Efficacy of adjunctive aripiprazole in patients with major depressive disorder who showed minimal response to initial antidepressant therapy

To evaluate the efficacy of adjunctive aripiprazole in patients with minimal response to prior antidepressant therapy (ADT). Pooled data from three randomized, double-blind, placebo-controlled studies assessing the efficacy of adjunctive aripiprazole to ADT in patients with major depressive disorder who had a minimal response [< 25% reduction on the Montgomery-?sberg Depression Rating Scale (MADRS)] to an 8-week prospective ADT. During the 6-week, double-blind adjunctive phase, response was defined as at least 50% reduction in the MADRS score and remission as at least 50% reduction in MADRS score and a MADRS score ≤ 10. Rates were examined using analysis of covariance and Cochran-Mantel-Haenszel tests. Kaplan-Meier curves were used to calculate time to response and remission. Of 1038 patients, 72% (n=746) exhibited a minimal response to ADT (ADT minimal responder). Time to response and remission were significantly shorter for ADT minimal responders receiving aripiprazole+ADT versus adjunctive placebo+ADT. ADT minimal responders on aripiprazole+ADT showed significantly greater improvements in MADRS score at endpoint compared with minimal responders on placebo+ADT (-10.3 vs. -6.5, P<0.0001). In addition, ADT minimal responders exhibited significantly higher response rates with aripiprazole+ADT than placebo+ADT (36 vs. 19%, respectively, P<0.0001) and higher remission rates (24 vs. 12%, respectively, P<0.0001). The numbers needed to treat with aripiprazole+ADT were six for response and eight for remission. Aripiprazole augmentation had a rapid and clinically meaningful effect in ADT minimal responders.     

Aripiprazole monotherapy in nonpsychotic bipolar I depression: results of 2 randomized, placebo-controlled studies

Although most treatment research on bipolar disorder has focused on mania, depressive episodes occur more frequently among patients with bipolar disorder. Here, we report the results of 2 identically designed, 8-week, multicenter, randomized, double-blind, placebo-controlled studies (CN138-096 and CN138-146) to evaluate the efficacy and safety of aripiprazole monotherapy in outpatients with bipolar I disorder experiencing a major depressive episode without psychotic features. Patients were randomized to placebo or aripiprazole (initiated at 10 mg/d, then flexibly dosed at 5-30 mg/d based on clinical effect and tolerability). The primary end point was mean change from baseline to Week 8 (last observation carried forward) in the Montgomery-Asberg Depression Rating Scale total score. In Studies 1 and 2, respectively, 186 and 187 patients were randomized to aripiprazole, and 188 and 188 to placebo. Although statistically significant differences were observed during Weeks 1 to 6, aripiprazole did not achieve statistical significance versus placebo at Week 8 in either study in the change in Montgomery-Asberg Depression Rating Scale total (primary end point). In addition, despite early statistical separation on the Clinical Global Impressions Bipolar Version Severity of Illness-Depression score (key secondary end point), aripiprazole was not superior to placebo at end point. Aripiprazole was associated with a higher incidence of akathisia, insomnia, nausea, fatigue, restlessness, and dry mouth versus placebo. More patients discontinued with aripiprazole versus placebo in Study 1 (46.8% vs 35.1%) and Study 2 (41.2% vs 29.8%). Aripiprazole monotherapy-as dosed in this study design-was not significantly more effective than placebo in the treatment of bipolar depression at end point (Week 8).     

Combined treatment with sulpiride and paroxetine for accelerated response in patients with major depressive disorder

Although serotonin reuptake inhibitors are recommended as first-line agents for major depressive disorder, delayed onset of action is problematic, and faster effective treatment is needed. Sulpiride, a dopamine-mediated agent, has been reported to show faster antidepressant efficacy, and we examined the efficacy of adjunctive sulpiride in combination with paroxetine (PAX), compared with PAX alone, to clarify whether the combined treatment exerts faster effect. Forty-one major depressive disorder patients were enrolled in this 12-week open-label trial and were randomly assigned to a PAX (10-40 mg/d) or a PAX (10-40 mg/d) plus sulpiride (100 mg/d) group. Assessments included the Montgomery-Asberg Depression Rating Scale, the 17-item Hamilton Rating Scale for Depression, and the Zung Self-rating Depression Scale on an intent-to-treat basis, and safety was also monitored. Thirty-three patients completed the study. Both PAX + sulpiride and PAX treatments showed a mean reduction in the total Montgomery-Asberg Depression Rating Scale score of 34.4 to 5.6 and 32.2 to 10.4, respectively (P < 0.001). The combined treatment group had a significantly superior outcome in terms of the change in the total Montgomery-Asberg Depression Rating Scale, Hamilton Rating Scale for Depression, and Zung Self-rating Depression Scale scores between week 1 and the study end point (P < 0.05). Median times to response among responders alone for the combined treatment and monotherapy were 2 and 6 weeks, respectively. Both treatments were well tolerated, with no clinically significant differences in safety measures except for an elevation of prolactin in the combined treatment group. The combination treatment may be a safe and effective strategy for accelerating antidepressant response.     

A randomized, double-blind, and placebo-controlled trial of quetiapine augmentation of fluoxetine in major depressive disorder

The objective of this study was to investigate whether quetiapine, when compared with placebo, can speed the onset of action and improve the quality of response to fluoxetine treatment in patients suffering from major depressive disorder. A total of 114 patients with major depressive disorder were enrolled in an 8-week treatment study. Patients were initiated on a course of fluoxetine treatment and randomized to quetiapine or placebo. Quetiapine was flexibly dosed starting at 25 mg to a maximum of 100 mg daily. Mixed-effects regression showed that quetiapine plus fluoxetine did not achieve 50% reduction in the Montgomery-Asberg Depression Rating Scale score or improvement in Hamilton Anxiety Scale, Clinical Global Improvement (CGI)-Severity, and CGI-Improvement scores sooner than the fluoxetine plus placebo group; however both groups improved in all scores over time. Mixed-effects linear regression of insomnia scores showed that the quetiapine plus fluoxetine group improved significantly more rapidly compared with the fluoxetine plus placebo group. The study indicates that quetiapine plus fluoxetine did not achieve a reduction in the Montgomery-Asberg Depression Rating Scale score or improvement in Hamilton Anxiety Scale or CGI scores from baseline sooner than the fluoxetine plus placebo group. The combination of quetiapine and fluoxetine, however, improved sleep over fluoxetine alone over the first few weeks of treatment.     

Eight-week, placebo-controlled, double-blind comparison of the antidepressant efficacy and tolerability of bupropion XR and venlafaxine XR

The efficacy, safety and tolerability of bupropion XR and venlafaxine XR was assessed and compared with placebo in adult outpatients with major depressive disorder (MDD). Adults meeting DSM-IV criteria for MDD with a minimum Hamilton Depression Rating Scale (HAMD) 17-Item total score of > or =18 were randomized to eight weeks of double-blind treatment with either bupropion XR (150 mg/day), venlafaxine XR (75 mg/day) or placebo. At the end of the fourth week of treatment, a dosage increase to bupropion XR 300 mg/day or venlafaxine XR 150 mg/day was allowed if, in the opinion of the investigator, response was inadequate. The primary efficacy endpoint was mean change from baseline at week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score last observation carried forward (LOCF). Mean changes from baseline at week 8 (LOCF) in MADRS total score were statistically significant for bupropion XR and venlafaxine XR patients compared to the placebo group: -16.0 for bupropion XR (P = 0.006 vs placebo), -17.1 for venlafaxine XR (P < 0.001 vs placebo) and -13.5 for placebo. Secondary outcomes (including CGI-S, HAM-A, MEI, Q-LES-Q-SF, responder and remitter analyses) also improved significantly for both active treatment groups compared with placebo. The most frequently reported adverse events were dry mouth and insomnia for bupropion XR, and nausea, hyperhidrosis, fatigue, and insomnia for venlafaxine XR. In this double-blind, placebo-controlled trial, bupropion XR at doses up to 300 mg/day and venlafaxine XR at doses up to 150 mg/day demonstrated comparable antidepressant efficacy.     

Efficacy and safety of 30 mg/d and 45 mg/d nemifitide compared to placebo in major depressive disorder

Nemifitide is a novel pentapeptide antidepressant, which appears to be effective in the treatment of major depressive disorder (MDD). In the present study 81 patients with MDD, DSM-IV criteria were randomized following a 1-wk screening period to receive 30 mg/d nemifitide, 45 mg/d nemifitide or placebo in a 6-wk double-blind, multicentre, outpatient efficacy study. Nemifitide or placebo was delivered by subcutaneous injection for 2 wk daily for 5 days (Monday to Friday) in the first 2 wk and patients were followed up for a further 4 wk. The primary efficacy measure was the change from baseline on the Montgomery-Asberg Depression Rating Scale. Secondary measures included the 17-item Hamilton Psychiatric Rating Scale for Depression (HAMD), the CGI severity and improvement scale and the Carroll Self-Rating Scale for Depression. This proof-of-principle study demonstrated a statistically significant superiority of the 45-mg/d dose vs. placebo at the time-point of peak effect (1 wk after the end of treatment). There appeared to be a greater effect with the 45 mg/d nemifitide dose than with 30 mg/d. An additional exploratory analysis by stratification of all patients by severity above and below or equal to the median baseline HAMD score of 22 showed a higher percentage of responders for both doses of nemifitide with statistical separation from placebo for patients with baseline HAMD score of >22 (above the median). There was no significant difference among treatment groups for patients with baseline HAMD score of 相似文献   

Effects of PRX-00023, a novel, selective serotonin 1A receptor agonist on measures of anxiety and depression in generalized anxiety disorder: results of a double-blind, placebo-controlled trial

PRX-00023, a serotonin 1A receptor agonist, was designed to provide high potency and selectivity for its target. To assess the possible therapeutic utility in anxiety, a randomized, double-blind, placebo-controlled trial was conducted in 311 subjects who met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, for generalized anxiety disorder. All subjects underwent a 1-week placebo run-in and were randomized to receive once-daily capsules containing either PRX-00023 (80 mg/d) or placebo for an additional 8 weeks. The primary outcome measure was the Hamilton Anxiety Scale (HAM-A). The Montgomery-Asberg Depression Rating Scale was used as a secondary endpoint to measure depressive symptoms. Statistical testing was performed with analysis of covariance, between baseline and week 8, with baseline values as a covariate. The anxiolytic effect of PRX-00023, compared with placebo, showed trends across all anxiolytic measures but failed to reach significance on the primary endpoint (HAM-A total score). Among the components of the HAM-A total score, the anxious mood item was significantly different from placebo in the PRX-00023-treated group (-1.015 vs -0.748; P = 0.02). The scores of the Montgomery-Asberg Depression Rating Scale were significantly improved compared with placebo at week 8 (-4.5 vs -1.6; P = 0.0094 in the last observation carried forward analysis). PRX-00023 was well tolerated; of note, there were no drug-related serious adverse events, and more patients discontinued due to adverse events in the placebo group (2.9%) than in the PRX-00023 group (1.4%). The most common adverse event was headache, observed in 15.7% and 10.9% of PRX-00023- and placebo-treated patients, respectively. Furthermore, there was no evidence of impaired sexual function, as measured by the Massachusetts General Hospital Sexual Function Scale. Collectively, these results support further clinical investigation of higher doses of PRX-00023 in anxiety and depression.     

Aripiprazole: in major depressive disorder

Aripiprazole, an oral quinolinone, is the first atypical antipsychotic agent to be approved in the US as adjunctive treatment in adult patients with major depressive disorder (MDD). In two large, well-designed trials in patients with MDD who had an inadequate response to standard antidepressant therapy, 6 weeks' adjunctive therapy with aripiprazole 2-20 mg/day improved mean Montgomery Asberg Depression Rating Scale (MADRS) total scores (primary endpoint) to a significantly greater extent than adjunctive placebo treatment. Improvements in mean MADRS total score during the double-blind phase favoured adjunctive aripiprazole treatment from 1-2 weeks onward, with per-protocol subgroup analyses showing that mean changes were not affected by the specific standard antidepressant therapy used, age or sex of the patient or the mean MADRS total scores at the start of double-blind adjunctive therapy. In general, secondary endpoint scores, including those for the Sheehan Disability Scale, Clinical Global Impression (CGI) Improvement scale and CGI Severity of Illness scale, improved to a significantly greater extent with adjunctive aripiprazole than with adjunctive placebo treatment, with significantly higher response and remission rates in the aripiprazole groups. In these two pivotal trials, adjunctive aripiprazole 2-20 mg/day was generally well tolerated, with most treatment-emergent adverse events being of mild to moderate severity.     

Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder

Patients (n = 150) were randomized to a 6-week, double-blind study to evaluate the relative efficacy and safety of mirtazapine, amitriptyline, and placebo in the treatment of major depressive disorder symptoms. Average daily modal doses were mirtazapine, 18 mg; amitriptyline, 111 mg; and placebo, 4.6 capsules. Mirtazapine- and amitriptyline-treated patients had statistically significantly greater mean Hamilton Rating Scale for Depression (HAM-D) score reductions (weekly visits 1, 2, 4, and endpoint) compared to placebo. These findings were supported by the Montgomery-Asberg Depression Rating Scale (MADRS); the Zung Self-rating Depression Scale (SDS); and the Clinical Global Impressions (CGI) scales. Somnolence and weight gain were the only adverse clinical experiences (ACEs) reported substantially more often by mirtazapine-treated patients than by those in the placebo group. However, more amitriptyline-treated patients reported decreased visual accommodation, dry mouth, dyspepsia, constipation, tachycardia, hypertension, hypotension, discoordination, dizziness, and tremor than mirtazapine- or placebo-treated patients. Results of this study indicate that mirtazapine is more effective than placebo in the treatment of these patients, and superior to amitriptyline in respect to anticholinergic and cardiovascular effects.     

Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study)

This study evaluated the efficacy and tolerability of quetiapine monotherapy for depressive episodes in patients with bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were randomized to 8 weeks of double-blind treatment with quetiapine (300 or 600 mg/d; once daily, evening dosing) or placebo. Patients were assessed weekly using the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D). The primary end point was change in MADRS total score from baseline to Week 8 (analysis of covariance/last-observation-carried-forward analysis). Of 509 patients randomized, 59% completed the study. Improvements from baseline in mean MADRS total scores were significantly greater with quetiapine 300 and 600 mg/d than with placebo from first evaluation (Week 1) through Week 8 (both P 相似文献   

The effectiveness and safety of adjunctive aripiprazole in Taiwanese patients with antidepressant-refractory major depressive disorder: a prospective, open-label trial

There is currently no published clinical trial on the safety and effectiveness of aripiprazole in Taiwanese patients with treatment-refractory major depressive disorder. We were interested in determining the applicability of current recommended doses of aripiprazole as an adjunct to antidepressant therapy in this population. We conducted a prospective, open-label nonrandomized, 4-week flexibly dosed (2.5-5 mg/d) trial with aripiprazole augmentation in 9 Taiwanese patients who had a history of nonresponse to at least 2 adequate courses of antidepressant therapy with different types of antidepressants. The primary end point for clinical effectiveness was mean change in the 17-item Hamilton Rating Scale for Depression at the end of the 4-week trial. Secondary end points for clinical effectiveness included mean change in Beck Depression Inventory and Beck Anxiety Inventory scores. The Systematic Assessment of Treatment Emergent Events-General Inquiry was used to assess adverse effects. All patients completed the trial and responded to treatment; the remission rate was 77.8%. The mean daily dose of adjunctive aripiprazole was 4.2 mg. Common treatment-emergent adverse events included insomnia and sedation (33.3%) and akathisia (22.2%). We found high effectiveness despite a lower mean daily dose of adjunctive aripiprazole (4.2 mg) when compared with previously reported findings; however, we also observed a higher frequency of treatment-emergent adverse effects. Additional studies are required to ascertain whether there are ethnic differences in the pharmacokinetics and/or pharmacodynamics of aripiprazole in treatment-refractory depression.     

A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in the treatment of major depressive disorder

The antidepressant efficacy and safety of desvenlafaxine succinate (desvenlafaxine) were evaluated in a phase III, double-blind, placebo-controlled study. Outpatients with a primary diagnosis of major depressive disorder were treated with fixed once-daily doses of desvenlafaxine 200 or 400 mg for 8 weeks. The primary efficacy measure was change from baseline on the 17-item Hamilton Rating Scale for Depression. At the final on-therapy evaluation, adjusted mean change from baseline in 17-item Hamilton Rating Scale for Depression total score was greater for desvenlafaxine 200 and 400 mg/day vs. placebo. Both desvenlafaxine doses showed greater efficacy than placebo on the secondary efficacy measures, including the Clinical Global Impressions-Improvement scale scores, Montgomery-Asberg Depression Rating Scale scores, CGI-Severity, and 17-item Hamilton Rating Scale for Depression response rate. Desvenlafaxine 200 mg/day was also significantly better than placebo on remission, Visual Analog Scale-Pain Intensity overall scores, and some Visual Analog Scale-Pain Intensity subscale scores. Desvenlafaxine 400 mg/day was significantly better than placebo on selected Visual Analog Scale-Pain Intensity subscale scores. Most adverse events were mild or moderate in severity, and safety assessments revealed few clinically significant changes in vital signs, laboratory tests, and electrocardiogram results. These data provide support for the efficacy and safety of desvenlafaxine in the treatment of major depressive disorder.     

Number needed to treat and time to response/remission for quetiapine monotherapy efficacy in acute bipolar depression: evidence from a large, randomized, placebo-controlled study

The objectives of this analysis are to elucidate the clinical significance of antidepressant effects with quetiapine by evaluating number needed to treat as well as time to response and remission with quetiapine monotherapy in patients with acute bipolar depression. A post-hoc analysis was conducted of 542 patients with bipolar I or II disorder, (moderate to severe depression), randomized to 8 weeks of double-blind treatment with quetiapine 600 mg/day (n=180), quetiapine 300 mg/day (n=181), or placebo (n=181). Number needed to treat, time to response (> or =50% reduction from baseline in Montgomery-Asberg Depression Rating Scale total score) and time to remission (Montgomery-Asberg Depression Rating Scale total score < or =12) were evaluated. Response rates at week 8 were 58.2 and 57.6% for quetiapine 600 and 300 mg/day, respectively, and 36.1% for placebo (P<0.001). Remission rates were 52.9% for both quetiapine groups and 28.4% for placebo (P<0.001). The number needed to treat was five for both response and remission for quetiapine (600 and 300 mg/day) compared with placebo. Median time to response and remission were significantly shorter with quetiapine 600 and 300 mg/day than placebo. No between-group difference was found in the incidence of treatment-emergent mania or hypomania (quetiapine 600 mg/day: 2.2%, quetiapine 300 mg/day: 3.9, and placebo: 3.9%). In conclusion, quetiapine compared with placebo significantly reduces time to response and remission compared with placebo, and has a favorable number needed to treat.     

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.     

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

Escitalopram, a selective serotonin reuptake inhibitor (SSRI), was compared to placebo in a study of patients with major depressive disorder (DSM-IV) who had baseline Montgomery-Asberg Depression Rating Scale (MADRS) total scores >or=22 and 相似文献   

A 24-week randomized study of olanzapine versus ziprasidone in the treatment of schizophrenia or schizoaffective disorder in patients with prominent depressive symptoms

OBJECTIVE: The objective of this study is to compare olanzapine with ziprasidone therapy in patients with schizophrenia or schizoaffective disorder and experiencing depressive symptoms. METHODS: This randomized, double-blind, 24-week, fixed-dose study compared olanzapine (n = 202) and ziprasidone (n = 192) for patients with schizophrenia or schizoaffective disorder and experiencing prominent depressive symptoms. Outcome measures included change in Calgary Depression Scale for Schizophrenia (CDSS) score from baseline to 8 weeks (primary outcome) and changes in CDSS, Montgomery-Asberg Depression Rating Scales, Positive and Negative Syndrome Scale, and Global Assessment of Functioning (GAF) scores for 24 weeks. Statistical analyses included mixed-effects model repeated measures (primary analysis) and change from baseline to last observation carried forward (LOCF). RESULTS: At baseline, patients had moderate depressive symptoms (mean Montgomery-Asberg Depression Rating Scales total score, 27.3). For 8 weeks, patients treated with olanzapine or ziprasidone had significant improvements on CDSS. Treatment group differences were not statistically significant (P = 0.493, mixed-effects model repeated measures; P = 0.497, LOCF). For 24 weeks, olanzapine-treated patients showed significantly greater improvements in depressive symptoms (results varied by depression measure and statistical approach) and GAF (P < 0.017, LOCF). A significantly higher proportion of olanzapine-treated patients completed the study (44.6% vs 29.7%; P = 0.003) and remained longer on medication (median, 163 vs 73 days, P < 0.001), compared with ziprasidone-treated patients. Olanzapine-treated patients experienced significantly (P < 0.05) greater increases in triglycerides, HgbA1c, and weight. CONCLUSIONS: For 24 weeks, olanzapine-treated patients had greater and more sustained participation in treatment, during which time significantly greater improvements were observed in depressive symptoms and GAF scores, along with increases in weight and certain metabolic parameters as compared with ziprasidone-treated patients.     

Selegiline transdermal system in the prevention of relapse of major depressive disorder: a 52-week, double-blind, placebo-substitution, parallel-group clinical trial

The selegiline transdermal system (STS) is a monoamine oxidase inhibitor (MAOI) with unique pharmacokinetic and pharmacodynamic properties that was developed to overcome limitations of orally administered MAOIs, particularly dietary tyramine restrictions. We present data from a long-term study assessing the safety and efficacy of initial and continuation STS therapy in patients with major depressive disorder (MDD). After 10 weeks of treatment with STS 6 mg/24 h, 322 patients who responded with a 17-item Hamilton Depression Rating Scale score of 10 or less were randomly assigned to double-blind treatment with STS 6 mg/24 h or placebo for 52 weeks. Relapse was defined as meeting the following criteria on 2 consecutive visits: (1) 17-item Hamilton Depression Rating Scale score of 14 or more, (2) a Clinical Global Impression of Severity score of 3 or more with a 2-point increase from double-blind baseline, and (3) the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a major depressive episode. At study week 52, significantly fewer STS patients experienced relapse of major depressive episode (25/149 [16.8%]) compared with placebo (50/163 [30.7%]) (P = 0.0025). In addition, patients receiving STS experienced a significantly longer time to relapse compared with those receiving placebo (P = 0.0048). The safety profile of STS was similar to placebo, with the exception of application-site reactions (STS, 15.2%; placebo, 3.7%). No cases of hypertensive crisis were reported, despite the lack of requirement for dietary tyramine restrictions. In conclusion, STS was well tolerated and efficacious in maintaining a sustained response in MDD patients. The results of this study suggest that STS may be suitable in the long-term treatment of MDD.     

Aripiprazole in the treatment of acute manic or mixed episodes in patients with bipolar I disorder: a 3-week placebo-controlled study

This study compares the efficacy, safety, and tolerability of a partial dopamine agonist, aripiprazole, with placebo in the treatment of patients with bipolar I disorder experiencing an acute manic or mixed episode. In total, 272 hospitalized patients were randomized to aripiprazole 30 mg/day or placebo in this 3-week, double-blind, placebo-controlled trial. Dosing could be reduced to 15 mg/day for tolerability and, subsequently, increased to 30 mg/day based on clinical response. Primary efficacy measure was mean change from baseline to endpoint in Young Mania Rating Scale (YMRS) total score; response was defined as > or = 50% decrease from baseline YMRS score. Aripiprazole-treated patients demonstrated significantly greater improvement from baseline to endpoint in mean YMRS total scores compared with placebo-treated patients as early as Day 4 and sustained through Week 3. A significantly higher response rate was observed in aripiprazole-treated patients (53% vs. 32% at endpoint). Aripiprazole produced significantly greater improvements from baseline on other efficacy assessments compared with placebo, including Clinical Global Impression - Bipolar Version Severity and Improvement scores. The 30 mg/day dose was maintained by 85% of aripiprazole-treated patients. Incidence of discontinuations due to adverse events was similar for aripiprazole (8.8%) and placebo (7.5%). Aripiprazole treatment resulted in no significant difference from placebo in change in mean body weight and was not associated with elevated serum prolactin or QTc prolongation. In conclusion, aripiprazole demonstrated superior efficacy to placebo in the treatment of patients with bipolar I disorder presenting with acute manic or mixed episodes, and exhibited a favourable safety and tolerability profile.     

Aripiprazole for the treatment of psychosis in patients with Alzheimer's disease: a randomized, placebo-controlled study

This study compared the efficacy, safety, and tolerability of aripiprazole, a novel antipsychotic, with placebo in patients with psychosis associated with Alzheimer's Disease (AD). This 10-week, double-blind, multicenter study randomized 208 outpatients (mean age, 81.5 years) with AD-associated psychosis to aripiprazole (n = 106) or placebo (n = 102). The initial aripiprazole dose of 2 mg/d was titrated upwards (5, 10, or 15 mg/d) according to efficacy and tolerability. Evaluations included Neuropsychiatric Inventory (NPI) Psychosis subscale and Brief Psychiatric Rating Scale (BPRS), adverse event (AE) reports, extrapyramidal symptoms (EPS) rating scales, and body weight. Overall, 172 patients (83%) completed the study. Mean aripiprazole dose at end point was 10.0 mg/d. The NPI Psychosis subscale score showed improvements in both groups (aripiprazole, -6.55; placebo, -5.52; P = 0.17 at end point). Aripiprazole-treated patients showed significantly greater improvements from baseline in BPRS Psychosis and BPRS Core subscale scores at end point compared with placebo. AEs were generally mild to moderate in severity and included (aripiprazole vs. placebo): urinary tract infection (8% vs. 12%), accidental injury (8% vs. 5%), somnolence (8% vs. 1%), and bronchitis (6% vs. 3%). Somnolence was mild and not associated with falls or accidental injury. There were no significant differences from placebo in EPS scores, or clinically significant ECG abnormalities, vital signs, or weight. In conclusion, aripiprazole showed similar improvements to placebo in psychotic symptoms as assessed by NPI Psychosis subscale scores, but significantly greater effects on BPRS Core and Psychosis assessments in community-living AD patients with psychosis. Aripiprazole was safe and well tolerated in this patient population.     

The efficacy and tolerability of tiagabine in adult patients with post-traumatic stress disorder

The aim of this study was to evaluate the efficacy and tolerability of tiagabine in adult patients with post-traumatic stress disorder (PTSD). This 12-week, multicenter, double-blind study randomized patients to receive either tiagabine or placebo. Tiagabine (administered in divided doses) was initiated at 4 mg/d (2 mg BID) and individually titrated of up to 4 mg/d weekly to a maximum dose of 16 mg/d. Assessments included the Clinician-Administered PTSD Scale, Clinical Global Impressions of Change, Treatment Outcome PTSD Scale, Davidson Trauma Scale, Connor-Davidson Resilience Scale, Sheehan Disability Scale, Massachusetts General Hospital Sexual Functioning Questionnaire, and Montgomery-Asberg Depression Rating Scale. A total of 232 patients (tiagabine, n = 116; placebo, n = 116) were randomized. There were no significant differences in change from baseline in the Clinician-Administered PTSD Scale total score at final visit for tiagabine compared with placebo (P = 0.85). Similarly, no significant differences were observed with tiagabine on the other efficacy outcome measures (described above) compared with placebo. Tiagabine was generally well tolerated and not associated with weight gain, changes in sexual function, or worsening of depressive symptoms. Tiagabine was not significantly different from placebo in the treatment of symptoms of PTSD. Additional studies are needed to assess the role of drugs that target the gamma-aminobutyric acid system in the treatment of PTSD.