Bupropion sustained-release for the treatment of dysthymic disorder: an open-label study

Many studies of antidepressants in the treatment of dysthymic disorder (DD) have been conducted, but none has included bupropion sustained-release (SR). The aim of this study was to provide preliminary data on the tolerability and effectiveness of bupropion SR for patients with DD. Twenty-one adult subjects meeting DSM-IV criteria for DD were enrolled in this 8-week open-label study. Bupropion SR was initiated at 150 mg/day and was increased to a maximum of 200 mg, twice daily. Response was defined as a 50% or greater decrease in score on the Hamilton Rating Scale for Depression (HAM-D). Of these 21 subjects, 15 (71.4%) responded to treatment. All paired sample t-tests were highly significant, demonstrating average improvement on all measures of symptomatology and functioning. Subject scores on the HAM-D decreased from 21.7 +/- 5.6 at baseline to 5.9 +/- 3.6 at week 8 (t[19] = 12.74, p < 0.001). The average final dosage was 364 mg/day. None of the subjects dropped out during the trial. Patients with a history of alcohol or chemical abuse were significantly less likely to respond to bupropion. Side effects were reported by eight subjects (38.1%), and the most frequently reported effects were headache, decreased appetite, insomnia, gastrointestinal problems, restlessness, and tremulousness. These findings suggest the effectiveness and high tolerability of bupropion SR for the treatment of DD. Double-blind prospective studies are needed for the comparison of bupropion SR to both placebo and other medications, assessing both initial and sustained responses to treatment.     

Escitalopram treatment of pathological gambling with co-occurring anxiety: an open-label pilot study with double-blind discontinuation

Although co-occurring disorders are common in pathological gambling (PG), investigations of the response to pharmacotherapy in individuals with PG and co-occurring psychiatric symptomatology are limited. Thirteen subjects with DSM-IV PG and co-occurring anxiety were treated in a 12-week open-label trial of escitalopram. Subjects were assessed with the Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS; primary outcome measure), the Hamilton Anxiety Rating Scale (HAM-A), the Clinical Global Impressions scale (CGI), and measures of psychosocial functioning and quality of life. Those subjects who 'responded' (defined as a 30% or greater reduction in PG-YBOCS total score at endpoint) were offered inclusion in an 8-week double-blind discontinuation phase. PG-YBOCS scores decreased from a mean of 22.2+/-4.5 at baseline to 11.9+/-10.7 at endpoint (P=0.002) and 61.5% were responders. Scores on the HAM-A decreased by 82.8% over the 12-week period (mean of 15.9+/-3.2 at baseline to a mean of 2.8+/-3.6 at endpoint) (P<0.001). On the CGI, 38.5% of subjects (n=5) were 'very much improved' and 23.1% (n=3) were 'much improved' by study endpoint. The Sheehan Disability Scale, Perceive Stress Scale and Quality of Life Inventory all showed improvement (P< or = 0.001, P=0.002 and P=0.029, respectively). The mean end-of-study dose of escitalopram was 25.4+/-6.6 mg/day. Of three subjects assigned to escitalopram during the discontinuation phase, none reported statistically significant worsening of gambling symptoms. However, one subject assigned to placebo reported that gambling symptoms returned within 4 weeks. Open-label escitalopram treatment was associated with improvements in gambling and anxiety symptoms and measures of psychosocial functioning and quality of life. Larger, longer, placebo-controlled, double-blind studies are needed to evaluate further the safety and tolerability of escitalopram in the treatment of PG and co-occurring anxiety.     

Milnacipran efficacy in the prevention of recurrent depression: a 12-month placebo-controlled study. Milnacipran recurrence prevention study group

To compare the efficacy and assess the tolerability of milnacipran 50mg p.o. b.i.d. to placebo in the prevention of recurrence in depressed patients who had responded an acute treatment and had remained in remission during a 4-month continuation phase. Remission criteria were: a Hamilton Depression Rating Scale (HDRS) (21-item) < or = 8, improvement or disappearance of the initial symptoms, and an assessment of 'very much improved' or 'much improved' on the Clinical Global Impression (CGI) Subscale: Global Improvement. Recurrence was defined by a major depressive episode according to DSM-III-R criteria and a minimum score of 18 on the HDRS, with the need to treat the recurrence. The primary analysis was the rate of recurrence as a function of time in the intent-to-treat population. Groups were compared using the Cox model. Absolute recurrence rates were 16.3% (17/104) in milnacipran-treated patients and 23.6% (26/110) in placebo-treated patients, with a significant difference in the reduction of recurrence as a function of time (Kaplan Meier Survival Analysis analysis, P < 0.05). There was no difference in tolerability between groups. This study demonstrates that milnacipran is effective with good tolerability in preventing recurrence in major depressive disorder over 1 year in patients with recurrent depression who responded to acute treatment with milnacipran and continued their response for 18 weeks.     

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Escitalopram versus placebo in the treatment of dysthymic disorder

Numerous studies have assessed the acute efficacy of antidepressants, including selective serotonin reuptake inhibitors, in treating dysthymic disorder; however, escitalopram, the S-enantiomer of citalopram, has not been studied. Thirty-six outpatients with Structured Clinical Interview for DSM-III-R-diagnosed dysthymic disorder, aged 23-65 years (mean±SD=44.7±11 years), were randomly assigned to double-blind escitalopram (maximum dose 20?mg/day) versus placebo for 12 weeks. Inclusion criteria included age 18-65 years and Hamilton Depression Rating Scale (HDRS) score≥12. We hypothesized that escitalopram would be superior to placebo in the HDRS-24 item total score at week 12. We also hypothesized the superiority of escitalopram over placebo for secondary measures, including the percentage of participants classified as responders and remitters, as well as social functioning (Social Adjustment Scale), clinical global impression-improvement, Global Assessment of Functioning Scale. Participants' baseline HDRS-24 averaged 23.4±5.9. Final HDRS-24 scores at last observation carried forward did not differ significantly between escitalopram-treated (mean±SD=10.88±5.83) and placebo-treated individuals (mean±SD=16.4±6.34) (F=2.82, degrees of freedom=1,32, P=0.10). Significant differences favoring active medication were found on the Social Adjustment Scale and the Clinical Global Impression Severity and Global Assessment of Functioning Scale, but not in the percentages of responders or remitters. A larger study sample or higher escitalopram dose may show more significant placebo-medication differences.     

Comparison of the effects of mirtazapine and fluoxetine in severely depressed patients

INTRODUCTION: Depression is a major global problem associated with large medical, sociological and economic burdens. Mirtazapine (Remeron, Organon NV, The Netherlands) is an antidepressant with a unique mechanism of action that has similar or superior efficacy to TCAs and SSRIs in moderate-to-severe depression. However, this agent has not yet been tested in patients with severe depression alone. OBJECTIVE: To compare the antidepressant efficacy and tolerability of mirtazapine and fluoxetine and their effects on anxiety and quality of life in patients with severe depression (> or = 25 points on the first 17 items of the Hamilton Depression Rating Scale [HDRS-17]). METHODS: In this double-blind study, 297 severely depressed patients were randomised to receive mirtazapine 15-60 mg/day (n = 147) or fluoxetine 20-40 mg/day (n = 152) for 8 weeks. 294 subjects were actually treated and 292 included in the intent-to-treat population. Symptom severity was measured by the HDRS-17, Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) rating scale. Quality of life was self-assessed by patients using the Leeds Sleep Evaluation Questionnaire and the Quality of Life, Enjoyment and Satisfaction Questionnaire. Adverse events were recorded throughout the study. RESULTS: No statistically significant differences were noted between the two groups in change from baseline HDRS-17 score at any time point; both treatments were associated with large (approximately 15 points) decreases by study end. However, more mirtazapine-treated patients tended to exhibit a > or = 50% decrease in HDRS score (significant at day 7; 9.0% vs 0.7%, p = 0.002). Significant differences in favour of mirtazapine were also observed at day 14 for changes in MADRS scores (-10.9 vs -8.5, p = 0.006) and the proportion of patients with > or = 50% decrease in MADRS score (21.4% vs 10.9%, p = 0.031). On the CGI, the proportion of 'much/very much improved' patients tended to be greater with mirtazapine (significant at day 7; 9.7% vs 3.4%, p = 0.032). No significant between-group differences were observed for the majority of quality-of-life measures. However, mirtazapine produced significantly better improvements on 'sleeping assessment 1' (14.9 +/- 5.2 vs 13.7 +/- 5.4, p = 0.028) and 'sleeping assessment 2' (p = 0.013) than fluoxetine. Both agents were generally well tolerated but mirtazapine-treated patients experienced a mean weight gain of 0.8 +/- 2.7 kg compared with a mean decrease in weight of 0.4 +/- 2.1 kg for fluoxetine-treated patients (p < 0.001). CONCLUSIONS: Mirtazapine is as effective and well tolerated as fluoxetine in the treatment of patients with severe depression.     

Escitalopram (10-20 mg/day) is effective and well tolerated in a placebo-controlled study in depression in primary care

Escitalopram was compared to placebo in moderately to severely depressed patients in primary care with citalopram as the active reference. Patients were randomized to receive flexible doses of 10-20 mg/day escitalopram (n=155), 20-40 mg/day citalopram (n=160), or placebo (n=154) over an 8-week double-blind period. The primary efficacy parameter was the change from baseline to last assessment in the Montgomery-Asberg Depression Rating Scale total score. Escitalopram produced a statistically significant therapeutic difference of 2.9 points (P=0.002) compared to placebo, and escitalopram was consistently and statistically significantly more efficacious than placebo from week 1 onwards. Analysis of Clinical Global Impression-Severity and Clinical Global Impression-Improvement confirmed the primary efficacy results. By week 8, significantly more patients had responded to treatment with escitalopram than with citalopram (P=0.021) or placebo (P=0.009). Escitalopram was as well tolerated as citalopram and had a similar adverse event profile. Both escitalopram- and citalopram-treated patients had placebo-level adverse event withdrawal rates (3% and 4%, respectively). This study demonstrates the consistent antidepressant efficacy and excellent tolerability of escitalopram 10-20 mg/day in primary care patients with 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.     

Citalopram versus amitriptyline in elderly depressed patients with or without mild cognitive dysfunction: a danish multicentre trial in general practice

This double-blind, multicenter trial, carried out in general practice in Denmark, comprised 221 women and 70 men, aged 58 to 97 years, with major depression (with or without mild cognitive dysfunction) or dysthymia (DSM-III-R). Patients had a total score > or =13 on the 17-item Hamilton Depression Rating Scale (HDRS) and a score > or =20 on the Mini Mental State Examination scale. The efficacy and tolerability of citalopram (20-40 mg daily) and amitriptyline (50-100 mg daily) were compared over 12 weeks. The participating general practitioners were trained at corating sessions in the use of the HDRS and Melancholia Scale (MES) prior to and during the study. The inter-observer reliability was assessed to investigate if general practitioners were able to use scales that measure the severity of depression. The two treatments were considered equally effective; the 90% confidence interval for the difference between the treatment groups in change from baseline to end-point in HDRS total score (-0.84 to +1.23) was within the predefined interval (-4 to +4). Significantly more patients on citalopram (50%) than on amitriptyline (31%) reported no adverse events at all (P = .001). Moreover, patients on amitriptyline reported adverse events significantly earlier and more frequently than patients on citalopram. The inter-observer reliability was highly satisfactory, with intra-class correlation coefficients (ICC-U) of .83 for the HDRS and .82 for the MES; however, the ICC-U for the Clinical Global Impressions was .54, indicating a poorer consensus in the investigators clinical judgment. Training in the use of the HDRS and MES scales improved the inter-observer reliability.     

Treatment of generalized anxiety disorder with citalopram

Serotonin reuptake inhibitors (SSRI), such as venalafaxine and paroxetine, are used in the treatment of generalized anxiety disorder (GAD). Patients with GAD frequently have comorbid psychiatric disorders, such as depression. SSRIs are effective in the treatment of a variety of anxiety disorders and depression. Citalopram, a newer SSRI used in the treatment of depression, has not been studied for GAD. This is the first report of the use of citalopram, the most selective SSRI, for the treatment of GAD in a retrospective case observation study. Thirteen patients diagnosed with GAD were treated with citalopram at an academic outpatient clinic. The main outcome measures were the Hamilton Rating Scale for Anxiety (HAM-A), Hamilton Depression Rating Scale (HAM-D) and Clinical Global Impressions of Severity (CGI-S; at baseline) and Improvement (CGI-I). The mean age of the patients was 38 years. The mean dose of citalopram at endpoint was 33 mg/day (range 10-60 mg/day). After 12 weeks of treatment with citalopram, all 13 patients experienced full or partial improvement in GAD and depressive symptoms leading to meaningful improvement in social and occupational functioning. Mean baseline HAM-A scores (mean+/-SEM) decreased from 22.2+/-1.3 to 6.2+/-0.9 after citalopram treatment. The mean CGI-I score was 1.8+/-0.2 with 11 of the 13 patients responding (CGI-I of 1 or 2). These data suggest that citalopram may be an effective treatment for GAD. Several patients who had failed previous treatment with other SSRIs responded to citalopram, suggesting that a second SSRI, such as citalopram, may be beneficial in this population. A larger placebo-controlled study of citalopram is warranted in GAD.     

Alprazolam: an antidepressant? Alprazolam, desipramine, and an alprazolam-desipramine combination in the treatment of adult depressed outpatients

The antidepressant efficacy of alprazolam (ALP) was tested in a double-blind controlled comparison with desipramine (DMI) and an ALP-DMI combination in outpatients diagnosed with major depressive disorder by Research Diagnostic Criteria (90% met criteria for endogenous subtype). Following a placebo period of at least 1 week, subjects who continued to meet severity criteria defined by Hamilton Depression Rating Scale (HDRS) scores were administered oral doses of the active medication (N = 79), in a dose ratio of 1 mg ALP:50 mg DMI:1 mg ALP + 50 mg DMI. Treatment continued for 6 weeks, and all subjects who completed at least 2 weeks (N = 69) were included in endpoint analyses. Following the placebo baseline, symptoms were rated again at day 5 and at the end of weeks 1, 2, 4, and 6. Final doses averaged 4.6 +/- 1.3 mg for the ALP group, 230 +/- 61 mg for the DMI group, and 4.6 +/- 1.2 mg ALP + 229.5 +/- 1.2 mg DMI for the combination group. The final outcome was a comparable degree of improvement at the endpoint among the three treatment groups on measures of depression (HDRS and Beck Depression Inventory), anxiety (Hamilton Anxiety Rating Scale), and global improvement (Global Assessment Scale, and Physician and Patient Global Impressions). A similar outcome was found for the subgroup of patients who completed all 6 weeks (N = 56). Endpoint analyses also showed that ALP-treated subjects responded sooner and continued to show improvement throughout the course of the study on measures of depression, anxiety, and global status. These results suggest that ALP alone is as effective as a standard tricyclic for the acute treatment of patients with major depressive disorder and that significant improvement may occur within the first week of medication. Side effect profiles were compared among treatment groups and are discussed, as are other clinical studies that have investigated ALP's potential antidepressant efficacy.     

Citalopram concentrations and response in obsessive-compulsive disorder. Preliminary results

OBJECTIVE: Citalopram, a highly potent SSRI, is effective in the treatment of depressive disorders and obsessive-compulsive disorder (OCD); however, very few studies have reported concentration-effect relationships for SSRIs. The aim of this study was to investigate the relationship between citalopram concentrations and clinical response in patients with OCD. METHODS AND STUDY DESIGN: Fifteen patients (aged 18-65 years) with a DSM-IV diagnosis of OCD were included in this open-label, single-blind study. Citalopram was started at a dosage of 20 mg/day; the dosage was increased to a maximum of 60 mg/day by the third week, on the basis of clinical need and tolerability. The dosage then remained unchanged until the end of the 10-week study. Clinical assessments were made at baseline, weekly for the first four weeks and then at weeks 6, 8 and 10. The assessment scales used were the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Clinical Global Impression Scale (CGI) and the Hamilton Depression Rating Scale (HDRS). Plasma citalopram concentrations were determined using a high performance liquid chromatography method after solid phase extraction. RESULTS: One patient was withdrawn from the study because of poor compliance. Of the 14 patients who completed the study, nine did not meet the treatment response criterion of an improvement of >25% from the baseline total Y-BOCS score and a score of < or =3 for the global improvement item of the CGI (these patients were termed non-responders), while five did (responders). There were no differences in the main demographic and baseline clinical variables between responders and non-responders. Steady-state citalopram concentrations were similar in the two groups, suggesting that the anti-obsessional effects of citalopram were not related to pharmacokinetic differences between responders and non-responders. There was no linear relationship between steady-state citalopram concentrations and response. The citalopram concentrations and Y-BOCS scores of individual responders obtained at baseline and various study timepoints showed a sigmoid relationship when analysed using the E(max) (maximum change in Y-BOCS score) model, with a mean EC(50) value (drug concentration that elicits 50% of the E(max)) of 152 microg/L, whereas a similar analysis of the non-responders generated a flat line. CONCLUSION: The results of this preliminary study suggest that plasma citalopram concentrations may be related to the clinical response in responders, but do not seem to account for the lack of clinical effect in non-responders. These data, as well as the usefulness of the model in relating plasma concentrations to response, even after repeated administration, need to be validated by further investigations.     

Short‐term and long‐term evaluation of selective serotonin reuptake inhibitors in the treatment of panic disorder: fluoxetine vs citalopram

This double‐blind study evaluates the efficacy and tolerability of fluoxetine and citalopram in the acute and long‐term treatment of panic disorder in 42 patients meeting DSM‐IV criteria for panic disorder with or without agoraphobia. Fluoxetine and citalopram showed similar efficacy in the treatment of panic disorder patients. On the basis of HRSA and PASS mean score evaluation, fluoxetine was more rapid than citalopram in reducing generalized anxiety symptoms, spontaneous panic attacks and anticipatory anxiety. Fluoxetine appeared to be effective at a dosage of 10 mg/day, while citalopram reached the same efficacy at a dosage of 30 mg/day. Long‐term evaluation has demonstrated high rates of persistent full remission with both drugs. Copyright © 1999 John Wiley & Sons, Ltd.     

Carbamazepine augmentation in depressive patients non-responding to citalopram: a pharmacokinetic and clinical pilot study.

Citalopram is a chiral antidepressant drug. Its eutomer, S-citalopram (escitalopram), has recently been introduced as an antidepressant. In an open pilot study, four outpatients and two inpatients with a major depressive episode (ICD-10), and who were nonresponders to a 4-week pretreatment with 40-60 mg/day citalopram, were comedicated for another 4-week period with carbamazepine (200-400 mg/day). Some of the patients suffered also from comorbidities: Phobic anxiety disorder with panic attacks (n=2), generalised anxiety disorder, alcohol abuse, dependent personality disorder, hypertension (n=1). After a 4-week augmentation therapy with carbamazepine, a significant (P<0.03) decrease of the plasma concentrations of S-citalopram and R-citalopram, by 27 and 31%, respectively, was observed. Apparently, the probable induction of CYP3A4 by carbamazepine results in a nonstereoselective increase in N-demethylation of citalopram. Moreover, there was a significant (P<0.03) decrease of the ratio S/R-citalopram propionic acid derivative, the formation of it being partly regulated by MAO-A and MAO-B. Already, within 1 week after addition of carbamazepine, there was a slight but significant (P<0.03) decrease of the MADRS depression scores, from 27.0+/-7.7 (mean+/-S.D.) to 23.3+/-6.6, and the final score on day 56 was 18.8+/-10.9. The treatment was generally well tolerated. There was no evidence of occurrence of a serotonin syndrome. After augmentation with carbamazepine, treatment related adverse events were: Nausea in one case, diarrhea in one case, and rash in two cases. In conclusion, the results of this pilot study suggest that carbamazepine augmentation of a citalopram treatment in previous nonresponders to citalopram may be clinically useful, but that in addition carbamazepine can lead to a decrease of the plasma concentrations of the active enantiomer escitalopram.     

Combination of citalopram plus paliperidone is better than citalopram alone in the treatment of somatoform disorder: results of a 6-week randomized study

The objective of this study was to evaluate the effectiveness and tolerability of citalopram versus citalopram plus paliperidone combination therapy in patients with somatoform disorders (SDs). In this 6-week, randomized, fixed-dose study, 60 patients with SD (ICD-10 F45.0), undifferentiated SD (F45.1), and somatoform autonomic dysfunction (F45.3) were randomly assigned to receive citalopram (20 mg/day) with or without paliperidone (3 mg/day). Four scales were used to evaluate effectiveness and tolerability at baseline and at the end of the second, fourth, and sixth week after treatment: Somatoform Disorders Screening Symptoms-7 (SOMS-7), Hamilton Anxiety Scale (HAMA), 17-item Hamilton Depression Scale (HAMD-17), and Treatment Emergent Symptom Scale (TESS). The rater was blinded to the kind of treatment patients received. (i) In the intention-to-treat population (N = 51), the overall response ratio (50% reduction in SMOS-7 scores) was significantly higher in the citalopram-paliperidone group compared with the citalopram group after a 6-week treatment (71.4 vs. 38.10%, χ2 = 4.71, P = 0.03). (ii) The SOMS-7 and somatic subscore of the Hamilton Anxiety Scale (HAMA-SOM) total score of the citalopram plus paliperidone group decreased more significantly than that of the citalopram group, and a significant difference could be observed at the end of 4 weeks of treatment. (iii) There was no significant difference between the two groups in adverse effects, and no serious adverse event was reported in both groups. Our findings indicate that a combination with paliperidone is significantly better than monotherapy with citalopram whether synergistic or add-on for patients with SDs. Our results call for future studies with larger sample sizes and a longer duration to draw more definitive conclusions.     

Double-Blind Randomized Controlled Pilot Study of the Efficacy and Tolerability of Pirlindole,a Reversible Inhibitor of Monoamine Oxidase A,and Mianserin,in the Treatment of Depression

This double-blind randomized pilot study aimed to compare the efficacy and the tolerability of pirlindole (150–225 mg/day), a reversible inhibitor of monoamine oxidase A, and mianserin (60–90 mg/day) in the treatment of major depression. Forty patients were included in the trial (20 pirlindole and 20 mianserin) and 38 patients (18 pirlindole and 20 mianserin) completed the whole study (28 days of administration). Both treatments exhibited highly significant improvements in the Hamilton Depression Rating Scale score (HDRS), the Hamilton Anxiety Rating Scale score (HARS) and the Beck auto-evaluation scale score (BECK) from day 7 up to day 28. The evolution of the HDRS score in the two groups did not differ significantly. The evolution of the HARS and BECK scores taken separately and the evolution of the combined total score (HDRS + HARS + BECK) significantly differed between the two groups, pirlindole producing a significantly higher decrease than mianserin in the two separate scores on day 28 and on days 21 and 28 in the case of the combined total score. Two patients experienced adverse reactions, one in the pirlindole group complained of sleep disturbances and one in the mianserin group suffered from dry mouth. The results of this study attest to the efficacy and tolerability of pirlindole in the treatment of depression. © 1997 John Wiley & Sons, Ltd.     

An open-label study of citalopram for major depression following traumatic brain injury

Major depression is associated with substantial psychosocial dysfunction and post-concussive symptomatology following traumatic brain injury (TBI). Studies to date of anti-depressant treatment for major depression post-TBI have been limited by small sample size. The goal of the present study is to examine the rates of response and remission associated with citalopram treatment for major depression following traumatic brain injury. Subjects with major depression following mild-to moderate TBI were treated with open-label citalopram with a starting dose of 20 mg/day to a maximum of 50 mg/day for either 6 weeks (n = 54) or 10 weeks (n = 26). The Hamilton Depression Rating Scale (HAMD) was used to assess depression severity. Response was defined by a 50% reduction in HAMD score, and remission was defined by a HAMD score of < or =7. The mean HAMD at baseline and 6 weeks were 23.66 (SD 6.8) and 16.30 (SD 9.3), respectively (t[53] = 7.157, p < 0.0001). The mean HAMD at 10 weeks was 12.96 (SD 7.9) (t[25] = 7.323, p < 0.0001). At 6 weeks, 54 subjects were assessed and 27.7% responded with 24.1% in remission. At 10 weeks, 26 subjects were assessed and 46.2% responded with 26.9% in remission. The response rate in the present sample was substantially lower than previously reported for patients with TBI, but comparable to the results of the largest effectiveness trial of citalopram for general out-patients with major depression in the absence of TBI.     

Duloxetine as an SNRI treatment for generalized anxiety disorder: results from a placebo and active-controlled trial

This study examined the efficacy and tolerability of duloxetine 60-120 mg/day for the treatment of patients with generalized anxiety disorder. This was a multicenter, randomized, double-blind, flexible-dose, placebo and active-controlled (venlafaxine extended-release 75-225 mg/day) trial designed to assess duloxetine 60-120 mg/day during 10 weeks of treatment in adults with Diagnostic and statistical manual of mental disorders-IV-defined generalized anxiety disorder. The primary efficacy outcome measure was mean change from baseline to endpoint in the Hamilton Anxiety Rating Scale total score assessed using analysis of covariance. A total of 487 patients were randomly assigned to duloxetine (n=162), venlafaxine XR (n=164), or placebo (n=161). Significantly greater improvement on the Hamilton Anxiety Rating Scale total score occurred in the duloxetine (P=0.007) and venlafaxine XR (P<0.001) groups compared with the placebo group. Overall discontinuation rates did not differ among the three groups, but adverse event-related discontinuation was significantly higher in the duloxetine (14.2%, P<0.001) and venlafaxine XR (11.0%, P=0.001) groups than in the placebo group (1.9%). During the 2-week drug-tapering phase, discontinuation-emergent adverse events were significantly greater in the venlafaxine XR group (26.9%, P=0.04), but not in the duloxetine group (19.4%, P=0.448) compared with placebo (15.8%). Duloxetine 60-120 mg/day and venlafaxine XR 75-225 mg/day were each efficacious treatments for patients with generalized anxiety disorder.     

Efficacy and tolerability of extended release quetiapine fumarate monotherapy in the acute treatment of generalized anxiety disorder: a randomized, placebo controlled and active-controlled study

The main objective of this study was to evaluate efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in generalized anxiety disorder (GAD). This was a 8 week randomized, 2-week follow-up, double-blind, placebo-controlled, and active-controlled study. Patients were randomized to quetiapine XR 150 (n=219) or 300 mg/day (n=207); escitalopram, 10 mg/day (n=213); or placebo (n=215). The primary endpoint was the change from randomization at week 8 in Hamilton Anxiety Rating (HAM-A) total score. Week 8 mean HAM-A total score was significantly reduced from randomization with quetiapine XR 150 mg/day (-13.9, P<0.001), 300 mg/day (-12.3, P<0.05) and escitalopram (-12.3, P<0.05) versus placebo (-10.7); significant improvements with quetiapine XR (150 and 300 mg/day) versus placebo (P<0.001) were also shown at day 4. At week 8, significant improvements versus placebo were observed in HAM-A psychic [quetiapine XR (both doses) and escitalopram] and somatic (quetiapine XR 150 mg/day and escitalopram) cluster scores and HAM-A response and remission rates (quetiapine XR 150 mg/day). Most common adverse events were dry mouth, somnolence and sedation (quetiapine XR), headache, and nausea (escitalopram). In patients with GAD, quetiapine XR (150 and 300 mg/day) demonstrated significant efficacy at week 8 with symptom improvement as early as day 4. We concluded that quetiapine XR safety and tolerability results were consistent with the known profile of quetiapine.     

Efficacy and tolerability of mirtazapine versus citalopram: a double-blind, randomized study in patients with major depressive disorder. Nordic Antidepressant Study Group

We aimed to compare the antidepressant and anxiolytic effects, tolerability and effects on quality of life of mirtazapine and citalopram in a randomized, double-blind, multicentre, 8-week study. Patients with a Major Depressive Episode (DSM-IV) and a baseline score of > or = 22 on the Montgomery-Asberg Depression Rating Scale (MADRS) were randomized to 8 weeks treatment with either mirtazapine (n = 137, 15-60 mg/day) or citalopram (n = 133, 20-60 mg/day). Efficacy was evaluated by the MADRS, Hamilton Anxiety Scale (HAM-A), Clinical Global Impression scales (CGI), the Leeds Sleep Evaluation Questionnaire (LSEQ) and Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ). The efficacy analyses were performed on the Intent-To-Treat Group using the Last Observation Carried Forward method. Vital signs and laboratory variables are measured and adverse events recorded at each weekly visit. The magnitude of reduction from baseline in group mean MADRS scores was large in both groups, reaching after 8 weeks of treatment mean scores of 9.1 in the mirtazapine group and 8.9 in the citalopram group. Both treatments also resulted in a substantial improvement in anxiety symptoms, sleep disturbances and quality of life, and high percentage of responders. However, at day 14, statistically significantly larger magnitudes of change favouring mirtazapine were present in the group mean MADRS, HAM-A and CGI-Severity of illness and Quality of life scores. A difference of 2.3 points on MADRS favouring mirtazapine is considered indicative for a clinically relevant superiority between two proven antidepressants. Mirtazapine treatment was also related to faster improvement of sleep, quality of sleep and improved alertness following awakening, as shown by statistically significant differences on the self-rating LSEQ at various time points. There were no differences between two treatment groups on self-rating QLSEQ. Both drugs were well tolerated, with a low number of patients in either group prematurely terminating the study due to adverse events (mirtazapine: 3.6%, citalopram, 3.0%). Sweating and nausea were statistically significantly more frequent in the citalopram group and increased appetite and complaints of weight increase in the mirtazapine group. There were no clinically relevant changes in laboratory parameters and vital sign variables with either treatment, except for clinically relevant increase in body weight, occurring more frequently in mirtazapine patients. In this study, mirtazapine and citalopram were equally effective in reducing symptoms of depression and anxiety, and well tolerated. However, mirtazapine was significantly more effective than citalopram after 2 weeks of treatment on the MADRS, HAM-A and CGI Severity of illness and Quality of life scales. This finding, consistently present at all major efficacy variables, suggests potentially faster onset of efficacy of mirtazapine over citalopram.