Improvement of Positive and Negative Syndrome Scale cognitive score associated with olanzapine treatment of acute mania

OBJECTIVE: This study analyzed the effect of olanzapine on a psychopathology-based scale assessing abnormal thought processes and examined the relationship between improvement on this scale and mania and depression improvement in acutely manic patients. METHODS: The study sample (N = 254) was pooled from two double-blind, randomized, placebo-controlled clinical trials. Disturbance in thought processes was measured by the Positive and Negative Symptom Scale cognitive component (PANSS-Cognitive) score. Mood severity was measured by the Young-Mania Rating Scale (Y-MRS) and Hamilton Depression Inventory (HAM-D). Last-observation-carried-forward (LOCF) changes from baseline to endpoint (Week 3) were presented for patients who had at least one post-baseline assessment. RESULTS: Olanzapine-treated patients experienced modest but significant improvement in PANSS-Cognitive score (olanzapine: -4.25 n = 124; placebo: -1.69 n = 120, p < 01), regardless of age, gender, mania subtype (pure, mixed), course (rapid or non-rapid cycling), or the presence or absence of psychotic features. PANSS-Cognitive improvement was more highly correlated with mania than depression improvement. CONCLUSION: Olanzapine improved abnormal thought processes measured by the PANSS-Cognitive score in patients with acute mania. This improvement in thought processes was significantly associated with improvement in acute mania. More sensitive and specific neuropsychological testing could help clarify whether improvement in thought processes on olanzapine was independent of mania reduction.     

Acute dysphoric mania: treatment response to olanzapine versus placebo

A substantial number of patients with mania have significant concomitant depressive features, and they may respond differently to mood stabilizers than patients with pure mania. This post-hoc analysis explored the response characteristics of olanzapine versus placebo in bipolar I manic patients with dysphoric and nondysphoric mania (differentiated by baseline Hamilton Depression Rating Scale [HAM-D] score of >20). Two similar, double-blind, randomized trials comparing olanzapine, 5-20 mg, to placebo were pooled for these analyses (N = 246). Mean changes in Young-Mania Rating Scale (Y-MRS) and HAM-D scores during 3 weeks of treatment were examined. Twenty-eight percent of patients had dysphoric mania (olanzapine, n = 33; placebo, n = 35). Among these patients, olanzapine-treated patients had greater improvement within 1 week than did placebo-treated patients on both mania ratings (Y-MRS: -9.7 vs. -3.0 points; = 0.011) and depressive symptom ratings (HAM-D: -9.9 vs. -5.4 points; = 0.025). Among those manic subjects without prominent depressive symptoms (olanzapine, n = 91; placebo, n = 87), mean Y-MRS improvement from baseline to endpoint with olanzapine (-11.5 points) versus placebo (-6.13 points) was comparable to the improvement seen with olanzapine versus placebo in the dysphoric mania subgroup ( = 0.476, test of interaction). In acutely ill manic patients with significant depressive symptoms, olanzapine demonstrated a broad spectrum of efficacy, effectively treating both manic and depressive symptoms. The magnitude of the antimanic response appears similar, regardless of baseline depressive features. Additional experience with putative mood stabilizers and atypical agents in mixed mania should include an exploration of their efficacy in treating both manic and depressive mood symptoms.     

Pharmacotherapy of generalized anxiety disorder: results of duloxetine treatment from a pooled analysis of three clinical trials

ABSTRACT

Objective: Duloxetine is a serotonergic noradrenergic reuptake inhibitor with demonstrated efficacy in each of three independent studies for treatment of adults with generalized anxiety disorder (GAD). A pooled dataset from all completed trials is provided here to show the most likely clinical outcomes associated with duloxetine treatment for GAD.

Research design and methods: Data were summed at the individual patient level from three double-blind, placebo-controlled trials of duloxetine treatment: two were 10-week flexible-dose 60–120?mg/day and one was 9-week fixed dose 60 or 120?mg/day. Inclusion/exclusion criteria were consistent across studies.

Main outcome measures: Efficacy measures included the Hamilton Anxiety Scale (HAMA) and Sheehan Disability Scale (SDS). Adverse events were queried at every visit in each study.

Results: Patients were randomly assigned to duloxetine (n = 668) or placebo (n = 495) treatment. Mean age was 42.4 years; 65% were female. Duloxetine-treated patients improved significantly more from baseline to endpoint on HAMA total score (mean = –11.1 points) compared with placebo-treated patients (mean = –8.0 points, p ≤ 0.001). On the SDS global functioning score, patients in the duloxetine group had a mean improvement from baseline of 46% compared with 25% in the placebo group (?p ≤ 0.001). Nausea was the most common of twelve treatment-emergent adverse events that occurred in the duloxetine group.

Limitations: Pooled studies were not for long-term treatment and did not include patients with comorbid psychiatric conditions.

Conclusions: In this sample of more than 1100 patients, duloxetine was efficacious for reducing anxiety severity and for increasing patients’ overall role functioning in GAD.     

Olanzapine compared to lithium in mania: a double-blind randomized controlled trial

Neuroleptics are of established efficacy in mania. Controlled data on the use of olanzapine in mania is however, absent. In this study, 30 patients meeting DSM-IV criteria for mania were randomly allocated to receive either olanzapine or lithium in a 4 week double-blind randomized controlled design. There were no significant outcome differences between the two groups on any of the primary outcome measures, the Brief Psychiatric Rating Scale (lithium 28.2; olanzapine 28.0; P = 0.44); Clinical Global Impression (CGI) improvement scale (lithium 2.75, olanzapine 2.36; P = 0.163) or the Mania Scale (lithium 13.2, olanzapine 10.2; P = 0.315). Olanzapine was however, significantly superior to lithium on the CGI-severity scale at week 4 (lithium 2.83, olanzapine 2.29; P = 0.025). Olanzapine did not differ from lithium in terms of treatment emergent extrapyramidal side-effects as measured by the Simpson-Angus Scale. Olanzapine appears to be at least as effective as lithium in the treatment of mania.     

The effect of montelukast on rhinitis symptoms in patients with asthma and seasonal allergic rhinitis

SUMMARY

Objective: The objective of this study was to evaluate montelukast 10?mg daily as treatment for allergic rhinitis in patients with symptomatic allergic rhinitis and active asthma during the allergy season.

Methods: This was a multicenter study of 831 patients (ages 15?years–85?years) with seasonal allergen sensitivity, active symptoms of seasonal allergic rhinitis, and active asthma. Following a single-blind, placebo run-in period of 3?days–5?days, patients were randomized to oral montelukast 10?mg (n = 415) or placebo (n = 416) daily during the 2-week, double-blind, active-treatment period.

Main outcome measures: The primary endpoint was Daily Rhinitis Symptoms score, average of Daytime Nasal Symptoms and Nighttime Symptoms, as self-rated by patients on a 0–3 scale on daily diaries.

Results: Montelukast reduced the Daily Rhinitis Symptoms score: difference between montelukast and placebo in mean change from baseline was –0.12 [95% CI –0.18, –0.06; p ≤ 0.001]. Similar improvements were seen in Daytime Nasal Symptoms (–0.14 [–0.21, –0.07; p ≤ 0.001]) and Nighttime Symptoms (–0.10 [–0.16,–0.04; p ≤ 0.001]). Improvements (p < 0.05) were seen in Daytime Eye Symptoms and in the secondary endpoints of Global Evaluations of AR by Patient and by Physician, and Rhinoconjunctivitis Quality of Life. In exploratory analyses, improvement in rhinitis symptoms was numerically (though not statistically) larger in patients with greater levels of asthma at study start. Montelukast provided benefit in the Global Evaluations of Asthma by Patient and by Physician: mean differences were –0.24 [–0.41, –0.06; p = 0.008] and –0.17 [–0.33,–0.01; p = 0.037]. Similarly, as-needed β-agonist use (puffs/day) was reduced with montelukast (?p ≤ 0.005).

Conclusion: Montelukast provides significant relief from symptoms of seasonal allergic rhinitis, while also conferring a benefit for asthma, in patients with both allergic rhinitis and asthma.     

Comparison of the Internal State Scale to Clinician-Administered Assessments in Patients with Bipolar Disorder and Alcohol Abuse or Dependence

Abstract

Objectives: Self-report measures require less clinician time to administer than clinician-rated assessments. The Internal State Scale (ISS) is a well-validated self-report measure that assesses symptoms of mania and depression in patients with bipolar disorder (BPD). However, the ISS has never been specifically evaluated in patients with BPD and comorbid substance misuse. Substances can induce mood symptoms complicating diagnosis and mood state assessment.

Methods: The ISS was compared with the Hamilton Rating Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS) in 21 patients with BPD and alcohol abuse/dependence at baseline and for up to 16 weeks postbaseline. In addition, ISS-determined mood state was compared to mood state from a structured diagnostic interview.

Results: Significant baseline correlations were observed between the ISS depression subscale and HRSD, ISS activation subscale and YMRS, and ISS perceived conflict subscale and BPRS. Significant correlations of baseline to exit change scores were found between the ISS activation and YMRS, but not ISS depression and HRSD, or ISS perceived conflict and BPRS. All participants had a mixed mood state by structured diagnostic interview. The ISS diagnosed the manic/hypomanic portion of this mood state in 76% of participants but found depression in only 38%.

Conclusions: As in BPD patients without substance abuse, the ISS generally showed correlations with clinician-rated scales at baseline, with less strong correlations observed on change scores. The ISS diagnosis of mania or hypomania appeared to correspond more highly than depression with the findings from a structured diagnostic interview.     

A comparative study of the efficacy of acute and continuation treatment with escitalopram versus duloxetine in patients with major depressive disorder

ABSTRACT

Objective: This study evaluated the efficacy and tolerability of escitalopram and duloxetine in the treatment of major depressive disorder (MDD).

Research design and methods: Patients were randomised to 24 weeks of double-blind treatment with fixed doses of escitalopram (20?mg) (n = 143) or duloxetine (60?mg) (n = 151). The primary analysis of efficacy was an analysis of covariance (ANCOVA) of change from baseline to endpoint (week 24) in MADRS total score (last observation carried forward).

Main outcome measures; Results: At week 8, the mean change from baseline in total MADRS score was –19.5 for patients treated with escitalopram (n = 141) and –17.4 for patients treated with duloxetine (n = 146), a difference of 2.1 points (?p < 0.05). At week 8, the proportion of responders (≥?50% decrease in MADRS) was 69% (escitalopram) and 58% (duloxetine) (?p < 0.05) and remission (MADRS ≤?12) rates were 56% (escitalopram) and 48% (duloxetine) (NS). For the primary endpoint, the mean change from baseline in total MADRS score at week 24 was –23.4 for patients treated with escitalopram and –21.7 for patients treated with duloxetine, a difference of 1.7 points (?p = 0.055, one-sided). The difference in mean change from baseline in MADRS total score favoured escitalopram at weeks 1, 2, 4, 8, 12 and 16 (?p < 0.05). The overall withdrawal rates were 22% (escitalopram) and 25% (duloxetine) (NS). The withdrawal rate due to adverse events was lower for escitalopram (9%) compared to duloxetine (17%) (?p < 0.05) and significantly more patients treated with duloxetine reported insomnia (12.6% vs. 4.9%) and constipation (8.6% vs. 2.8%).

Conclusion: Escitalopram was superior to duloxetine in acute treatment and at least as efficacious and better tolerated in long-term treatment of MDD.     

A Double-blind,Randomised Comparative Trial of Amisulpride Versus Olanzapine in the Treatment of Schizophrenia: Short-term Results at Two Months

Summary

Objective: To compare the efficacy and safety of the atypical antipsychotics amisulpride and olanzapine in the treatment of acute psychotic exacerbations of schizophrenia.

Design and setting: A multinational, double-blind randomised clinical trial.

Patients and treatment:Three hundred and seventy-seven patients with predominantly positive symptomatology were treated for six months with either amisulpride (200-800?mg/d) or olanzapine (5-20?mg/d).

Main outcome measures: Short-term results were analysed after two months of treatment. The primary efficacy measure was the change of score on the Brief Psychiatric Rating Scale (BPRS). Other measures of efficacy and safety were also evaluated.

Results: Psychotic symptoms, as measured on the BPRS score, improved with both treatments, amisulpride being equivalent to olanzapine. All BPRS factor scores, as well as depressive symptoms, improved to a similar extent with both treatments. Less than five per cent of patients withdrew for adverse events, and there was no evidence for the emergence of extrapyramidal symptoms with either treatment. Statistically significant greater weight gain (2.7?±?3.9?kg) was observed during the study in the olanzapine group, compared with the amisulpride group (0.9?±?3.2?kg, p?<?0.0001).

Conclusions: Amisulpride and olanzapine show equivalent efficacy at 2 months in the treatment of acute psychotic exacerbations of schizophrenia. Amisulpride offers a significant advantage in preserving body weight.     

喹硫平或奥氮平联合丙戊酸钠缓释片治疗维族双相障碍精神病的疗效研究

目的 探讨喹硫平、奥氮平联合丙戊酸钠缓释片对维族双相障碍精神病临床疗效的影响。方法 选择2015年6月—2016年6月在乌鲁木齐市第四人民医院治疗双相障碍精神病的患者100例,随机分为2组,每组50例,对照组患者服用奥氮平联合丙戊酸钠缓释片,观察组患者服用喹硫平联合丙戊酸钠缓释片,服药1、4、8周时患者于医院进行复查,填写17项HMDM评分表、BRMD评分表以及GSI-IS评分表评估两组患者在不同时间的抑郁、躁狂情况和临床疗效。结果 两组患者在治疗期间,临床症状减轻,治疗1、4、8周时HMDM评分、BRMD评分以及GSI-IS评分均显著低于治疗前（P＜0.05）,且随疗程的延长,症状趋于减轻甚至消失;观察组各量表评分比对照组低,但是统计学分析无显著差异。记录两组患者治疗过程中发生不良反应的情况,结果显示观察组患者不良反应的总发生率和头晕嗜睡的发生率较对照组明显降低（P＜0.05）。结论 奥氮平或喹硫平联合丙戊酸钠缓释片可以有效控制维族双相障碍患者抑郁、躁狂症状,且奥氮平联合丙戊酸钠缓释片可以显著降低不良反应发生率,值得临床推广应用。     

Open-label olanzapine treatment in bipolar I disorder: clinical and work functional outcomes

ABSTRACT

Objectives: The objective of this study was to describe clinical and work functional outcomes associated with 6‐month open‐label olanzapine treatment for bipolar I disorder.

Methods: The study consisted of 249 patients entering a 6‐month open label phase after 12 weeks of acute double-blind haloperidol or olanzapine treatment. Baseline for analysis was defined as the beginning of open-label treatment. The clinical outcomes were symptomatic remission defined by a Y‐MRS total score ≤ 12 and a HAM‐D total score ≤ 8 at the end of 6 months of treatment. The work functional outcomes included work functional scores, the proportion of patients who reported to ‘work’ as employee, volunteers, students, or house workers and the proportion of patients who specifically reported to ‘work for pay’.

Results: A total of 240 patients reported work functional outcomes post open-label baseline. Among them, 15.4% patients moved into a ‘work group’ from a ‘no-work group’ at baseline, while 7.1% did the opposite (?p = 0.0065) and 13.3% reported an improvement to ‘work for pay’ status from a ‘not working for pay’ status at baseline, while there was 4.2% of worsening in employment status (?p = 0.0007). Overall, improvement in the work functional score was found at all post-baseline time points, beginning at month two (?p = 0.003).

Limitations: Results of this study need to be confirmed by double-blind randomized controlled studies. There was a lack of detailed information on work functioning from the questionnaire.

Conclusions: Open‐label olanzapine treatment for 6 months was associated with improvements in work functional outcomes in patients with bipolar disorder.     

Quetiapine in schizophrenia: onset of action within the first week of treatment

SUMMARY

Objective: Three placebo-controlled clinical trials have established the efficacy of the atypical antipsychotic quetiapine (Seroquel*) in schizophrenia. These trials were designed and powered to detect a treatment difference in the primary endpoint at Week 6. The objective of the current analysis was to investigate the effect of quetiapine at earlier timepoints.

Research design and methods: A combined analysis of data from three acute, double-blind, placebo-controlled, randomised trials was carried out. The trials comprised hospitalised patients with an acute exacerbation of chronic or subchronic schizophrenia who were randomised to receive quetiapine 150–750?mg/day (n = 422) or placebo (n = 198). Symptoms were assessed using changes from baseline to Week 1 in the Brief Psychiatric Rating Scale (BPRS) total score, BPRS positive symptom cluster score and the individual BPRS items of excitement, tension and depression. Changes from baseline to Weeks 1–6 were calculated for BPRS Factor 1 scores (which measures mood symptoms) and Scale for Assessment of Negative Symptoms (SANS) summary scores.

Results: Within 1?week, overall symptom improvement (BPRS total score) was significantly (?p < 0.05) greater with quetiapine than with placebo; improvement also occurred in individual BPRS items of excitement, tension and depression. Improvement in negative symptoms was significantly (?p < 0.05) greater with quetiapine than with placebo from Week 1, as was the BPRS Factor I score from Week 2. More quetiapine- than placebo-treated patients showed a response of positive symptoms to treatment within 1?week (?p < 0.05).

Conclusions: The beneficial effects of quetiapine are observed within 1?week across a broad spectrum of symptoms.     

A randomized, 1-year follow-up study of olanzapine and risperidone in the treatment of negative symptoms in outpatients with schizophrenia

OBJECTIVE: To evaluate the efficacy of olanzapine compared with risperidone in negative symptoms, after 1 year of treatment, in schizophrenic outpatients with prominent negative symptoms. METHODS: This was a multicenter, randomized, monitored, open-label, parallel, dose-flexible, 1-year study of outpatients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) with prominent negative symptoms (Scale for the Assessment of Negative Symptoms [SANS] summary score > or =10) previously treated with conventional antipsychotics. Patients were randomly assigned to treatment with an initial dose of olanzapine 10 mg/d or more (n = 120) or risperidone 3 mg/d or more (n = 115). The primary efficacy measure was the SANS summary score. Secondary efficacy measures included Scale for the Assessment of Positive Symptoms, Clinical Global Impression of Severity Scale, Calgary Depression Scale, and Social Functioning Scale. The response rate was defined as 30% or more of improvement in the SANS summary score. RESULTS: The mean dose throughout the study was 12.2 mg/d (+/-5.8 mg/d) for olanzapine and 4.9 mg/d (+/-2.0 mg/d) for risperidone. At 1 year, olanzapine patients showed significantly higher improvement than risperidone patients on the SANS summary (P = 0.015) and on the affective flattening (P = 0.007) and avolition/apathy (P = 0.028) SANS subscales. There were also significant improvements in favor of olanzapine in the Scale for the Assessment of Positive Symptoms summary (P = 0.021), Clinical Global Impression of Severity (P = 0.008), and Social Functioning Scale total (P < 0.001) scores. The response rate was greater (P = 0.001) in the olanzapine cohort (69.2%) than in the risperidone cohort (48.7%). Olanzapine patients reported less extrapyramidal side effects but a higher incidence of clinically important body weight increase than risperidone patients. CONCLUSIONS: Long-term treatment with olanzapine was associated with significantly better improvement in negative symptoms as compared with risperidone-treated schizophrenic outpatients with prominent negative symptoms.     

Outcomes for Latin American versus White patients suffering from acute mania in a randomized, double-blind trial comparing olanzapine and haloperidol

Data from a published double-blind randomized trial comparing olanzapine versus haloperidol in acute mania were used to address the response and tolerability of Latin American patients. Primary efficacy end point was the remission rate (Young Mania Rating Scale score 相似文献   

Longer-term treatment of patients with bipolar disorder: a 9-month observational study in Central and Eastern Europe,the Middle East and Africa

ABSTRACT

Objective: To compare the longer-term outcomes of pharmacological treatment of patients with a diagnosis of bipolar affective disorder currently suffering a manic or hypomanic episode prescribed olanzapine or non-olanzapine medication in naturalistic, clinical practice settings in Bosnia-Herzegovina, Slovakia, Slovenia, Turkey, Saudi Arabia and Egypt.

Research design and methods: Prospective, observational, non-interventional study conducted over 9 months. Inpatients or outpatients who initiated or changed oral bipolar mania medication were grouped into (1) those prescribed olanzapine at baseline (n?=?569) and (2) those not prescribed olanzapine (n?=?325).

Main outcome measure(s): The change from baseline in the Clinical Global Impression Severity scale for bipolar disorder (CGI-BP-S), the rates of symptomatic response and remission (based on CGI-BP-S) and the frequency and nature of treatment-emergent adverse events. Analyses included (1) linear or logistic regression, with adjustment for confounders, based on the last observation carried forward and (2) weighted repeated measures models that adjusted for treatment switching and patient drop-out.

Results: When results were adjusted for treatment switching and patient drop-out, patients prescribed olanzapine had significantly better CGI-BP-S scores (mean difference?=??0.24; 95% confidence interval [CI] ?0.33, ?0.16; p?<?0.001) and significantly greater odds of treatment response (odds ratio [OR] =?1.86; 95% CI 1.31, 2.65; p?<?0.001) and symptom remission (OR?=?1.65; 95% CI 1.18–2.32; p?=?0.003) than those not prescribed olanzapine. The frequency of most adverse events decreased in both groups. Patients prescribed olanzapine had significantly greater weight gain from baseline (mean increase?=?2.66?kg; 95% CI 2.35, 2.98) compared with those not prescribed olanzapine (mean increase?=?1.85?kg; 95% CI 1.51, 2.19; p?<?0.001).

Conclusions: Inclusion of olanzapine is of benefit for pharmacological treatment of patients with bipolar disorder. However, the favourable outcomes observed cannot be directly attributed to olanzapine alone because of the high prevalence of polypharmacy in the patient population.     

An open-label evaluation of rifaximin in the treatment of active Crohn's disease

ABSTRACT

Objective: This open-label study was conducted as a preliminary assessment of rifaximin (200?mg TID for 16 weeks) for the treatment of active Crohn's disease in patients (n = 29) with symptoms for at least 3 months before screening and a Crohn's Disease Activity Index (CDAI) score > 220 and < 400.

Results: At the end of month 4, mean ± SD CDAI score was reduced by 43% compared with baseline in the intent-to-treat population (n = 29; baseline = 278 ± 51; month 4 = 159 ± 102; p < 0.0001 month 4 versus baseline). A similar pattern of results was observed in the per-protocol population (i.e., patients at least 70% compliant with the treatment regimen and having no protocol violations thought to affect efficacy results; n = 16), in which mean CDAI scores at month 4 were reduced by 41% from a baseline of 262.9 ± 38.2 to 155.6 ± 104.5 (?p = 0.0009 month 4 versus baseline). Fifty-nine percent of patients (59%) had a ≥ 70‐point improvement in CDAI score beginning with the first assessment at the end of month 1. By the end of the treatment period, 78% of patients had a ≥ 70‐point improvement in CDAI score. Clinical remission, defined as CDAI score < 150, was observed at the end of treatment months 1, 2, 3, and 4 in 41%, 56%, 56%, and 59% of patients, respectively. Twenty-three (23) patients completed the 4-month course of rifaximin therapy, and 6 prematurely withdrew. The most common adverse events were abdominal pain, fatigue, and headache.

Conclusion: These data, which are consistent with the possibility that rifaximin may be useful for active Crohn's disease, warrant confirmation in a randomized, double-blind, placebo-controlled trial.     

Efficacy of etoricoxib 60 mg/day and diclofenac 150 mg/day in reduction of pain and disability in patients with chronic low back pain: results of a 4‐week,multinational, randomized,double-blind study

ABSTRACT

Background and methods: The efficacy and safety of etoricoxib 60?mg/day in patients with established chronic low back pain (CLBP) were compared with those of diclofenac 150?mg/day in a 4‐week, multicentre, randomized, double-blind, parallel-group trial. Four hundred and forty-six adult patients with CLBP (Quebec Task Force on Spinal Disorders Class 1 or 2) and with worsening pain upon discontinuation of pre-study analgesic medication were enrolled in the study.

The study primary efficacy endpoint was change from baseline in Low Back Pain Intensity Scale (LBP‐IS) score over the 4‐week treatment period. Secondary and other efficacy endpoints included: changes in Roland and Morris Disability Questionnaire (RMDQ), Patient Global Assessment of Response to Therapy (PGART) and Low Back Pain Bothersomeness Scale (LBP-BS) scores. Early efficacy was assessed using PGART and LBP‐IS scores 4?h after the first dose on the mornings of Days 1, 2 and 3. The overall safety and tolerability of etoricoxib 60?mg/day during 4 weeks of treatment were also assessed.

Results: The least-squares mean time-weighted change from baseline LBP‐IS score over 4 weeks was –32.94?mm (95% CI –36.25, –29.63) for etoricoxib, indicating substantial efficacy in relief of pain. The treatment difference for the primary outcome was 2.51?mm (95% CI –1.50, 6.51), fulfilling the prespecified equivalence criterion of 95% confidence interval wholly within ± 10?mm. Etoricoxib improved all secondary and other efficacy outcomes.

There were no statistically significant between-group differences in the proportion of patients with one or more clinical adverse events (AEs) (etoricoxib 35%, diclofenac 39%), or the proportion of patients who discontinued due to AEs (etoricoxib 7%, diclofenac 5%).

Conclusions: The results of this study confirm that, for adult patients with CLBP, etoricoxib 60?mg once daily over 4 weeks is effective for relief of pain and improvement of physical function and comparable to high-dose diclofenac 150?mg daily.     

Olanzapine for schizophrenia refractory to typical and atypical antipsychotics: an open-label, prospective trial

The role of olanzapine in treatment-resistant schizophrenia is still unresolved. This article presents an open-label, prospective, 14-week trial with olanzapine in patients with schizophrenia and schizoaffective disorder selected for unambiguous resistance to either clozapine or risperidone and to typical antipsychotics. Forty-three inpatients (mean age, 41.6 years; mean duration of illness, 21.7 years) were enrolled and treated after cross-titration from their previous antipsychotic treatment with olanzapine 10 to 40 mg daily without any concomitant antipsychotic medication. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions Scale, and the Extrapyramidal Symptom Rating Scale. The change with olanzapine treatment was associated with a PANSS total score improvement of 3.7 (SD = 15.6; not significant). There was a significant improvement for the PANSS cognitive and depression/anxiety factors, whereas the PANSS excitement factor worsened. The improvement rate was superior in patients receiving olanzapine doses higher than 20 mg. A total of 16.7% of patients reached response criteria set forth by a previous study. There was a significant decrease in extrapyramidal side effects (t = 2.04; p < 0.05) and statistically significant, yet modest, weight gain. These results indicate that olanzapine is only modestly effective in these severely treatment-resistant patients with schizophrenia. However, a trial with olanzapine can be recommended in these patients before moving to augmentation strategies, given the lack of proven alternatives and the observation that 16.7% of patients reached the response criteria.     

The relationship between functional outcomes and the treatment of anxious and painful somatic symptoms in patients with generalized anxiety disorder

ABSTRACT

Objective: To examine the relationship between global functional impairment and the treatment of anxious symptoms and painful somatic symptoms (PSS) in patients with generalized anxiety disorder (GAD).

Research design and methods: Data from two double-blind, placebo-controlled trials in adult outpatients meeting DSM-IV criteria for GAD were pooled. In the first trial (9-week, fixed-dose treatment period), patients were randomized to duloxetine 60?mg QD (n = 168), duloxetine 120?mg QD (n = 170), or placebo (n = 175). In the second trial (10-week, flexible-dose treatment period), patients were randomized to 60–120?mg QD of duloxetine (n = 168) or placebo (n = 159). Path analysis was used to assess the relative contributions of changes in psychic and somatic anxiety and PSS on improved functional outcomes. Clinical trial registration information: Study 1: NCT00122824; Study 2: study completed before registration required.

Main outcome measures: Sheehan Disability Scale (SDS), Hamilton Anxiety Rating Scale (HAMA), and Visual Analog Scale for overall pain (VAS).

Results: There was a moderate correlation (0.45, p < 0.05) at endpoint between changes in global functional impairment and changes in psychic anxiety (controlling for somatic anxiety and PSS); whereas the correlation between changes in global functional impairment and changes in somatic anxiety (controlling for psychic anxiety and PSS) was weak (0.09, p < 0.05). The correlation between changes in global functional impairment and changes in PSS (controlling for psychic and somatic anxiety) was weak (0.27, p < 0.05). Path analysis revealed that 37% of the total improvement in functional impairment (Sheehan Disability Scale total score) due to duloxetine treatment was independent of improvement in the Hamilton Anxiety Rating Scale (HAMA) psychic and somatic anxiety subscale scores or Visual Analog Scale for overall pain (VAS) score. Improvement in psychic anxiety accounted for 47% of the total treatment effect on improvement of functional impairment, whereas 7% and 9% of the improvement in functional impairment was accounted for by improvements in somatic anxiety and overall pain, respectively.

Limitations: This was a post-hoc exploratory analysis. Patients with co-morbid Major Depressive Disorder (MDD) or significant depressive symptoms were excluded from these GAD studies.

Conclusions: In patients with GAD, there was a moderate correlation between improvement in psychic anxiety symptoms and improvement in global functional impairment, whereas the correlation between improvements in somatic anxiety or PSS and improvement in global functional impairment was low. Most of the treatment effect of duloxetine in improvement of functional impairment was mediated through improvement in psychic anxiety, with smaller contributions through improvement in somatic anxiety and PSS. Some of the improvement in functional impairment for duloxetine-treated patients was independent of improvement through any of these domains.     

Quetiapine monotherapy for mania associated with bipolar disorder: combined analysis of two international,double-blind,randomised, placebo-controlled studies

ABSTRACT

Objective: To evaluate the efficacy and safety of quetiapine monotherapy for mania in bipolar disorder by an a priori defined combined analysis of data from two placebo-controlled studies.

Method: The intent-to-treat (ITT) populations from two studies of patients with DSM-IV bipolar I disorder, manic episode, randomised to 12 weeks of double-blind treatment with quetiapine (up to 800?mg/day) or placebo were combined. The primary efficacy endpoint was change in Young Mania Rating Scale (YMRS) score from baseline to Day 21. Secondary endpoints included change from baseline in YMRS to Day 84, YMRS response and remission rates and change from baseline to Days 21 and 84 in the Montgomery–Asberg Depression Rating Scale (MADRS), Clinical Global Impressions (CGI), Clinical Global Impressions – Bipolar (CGI-BP) and the Positive and Negative Syndrome Scale (PANSS). These endpoints were analysed as continuous variables, using an analysis of covariance (ANCOVA), with the baseline as covariate. In order to account for any difference in response between studies, the analyses were stratified by study as a fixed effect, and centre as a random effect. The Cochran–Mantel–Haenszel test was used to analyse binary variables. A chi square test was used to compare the frequency of adverse events between the treatment groups.

Results: The combined analysis included a total of 403 patients from two quetiapine monotherapy studies in patients with bipolar I disorder. A significant improvement in YMRS score was observed from Day 4 (?p = 0.021) onward in the quetiapine group compared with placebo. The treatment advantage of quetiapine over placebo continued to increase to Day 21 (?p < 0.001) and Day 84 (?p < 0.001). Significantly more quetiapine-treated than placebo-treated patients achieved a response (?p < 0.001). The average quetiapine dose in responders was approximately 600?mg daily. Of adverse events occurring in ≥ 5% of patients, quetiapine-treated patients had a significantly greater incidence versus placebo of somnolence (16.3% vs. 4.0%), dry mouth (15.8% vs. 3%), weight gain (9.1% vs. 1.5%) and dizziness (6.7% vs. 2.5%).

Conclusions: The data from this combined analysis support the results from the individual studies and indicate that quetiapine monotherapy is effective across a broad range of mood symptoms, fast-acting and well tolerated in the treatment of mania.     

Efficacy and tolerability of twice-daily pregabalin for treating pain and related sleep interference in postherpetic neuralgia: a 13‐week,randomized trial

ABSTRACT

Objective: This trial evaluated the efficacy and safety of pregabalin dosed twice daily (BID) for relief of neuro-pathic pain associated with postherpetic neuralgia (PHN).

Research design and methods: The 13‐week, double-blind, placebo-controlled study randomized 370 patients with PHN to pregabalin (150, 300, or 600?mg/day BID) or placebo.

Main outcome measures: Primary efficacy measure was endpoint mean pain score from daily pain diaries. Secondary efficacy measures included endpoint mean sleep-interference score from daily sleep diaries and Patient Global Impression of Change (PGIC). Safety evaluations included adverse events (AEs), physical and neurologic examinations, 12-lead ECG, vital signs, and laboratory testing.

Results: Pregabalin provided significant, dose-proportional pain relief at endpoint: difference from placebo in mean pain score, 150?mg/day, –0.88, p = 0.0077; 300?mg/day, –1.07, p = 0.0016; 600?mg/day, –1.79, p = 0.0003. Weekly mean pain scores significantly improved as early as week 1. Sleep interference in all pregabalin groups was also significantly improved at endpoint, compared with placebo (?p < 0.001), beginning at week 1 (?p < 0.01). At study termination, patients in the 150 (p = 0.02) and 600?mg/day (p = 0.003) groups were more likely to report global improvement than were those in the placebo group.

Most AEs were mild or moderate. Among pregabalin-treated patients, 13.5% withdrew due to AEs, most commonly for dizziness (16 patients, 5.8%), somnolence (8, 2.9%), or ataxia (7, 2.5%).

Conclusions: Pregabalin, dosed BID, reduced neuropathic pain associated with PHN and was well tolerated. It also reduced the extent to which pain interfered with sleep. Pregabalin's effects were seen as early as week 1 and were sustained throughout the 13‐week study.