the placebo group was 55.8% and 39.5% at week 4 (P=0.097) and 72.0% and 53.4% at week 12 (P=0.059), respectively. Controlling for baseline characteristics, more reduction was observed in pain (z=-2.67, P=0.008) and global severity scores (z=-3.08, P=0.002) in the citalopram group compared with the placebo group. Changes in depression, anxiety, and somatization scores were comparable between the two groups. Receiving citalopram (OR=7.718, P=0.006), father education level (OR=3.179, P=0.040), baseline pain score (OR=5.621, P<0.001), baseline somatization score (OR=0.863, P=0.017), and change in somatization severity (OR=1.168, P=0.039) were predictors of treatment response at week 4. The association of receiving citalopram and treatment response at week 12 was not statistically significant (OR=2.944, P=0.096). Conclusion: Four-week treatment with citalopram is effective in reducing pain in children with FAP, independent from patients’ baseline psychological status or psychotropic effects of the drug. Keywords: Abdominal Pain, Antidepressive Agents, Child, Serotonin Reuptake Inhibitors, Randomized Controlled Trial.

Differential, but not opponent, effects of l-DOPA and citalopram on action learning with reward and punishment

RationaleDecision-making involves two fundamental axes of control namely valence, spanning reward and punishment, and action, spanning invigoration and inhibition. We recently exploited a go/no-go task whose contingencies explicitly decouple valence and action to show that these axes are inextricably coupled during learning. This results in a disadvantage in learning to go to avoid punishment and in learning to no-go to obtain a reward. The neuromodulators dopamine and serotonin are likely to play a role in these asymmetries: Dopamine signals anticipation of future rewards and is also involved in an invigoration of motor responses leading to reward, but it also arbitrates between different forms of control. Conversely, serotonin is implicated in motor inhibition and punishment processing.ObjectiveTo investigate the role of dopamine and serotonin in the interaction between action and valence during learning.MethodsWe combined computational modeling with pharmacological manipulation in 90 healthy human volunteers, using levodopa and citalopram to affect dopamine and serotonin, respectively.ResultsWe found that, after administration of levodopa, action learning was less affected by outcome valence when compared with the placebo and citalopram groups. This highlights in this context a predominant effect of levodopa in controlling the balance between different forms of control. Citalopram had distinct effects, increasing participants’ tendency to perform active responses independent of outcome valence, consistent with a role in decreasing motor inhibition.ConclusionsOur findings highlight the rich complexities of the roles played by dopamine and serotonin during instrumental learning.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-013-3313-4) contains supplementary material, which is available to authorized users.

Baseline Factors Predicting Placebo Response to Treatment in Children and Adolescents With Autism Spectrum Disorders

The finding of factors that differentially predict the likelihood of response to placebo over that of an active drug could have a significant impact on study design in this population. To identify possible nonspecific, baseline predictors of response to intervention in a large randomized clinical trial of children and adolescents with autism spectrum disorders. Randomized clinical trial of citalopram hydrobromide for children and adolescents with autism spectrum disorders and prominent repetitive behavior. Baseline data at study entry were examined with respect to final outcome to determine if response predictors could be identified. A total of 149 children and adolescents 5 to 17 years of age (mean [SD] age, 9.4 [3.1] years) from 6 academic centers were randomly assigned to citalopram (n = 73) or placebo (n = 76). Participants had autistic disorder, Asperger syndrome, or pervasive developmental disorder, not otherwise specified; had illness severity ratings that were moderate or more than moderate on the Clinical Global Impression-Severity scale; and scored moderate or more than moderate on compulsive behaviors measured with the modified Children's Yale-Brown Obsessive-Compulsive Scale. Twelve weeks of treatment with citalopram (10 mg/5 mL) or placebo. The mean (SD) maximum dose of citalopram was 16.5 (6.5) mg by mouth daily (maximum dose, 20 mg/d). A positive response was defined as having a score of at least much improved on the Clinical Global Impression-Improvement scale at week 12. Baseline measures included demographic (sex, age, weight, and pubertal status), clinical, and family measures. Clinical variables included baseline illness severity ratings (the Aberrant Behavior Checklist, the Child and Adolescent Symptom Inventory, the Vineland Adaptive Behavior Scales, the Repetitive Behavior Scale-Revised, and the Children's Yale-Brown Obsessive-Compulsive Scale). Family measures included the Caregiver Strain Questionnaire. Several baseline predictors of response were identified, and a principal component analysis yielded 3 composite measures (disruptive behavior, autism/mood, and caregiver strain) that significantly predicted response at week 12. Specifically, participants in the placebo group were significantly less likely than participants in the citalopram group to respond at week 12 if they entered the study more symptomatic on each of the 3 composite measures, and they were at least 2 times less likely to be responders. This analysis suggests strategies that may be useful in anticipating and potentially mitigating the nonspecific response in randomized clinical trials of children and adolescents with autism spectrum disorders. clinicaltrials.gov Identifier: NCT00086645.

No Effects of Antidepressants on Negative Symptoms in Schizophrenia

Negative symptoms are common in schizophrenia, but often difficult to differentiate from depression. They are associated with long-term impairment and do not respond well to current treatment approaches. Even though antidepressants are commonly prescribed in schizophrenia, their beneficial effect is still under debate. In the present study, we aimed to investigate the effect of serotonergic versus noradrenergic antidepressant add-on therapy on negative symptoms in schizophrenia. Fifty-eight patients with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and with predominant negative symptoms were randomized in a double-blind design to add-on treatment with citalopram, reboxetine, or placebo for 4 weeks. Analysis of covariance with repeated-measures design was used to compare improvement between treatment groups in scores of the Positive and Negative Syndrome Scale and the Hamilton Rating Scale for Depression. A χ² test was used to compare responder rates between treatment groups. Repeated-measures analysis of covariance revealed no differences between treatment groups over time (treatment × time, not statistically significant) for Positive and Negative Syndrome Scale subscales. Although a subgroup analysis in subjects fulfilling the criteria for minor depression was suggestive of higher responder rates in the citalopram group compared with reboxetine, the results did not reach significance level. Our findings do not support a beneficial effect of adjunctive antidepressant treatment on negative symptoms in schizophrenia. However, depressive symptoms are reduced in patients with minor depression by citalopram but not reboxetine, which is in line with previous findings.

Investigation on the binding activities of citalopram with human and bovine serum albumins

The binding interactions of citalopram (CIT), an efficient antidepressant, with human serum albumin (HSA) and bovine serum albumin (BSA) were investigated by a series of spectroscopic methods including fluorescence, UV–vis absorption, circular dichroism (CD) and 1H nuclear magnetic resonance (1H NMR). The fluorescence quenching and UV–vis absorption studies reveal that CIT could form complexes with both HSA and BSA. The CIT–BSA complex exhibits higher binding affinity than CIT–HSA complex. The thermodynamic study further suggests that the interactions between CIT and SAs are mainly driven by hydrophobic forces and hydrogen bonds. The 1H NMR analysis indicates that the participation of different functional groups of CIT is unequal in the complexation of CIT–HSA and CIT–BSA. Site marker competitive experiments show that the interactions between CIT and SAs primarily locate at sub-domain II A (site I). The effects of CIT on the conformation of SAs are further analyzed via synchronous fluorescence, three-dimensional fluorescence and CD spectra techniques. The results prove that the presence of CIT decreases the α-helical content of both SAs and induces the slight unfolding of the polypeptides of protein. Additionally, the conformational change of BSA induced by CIT is larger than that of HSA.

Pre-symptomatic functional brain changes in PS1 E280A mutation carriers compared to other biomarkers: Pilot data from the Alzheimer's Prevention Initiative Biomarker project

mg of citalopram prior to the start of the central nervous system stable isotope labeling kinetics study of Abeta, as previously described. A lumbar catheter was placed and hourly sampling of blood and CSF was conducted during and after administration of a stable-isotope labeled amino acid (13C6-leucine). Metabolism of Abeta was measured using stable isotope labeling kinetics (SILK-Ab ) assay (as in Bateman et al., 2006) with the addition of stable isotope spike absolute quantitation (SISAQ ) to allow for quantitation of Abeta concentrations (C2N Diagnostics). Results: Placebo (n1⁄4 9) and citalopram (n1⁄4 11) treated subjects did not differ on any demographic variables. Citalopram-treated subjects had significantly lower mean total Abeta concentrations (36.7 +/10.5) ng/mL than placebo-treated (54.6 +/15.5) ng/mL (p 1⁄4 0.007) over the hours 5-36. During the same period there was a trend towards lower newly generated Abeta (p 1⁄4 0.06) in the citalopram group (7.5 +/1.3) ng/mL vs placebo (9.3 +/1.4) ng/mL however the groups did not differ in their fractional synthesis or clearance rates.Conclusions:We corroborate our prior findings in a prospective human study showing that citalopram lowers Abeta concentrations compared with placebo. We had also expected to see a lower rate of Abeta production and a decrease in newly generated Abeta, thus we are currently replicating and extending our results. The ability to decrease Abeta concentrations is potentially important as a preventive strategy for AD.