Citalopram In Major Depressive Disorder Research Articles

Efficacy of empagliflozin as adjunctive therapy to citalopram in major depressive disorder: a randomized double-blind, placebo-controlled clinical trial

BackgroundMajor depressive disorder is one of the most common psychiatric disorders, which is associated with a high disease burden. Current treatments using antidepressants have limitations, so using medication with neuromodulating and anti-inflammatory properties alongside them could be helpful. In a clinical trial, we studied the effectiveness of empagliflozin, a blood sugar-lowering drug, as an adjunctive therapy to reduce the severity of depression symptoms.MethodsA number of outpatients with moderate to severe depression (Hamilton Depression Rating Scale (HDRS) > = 17) who were not under related medication or had not taken medication for at least the last two months, had an age range of 18–60 years and had written informed consent to enter the study (N = 90) were randomly divided into two groups receiving placebo or empagliflozin (10 mg daily) combined with citalopram (40 mg daily) based on permuted block randomization method in an 8-week randomized, double-blind, placebo-controlled clinical trial. They were evaluated using the HDRS in weeks 0, 4, and 8.ResultsHDRS scores were equal to 28.42(± 3.83), 20.20(± 3.82), and 13.42(± 3.42) in the placebo group during weeks 0,4, and 8, respectively. These scores were 27.36(± 3.77), 13.76(± 1.40), and 7.00(± 1.13), respectively, for the group treated with empagliflozin. Compared to the control group, patients treated with empagliflozin using repeated-measures ANOVA showed greater improvement in reducing the severity of depression symptoms over time (p value = 0.0001).ConclusionsConsidering the promising findings in this clinical trial, further study of empagliflozin as adjunctive therapy in MDD with larger sample sizes and longer follow-ups is recommended.

Lavender and dodder combined herbal syrup versus citalopram in major depressive disorder with anxious distress: A double-blind randomized trial

BackgroundMajor depressive disorder (MDD) accompanied by anxious distress is a chronic and disabling disorder. Its conventional drug therapies often have low patient compliance due to drug-related side effects. In Persian medicine, lavender-dodder syrup is one formula often recommended for such disorders. ObjectiveThis study compares the effects of lavender-dodder syrup to the standard drug, citalopram, for treating MDD with anxious distress. Design, setting, participants and interventionThis six-week, double-blind, randomized, clinical trial was carried out in a psychiatric outpatient clinic. During the six-week intervention period, patients in citalopram group received citalopram tablets 20 mg/d plus 5 mL placebo syrup every 12 h; patients in group B received placebo tablets once daily plus 5 mL of lavender-dodder herbal syrup every 12 h. Main outcome measuresPrimary outcome measures, depression and anxiety, were evaluated using the Hamilton Depression/Anxiety Rating Scales, and were scored at the beginning of the study and at weeks three and six. Secondary outcome measures including response to treatment and remission rates were also compared between the two groups. ResultsFifty-six participants with MDD and anxious distress were randomly assigned to two groups. Mean depression scores significantly decreased in citalopram and herbal groups at weeks three and six (time effect: P < 0.001), although the observed changes were not significantly different between the groups (intervention effect: P = 0.61). Mean anxiety scores were not significantly different between the two groups at week three (P = 0.75). However, at the end of week six, the observed decrease was significantly higher in the herbal syrup group than the citalopram group (intervention effect: P = 0.007). ConclusionThe herbal syrup is an effective and tolerable supplement for treating MDD with anxious distress.Trial registration number: IRCT2016102430459N1 on Iranian Registry of Clinical Trials.

Epigenetic regulation of synapsin genes in mood disorders.

The synapsins are a family of neuronal phosphoproteins consisting of SYN1 at chrXp11.3, SYN2 at chr3p25, and SYN3 at chr22q12.3 with alternative splicing leading to as many as 10 isoforms. They are involved in synaptic transmission and plasticity, as well as various stages of neurodevelopment, including axon outgrowth and synapse formation (Cesca et al, 2010). All synapsins are highly concentrated at presynaptic nerve terminals of central neurons and associated with the cytoplasmic surface of synaptic vesicles, but SYN3 has markedly distinct developmental expression and subcellular distribution, suggesting divergent function (Pieribone et al, 2002). Therefore, not surprisingly, a role for synapsins in neuropsychiatry has been suggested and, indeed, several studies have indicated that genetic variants at these genes can be associated with epilepsy, autism, schizophrenia, and bipolar disorder (BD) (Cesca et al, 2010). Furthermore, mRNA- and protein-level postmortem brain studies have suggested dysregulation of these genes in both BD and major depressive disorder (MDD) (Cesca et al, 2010; Cruceanu et al, 2012). Thus, the study of mechanisms responsible for this dysregulation in mood disorders becomes pertinent. In the last few years, evidence has emerged suggesting that epigenetics play a role in neuropsychiatric disorders (Jiang et al, 2008), thus it is plausible that the dysregulation observed in synapsin expression could be attributed in part to epigenetic mechanisms. We found evidence that enrichment of H3K4me3—an epigenetic mark associated with increased transcription—at the promoters of SYN1 and SYN2, but not SYN3 is correlated with increased expression of these genes in the prefrontal cortex of patients with BD and MDD compared with controls (Cruceanu et al, 2012, see Figure 1). These findings are encouraging, but future research should better characterize these mechanisms by exploring the role of other chromatin epigenetic marks and brain-region specificity. In addition, the role of DNA methylation, an equally important epigenetic mechanism, should be investigated. In silico analyses have detected rich CpG islands at the proximal promoters of SYN1 (845 bp) and SYN2 (975 bp), as well as at a distal promoter of SYN3 (613 bp) (Miklem and Hillier, 2012, see Figure 1). To date there is no evidence in the literature of altered DNA methylation at synapsins in mood disorders, although one study of a single schizophrenia patient suggests potentially variably methylated sites in the distal CpG island of SYN3 (Murphy et al, 2008). Interestingly, the CpG islands at SYN1 and SYN2 are immediately preceded by regions of enriched H3K4me3 in mood disorders (Cruceanu et al, 2012, see Figure 1). The same is not true for SYN3, and considering this gene's distinct expression profile and potential implication throughout neurogenesis (Pieribone et al, 2002), perhaps different mechanisms regulate SYN3. The figure illustrates our current knowledge of the synapsin genes' structure, as well as the epigenetic mechanisms that have been identified in psychiatric disorders to date. Figure 1 Potential epigenetic mechanisms at the promoter regions of synapsin genes. Upper panel: the SYN1 gene (chrX:47 431 300–47 479 256). In silico analysis predicts a CpG island 845 bp in size at the 5′end ... In conclusion, brain expression differences seen in synapsin genes in mood disorders may be explained in part by differences in H3K4me3. These results need additional and independent confirmation. Moreover, considering that promoter DNA methylation can modulate gene expression and lead to neuropsychiatric phenotypes, a study of DNA methylation patterns at the synapsin promoters is warranted. On the basis of growing evidence suggesting that epigenetic mechanisms may be involved in altered regulation of synapsins in mood disorders, it would be of interest to study these genes as potential therapeutic targets or biomarkers of treatment response. Evidence is starting to emerge pointing to epigenetic marks as potential biomarkers of treatment response. For instance, for brain-derived neurotrophic factor (BDNF), (Lopez et al, 2010) showed that promoter H3K27me3 levels could serve as a biomarker of response to citalopram in MDD, and (D'Addario et al, 2012) found distinct DNA methylation patterns at the BDNF promoter in BD patients depending on mood-stabilizer and antidepressant therapy. Although no such evidence has yet emerged for synapsins, a recent study showed that lithium, one of the most commonly prescribed drugs for BD, can modulate SYN2 expression in neuronal cell types (Cruceanu et al, 2012). Thus, an investigation of synapsin epigenetics in the brain compared with the periphery would be an interesting next step in elucidating their potential to serve as biomarkers for mood disorders or their treatment.

P02-04 - Area-specific occupancy of the serotonin transporter by escitalopram and citalopram in major depressive disorder

IntroductionThe serotonin transporter (SERT) occupancy after long-term antidepressant treatment (steady-state) at minimum clinical doses has been reported to be approximately 80% (e.g., Meyer 2007, J.Psychiatry Neurosci;32(2):86-102, review). However, this value is mostly calculated in the striatum, therefore the occupancy values in other brain areas might be better associated to clinical parameters.ObjectivesTo compare the SERT occupancy of the striatum to occupancy values in six other brain areas.Methods18 patients with major depressive disorder (MDD) received either escitalpram (10mg/d) or citalopram (20mg/d) in a double-blind, longitudinal study. They underwent three PET scans using the radioligand [11C]DASB: PET1 baseline, PET2 six hours after the first drug intake and PET3 after three weeks of treatment. Occupancy of SERT at PET3 was analyzed in seven regions partly associated with alterations in MDD: striatum, subgenual part of the anterior cingulate cortex (sgACC), ACC, amygdala, inferior frontal cortex (IFC), superior frontal cortex (SFC), superior parietal cortex (SPC). ROI-based quantification was performed in PMOD.ResultsThere was a huge range in occupancy values of different areas: amygdala (93.5% ± 6.9%, mean ± SD), SPC (90.8% ± 8.0%), ACC (86.0% ± 13.2%), sgACC (79.1% ± 23.6%), striatum (78.8% ± 4.9%), SPF (64.0% ± 26.4%), IFC (54.4% ± 21.7%). We found significant differences in occupancy values between striatum and the ACC, amygdala, IFC, SFC, SPC (t-test, p &lt; 0.05).ConclusionsIn this study we show significant differences in SERT occupancy between brain areas ranging between 54.4% and 93.5%. According to the area-specific effects of changes in serotonergic neurotransmission, regional occupancy values, especially in limbic areas, might be considered in the association to clinical response.

Efficacy and safety of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, randomized, double-blind, flexible-dose study

S-citalopram (escitalopram) is the very active moiety of citalopram. It has been shown in many studies to be an effective and safe antidepressant for treating major depressive disorder (MDD). The aim of our study was to compare the efficacy and safety of escitalopram vs citalopram in Chinese MDD patients. In the double-blind study, 240 MDD patients were randomly assigned to treatment for 6 weeks either with escitalopram (10-20 mg/d) or citalopram (20-40 mg/d). The primary efficacy measurement was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the end of study. The secondary efficacy measurements were response and remission rates. The adverse events (AEs) were recorded by the investigator. Two hundred and three (85%) patients completed the trial. The average dose was 13.9 mg/d in the escitalopram group and 27.6 mg/d in the citalopram group. No significant differences were found between the two groups in the change in HAMD-17 total score, response, and remission rate. These results were similar in severe MDD patients. No significant differences were found between the two groups in AEs. No serious AEs were observed in this study. The study suggests that escitalopram 10-20 mg/d are as effective and safe as citalopram 20-40 mg/d in the short-term treatment for Chinese MDD patients.

Differences in the dynamics of serotonin reuptake transporter occupancy may explain superior clinical efficacy of escitalopram versus citalopram

Escitalopram the S-enantiomer of the racemate citalopram, is clinically more effective than citalopram in the treatment of major depressive disorder. However, the precise mechanism by which escitalopram achieves superiority over citalopram is yet to be determined. It has been hypothesized that the therapeutically inactive R-enantiomer competes with the serotonin-enhancing S-enantiomer at a low-affinity allosteric site on serotonin reuptake transporters (SERTs), and reduces the effectiveness of the S-enantiomer at the primary, high-affinity serotonin-binding site. This study summarizes the results of two recent single-photon emission computerized tomography studies measuring SERT occupancy in citalopram-treated and escitalopram-treated healthy volunteers, after a single dose and multiple doses (i.e. under steady-state conditions). The single-dose study showed no attenuating effect of R-citalopram. After multiple dosing, however, SERT occupancy was significantly reduced in the presence of R-citalopram. Under steady-state conditions, R-enantiomer concentrations were greater than for the S-enantiomer because of slower clearance of R-citalopram. A pooled analysis suggests that build-up of the R-enantiomer after repeated citalopram dosing may lead to increased inhibition of S-enantiomer occupancy of SERT. This review adds to the growing body of evidence regarding differences in the dynamics of SERT occupancy, that is, molecular mechanisms underlying the often-observed superior clinical efficacy of escitalopram compared with citalopram in major depressive disorder.

Efficacy and tolerability of escitalopram versus citalopram in major depressive disorder: A 6-week, multicenter, prospective, randomized, double-blind, active-controlled study in adult outpatients

Background: The S-enantiomer of citalopram (escitalopram) is the active moiety linked to the anti-depressant effects associated with citalopram (the racemate). For escitalopram to be approved for the treatment of depression in Europe, findings from clinical trials of escitalopram are required to match previous results from studies of the racemate, citalopram. Objective: The aim of this study was to compare the efficacy and tolerability of escitalopram and citalopram in outpatients with major depressive disorder (MDD). Methods: This prospective, randomized, double-blind, active-controlled study was conducted at 8 psychiatric outpatient clinics in the Federation of Russia. Adult outpatients aged 25 to 45 years with MDD and a total score >25 on the Montgomery-Asberg Depression Rating Scale (MADRS) were eligible. Patients were randomly assigned to receive 6 weeks of treatment with fixed daily doses of escitalopram 10 rag, citalopram 10 rag, or citalopram 20 rag. Efficacy assessments were made at weeks 0 (baseline), 1, 4, and 6 (study end or last observation carried forward). The primary efficacy parameter was the change from baseline in MADRS total score. Secondary measures were the change from baseline in MADRS total score in a subgroup of severely depressed patients (baseline MADRS total score, >35), MADRS core depression subscale score, and Clinical Global Impression-Severity and Improvement (CGI-S and CGI-I) scores; and the proportions of patients classified as responders and remitters at study end. Tolerability was assessed using adverse events (AEs) recorded by the investigator. Results: Of 330 assessable randomized patients, 8 withdrew, including 7 who withdrew consent and 1 who withdrew due to recurrence of a preexisting event. Thus, 322 patients were included in the assessment (mean age, 35 years; 41.6% male; all white; escitalopram 10 rag, 108 patients; citalopram 10 rag, 106; citalopram 20 rag, 108). At study end, the mean (SE) change from baseline in MADRS total score was significantly greater in the escitalopram arm than in the 10- and 20-rag citalopram arms (-28.70 [0.78] vs -20.11 [0.80] and -25.19 [0.78]; both, P < 0.001). Improvements were more marked in the severely depressed subgroup (-30.33 [0.95] vs -20.87 [0.99] and -26.34 [0.91]). Changes in the CGI-S and CGI-I scores and the rates of response and remission were significantly greater in the escitalopram group compared with those in the citalopram 10- and 20-rag groups (CGI-S: -2.60 [0.10] vs -1.61 [0.10] and -2.05 [0.10]; CGI-I: +1.58 [0.09] vs +2.35 [0.10] and +1.80 [0.09]; response: 95.4% vs 44.3% and 83.3%; remission: 89.8% vs 25.5% and 50.9% [all, P < 0.001]). Mean (SE) changes from baseline in core depression subscale score were -19.00 (0.59), -13.00 (0.60), and -16.52 (0.58) with escitalopram, citalopram 10 rag, and citalopram 20 mg, respectively. The prevalence of AEs was significantly lower in the escitalopram group (7) compared with the citalopram groups (16 and 19 in the 10- and 20-mg groups, respectively; both, P < 0.05). Nausea (2 [1.9%], 5 [4.7%], and 7 [6.5%] patients in the escitalopram and citalopram 10- and 20-mg groups, respectively) and headache (1 [0.9%], 2 [1.9%], and 4 [3.7%]) were the most frequently reported AEs. Conclusions: The results from this study suggest that escitalopram 10 mg was more effective than citalopram 10 and 20 mg at 6 weeks in these adult outpatients with MDD. All treatments were well tolerated. (Clin Ther. 2007;29:2319-2332) Copyright © 2007 Excerpta Medica, Inc.

Effectiveness and acceptability of sertraline and citalopram in major depressive disorder: pragmatic randomized open‐label comparison

Citalopram and sertraline are widely prescribed selective serotonin reuptake inhibitors (SSRIs). There is no conclusive evidence to show superiority of citalopram or sertraline in terms of efficacy or tolerability. Hence this study was designed to compare short term efficacy and safety of citalopram and sertraline in major depressive disorder (MDD) in Indian patients. In an open, randomized study, 100 patients were divided into two groups. In Group A (n = 50) patients received citalopram (20-60 mg/day) for 6 weeks. In Group B (n = 50) patients received sertraline (50-150 mg/day) for 6 weeks. Patients were evaluated at baseline and then at 1, 2, 3, 4, 5, and 6 weeks. There was significant improvement in Hamilton depression rating scale (HDRS), Montgomery and Asberg depression rating scale (MADRS) and Amritsar depressive inventory (ADI) scores (p < 0.05) with both the drugs. However, the decrease in score was more with citalopram (p < 0.05). Onset of action of citalopram was earlier as compared to sertraline (p < 0.05). The number of responders and remitters was also more with citalopram (p < 0.05). No serious adverse event was reported in either of the groups. Citalopram had shown better efficacy, earlier onset of action and more number of responders and remitters as compared to sertraline in MDD in Indian patients.

Cost-effectiveness of escitalopram vs. citalopram in major depressive disorder

Clinical trials have shown better efficacy of escitalopram over citalopram, and review-based economic models the cost-effectiveness of escitalopram vs. citalopram (brand and generic). No head-to-head clinical trial has, however, evaluated the cost-effectiveness of both drugs so far. The aim of this study was to assess the relative cost-effectiveness of escitalopram compared with citalopram in patients with major depressive disorder. An economic evaluation was conducted alongside a double-blind randomized clinical trial conducted by general practitioners and psychiatrists comparing fixed doses of escitalopram (20 mg/day) or citalopram (40 mg/day) over 8 weeks in ambulatory care patients with major depressive disorder (baseline Montgomery-Asberg Depression Rating Scale score > or =30). Resources use was recorded using a standardized form recording use of healthcare services and days of sick leave for the 2-month prestudy period and for the 8-week study period. Statistically significant improvements were observed in patients treated with escitalopram. Mean per-patient costs for the escitalopram group, compared with the citalopram group, were 41% lower (96 euro vs. 163 euro; P<0.05) from a healthcare perspective. Differences were mostly related to lower hospitalization costs for escitalopram compared with citalopram recipients, assuming a parity price between escitalopram and citalopram. Bootstrapped distributions of the cost-effectiveness ratios also showed better effectiveness and lower costs for escitalopram compared with citalopram. Escitalopram is significantly more effective than citalopram, and is associated with lower healthcare costs. This prospective economic analysis demonstrated that escitalopram is a cost-effective first-line treatment option for major depressive disorder.

Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder

Pre-clinical studies, active-control clinical trials and meta-analyses indicate that escitalopram (S-citalopram) might be more effective than citalopram, the racemic mixture of S- and R-citalopram. The present study aimed to confirm the superior efficacy of escitalopram over citalopram. A double-blind, randomized clinical trial was performed in which general practitioners and psychiatrists compared fixed doses of escitalopram (20 mg/day) with citalopram (40 mg/day) over 8 weeks in outpatients with major depressive disorder (MDD) [baseline Montgomery-Asberg Depression Rating Scale (MADRS) score > or =30]. Primary efficacy parameter was change from baseline to last assessment in the MADRS total score. Out of 138 (aged 44.1+/-10.9 years; initial MADRS score 36.3+/-4.8) and 142 (aged 46.2+/-11.1 years; initial MADRS score 35.7+/-4.4) evaluable patients who were randomized to escitalopram and citalopram, respectively, six and 15 withdrew prematurely (P=0.05). The MADRS score decreased more in the escitalopram than in the citalopram arm (-22.4+/-12.9 versus -20.3+/-12.7; P<0.05). There were more treatment responders with escitalopram (76.1%) than with citalopram (61.3%, P<0.01). Adjusted remitter rates were 56.1% and 43.6%, respectively (P<0.05). Tolerability was similar in both groups. This randomized double-blind trial confirms that escitalopram has a superior effect to citalopram in MDD.

Neuroendocrine, biochemical and pharmacokinetic effects of a long-term treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram in major depressive disorder

Neuroendocrine, biochemical and pharmacokinetic effects of a long-term treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram in major depressive disorder