The efficacy and safety of a new enteric-coated formulation of fluoxetine given once weekly during the continuation treatment of major depressive disorder

BACKGROUND: A simple, once-weekly dosing regimen could be a convenient alternative for many patients during long-term treatment of depression. Such a strategy might also be effective for improving medication compliance and the outcome of continuation treatment. The safety and effectiveness of a new formulation of enteric-coated fluoxetine (90 mg) given once weekly was tested during the continuation treatment of major depressive disorder. METHOD: Patients meeting DSM-IV criteria for major depressive disorder with modified 17-item Hamilton Rating Scale for Depression (HAM-D-17) scores > or = 18 and Clinical Global Impressions-Severity of Illness scale (CGI-S) scores > or = 4 were treated 13 weeks with open-label 20 mg/day of fluoxetine in a multicenter U.S. study. Responders (N = 501) were randomly assigned to receive 20 mg of fluoxetine daily, placebo, or 90 mg of enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. The primary efficacy measure was the percentage of patients who relapsed. Time to relapse was tested over the 25-week continuation period using log-rank analyses of the Kaplan-Meier estimates of relapse rates. Additional analyses of efficacy included comparison of change from baseline to endpoint for the HAM-D-17, CGI-S, and HAM-D-28 subscales by last observation carried forward (LOCF). Safety measures included comparison of treatment-emergent adverse events, both spontaneous and solicited (using the Association for Methodology of Documentation in Psychiatry-Module 5), vital signs, and laboratory measures. RESULTS: Relapse rates for patients assigned to fluoxetine, either 20 mg daily or 90 mg weekly, were significantly lower than for placebo by log-rank analysis and LOCF analyses of secondary efficacy measures. Efficacy did not significantly differ between the 2 active drug groups by these measures. Enteric-coated fluoxetine at a once-weekly dose of 90 mg was well tolerated, and its safety profile was similar to that of daily 20 mg of fluoxetine. CONCLUSION: The formulation of enteric-coated fluoxetine taken once weekly is effective, safe, and well tolerated for continuation treatment of depression in patients who responded to acute treatment with 20 mg/day of fluoxetine. Monitoring during long-term treatment for evidence of sustained remission is important regardless of dosing regimen.     

Patient compliance to a new enteric-coated weekly formulation of fluoxetine during continuation treatment of major depressive disorder

BACKGROUND: A new formulation of enteric-coated fluoxetine given once weekly could be a useful option for the long-term treatment of depression, but compliance to once-weekly fluoxetine treatment has not been assessed. METHOD: Patients were adults from the United Kingdom who had responded to fluoxetine treatment for a current episode of depression (DSM-IV criteria). In the baseline assessment phase, all patients (N = 117) were continued on 20 mg of open-label fluoxetine once daily for 4 weeks. In the follow-up phase, patients (N = 109) were randomly assigned to once-weekly or once-daily fluoxetine for 3 months. Patient compliance was monitored by electronic devices during both phases of the study. RESULTS: Compliance to once-weekly fluoxetine treatment was higher than compliance to once-daily fluoxetine (85.9% vs. 79.4%, respectively). CONCLUSION: Once-weekly fluoxetine treatment allows for new flexibility for both the clinician and the patient, and this study alleviates the concern that patients will forget weekly doses.     

An open study of triiodothyronine augmentation of selective serotonin reuptake inhibitors in treatment-resistant major depressive disorder

OBJECTIVE: In an open trial, we investigated the efficacy of triiodothyronine (T(3)) adjuvant to selective serotonin reuptake inhibitors (SSRIs) in subjects with major depressive disorder (MDD) resistant to SSRI treatment. METHOD: Twenty subjects who met DSM-IV criteria for MDD (mean +/- SD age = 44.3 +/- 10.3 years; 55% [N = 11] women) and had failed to respond to a course of treatment of at least 8 weeks with an SSRI antidepressant were enrolled in a 4-week open-label augmentation treatment with T(3) 50 microg/day. Atypical and melancholic sub-types of MDD were diagnosed using Structured Clinical Interview for DSM-IV Axis I Disorders criteria. We administered the 17-item Hamilton Rating Scale for Depression (HAM-D-17) 4 times during the study (which was conducted between 2001 and 2003). RESULTS: During T(3) augmentation, the severity of depression decreased from an initial mean +/- SD HAM-D-17 score of 20.5 +/- 3.6 to a final HAM-D-17 score of 14.0 +/- 7.1 (p < .001). Seven subjects (35.0%) were treatment responders (HAM-D-17 reduction >or= 50%), and 6 subjects (30.0%) achieved clinical remission (final HAM-D-17 相似文献   

Efficacy and safety of mirtazapine in major depressive disorder patients after SSRI treatment failure: an open-label trial

OBJECTIVE: To evaluate the efficacy and safety of mirtazapine in depressed outpatients who have shown nonresponse or intolerance to selective serotonin reuptake inhibitor (SSRI) therapy. METHOD: In this open-label, 8-week study, the efficacy and safety of mirtazapine among 103 outpatients with DSM-IV major depressive disorder who had failed previous therapy with an SSRI (fluoxetine, paroxetine, or sertraline) were evaluated. The primary efficacy measure was the 17-item Hamilton Rating Scale for Depression (HAM-D-17), and safety assessments included reported adverse events, routine laboratory assessments, physical examinations, and assessments of vital signs. A 4-day washout period followed by mirtazapine treatment was compared with an immediate switch from the SSRI to mirtazapine. RESULTS: Based on mean HAM-D-17 scores at endpoint and response rates of 48% based on the criterion of > or = 50% reduction in HAM-D-17 score, mirtazapine was found to be an effective treatment for a substantial proportion of patients for whom an SSRI was ineffective and/or poorly tolerated. Mirtazapine was well tolerated, with sedation and appetite increase/weight gain the most commonly reported adverse events. In addition, no difference in efficacy, safety, or tolerability was observed for patients undergoing an immediate switch from an SSRI (after having been tapered to the minimal effective dose) to mirtazapine, compared with those undergoing the imposition of a 4-day drug-free washout. CONCLUSION: These results suggest that an immediate switch to mirtazapine may be a valid therapeutic option among patients who cannot tolerate or do not respond to SSRIs.     

Long-term treatment outcomes of depression with associated anxiety: efficacy of continuation treatment with fluoxetine

BACKGROUND: Severity of anxiety does not appear to influence the antidepressant response to fluoxetine during acute treatment of major depressive disorder (MDD). We report a retrospective pooled analysis of 2 studies to assess the effect of associated anxiety on the efficacy of fluoxetine in the continuation treatment phase of MDD. METHOD: Patients whose MDD remitted (study 1) or responded (study 2) after approximately 12 to 13 weeks of open-label treatment with fluoxetine 20 mg daily were randomly assigned in double-blind fashion to placebo, continued treatment with fluoxetine 20 mg daily, or, in study 2 only, treatment with enteric-coated fluoxetine 90 mg once weekly, for at least 25 weeks. Both studies included male and female outpatients who met criteria for MDD as assessed by DSM-III-R (study 1) or DSM-IV (study 2). Patients were categorized into high anxiety (> or = 7) or low anxiety (< 7) subgroups based on baseline Hamilton Rating Scale for Depression (HAM-D) anxiety/somatization subfactor scores. Subgroups were compared by therapy for time from randomization to relapse and change in efficacy scores. RESULTS: No significant differences in time to relapse were observed between anxiety subgroups in either active treatment group. However, in patients switched to placebo for continuation treatment, the high anxiety subgroup had a significantly higher risk of relapse than those with low anxiety (risk ratio = 1.63, p =.013). Significant differences between anxiety groups were seen in change in HAM-D anxiety/somatization subfactor scores in the fluoxetine 20 mg and placebo treatment groups, and in change in HAM-D-17 scores in the placebo treatment group (p <.05). CONCLUSION: Although high baseline anxiety does not appear to impact the benefit of continuation therapy with fluoxetine, it does appear to predict increased risk of relapse in individuals who do not remain on antidepressant therapy for the duration of continuation treatment.     

Suizidalität bei depressiven Kindern und Jugendlichen unter Behandlung mit selektiven Serotoninwiederaufnahmehemmern

Due to concerns that selective serotonin reuptake inhibitors (SSRI) might be associated with an increased risk of suicidal ideation and suicide attempts in depressive children and adolescents, treatment with these drugs is controversial. All available data from randomised controlled trials on SSRIs treating depression in these age groups were examined regarding efficacy and suicidality. Results suggest that fluoxetine and, less clearly, sertraline are effective in such treatment. A meta-analysis yielded no statistically significant difference between treatment with SSRI and placebo with regard to the occurrence of suicidal behavior. Following evidence-based criteria, the risk:benefit ratio is favourable for fluoxetine and sertraline. Their use in the pharmacotherapy of depressive children and adolescents is indicated.     

Depression-free days as a summary measure of the temporal pattern of response and remission in the treatment of major depression: a comparison of venlafaxine,selective serotonin reuptake inhibitors,and placebo

BACKGROUND: This article develops and applies depression-free days (DFDs) as a summary measure of the temporal pattern of response and remission in a comparison of venlafaxine (a dual-action serotonin-norepinephrine reuptake inhibitor) with selective serotonin reuptake inhibitors (SSRIs) and placebo. METHOD: Weekly data on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) from 2046 patients with DSM-III-R/IV-established moderate-to-severe major depression, participating in 1 of 8 randomized, double-blind, controlled studies that compared venlafaxine with an SSRI (fluoxetine, paroxetine, or fluvoxamine) or with both placebo and an SSRI, were used to estimate DFDs. Maximum DFDs were imputed to maintained HAM-D-17 scores < or = 7 (asymptomatic depression) over time, minimum DFDs to persistent HAM-D-17 scores > or = 15 (acutely symptomatic depression), and prorated DFDs to intermediate HAM-D-17 scores. A secondary construct was developed to test sensitivity to a less stringent upper threshold of acutely symptomatic depression (HAM-D-17 score > or = 22). Using a tertiary construct, sensitivity to a more stringent lower threshold representing elimination of residual symptoms was also evaluated. The construct validity of the primary and the secondary DFDs measures was assessed in terms of their correlation with sustained low clinical global severity of illness (scores of 1 or 2 on the Clinical Global Impressions-Severity of Illness scale). for each construct, DFDs were compared across the 3 treatment groups and corresponding effect sizes were generated. RESULTS: Overall, sustained low clinical global severity of illness was associated with 38.3 median (interquartile range, 29.8 to 44.2) DFDs relative to 5.7 (interquartile range, 0 to 20.6) median DFDs associated with nonsustained low clinical global severity; similar differences emerged in terms of sustained asymptomatic depression. The venlafaxine group (N = 851) experienced a median of 18.8 (interquartile range, 0.4 to 34.6) DFDs compared with a median of 13.6 (interquartile range, 0 to 29.8) DFDs in the SSRI group (N = 749) and 7.4 (interquartile range, 0 to 26.2) DFDs in the placebo group (N = 446) (p <.0001 overall; venlafaxine vs. SSRIs, p =.0015, effect size = 0.2; venlafaxine vs. placebo, p <.0001, effect size = 0.4; and SSRIs vs. placebo, p =.0007, effect size = 0.2). The secondary and tertiary DFDs constructs yielded similar, albeit narrower, differences in all comparisons. CONCLUSION: The construct of DFDs was found to be a useful summary measure of sustained remission. Active treatments were associated with more DFDs than placebo, and venlafaxine with more DFDs than SSRIs, consistent with corresponding differences in sustained remission.     

Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting with major depressive disorder.

BACKGROUND: Insomnia and major depressive disorder (MDD) can coexist. This study evaluated the effect of adding eszopiclone to fluoxetine. METHODS: Patients who met DSM-IV criteria for both MDD and insomnia (n = 545) received morning fluoxetine and were randomized to nightly eszopiclone 3 mg (ESZ+FLX) or placebo (PBO+FLX) for 8 weeks. Subjective sleep and daytime function were assessed weekly. Depression was assessed with the 17-item Hamilton Rating Scale for Depression (HAM-D-17) and the Clinical Global Impression Improvement (CGI-I) and Severity items (CGI-S). RESULTS: Patients in the ESZ+FLX group had significantly decreased sleep latency, wake time after sleep onset (WASO), increased total sleep time (TST), sleep quality, and depth of sleep at all double-blind time points (all p < .05). Eszopiclone co-therapy also resulted in: significantly greater changes in HAM-D-17 scores at Week 4 (p = .01) with progressive improvement at Week 8 (p = .002); significantly improved CGI-I and CGI-S scores at all time points beyond Week 1 (p < .05); and significantly more responders (59% vs. 48%; p = .009) and remitters (42% vs. 33%; p = .03) at Week 8. Treatment was well tolerated, with similar adverse event and dropout rates. CONCLUSIONS: In this study, eszopiclone/fluoxetine co-therapy was relatively well tolerated and associated with rapid, substantial, and sustained sleep improvement, a faster onset of antidepressant response on the basis of CGI, and a greater magnitude of the antidepressant effect.     

A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients.

Depression is associated with considerable morbidity and mortality. As depressive disorders carry a high risk of relapse, treatment strategies include the use of a 6-month continuation period after resolution of the acute episode. Tolerability is of major importance when determining compliance and outcome during long-term therapy. Due to the superior tolerability profile of the selective serotonin reuptake inhibitors (SSRIs) over the older tricyclic antidepressants (TCAs), the former may be more suitable for extended therapy. Comparative studies have not shown differences between the SSRIs in terms of efficacy, but side-effect profiles may vary. A multicenter, double-blind, comparative study of sertraline and fluoxetine was carried out in outpatients fulfilling DSM-III-R criteria for major depressive disorder. Patients were randomised to receive sertraline (50-150 mg, n = 118) or fluoxetine (20-60 mg, n = 120) for 24 weeks. Assessments for depression (HAM-D, HAD, CGI-I, CGI-S), anxiety (Covi), sleep (Leeds Sleep Evaluation scale) and quality of life (SIP) were made at study entry and at weeks 2, 4, 8, 12, 18 and 24. All adverse events were recorded to allow evaluation of tolerability. In total, 88 patients in the sertraline group completed the study compared with 79 in the fluoxetine group. Side effects were responsible for the premature treatment withdrawal of seven (6%) sertraline patients and 12 (10%) fluoxetine patients. Two-hundred and thirty-four patients were included in an ITT analysis up to last visit (116 sertraline, 118 fluoxetine). At study endpoint, both treatments produced a significant improvement over baseline on all efficacy variables (P < 0.001). Although the magnitude of global changes in depression, anxiety, and quality of life was larger with sertraline than fluoxetine, none of the between-group differences reached statistical significance. However, significant differences in favour of sertraline were observed for individual HAM-D items including item 4 (insomnia onset) (P = 0.04), item 9 (agitation) (P = 0.02), and item 13 (general somatic symptoms) (P = 0.008). In addition, sertraline was associated with significantly superior performance on the Leeds Sleep Evaluation scale and on SIP items relating to sleep and rest, emotional behaviour and ambulation. Both sertraline and fluoxetine were well tolerated with no significant differences between treatments.     

Remission rates following antidepressant therapy with bupropion or selective serotonin reuptake inhibitors: a meta-analysis of original data from 7 randomized controlled trials

BACKGROUND: Although it is widely believed that the various classes of antidepressants are equally effective, clinically meaningful differences may be obscured in individual studies because of a lack of statistical power. The present report describes a meta-analysis of original data from a complete set of studies comparing the norepinephrine/dopamine reuptake inhibitor (NDRI) bupropion with selective serotonin reuptake inhibitors (SSRIs; sertraline, fluoxetine, or paroxetine). METHOD: Individual patient data were pooled from a complete set of 7 randomized, double-blind studies comparing bupropion (N = 732) with SSRIs (fluoxetine, N = 339; sertraline, N = 343; paroxetine, N = 49) in outpatients with major depressive disorder (DSM-III-R or DSM-IV); 4 studies included placebo (N = 512). Response and remission rates were compared at week 8 or endpoint in both the intent-to-treat sample, using the last-observation-carried-forward (LOCF) method to account for attrition, and the observed cases. Tolerability data, including incidence of sexual side effects, were also compared. RESULTS: The LOCF response and remission rates for the bupropion (62% and 47%) and SSRI (63% and 47%) groups were similar; both active therapies were superior to placebo (51% and 36%; all comparisons, p < .001). The same pattern of results was demonstrated on the observed cases analyses. Although bupropion and SSRIs were generally well tolerated, SSRI therapy resulted in significantly higher rates of sexual side effects as compared to both bupropion and placebo. SSRIs were also associated with more somnolence and diarrhea, and bupropion was associated with more dry mouth. CONCLUSION: Bupropion and the SSRIs were equivalently effective and, overall, both treatments were well tolerated. The principal difference between these treatments was that sexual dysfunction commonly complicated SSRI therapy, whereas treatment with bupropion caused no more sexual dysfunction than placebo.     

Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment

BACKGROUND: The effects of extended selective serotonin reuptake inhibitor (SSRI) treatment on weight are not well characterized. Also unknown is whether different agents have differential effects. To examine these questions, we assessed weight changes in patients randomly assigned to long-term treatment with fluoxetine, sertraline, or paroxetine. METHOD: Patients (N = 284) with major depressive disorder (DSM-IV) were randomly assigned to double-blind treatment with fluoxetine (N = 92), sertraline, (N = 96), or paroxetine (N = 96) for a total of 26 to 32 weeks. The mean percent change in weight was compared for each group, as was the number of patients who had > or = 7% weight increase from baseline. RESULTS: Patients (fluoxetine, N = 44; sertraline, N = 48; paroxetine, N = 47) who completed the trial were included in these analyses. Paroxetine-treated patients experienced a significant weight increase, fluoxetine-treated patients had a modest but nonsignificant weight decrease, and patients treated with sertraline had a modest but nonsignificant weight increase. The number of patients whose weight increased > 7% from baseline was significantly greater for paroxetine-treated compared with either fluoxetine-treated or sertraline-treated patients. CONCLUSION: Risk of weight gain during extended SSRI treatment differs depending on which SSRI is used.     

Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo.

BACKGROUND: Most examinations of the clinical efficacy of drugs used to treat depression pool subjects across gender and age groups. This investigation compared these patient subpopulations on the basis of remission and response rates associated with venlafaxine and selective serotonin reuptake inhibitor (SSRI) treatment. METHOD: A meta-analysis of original data from 8 comparable double-blind, active-controlled, randomized clinical trials (4 also placebo-controlled) was conducted. Antidepressant efficacy was assessed for patients (N = 2,045) aged 18 to 83 years (subgroups: < or = 40, 41-54, 55-64, and > or = 65 years) who met DSM-III-R criteria for major depression or DSM-IV criteria for major depressive disorder and were randomly assigned to receive venlafaxine (immediate release, N = 474; extended release, N = 377), one of several SSRIs (N = 748), or placebo (N = 446) for up to 8 weeks. Symptoms of depression were assessed using the Hamilton Rating Scale for Depression (HAM-D). Remission was defined as a HAM-D-17 score < or = 7, response was defined as > or = 50% decrease in HAM-D-21 score, and absence of depressed mood was defined as a HAM-D depressed mood item score of 0. RESULTS: We detected no significant age-by-treatment, gender-by-treatment, or age-by-gender-by-treatment interactions; men and women of different ages within a given antidepressant treatment group exhibited similar rates of remission, response, and absence of depressed mood. Regardless of age or gender, remission rates during venlafaxine therapy were significantly higher than during SSRI therapy (remission rates at week 8: venlafaxine, 40%-55% vs. SSRI, 31%-37%; p < .05). Regardless of patient age or gender, onset of remission was more rapid with venlafaxine than with SSRI treatment. By contrast, rates of absence of depressed mood with venlafaxine (34%-42%) and SSRIs (31%-37%) did not differ significantly and tended to be similar for all patient subgroups. CONCLUSION: These data suggest that men and women have comparable responses to SSRIs and venlafaxine across various age groups. Moreover, patients exhibited a more rapid onset and a greater likelihood of remission with venlafaxine therapy than with SSRI therapy regardless of age or gender.     

Escitalopram in major depressive disorder: a multicenter, randomized, double-blind, fixed-dose, parallel trial in a Chinese population

Escitalopram, the S-enantiomer of citalopram and the most selective of the selective serotonin reuptake inhibitor (SSRI) has been shown to be efficacious in the treatment of major depression in white populations. Our aim in this study was to investigate the efficacy and tolerability of escitalopram in Chinese patients with moderate to severe major depression. Patients who met DSM-IV criteria for a major depressive episode were enrolled in this multicenter, randomized, double-blind, fixed-dose comparison trial. Patients were given escitalopram 10 mg/day or fluoxetine 20 mg/day for 8 weeks. All patients were assessed with the 17-item Hamilton Depression Rating Scale (HAM-D-17) and the Montgomery-Asberg Depression Rating Scale (MADRS). Tolerability was assessed on the basis of adverse effects (measured with a locally developed checklist), regular biochemical tests, and electrocardiograph (ECG) assessments. Two hundred forty patients were enrolled and randomized to escitalopram (123 patients) or fluoxetine (117 patients). The HAM-D-17 total scores of both groups decreased significantly from baseline, but there was no significant difference at week 8 between the two groups (15.8 for escitalopram and 14.7 for fluoxetine; P >.05). There were no significant differences in response rates at all visits after treatment based on either HAM-D-17 or MADRS. A post hoc analysis indicated that escitalopram was superior to fluoxetine on two items of the HAM-D-17: "depressed mood" (P =.023) and "work and interest" (P =.024). The adverse events reported in the escitalopram and fluoxetine groups were comparable, and most were mild to moderate. Both drugs showed good compliance profiles. Escitalopram 10 mg/day is at least as efficacious as fluoxetine 20 mg/day and well tolerated in Chinese patients with major depression, with possible superiority in some core symptoms such as "depressed mood" and "work and interest."     

Pindolol augmentation in depressed patients resistant to selective serotonin reuptake inhibitors: a double-blind, randomized, controlled trial

BACKGROUND: Studies of pindolol augmentation of antidepressants in major depressive disorder have produced mixed results, and data in treatment-resistant patients are limited. Here, we report on a double-blind, randomized, controlled 6-week study of pindolol augmentation of selective serotonin reuptake inhibitors (SSRIs) in depressed outpatients resistant to SSRI monotherapy. METHOD: Forty-two outpatients with DSM-IV major depressive disorder who had an insufficient response to an adequate trial of an SSRI (fluoxetine, paroxetine, or sertraline) were randomly assigned to pindolol, 2.5 mg t.i.d., or sham augmentation, in addition to continued SSRI administration. For separate analysis, the control group underwent a single-blinded switch to pindolol, 2.5 mg t.i.d., from week 4 through week 6, while the active group was continued on pindolol augmentation (hemi-crossover design). Change in Hamilton Rating Scale for Depression (HAM-D) score from baseline to the end of week 3 was the primary outcome measure. Data were gathered from February 1994 to August 1998. RESULTS: Thirty-eight patients completed at least 1 week on protocol, with 21 and 17 randomly assigned to the pindolol and control groups, respectively. After 3 weeks on protocol, partial response rates (i.e., minimum 50% decrease from baseline in HAM-D score and maximum absolute score of 15) for the pindolol (19% [4/21]) and control (24% [4/17]) groups were comparable. At 3 weeks, the pindolol and control groups demonstrated mean +/- SD decreases in HAM-D scores of 6.5 +/- 9.8 and 9.7 +/- 7.2, respectively. There were no significant differences in antidepressant response or side effects between the 2 groups. CONCLUSION: These results do not support the efficacy of pindolol in augmenting clinical response to SSRIs in treatment-resistant depressed patients.     

Cost-utility of selective serotonin reuptake inhibitors for depression in primary care in Catalonia

OBJECTIVE: To determine the cost-utility of selective serotonin reuptake inhibitors (SSRIs) for treating depressive disorders prescribed in primary care (PC). METHOD: A total of 301 participants beginning antidepressant treatment with an SSRI were enrolled in a prospective 6-month follow-up naturalistic study. Incremental cost-utility ratios (ICUR) were obtained for several comparisons among different SSRIs. To address uncertainty in the ICUR's sampling distribution, non-parametric bootstrapping was carried out. RESULTS: Taking into account adjusted total costs and incremental quality of life gained, fluoxetine dominated paroxetine and citalopram with 63.4% and 79.3% of the bootstrap replications in the dominance quadrant, respectively. Additionally, fluoxetine was cost-effective over sertraline with 83.4% of the bootstrap replications below the threshold of 33,936 US$/quality-adjusted life year (30,000 euro/QALY). CONCLUSION: Fluoxetine seems to be a better cost-utility SSRI option for treating depressive disorders in PC.     

Quetiapine adjunct to selective serotonin reuptake inhibitors or venlafaxine in patients with major depression, comorbid anxiety, and residual depressive symptoms: a randomized, placebo-controlled pilot study

This double-blind, placebo-controlled study examined the efficacy and tolerability of quetiapine in combination with selective serotonin reuptake inhibitors (SSRIs)/venlafaxine in 58 patients with major depressive disorder, comorbid anxiety symptoms (HAM-A-14 score > or =14), and residual depressive symptoms (HAM-D-17 score > or =18, CGI-S score > or =4). Patients had received an SSRI/venlafaxine (at a predefined therapeutic dose) for > or =6 weeks. Overall, 62% (18/29) of quetiapine- and 55% (16/29) of placebo-treated patients completed the study. The mean change in HAM-D and HAM-A total scores from baseline to Week 8 (primary endpoint) was significantly greater with quetiapine (mean dose 182 mg/day) than placebo: -11.2 vs. -5.5 (P=.008) and -12.5 vs. -5.9 (P=.002), respectively. The onset of quetiapine efficacy (HAM-D/HAM-A/CGI-I) was rapid (by Week 1) and continued through to Week 8. Significant differences (P<.05) from baseline to Week 8 were observed between groups in 7/17 HAM-D (including feelings of guilt, suicide) and 6/14 HAM-A items (including tension, cardiovascular symptoms). Response (> or =50% decrease in total score) was higher for quetiapine than placebo: HAM-D, 48% vs. 28% (not significant, NS); HAM-A, 62% vs. 28% (P=.02). Remission (total score < or =7) was higher for quetiapine than placebo: HAM-D, 31% vs. 17% (NS); HAM-A, 41% vs. 17% (NS). CGI-S, CGI-I, and the Global Assessment Scale showed that quetiapine was significantly more effective than placebo. For quetiapine, adverse events (AEs) were similar to those previously observed; sedation/somnolence/lethargy was the most commonly reported. Here quetiapine was shown to be effective as augmentation of SSRI/venlafaxine therapy in patients with major depression, comorbid anxiety, and residual depressive symptoms, with no unexpected tolerability issues. Further studies are warranted.     

Psychostimulant augmentation during treatment with selective serotonin reuptake inhibitors in men with paraphilias and paraphilia-related disorders: a case series

BACKGROUND: We describe an open trial of psychostimulants (primarily methylphenidate sustained release [SR]) added to selective serotonin reuptake inhibitors (SSRIs; primarily fluoxetine) during the course of pharmacologic treatment of men with paraphilias and paraphilia-related disorders (PRDs). METHOD: Twenty-six men with paraphilias (N = 14) or PRDs (N = 12) were assessed for life-time mood disorders and attention-deficit/hyperactivity disorder (ADHD) as defined by DSM-IV. All men were assessed at baseline for total sexual outlet and average time per day associated with paraphilia/PRD sexual behaviors. The indications for the addition of a psychostimulant to a stable dose of SSRI included the retrospective diagnosis of ADHD with persistent adult symptoms despite pharmacotherapy with an SSRI (N = 17); residual paraphilia/PRD fantasies, urges, and activities despite SSRI pharmacotherapy (N = 16); the persistence or presence of residual depressive symptoms despite SSRI pharmacotherapy (N = 6); relapse or loss of SSRI efficacy during the treatment of sexual impulsivity disorders (N = 4); and treatment of SSRI-induced side effects (N = 4). RESULTS: SSRI pharmacotherapy (mean +/- SD duration = 8.8+/-11.1 months) had statistically significant effects in diminishing paraphilia/PRD-related total sexual outlet (p < .001) and average time/day spent in paraphilia/PRD sexual behavior (p < .001). Addition of methylphenidate SR (mean dose = 40 mg/day; mean +/- SD duration = 9.6+/-8.2 months) was associated with additional statistically significant effects on paraphilia/PRD-related total sexual outlet (p = .003) and average time per day (p = .04) in addition to improvement of putative residual ADHD and depressive symptoms. CONCLUSION: Methylphenidate SR can be cautiously and effectively combined with SSRI antidepressants to ameliorate paraphilias and paraphilia-related disorders for the indications listed above.     

Are typical starting doses of the selective serotonin reuptake inhibitors sub-optimal? A meta-analysis of randomized,double-blind,placebo-controlled,dose-finding studies in major depressive disorder

The purpose of this meta-analysis is to examine the relationship between selective serotonin reuptake inhibitor (SSRI) starting dose and treatment outcome in major depressive disorder (MDD). Medline/Pubmed, EMBASE, the Cochrane database, as well as a number of online clinical trial registries were searched for double-blind, placebo-controlled, fixed-dose trials comparing different starting doses of SSRIs for MDD. Data from nine trials (n=2340) were combined using a random-effects model. Patients randomized to receive the usual starting dose (10 mg escitalopram; 20 mg fluoxetine, paroxetine, citalopram; 50 mg sertraline and fluvoxamine) were less likely to respond than patients who received higher starting doses (RR=0.9; P=0.04; response rate 50.8 vs. 54.8%). The rate of discontinuation due to adverse events was lower among the usual starting dose group (9.8%) compared to the higher starting dose group (16.5%).Initiating treatment with SSRIs at doses higher than those typically used in clinical trials/settings is associated with higher response rates but also higher rates of discontinuation due to intolerance. Developing treatment strategies allowing clinicians to deliver higher initial SSRI doses while enhancing the tolerability of treatment may represent an alternative approach to improving the efficacy of treatment of MDD.     

A randomized, controlled trial of the effectiveness of cognitive-behavioral therapy and sertraline versus a waitlist control group for anxiety disorders in older adults.

OBJECTIVE: This study is the first to investigate the relative effectiveness of cognitive-behavioral therapy (CBT) compared with a selective serotonin reuptake inhibitor (SSRI; sertraline) in a randomized, controlled trial on the treatment of anxiety disorders in older adults. METHOD: Eighty-four patients 60 years of age and over with a principal diagnosis of generalized anxiety disorder, panic disorder, agoraphobia, or social phobia were randomly assigned to one of three conditions: 15 sessions of CBT, pharmacologic treatment with an SSRI (sertraline; maximum dosage 150 mg), or a waitlist control group. Participants completed measures of primary outcome (anxiety) and coexistent worry and depressive symptoms at baseline, posttreatment, and at three-month follow up. RESULTS: Attrition rates were high in both treatment groups. Consequently, findings are based on a relatively small sample of completers (N = 52). Although both CBT and sertraline led to significant improvement in anxiety, worry, and depressive symptoms both at posttreatment and at three-month follow up, sertraline showed superior results on worry symptoms. Effect size estimates for CBT were in the small to medium range both at posttreatment (mean d = 0.42) and at three-month follow up (mean d = 0.35), whereas effect sizes for sertraline fell into the large range (posttreatment mean d = 0.94 and three-month follow up mean d = 1.02). The waitlist condition showed virtually no effects (posttreatment mean d = .03). CONCLUSIONS: Our findings strongly suggest that the pharmacologic treatment of late-life anxiety with SSRIs has not been given the proper attention in research to date.