Search

Background: Agomelatine is an antidepressant drug that acts as an agonist of melatoninergic MT1/2 receptors and an antagonist of serotonergic 5-HT2C receptors. Studies suggest that agomelatine has anxiolytic properties in social anxiety, but there are no studies that assessed the effects of this compound in human experimental anxiety induced by a public speaking test. The objective of our investigation was to assess the effects of agomelatine on human experimental anxiety using the Simulation Public Speaking Test (SPST)., Methods: Agomelatine (25 mg, n = 14), citalopram (20 mg, n = 14), venlafaxine (75 mg, n = 14), or placebo (n = 14) were administered in single doses to healthy volunteers in a double-blind study. Subjective anxiety was assessed with the Visual Analogue Mood Scale. Arterial blood pressure, heart rate, and blood levels of prolactin and cortisol were also recorded, as well as plasma levels of the 3 drugs., Results: The SPST induced significant subjective, physiological, and hormonal effects in all groups. The SPST also increased the anxiety and decreased mental sedation Visual Analogue Mood Scale factors during the anticipatory and performance phases of the test. Citalopram increased anxiety during the test in females, whereas agomelatine and venlafaxine were not different from placebo., Conclusions: Confirming previous results, a serotonin selective reuptake inhibitor, citalopram, caused an anxiogenic effect in the SPST only in females. Acute administration of a low dose of agomelatine failed to modify the behavioral and physiological changes caused by this test. Future studies using higher doses and repeated administration should investigate if agomelatine behavioral and physiological effects could be detected in human experimental anxiety models., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Tobacco smoking rates in depressive patients are higher compared with the general population. Smoking was demonstrated to accelerate the metabolism of different drugs metabolized by CYP1A2, but possibly also by CYP2C19 and CYP3A4. The principle aim of the present investigation from 2015 to 2018 was to determine the differences in the pharmacokinetics of escitalopram between smokers and nonsmokers., Methods: A group of nonsmokers (n = 88) was compared with smokers (n = 36), both receiving escitalopram, using the Mann-Whitney U test. Linear regression analysis was used to account for the impact of escitalopram dose, age, and sex in addition to smoking on the steady-state serum concentration of escitalopram., Results: Smokers received by mean 17.6% higher doses of escitalopram (P = 0.026) but showed 31.9% lower serum concentrations (P = 0.031). To control for confounders, linear regression analysis showed that dose (P < 0.001), sex (P = 0.03), and smoking tobacco (P = 0.027) did significantly influence serum concentrations of escitalopram with higher levels in women and nonsmokers., Conclusions: Notwithstanding higher daily doses, smokers had significantly lower serum concentrations of escitalopram. In concordance with previous results, besides CYP1A2, a possible induction of CYP2C19 and CYP3A4 by tobacco smoke, resulting in lower serum concentrations of escitalopram in smokers than in nonsmokers, is suggested. Therefore, to provide personalized therapy, clinicians should consider smoking status and inform patients on the interactions of smoking and escitalopram metabolism.

Purpose/background: According to available international clinical guides, tricyclic antidepressants are our first- or second-line treatment of choice for severe unipolar major depression. However, the therapeutic option after an unsuccessful response to a tricyclic antidepressant drug in unipolar major depression is still unclear., Methods/procedures: This 10-week randomized open-label study assessed the effectiveness of add-on lithium (adjusted to plasma levels) compared with add-on citalopram (30 mg/d) in 104 severe unipolar major depressive patients after a 10-week unsuccessful imipramine (adjusted to plasma level). Efficacy analyses examined changes in the severity of depression symptoms from baseline visit to endpoint and the comparative remission rate between treatment subgroups., Findings/results: The randomized sample consisted of 104 imipramine-resistant severe unipolar major depressed patients. Both, the percentage of remitters (40.4% vs 21.1%, P = 0.034) and the mean reduction of the Hamilton Depression Rating Scale score (58.8% vs 42.5%, P = 0.005) were significantly greater in the add-on citalopram subgroup at endpoint visit., Implications/conclusions: Although we should be cautious about generalizing these results to patients with a less severe unipolar major episode, results from the present study suggest that add-on citalopram is a very effective treatment option in unipolar major depressive episodes after an unsuccessful imipramine regimen.

Background: Open-label trials suggest that escitalopram (up to 20 mg/d) is an effective treatment for some, but not all posttraumatic stress disorder (PTSD) patients. Higher doses of escitalopram effectively reduced major depression symptoms in patients who had not responded to regular doses. The current study examines the efficacy, tolerability, and adherence to high-dose escitalopram in PTSD., Methods: Forty-five PTSD patients received 12 weeks of gradually increasing doses of escitalopram reaching 40 mg daily at 4 weeks. Among those, 12 participants received regular doses of antidepressants at study onset including escitalopram (n = 7). The Clinician-Administered PTSD Scale (CAPS) evaluated PTSD symptoms severity before treatment, at 3 months (upon treatment termination), and at 6 months (maintenance effect). A 20% reduction in CAPS scores was deemed clinically significant., Results: Adverse events and medication adherence were monitored at each clinical session. Linear mixed-models analysis showed a significant reduction of mean CAPS scores (11.5 ± 18.1 points) at 3 months and maintenance of gains by 6 months (F2,34.56 = 8.15, P = 0.001). Eleven participants (34.3%) showed clinically significant improvement at 3 months. Only 9 participants (20%) left the study. There were no serious adverse events and few mild ones with only 2 adverse events (diarrhea, 11.1%; drowsiness, 11.1%) reported by more than 10% of participants., Conclusion: High doses of escitalopram are tolerable and well adhered to in PTSD. Their beneficial effect at a group level is due to a particularly good response in a subset of patients.Variability in prior pharmacological treatment precludes a definite attribution of the results to high doses of escitalopram.

Major depressive disorder is a devastating mental illness leading to a lifetime prevalence of higher than 16% on individuals. The treatment delay and inevitable adverse effects are major limitations of current depression interventions. Emerging evidence indicates that curcumin produced significant antidepressant properties in depression in both rodents and humans without adverse effects. Therefore, it is necessary to further clarify the antidepressant actions of curcumin and the underlying mechanism in depressed patients. A total of 108 male adults aged between 31 and 59 years were systematically recruited in Tianjin Anding Hospital. Subjects were administered the Chinese version of 17-item Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale that measures different scores of depressive symptoms. The subjects were asked to take 2 capsules containing either 1000 mg of curcumin or placebo soybean powder daily for 6 weeks on the basis of their current antidepressant medications. The plasma levels of interleukin 1β, tumor necrosis factor α, brain-derived neurotrophic factor, and salivary cortisol were measured by enzyme-linked immunosorbent assay before and after curcumin or placebo treatment during the 6-week procedure. Chronic supplementation with curcumin produced significant antidepressant behavioral response in depressed patients by reduction of 17-item Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale scores. Furthermore, curcumin decreases inflammatory cytokines interleukin 1β and tumor necrosis factor α level, increases plasma brain-derived neurotrophic factor levels, and decreases salivary cortisol concentrations compared with placebo group. These findings indicate the potential benefits of further implications of supplementary administration of curcumin to reverse the development of depression and enhance the outcome of antidepressants treatment in major depressive disorder.

Objective: Posttraumatic stress disorder (PTSD) is a chronic disabling illness, resulting from exposure to extreme traumatic event. Although different pharmacologic agents are suggested for treatment of PTSD, none have been completely effective in eliminating symptoms. The purpose of this study was to assess the use of baclofen as an add-on to citalopram in treatment of PTSD., Methods: In this double-blind clinical trial, 40 Iranian combat veterans with PTSD were randomly assigned to 2 groups. The first group received a combination treatment of 20 to 60 mg/d citalopram and 40 mg/d baclofen, and the second group received 20 to 60 mg/d citalopram plus placebo. Symptom severity was assessed by Clinician-Administered PTSD Scale at the beginning of the study and after 2, 4, 6, and 8 weeks. Global Assessment of Functioning and Hamilton Rating Scale for Anxiety and Depression were also used at the same periods. Data were analyzed with independent t test and paired t test using SPSS software version 13 (IBM, Armonk, NY)., Results: Twenty-three male patients (baclofen group, 13 patients; placebo group, 10 patients) completed the study. Dropout from the treatment was not caused by adverse effects of the new medications in any of the subjects. Baclofen group showed significantly larger improvement in Clinician-Administered PTSD Scale total (P = 0.040), hyperarousal (P = 0.020), and avoidance (0.020) scores, Global Assessment of Functioning score (0.001), depression (P = 0.000), and anxiety (P = 0.000) after 8 weeks of treatment. No intergroup difference was found in improvement of reexperience symptoms (P = 0.740)., Conclusions: Baclofen showed to be an effective add-on to selective serotonin reuptake inhibitors in treatment of PTSD for better symptom recovery and functional improvement.

Studies of the 1970s and 1980s showed lithium monotherapy to be an effective treatment of acute unipolar major depressive disorder (MDD) and hence as a potential alternative to monoaminergic antidepressants.The objective was to conduct the first comparison of a lithium monotherapy with a modern antidepressant in the acute treatment of MDD. Results were compared with citalopram's efficacy as shown in a different but methodologically identical study (including same researchers, same time, and same place).Thirty patients with an acute MDD (Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM IV] I) were treated with lithium monotherapy (study 1) or with citalopram monotherapy (study 2, N = 32) for 4 weeks.Response rates (decrease in Hamilton Depression Rating Scale score >50%) were 50% for lithium and 72% for citalopram (P = 0.12). Citalopram-treated subjects showed a greater decrease in Hamilton Depression Rating Scale scores (significant at 2 weeks). In the lithium study, only patients with a recurrent episode (DSM-IV: 296.3) responded (15/22), as opposed to none of 8 patients with a first/single episode (DSM-IV: 296.2) (P = 0.002). Patients with a single episode responded significantly more often to citalopram than to lithium (P = 0.007). Both drugs were well tolerated. Only one patient (citalopram) terminated the study prematurely owing to adverse effects.Our results do not support the use of lithium as an alternative to SSRI in the treatment of acute MDD. The finding of a better response to lithium in patients with a recurrent depression has not been reported before and warrants replication. The comparison is limited by the lack of a randomized double-blind design.

We sought to examine the efficacy and safety of acamprosate augmentation of escitalopram in patients with concurrent major depressive disorder (MDD) and alcohol use disorders. Twenty-three adults (43% female; mean ± SD age, 46 ± 14 years) were enrolled and received 12 weeks of treatment with psychosocial support; escitalopram, 10 to 30 mg/d; and either acamprosate, 2000 mg/d (n = 12), or identical placebo (n = 11). Outcomes included change in clinician ratings of depressive symptoms, MDD response and remission rates, changes in frequency and intensity of alcohol use, retention rates, and adverse events. Twelve subjects (acamprosate, n = 7; placebo, n = 5) completed the study. There was significant mean reduction in ratings of depressive symptoms from baseline in both treatment arms (P < 0.05), with no significant difference between the groups. Those in the acamprosate group had a 50% MDD response rate and a 42% remission rate, whereas those in the placebo arm had a 36% response and remission rate (not significant). Those assigned to acamprosate had significant reduction in number of drinks per week and drinks per month during the trial, whereas those assigned to placebo demonstrated no significant change in any alcohol use parameter, but the between-group difference was not significant. There were no significant associations between change in depressive symptoms and change in alcohol use. Attrition rates did not differ significantly between the 2 arms. Acamprosate added to escitalopram in adults with MDD and alcohol use disorders was associated with reduction in the frequency of alcohol use. The present study was not powered to detect superiority versus placebo. Further study in a larger sample is warranted.

Objective: Antidepressant switch is a commonly used strategy in the absence of an adequate response, but optimum timing is not well established. We compared the efficacy of an early and a conventional antidepressant switch strategy in patients with major depressive disorder., Methods: Patients with no or minimal improvement (<30% reduction in baseline 17-item Hamilton Depression Rating Scale [HAMD17] score) after 4 weeks on escitalopram 10 mg/d were randomized to either early switch strategy with duloxetine 60 to 120 mg/d for 12 weeks (arm A) or conventional switch strategy (arm B): 4 further weeks on escitalopram 10 to 20 mg/d; then, in case of nonresponse (response, ≥ 50% reduction in HAMD17), switch to duloxetine 60 to 120 mg/d for 8 weeks, or continued escitalopram in responders. Co-primary end points were time to confirmed response and remission (HAMD17, ≤ 7). Strategies were compared using Kaplan-Meier, logistic regression, and repeated-measures analyses., Results: Sixty-seven percent (566 of 840) of patients showed no or minimal improvement and were randomized to arm A (282 patients) or arm B (284 patients). No between-strategy differences in time to confirmed response (25% Kaplan-Meier estimates, 3.9 vs 4.0 weeks, P = 0.213) or remission (6.0 vs 7.9 weeks, P = 0.075) were found. Rates of confirmed responders were similar (64.9% vs 64.1%); however, more patients randomized to early switch achieved confirmed remission (43.3% vs 35.6%; P = 0.048)., Conclusions: Although no differences in the primary end points were found, a higher remission rate was seen with the early switch strategy. Our findings suggest that further investigations to reevaluate the conventional approach to antidepressant switch strategy would be worthwhile.

Objective: The objective of this study was to explore the efficacy of combination therapy with citalopram plus omega-3 fatty acids versus citalopram plus placebo (olive oil) in the initial treatment of individuals with major depressive disorder (MDD). We hypothesized that combination therapy would lead not only to greater efficacy but also to a more rapid onset of therapeutic response., Methods: Forty-two subjects participated in this 9-week randomized, masked, placebo-controlled study of combination therapy (two 1 g capsules containing a blend of 900 mg of eicosapentaenoic acid, 200 mg of and docosahexaenoic acid, and 100 mg of other omega-3 fatty acids twice daily plus citalopram) versus monotherapy (two 1 g capsules of olive oil per day plus citalopram) treatment of MDD., Results: The combination therapy demonstrated significantly greater improvement in Hamilton Depression Rating scale scores over time (F = 7.32; df 1,177; P = 0.008) beginning at week 4 (t = -2.48; df 177; P = 0.014)., Conclusions: Combination therapy was more effective than monotherapy in decreasing signs and symptoms of MDD during the 8 weeks of active treatment; however, combination therapy did not seem to enhance the speed of the initial antidepressant response. These findings suggest that there may be an advantage to combining omega-3 fatty acids with a selective serotonin uptake inhibitor in the initial treatment of individuals with MDD. A larger definitive study is warranted.

This paper examines the relationship between plasma concentration of antidepressant and both clinical response and adverse effects in treatment-resistant depressed adolescents. Adolescents (n = 334) with major depression who had not responded to a selective serotonin reuptake inhibitor (SSRI) were randomized to 1 of 4 treatments: switch to another SSRI (fluoxetine, citalopram, or paroxetine), switch to venlafaxine, switch to SSRI plus cognitive behavior therapy, or switch to venlafaxine plus cognitive behavior therapy. Adolescents who did not improve by 6 weeks had their dose increased. Plasma concentrations of medication and metabolites were measured at 6 weeks in 244 participants and at 12 weeks in 204 participants. Adolescents treated with citalopram whose plasma concentration was equal to or greater than the geometric mean (GM) showed a higher response rate compared to those with less than the GM, with parallel but nonsignificant findings for fluoxetine. A dose increase of citalopram or fluoxetine at week 6 was most likely to result in response when it led to a change in concentration from less than the GM at 6 weeks to the GM or greater at week 12. Plasma levels of paroxetine, venlafaxine, or O-desmethylvenlafaxine were not related to clinical response. Exposure was associated with more cardiovascular and dermatologic side effects in those receiving venlafaxine. Antidepressant concentration may be useful in optimizing treatment for depressed adolescents receiving fluoxetine or citalopram.

Objective: This 7-week trial assessed the efficacy and tolerability of aripiprazole combined with escitalopram in the acute treatment of major depressive disorder, with psychotic features (MD-Psy)., Methods: Sixteen male and female patients with a Diagnostic Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of MD-Psy were recruited for this study from September 13, 2004 to August 9, 2006. Escitalopram and aripiprazole were flexibly dosed for 7 weeks, with maximum dosages of 20 and 30 mg/d, respectively. The 17-item Hamilton Rating Scale for Depression (HAM-D-17) and Structured Clinical Interview for DSM-IV psychosis module were used to measure depression and psychosis responses. The Barnes Akathisia Scale and the Simpson Angus Scale were used to assess for akathisia and extrapyramidal symptoms., Results: Thirteen of the 16 subjects completed the study. The MD-Psy response rate (50% or greater drop in HAM-D-17 and no psychosis) (intent-to-treat, last observation carried forward) was 62.5%, and the MD-Psy remission rate (HAM-D-17, <8, and no psychosis) (intent-to-treat, last observation carried forward) was 50.0%. Ten of the 16 subjects developed akathisia; however, 9 of the 10 subjects had resolution or partial resolution of akathisia with dose adjustment or treatment with propranolol., Conclusions: The combination of escitalopram and aripiprazole seems to be an effective and safe treatment for MD-Psy.

The aim of the present study was to evaluate the efficacy of short-term low-dose intravenous augmentative citalopram (10 mg/d) versus clomipramine (25 mg/d) versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors (SSRIs). Fifty-four patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, MDE and partial or no response to SSRIs per os (21-item Hamilton Depression Rating Scale [HAM-D21] score reduction, <50% or < or =25%, respectively, compared with pretreatment scores) were selected and randomized to citalopram (n = 18), clomipramine (n = 18), or placebo (n = 18) intravenous augmentation. The augmentation regimen lasted 5 days during which patients were maintained on their previous treatment with oral SSRIs. Analyses of variance with repeated measures on HAM-D(21), collected daily in blind-raters design, were performed to detect any change of depressive symptoms between the 3 groups. In addition, the number of responders and remitters was computed in the 3 groups of treatment. At end point, a significant treatment effect (F= 4.57; P = 0.015) and time-by-treatment effect (F = 11.22; P < 0.0001) were found on HAM-D21 total scores in favor of citalopram and clomipramine versus placebo, with a superiority of citalopram over clomipramine on overall symptoms (P = 0.05) as well as on anxiety-somatization symptoms (P = 0.027). The number of responders was significantly superior in the active treatment groups versus the placebo group ([chi](2)(2) = 16.36; P < 0.0001). The same result was found, considering the number of remitters ([chi](2)(2) = 13.50; P < 0.0001). Present findings suggest that both clomipramine and citalopram intravenous augmentation at low doses and for a short period are well tolerated and superior to placebo in major depressives with partial or no response to oral SSRIs with a possible superiority of citalopram over clomipramine with regard to anxiety-somatization symptoms. The lack of double-blind conditions and the limited sample size may limit the confidence in the reported results, and larger randomized controlled trials are warranted to confirm the present findings.

This is the first placebo-controlled trial evaluating the efficacy of the selective serotonin reuptake inhibitor (SSRI), escitalopram, in the treatment of premenstrual dysphoric disorder (PMDD). Women with PMDD (intention-to-treat population, n = 151) were treated intermittently for 3 months, during luteal phases only, with 10 mg/d escitalopram, 20 mg/d escitalopram, or placebo. Escitalopram was found to exert a marked and a dose-dependent symptom-reducing effect, 20 mg/d being clearly superior to 10 mg/d. Although the primary outcome parameter, that is, the sum of the symptoms irritability, depressed mood, tension, and affective lability, was decreased by 90% with 20 mg/d escitalopram, the effect of active treatment on breast tenderness, food craving, and lack of energy was more modest and not significantly different from that of placebo; this outcome supports our previous assumption that the former symptoms are more inclined to respond to intermittent administration of an SSRI than are the latter. Although the placebo response was high, the difference between the placebo group and the 20-mg/d escitalopram group with respect to the percentage of subjects displaying 80% or greater reduction in the rating of the cardinal symptom of PMDD, that is, irritability, was considerable: 30% versus 80%. Adverse events were those normally reported in SSRI trials, such as nausea and reduced libido, and were not more common in patients given 20 mg/d of escitalopram than in patients given the lower dose. This study supports the usefulness of escitalopram for the treatment of PMDD and sheds further light on how different components of this syndrome are differently influenced by intermittent administration of an SSRI.

This study is the first to directly compare the relative effects of duloxetine, escitalopram, and sertraline on the functional activity of the drug-metabolizing cytochrome P450 2D6 enzyme as assessed by changes in the pharmacokinetics of the cytochrome P450 2D6 model substrate drug, metoprolol. Single-dose pharmacokinetics of metoprolol were measured before and after 17 days of treatment with escitalopram 20 mg/d, duloxetine 60 mg/d, or sertraline 100 mg/d in young healthy male and female participants. The outcome measures were changes in metoprolol peak plasma levels, area under the plasma concentration-time curve, and clearance. The results were tested using paired t tests and independent t tests. The addition of each drug produced statistically significant changes in metoprolol pharmacokinetics. The rank order for the change in metoprolol area under the plasma concentration-time curve was duloxetine (180%) > escitalopram (89%) > sertraline (48% and 67%). Compared with sertraline, duloxetine produced statistically significantly larger changes in metoprolol pharmacokinetic parameters. The changes produced by escitalopram and sertraline were not statistically different.

In a European, multicenter, double-blind study, 244 adolescents, 13 to 18 years old, with major depression were randomized to treatment with citalopram (n = 124) or placebo (n = 120). One third of the patients in both groups withdrew from the study. No significant differences in improvement of scores from baseline to week 12 between citalopram and placebo were found. The response rate was 59% to 61% in both groups according to the Schedule for Affective Disorders and Schizophrenia for school-aged children-Present episode version (Kiddie-SADS-P) (depression and anhedonia scores < or =2) and Montgomery Asberg Depression Rating Scale (MADRS) (> or =50% reduction). Remission (MADRS score < or =12) was achieved by 51% of patients with citalopram and 53% with placebo. A post hoc analysis revealed that more than two thirds of all patients received psychotherapy during this study. For those patients not receiving psychotherapy, there was a higher percentage of Kiddie-SADS-P responders with citalopram (41%) versus placebo (25%) and a significantly higher percentage of MADRS responders and remitters with citalopram (52% and 45%, respectively) versus placebo (22% and 19%, respectively). Mild to moderate treatment-emergent adverse events were reported in 75% citalopram and 71% of placebo patients, most commonly headache, nausea, and insomnia. Serious adverse events occurred in 14% to 15% in both groups. Suicide attempts, including suicidal thoughts and tendencies, were reported by 5 patients in the placebo group and by 14 patients in the citalopram group (not significant) with no pattern with respect to duration of treatment, time of onset, or dosage. In contrast, the suicidal ideation (Kiddie-SADS-P) single item showed worsening more frequently in the placebo (18%) than in the citalopram group (8%).

The objective of this study was to compare efficacy and tolerability of the selective noradrenaline reuptake inhibitor reboxetine with the selective serotonin reuptake inhibitor citalopram, in the treatment of major depressive disorder (MDD). 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. Primary end-point was change from baseline in the Hamilton Depression Rating Scale (HAM-D, 21 items). Sexual function/dysfunction was measured by the Sexual Function scale (SF). Observed case analysis showed that both treatments yielded a gradual reduction of HAM-D scores: reboxetine with -21.4 and citalopram with -22.1 points (NS). LOCF analysis showed a greater reduction of the HAM-D scores with citalopram compared with reboxetine (-19.6 vs. -17.8; P = 0.034). The response rate was 90.3% for reboxetine and 92.7% for citalopram (NS). The most common side effect in the reboxetine group was dry mouth, and in the citalopram group sexual dysfunction. At week 24, anorgasmia was reported by 5.9% of the sexually active women in the reboxetine group vs 39% in the citalopram group. The dropout number was 91 in the reboxetine group, and 54 in the citalopram group. To summarize, both treatments gave a satisfactory antidepressant effect. The side effect profile differed between the groups, with a notably high prevalence of sexual dysfunctions in the citalopram group. The high number of dropouts in the reboxetine group, is considered as a result of the non-titration starting dose of 8 mg reboxetine per day, which gave a high incidence of early side-effects.

Purpose: Panic attacks may represent additional therapeutic problems in the elderly. The utility of citalopram in panic attacks has been widely investigated. Here, we compare the efficacy and safety of citalopram, with its S-enantiomer escitalopram at half dosage as to citalopram, in elderly patients who have panic attacks., Methods: This was an open community-based study. Forty patients who have panic attacks, according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, were enrolled. Fifty percent of the patients were assigned for 8 weeks' treatment with escitalopram, and the remaining 50% were assigned to treatment with citalopram. The primary outcome measure was the weekly rate of panic attacks. The secondary outcome measures were the Hamilton scale for anxiety and depression and the Cooper Disability Scale. Analysis of variance by repeated measures was applied to calculate differences between groups., Results: A similar decrease in weekly rate of panic attacks, in the scores of Hamilton Scale for anxiety and depression and in the Cooper Disability Scale scores, was observed in both groups after 8 weeks, but a significant variation of outcome measures from baseline was observed already after 2 weeks in the escitalopram group (P < 0.001) and only after 4 weeks in the citalopram group (P < 0.01)., Conclusions: Escitalopram could be considered among the drugs of first choice in elderly patients with panic attacks because of its good efficacy and safety and for the advantage of reducing the total dose and of a more rapid onset of action as compared with citalopram, although further studies are needed to confirm these results.

This study compared the stabilized duloxetine dose through approximately 12 weeks of treatment in patients initiating duloxetine therapy with that in patients switching to duloxetine from selective serotonin reuptake inhibitors or venlafaxine. All patients met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder. Patients (n = 112) exhibiting suboptimal response or poor tolerability to their current antidepressant medication (citalopram, escitalopram, fluvoxamine, paroxetine, sertraline, or venlafaxine) were switched to duloxetine 60 mg once daily (QD) without intermediate tapering or titration ("switching" group). A comparator group (n = 137), comprising patients not currently receiving antidepressant medication, was randomized to receive duloxetine 30 or 60 mg QD ("initiating" group). At the end of week 1, patients receiving 30 mg QD had their dose increased to 60 mg QD. During the remainder of the study, each patient's duloxetine dose could be titrated on the basis of degree of response within a range from 60 to 120 mg QD, with 90 mg QD as an intermediate dose. At the study end point, approximately one third of the patients in each treatment group were stabilized at each of the 3 studied duloxetine doses (60, 90, and 120 mg QD), and the distribution of stabilized doses among patients initiating duloxetine therapy did not differ significantly from that observed in patients switching to duloxetine. The efficacy of duloxetine in patients switching from selective serotonin reuptake inhibitor/venlafaxine did not differ significantly from that observed in untreated patients initiating duloxetine therapy (baseline-to-end point mean changes: 17-Item Hamilton Rating Scale for Depression total score, -13.1 vs. -13.5; Hamilton Rating Scale for Anxiety, -10.6 vs. -10.3; and Clinical Global Impression of Severity, -2.22 vs. -2.38, respectively). The rate of discontinuation caused by adverse events among patients switched to duloxetine was significantly lower than that in patients initiating duloxetine therapy (6.3% vs. 16.1%, P = 0.018). Treatment-emergent adverse events occurring in more than 10% of patients in both treatment groups were nausea, headache, dry mouth, insomnia, diarrhea, and constipation. In the first week of therapy, patients switched to duloxetine reported significantly lower rates of headache and fatigue compared with patients initiating duloxetine. Thus, the efficacy of duloxetine in switched patients was comparable to that observed in patients initiating duloxetine therapy. Immediate switching from a selective serotonin reuptake inhibitor or venlafaxine to duloxetine (60 mg QD) was well tolerated.

Cognitive enhancement in patients with schizophrenia is a major treatment priority. Because serotonergic approaches have been suggested as a possible mechanism to enhance cognition and many patients with schizophrenia are treated with selective serotonin reuptake inhibitor antidepressants, we evaluated a serotonin reuptake inhibitor, citalopram, as adjunctive therapy to atypical antipsychotic treatment for its cognitive enhancing effects in schizophrenic patients. Nineteen schizophrenic patients were treated in a randomized, placebo-controlled, crossover-designed 24-week study. In phase 1, subjects were randomized equally to 40 mg of citalopram or placebo and were evaluated prior to initiation of pharmacotherapy and at the end of phase 1 (after 12 weeks of treatment with double-blind agent). At the beginning of phase 2, subjects were crossed over to the other treatment and subsequently assessed after 12 weeks of treatment for symptom severity and cognitive performance. There were no statistically significant differences between citalopram 40 mg/d and placebo treatment on any clinical or cognitive measures. These results indicate that citalopram adjunctive treatment to atypical antipsychotics produces no significant cognitive improvement in patients with schizophrenia. Because the subjects in this study were all treated with atypical antipsychotics, it is possible that the pharmacologic profiles of atypical antipsychotic medications at serotonin receptors may have complicated the effects of citalopram augmentation. Further research on alternative serotonergic approaches to cognitive enhancement in schizophrenia is warranted.

In a double-blind trial, the selective serotonin reuptake inhibitor citalopram was administered to women with severe irritability and/or depressed mood in the luteal but not in the follicular phase of the menstrual cycle (premenstrual dysphoria). Treatment continued for three consecutive menstrual cycles. One group (N = 17 completers) was administered citalopram continuously at a constant dosage (20+/-10 mg/day) throughout the menstrual cycle. A second group (N = 17) also received citalopram continuously throughout the cycle, but at a lower dosage in the follicular phases (5 mg/day) than in the luteal phases (20+/-10 mg/day) (semi-intermittent treatment). A third group (N = 18) received citalopram (20+/-10 mg/day) in the luteal phase only and placebo during the follicular phase (intermittent treatment). A fourth group (N = 17) received placebo throughout the cycles. The side effects of active treatment were generally mild and transient. Intermittent administration of citalopram was clearly more effective than placebo with respect to both reduction in self-rated irritability and self-rated global improvement; it is of interest that intermittent treatment with citalopram also seemed more effective than continuous or semi-intermittent administration of the drug.

Sixty-nine depressive patients (DSM III criteria: 296.2, 296.3, 296.5, 300.4) were treated with 40 to 60 mg citalopram (CIT) daily for 4 weeks. Among them, 45 responded to treatment (improvement > 50% on the 21-item Hamilton Rating Scale for Depression [HAM-D]) and continued their treatment for another week before being released from the study. The 24 nonresponders were randomized and comedicated under double-blind conditions with lithium carbonate (Li) (2 x 400 mg/day) (CIT-Li group) or with placebo (CIT-Pl group) from days 29 to 35. For days 36 to 42, the patients of both subgroups were treated openly with Li (800 mg/day) in addition to the ongoing CIT treatment. On day 35, 6 of 10 patients responded to the CIT-Li combination, whereas 2 of 14 patients only responded to the CIT-Pl combination. This group difference reached significance (p < 0.05) on day 35 with lower HAM-D total scores in the CIT-Li group. No evidence was seen of a pharmacokinetic interaction between CIT and Li, and this combination was well tolerated. Patients were phenotyped with dextromethorphan and mephenytoin at baseline and at day 28. As evaluated at baseline, three patients (responders) were poor metabolizers of dextromethorphan and six patients (three responders and three nonresponders) of mephenytoin. On day 28, the ratio CIT/N-desmethylCIT (DCIT) in plasma was significantly higher in poor than in extensive metabolizers of mephenytoin (p = 0.0001), and there was a significant positive correlation between the metabolic ratio of dextromethorphan and the ratio DCIT/N-didesmethylCIT in plasma (p < 0.001). These findings illustrate the role of CYP2D6 and CYP2C19 in the metabolism of CIT. It can be concluded that Li addition to CIT is effective in patients not responding to CIT alone without any evidence of an accentuation or provocation of adverse events.