Severity and management of psoriasis within primary care.

BACKGROUND: Scottish Intercollegiate Guidelines Network and National Institute of Health and Care Excellence guidelines stress the importance of assessing patients with psoriasis for psoriatic arthritis, comorbidities associated with severe disease and quality of life (QoL). The purpose of the study was to evaluate the primary care management of psoriasis in relation to disease severity and QoL from a patient's perspective. METHODS: A cross-sectional survey of adults (≥18 years) with psoriasis managed in primary care was conducted in Scotland over 1-year (2012-2013). Patients with psoriasis were identified and invited to participate in the online/telephone survey. The questionnaires included; Dermatology Life Quality Index (DLQI), Self-Administered Psoriasis Area and Severity Index (SAPASI), Psoriasis Epidemiology Screening Tool (PEST). The primary outcome measure was DLQI. Secondary outcomes included; demographics; comorbidities; involvement of different body sites; SAPASI and PEST scores. Relationships between measures were analysed using univariate analysis. RESULTS: The mean age of patients (n = 905) was 54.5 years (SD = 16.1), 436 (48.2 %) were men, and median DLQI and SAPASI scores were 4.0 and 6.0, respectively. Current psoriasis treatments were topical only (587, 64.9 %), oral medications or phototherapy (122, 13.5 %), biologics (26, 3 %) and none (156, 17.2 %). Despite SIGN recommendations, 256 of 391 patients (65.5 %) with a DLQI >5 (at least a moderate effect on QoL) had not seen a specialist during the past year. According to PEST scores, 259 patients (28.6 %) had symptoms suggestive of psoriatic arthritis requiring rheumatology referral. CONCLUSION: National recommendations are not being fully implemented in primary care in patients with psoriasis or psoriatic arthritis.

Baseline characteristics and patient reported outcome data of patients prescribed etanercept: web-based and telephone evaluation.

BACKGROUND: The anti-TNF inhibitor, etanercept is administered as a once or twice weekly subcutaneous injection for the treatment of rheumatoid arthritis, psoriasis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis (JIA). Limited data from the patients' perspective are available on the use of biologics in the treatment of these chronic conditions and this evaluation was designed to collect data from patients who had been prescribed etanercept for the first time. This manuscript describes the self-reported baseline characteristics and health-related quality of life of patients prior to treatment. Follow-up data will be reported separately. METHODS: Patients throughout the United Kingdom prescribed etanercept were invited to participate in an evaluation of their condition and treatment using a data collection tool consisting of a web-based system supplemented by telephone reporting (PROBE). Outcome measures reported at baseline included demographic data, the condition being treated, previous treatment with biologic agents and current and previous medications. Questions modified from standard, validated quality of life questionnaires such as EQ-5D were incorporated and patients made a global assessment of the severity of their own illness using the CGI-S scale. RESULTS: A total of 344 patients/carers/parents participated in the evaluation at baseline, 290 (84%) by online questionnaire and 54 (16%) by telephone. Overall, the study population had a mean age of 53 years, was predominantly female (62%) and 20% had been previously treated with a biologic agent. A total of 191 (56%) patients were receiving treatment with etanercept for rheumatoid arthritis, 44 (13%) for psoriatic arthritis, 43 (13%) for ankylosing spondylitis, 35 (10%) for psoriasis, 9 (3%) for known juvenile idiopathic arthritis (JIA) and 22 (6%) for another condition/patient unsure/missing response. All patients were prescribed the 50 mg weekly dose of etanercept except for 1 patient with JIA (40 mg) dose and 2 patients with psoriasis (100 mg). Thirty-eight percent of patients with rheumatoid arthritis were not receiving treatment with methotrexate. CONCLUSIONS: The baseline characteristics and health-related quality of life of first time users of etanercept can be adequately described using self-reported patient data collected using an online questionnaire with a telephone option (PROBE).

Efficacy, safety and tolerability of escitalopram in doses up to 50 mg in Major Depressive Disorder (MDD): an open-label, pilot study.

BACKGROUND: Escitalopram is licensed for use at doses up to 20 mg but is used clinically at higher doses. There is limited published data at higher doses and none in the treatment of Major Depressive Disorder (MDD). METHODS: This open-label, pilot study was designed to investigate the efficacy, safety and tolerability of escitalopram in doses up to 50 mg in MDD. It was conducted in 60 primary care patients with MDD who had not responded to adequate treatment with citalopram. Patients were treated with escalating doses of escitalopram up to 50 mg for up to 32 weeks until they achieved remission (Montgomery-Asberg Depression Rating Scale [MADRS] ≤ 8) or failed to tolerate the dose. RESULTS: Forty-two patients (70%) completed the study. Twenty-one patients (35%) achieved remission with 8 of the 21 patients (38%) needing the 50 mg dose to achieve remission. Median time to remission was 24 weeks and median dose in remission was 30 mg. No significant safety issues were identified although tolerability appeared to decline above a dose of 40 mg with 26% of patients unable to tolerate 50 mg. Twelve (20%) patients had adverse events leading to discontinuation. The most common adverse events were headache (35%), nausea, diarrhoea and nasopharyngitis (all 25%). Minor mean weight gain was found during the study, which did not appear to be dose-related. Half of the patients who completed the study chose to continue treatment with escitalopram rather than taper down the dose at 32 weeks. CONCLUSIONS: Dose escalation with escitalopram above 20 mg may have a useful role in the management of patients with MDD, although further studies are needed to confirm this finding. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00785434.

A multicentre, randomised, double-blind, single-dose study assessing the efficacy of AMC/DCBA Warm lozenge or AMC/DCBA Cool lozenge in the relief of acute sore throat.

BACKGROUND: Clinically proven over-the-counter (OTC) treatment options are becoming increasingly important in the self-management of acute sore throat. The aim of this study was to determine the analgesic and sensorial benefits of two different amylmetacresol/2,4-dichlorobenzyl alcohol (AMC/DCBA) throat lozenge formulation variants, AMC/DCBA Warm lozenge and AMC/DCBA Cool lozenge, compared with an unflavoured, non-medicated placebo lozenge in the relief of acute sore throat due to upper respiratory tract infections. METHODS: In this multicentre, randomised, double-blind, single-dose study, 225 adult patients with acute sore throat were randomly assigned to receive either one AMC/DCBA Warm lozenge (n = 77), one AMC/DCBA Cool lozenge (n = 74) or one unflavoured, non-medicated lozenge (matched for size, shape and demulcency; n = 74). After baseline assessments, patients received their assigned lozenge and completed four rating assessments at 11 timepoints from 1 to 120 minutes post dose. Analgesic properties were assessed by comparing severity of throat soreness and sore throat relief ratings. Difficulty in swallowing, throat numbness, functional, sensorial and emotional benefits were also assessed. RESULTS: Both the AMC/DCBA Warm and AMC/DCBA Cool lozenge induced significant analgesic, functional, sensorial and emotional effects compared with the unflavoured, non-medicated lozenge. Sore throat relief, improvements in throat soreness and difficulty in swallowing, and throat numbness were observed as early as 1-5 minutes, and lasted up to 2 hours post dose. Sensorial benefits of warming and cooling associated with the AMC/DCBA Warm and AMC/DCBA Cool lozenge, respectively, were experienced soon after first dose, and in the case of the latter, it lasted long after the lozenge had dissolved. Emotional benefits of feeling better, happier, less distracted and less frustrated were reported in those taking either of the AMC/DCBA throat lozenge variants, with no differences in adverse events compared with the unflavoured, non-medicated lozenge. CONCLUSIONS: AMC/DCBA Warm and AMC/DCBA Cool lozenges are well-tolerated and effective OTC treatment options, offering functional, sensorial and emotional benefits to patients with acute sore throat, over and above that of the rapid efficacy effects provided. TRIAL REGISTRATION: ISRCTN: ISRCTN00003567.

Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety.

BACKGROUND: Melatonin is extensively used in the USA in a non-regulated manner for sleep disorders. Prolonged release melatonin (PRM) is licensed in Europe and other countries for the short term treatment of primary insomnia in patients aged 55 years and over. However, a clear definition of the target patient population and well-controlled studies of long-term efficacy and safety are lacking. It is known that melatonin production declines with age. Some young insomnia patients also may have low melatonin levels. The study investigated whether older age or low melatonin excretion is a better predictor of response to PRM, whether the efficacy observed in short-term studies is sustained during continued treatment and the long term safety of such treatment. METHODS: Adult outpatients (791, aged 18-80 years) with primary insomnia, were treated with placebo (2 weeks) and then randomized, double-blind to 3 weeks with PRM or placebo nightly. PRM patients continued whereas placebo completers were re-randomized 1:1 to PRM or placebo for 26 weeks with 2 weeks of single-blind placebo run-out. Main outcome measures were sleep latency derived from a sleep diary, Pittsburgh Sleep Quality Index (PSQI), Quality of Life (World Health Organzaton-5) Clinical Global Impression of Improvement (CGI-I) and adverse effects and vital signs recorded at each visit. RESULTS: On the primary efficacy variable, sleep latency, the effects of PRM (3 weeks) in patients with low endogenous melatonin (6-sulphatoxymelatonin [6-SMT]

Antidepressant treatment and cultural differences--a survey of the attitudes of physicians and patients in Sweden and Turkey.

BACKGROUND: The presenting symptoms of depression can be influenced by cultural differences. This study was conducted to compare the presenting symptoms and response to antidepressant medication of patients in Sweden and Turkey, two culturally different European countries. METHODS: Recruitment was triggered when adult patients were diagnosed with a depressive or anxiety disorder by a primary care physician and prescribed an antidepressant. Physicians and patients recorded presenting symptoms and completed relevant questionnaires just before and 8 weeks after starting treatment with an antidepressant. These included the Hospital Anxiety and Depression Scale (HADS), the Clinical Global Impressions (CGI) scale, the Sheehan Disability Scale (SDS), and Likert scales gauging the importance of physical and psychological symptoms. Patients also rated severity of prominent symptoms (depression, anxiety, stress, sleep and pain) from zero to ten. The outcomes were compared between patients from Sweden and Turkey using Fisher's Exact test and two-sample t-tests. RESULTS: The study was conducted in 460 patients (107, 23.3% in Sweden; 353, 76.7% in Turkey). Presenting symptoms differed between Sweden and Turkey, with Turkish patients more likely to present with physical symptoms, and report a higher number of physical symptoms (mean 2.4 vs. 1.4, p < 0.001). In both countries, the diagnosis made by the physician differed from that derived from the HADS score at the start of the study. The HADS diagnosis varied between the countries with significantly different proportions of patients in each country being diagnosed with depression alone, anxiety alone or depression with anxiety. While all symptoms improved after antidepressant treatment in both countries, Turkish patients showed a greater degree of response than Swedish patients in depression (p = 0.048), stress (p = 0.014) and pain (p < 0.001) as measured by the prominent symptoms assessment (PSA). CONCLUSIONS: The presenting symptoms of patients diagnosed with a depressive or anxiety disorder by a primary care physician and prescribed an antidepressant differ between Turkey and Sweden. Patients in Turkey were more likely to present with physical symptoms than patients in Sweden and present with more physical symptoms. After 8 weeks of antidepressant treatment, the improvement from baseline was greater in Turkish patients, and this was reflected in their improved functioning.

Creation and validation of a linear index to measure the health state of patients with depression in automated healthcare databases.

Background and objective: We previously built a weighted Depressive Health State Index (DHSI) based on 29 parameters routinely collected in an automated healthcare database (AHDB). We now propose a linear DHSI (L-DHSI) which is easier to use and to replicate across AHDBs. Methods: A historical cohort of patients with ≥1 episode of depression was identified in the Clinical Practice Research Datalink (CPRD). The DHSI was calculated for each treated episode of depression. Validation was performed by using validated definitions of remission (proxy and Patient Health Questionnaire 9 or PHQ-9) and comparing the L-DHSI between subgroups. Reliability was assessed using Cronbach's alpha. Results: Between 1 January 2006 and 31 December 2012, 309,279 episodes of depression were identified in the CPRD. Remission was observed in 5% of the patients with lowest L-DHSI scores and in 78% of the patients with highest L-DHSI scores. Although less sensitive than the weighted DHSI, the L-DHSI was reliable and relatively easy of use. The L-DHSI was highly correlated to the weighted DHSI (Spearman coefficient 0.790, p < 0.001). Conclusion: The L-DHSI represents a good balance between reliability, usability, and reproducibility. In addition, the linearity of this index allows for an easier interpretation than the original weighted DHSI.

Results and validation of an index to measure health state of patients with depression in automated healthcare databases.

Background and objective: A Depressive Health State Index (DHSI) based on 29 parameters routinely collected in an automated healthcare database (AHDB) was developed to evaluate the health state of depressive patients, and its evolution. The study objective was to describe and validate this DHSI. Methods: A historical cohort of patients with at least one episode of depression was identified in the Clinical Practice Research Datalink (CPRD). The DHSI was calculated for each episode of depression. Validation was performed by comparing the DHSI between subgroups and using validated definitions of remission (proxy and PHQ-9). Robustness was studied by assessing the impact of modifying parameters of the DHSI. Results: 309,279 episodes of depression were identified in the CPRD between 1 January 2006 and 31 December 2012. Remission was observed in 8% of the patients showing the lower DHSI scores and in 88% of the patients showing the higher DHSI scores. The DHSI was robust to a modification of the most frequent variables and to the removal of rare parameters. Conclusion: The DHSI is specific to depression severity (with remission rates in accordance with the expected variations of the DHSI) and robust. It represents a promising tool for the analysis of AHDBs.

Escitalopram and duloxetine in major depressive disorder: a pharmacoeconomic comparison using UK cost data.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) are approved for the treatment of major depressive disorder (MDD). The allosteric SSRI escitalopram has been shown to be at least as clinically effective as the SNRIs venlafaxine and duloxetine in MDD, with a better tolerability profile. In addition, escitalopram has been shown to be cost saving compared with venlafaxine. OBJECTIVE: To evaluate the cost effectiveness of escitalopram versus duloxetine in the treatment of MDD, and to identify key cost drivers. METHODS: The pharmacoeconomic evaluation was conducted alongside a 24-week, double-blind, multinational randomized study (escitalopram 20 mg/day and duloxetine 60 mg/day) in outpatients with MDD, aged 18-65 years, with Montgomery-Asberg Depression Rating Scale (MADRS) score >or=26 and Clinical Global Impression Severity (CGI-S) score >or=4, and baseline duration of the current depressive episode of 12 weeks to 1 year.The analysis was conducted on the full analysis set (FAS), which included all patients with >or=1 valid post-baseline health economic assessment. Effectiveness outcomes of the cost-effectiveness analyses (CEA) included the change in Sheehan Disability Scale (SDS) score (primary CEA), treatment response (MADRS score decrease >or=50%) and remission (MADRS score

Escitalopram and duloxetine in the treatment of major depressive disorder: a pooled analysis of two trials.

Pooled analyses have shown that escitalopram has superior effectiveness versus all comparators, including selective serotonin reuptake inhibitors and venlafaxine. Recent studies have compared escitalopram with duloxetine. Data from two randomized, double-blind studies that compared escitalopram (10-20 mg/day) and duloxetine (60 mg/day) were pooled and analysed for all patients and for the subsample of severely depressed patients [baseline Montgomery-Asberg Depression Rating Scale (MADRS) score > or =30]. Escitalopram (n=280) was superior to duloxetine (n=284) with respect to mean change from baseline in MADRS score at weeks 1, 2, 4 and 8 with a mean treatment difference at week 8 of 2.6 points (P<0.01). Similar results were seen for severely depressed patients, with a mean treatment difference of 3.7 points (P<0.01). Response and remission rates at week 8 were significantly higher for patients treated with escitalopram [response 67.1% for escitalopram compared with 53.2% for duloxetine, P<0.001; remission (MADRS< or =12) 54.3% for escitalopram compared with 44.4% for duloxetine, P<0.05]. The numbers needed to treat based on response and remission rates, in favour of escitalopram, were 8 and 11, respectively, for all patients (6 and 7, respectively, for severely depressed patients). Significantly fewer (P<0.001) patients (all cause and owing to adverse events) withdrew from the escitalopram group. This pooled analysis shows that over an 8-week treatment period, escitalopram (10-20 mg/day) is superior in both effectiveness and tolerability compared with duloxetine (60 mg/day).

Creating an index to measure health state of depressed patients in automated healthcare databases: the methodology.

Background and objective: Automated healthcare databases (AHDB) are an important data source for real life drug and healthcare use. In the filed of depression, lack of detailed clinical data requires the use of binary proxies with important limitations. The study objective was to create a Depressive Health State Index (DHSI) as a continuous health state measure for depressed patients using available data in an AHDB. Methods: The study was based on historical cohort design using the UK Clinical Practice Research Datalink (CPRD). Depressive episodes (depression diagnosis with an antidepressant prescription) were used to create the DHSI through 6 successive steps: (1) Defining study design; (2) Identifying constituent parameters; (3) Assigning relative weights to the parameters; (4) Ranking based on the presence of parameters; (5) Standardizing the rank of the DHSI; (6) Developing a regression model to derive the DHSI in any other sample. Results: The DHSI ranged from 0 (worst) to 100 (best health state) comprising 29 parameters. The proportion of depressive episodes with a remission proxy increased with DHSI quartiles. Conclusion: A continuous outcome for depressed patients treated by antidepressants was created in an AHDB using several different variables and allowed more granularity than currently used proxies.

A pharmacoeconomic evaluation of escitalopram versus citalopram in the treatment of severe depression in the United Kingdom.

BACKGROUND: Severe depression can increase the risk of psychiatric hospitalization, as well as inpatient and outpatient care; it may also lead to long-term absenteeism from work. However, the cost-effectiveness of antidepressant therapy for severe depression has been little studied. OBJECTIVE: The aim of this work was to investigate the cost-effectiveness of escitalopram compared with citalopram in patients with severe depression (Montgomery-Asberg Depression Rating Scale [MADRS] total score > or = 30) in the United Kingdom. METHODS: A probabilistic decision tree with a 6-month time horizon was adapted to the UK setting. The model incorporated clinical data, resource use directly related with care of severe depression, and lost productivity costs due to absenteeism. Primary results were remission (MADRS < or = 12) and costs (in year-2003 British pounds [1.00 British pound = 0.62 US dollars in January 2003]) of treatment calculated from the perspectives of UK society and the National Health Service (NHS). Secondary outcome was first-line success of treatment (ie, remission [MADRS < or = 12] without switch of drug). Remission, discontinuation, and response rates were derived from a meta-analysis of 506 patients with severe depression and extrapolated to 6 months. Standard UK price lists and literature were used to identify costs of resources. Societal costs of lost productivity were calculated using the human capital approach. RESULTS: Treatment of patients with escitalopram instead of citalopram rendered a higher overall remission rate (relative difference, 10.3%) and first-line success rate (relative difference, 35.4%). The mean cost per successfully treated patient was 15.7% (146 British pounds) lower for escitalopram (786 British pounds [range, 702-876 British pounds]) compared with citalopram (932 British pounds [range, 843-1028 British pounds]) from the NHS perspective and 15.6% (238 British pounds) lower for escitalopram (1283 British pounds [range, 1157-1419 British pounds]) than for citalopram (1521 British pounds [range, 1383-1675 British pounds]) from the societal perspective. The mean cost per severely depressed patient treated (overall study group) was 32 British pounds lower for escitalopram (422 British pounds [range, 404-441 British pounds]) than citalopram (454 British pounds [range, 436-471 British pounds]) from an NHS perspective and 50 British pounds lower for escitalopram (690 British pounds [range, 665-714 British pounds]) than citalopram (740 British pounds [range, 715-767 British pounds]) from the societal perspective. Using multivariate sensitivity analyses, we found that, in 99.8% of the cases, escitalopram was dominant from both perspectives at all ranges of probabilities tested. A sensitivity analysis on the acquisition cost of citalopram verified that, from the societal perspective, escitalopram remained the dominant strategy, even at a cost of 0.00 British pounds for citalopram. CONCLUSIONS: These results suggest that escitalopram is a cost-saving alternative to citalopram for the treatment of severe depression in the United Kingdom from the perspectives of both the NHS and society. Therefore, a possible advantage may exist at the population level in the treatment of severe depression with escitalopram in the United Kingdom.

A probabilistic cost-effectiveness analysis of escitalopram, generic citalopram and venlafaxine as a first-line treatment of major depressive disorder in the UK.

OBJECTIVES: To determine if escitalopram is cost-effective in the UK when compared with venlafaxine and generic citalopram in primary care treatment of Major Depressive Disorder (MDD). METHODS: A pre-existing cost-effectiveness model was adapted to reflect the practice in the UK. Adult patients (> 18 years) with MDD [baseline scores >/= 18 and

Impact of patient selection and study characteristics on signal detection in placebo-controlled trials with antidepressants.

An increasing rate of antidepressant trials fail due to large placebo responses. This analysis aimed to identify variables influencing signal detection in clinical trials of major depressive disorder. Patient-level data of randomized patients with a duloxetine dose ≥ 60 mg/day were obtained from Lilly. Total scores of the Hamilton Depression Rating scale (HAM-D) were used as efficacy endpoints. In total, 4661 patients from 14 studies were included in the analysis. The overall effect size (ES), based on the HAM-D total score at endpoint, between duloxetine and placebo was -0.272. Although no statistically significant interactions were found, the following results for factors influencing ES were seen: a very low ES (-0.157) in patients in the lowest baseline HAM-D category and in patients recruited in the last category of the recruitment period (-0.122). A higher ES in patients recruited in centers with a site-size at but not more than 2.5 times the average site-size for the study (-0.345). Study characteristics that resulted in low signal detection in our database were: <80% study completers, a HAM-D placebo response >5 points, a high variability of placebo response (SD > 7 points HAM-D), >6 post baseline visits per study, and use of an active control drug. Simpler trial designs, more homogeneous and mid-sized study sites, a primary analysis based on a higher cutoff blinded to investigators to avoid the influence of score inflation in mild patients and, if possible, studies without an active control group could lead to a better signal detection of antidepressive efficacy.

Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer's disease: a 6-month, randomized, placebo-controlled, multicenter trial.

PURPOSE: A link between poor sleep quality and Alzheimer's disease (AD) has recently been suggested. Since endogenous melatonin levels are already reduced at preclinical AD stages, it is important to ask whether replenishing the missing hormone would be beneficial in AD and whether any such effects would be related to the presence of sleep disorder in patients. PATIENTS AND METHODS: The effects of add-on prolonged-release melatonin (PRM) (2 mg) to standard therapy on cognitive functioning and sleep were investigated in 80 patients (men [50.7%], women [49.3%], average age 75.3 years [range, 52-85 years]) diagnosed with mild to moderate AD, with and without insomnia comorbidity, and receiving standard therapy (acetylcholinesterase inhibitors with or without memantine). In this randomized, double-blind, parallel-group study, patients were treated for 2 weeks with placebo and then randomized (1:1) to receive 2 mg of PRM or placebo nightly for 24 weeks, followed by 2 weeks placebo. The AD Assessment Scale-Cognition (ADAS-Cog), Instrumental Activities of Daily Living (IADL), Mini-Mental State Examination (MMSE), sleep, as assessed by the Pittsburgh Sleep Quality Index (PSQI) and a daily sleep diary, and safety parameters were measured. RESULTS: Patients treated with PRM (24 weeks) had significantly better cognitive performance than those treated with placebo, as measured by the IADL (P=0.004) and MMSE (P=0.044). Mean ADAS-Cog did not differ between the groups. Sleep efficiency, as measured by the PSQI, component 4, was also better with PRM (P=0.017). In the comorbid insomnia (PSQI ≥6) subgroup, PRM treatment resulted in significant and clinically meaningful effects versus the placebo, in mean IADL (P=0.032), MMSE score (+1.5 versus -3 points) (P=0.0177), and sleep efficiency (P=0.04). Median ADAS-Cog values (-3.5 versus +3 points) (P=0.045) were significantly better with PRM. Differences were more significant at longer treatment duration. PRM was well tolerated, with an adverse event profile similar to that of placebo. CONCLUSION: Add-on PRM has positive effects on cognitive functioning and sleep maintenance in AD patients compared with placebo, particularly in those with insomnia comorbidity. The results suggest a possible causal link between poor sleep and cognitive decline.

A survey of patient preferences for a placebo orodispersible tablet.

AIM: To assess the attitudes and preferences of patients currently being treated for depression or anxiety disorders with traditional oral antidepressants relative to a placebo orodispersible (ODT) formulation of escitalopram. METHODS: This was an open study collecting patient-reported outcome data from patients with anxiety or depression that were treated with oral antidepressant medication on Day 0 before and after receiving a single placebo ODT, and on Day 3 or 4 after receiving two further daily doses of placebo ODT. Patients aged 18-80 years who were currently receiving treatment with oral antidepressants were recruited from general practice and by advertising. Patients with significant symptoms of anxiety or depression (scoring ≥9 on either the depression or anxiety subscales of the Hospital Anxiety and Depression Scale) were included in the study. RESULTS: A total of 150 patients were enrolled in and completed the study. About 37% of the patients had had trouble with swallowing tablets, and patients with higher depression scores reported more general swallowing problems than those with lower scores (P = 0.002). Most patients (75.3%) believed that an ODT might work faster but that it would make no difference to the effectiveness of the medication (63.1%) or the number of side effects (81.3%). About 96% of the patients reported experiencing a pleasant taste following the placebo ODT, although seven patients did not like its taste or aftertaste. This study found that 80.7% of patients reported that the tablets were easy or very easy to get out of the packaging. CONCLUSION: Based on the results of the placebo version of escitalopram ODT, the escitalopram ODT is likely to be well accepted by patients suffering from anxiety or depressive symptoms.

Efficacy and safety of prolonged-release melatonin for insomnia in middle-aged and elderly patients with hypertension: a combined analysis of controlled clinical trials.

BACKGROUND: Add-on prolonged-release melatonin (PRM) in antihypertensive therapy has been shown to ameliorate nocturnal hypertension. Hypertension is a major comorbidity among insomnia patients. The efficacy and safety of PRM for primary insomnia in patients aged 55 years and older who are treated with antihypertensive drugs were evaluated. METHODS: Post hoc analysis of pooled antihypertensive drug-treated subpopulations from four randomized, double-blind trials of PRM and placebo for 3 weeks (N[PRM] = 195; N[placebo] = 197) or 28 weeks (N[PRM] = 157; N[placebo] = 40). Efficacy measurements included Leeds Sleep Evaluation Questionnaire scores of quality of sleep and alertness and behavioral integrity the following morning after 3 weeks, and sleep latency (daily sleep diary) and Clinical Global Impression of Improvement (CGI-I) after 6 months of treatment. Safety measures included antihypertensive drug-treated subpopulations from these four and three additional single-blind and open-label PRM studies of up to 1 year (N[PRM] = 650; N[placebo] = 632). RESULTS: Quality of sleep and behavior following wakening improved significantly with PRM compared with placebo (P < 0.0001 and P < 0.0008, respectively). Sleep latency (P = 0.02) and CGI-I (P = 0.0003) also improved significantly. No differences were observed between PRM and placebo groups in vital signs, including daytime blood pressure at baseline and treatment phases. The rate of adverse events normalized per 100 patient-weeks was lower for PRM (3.66) than for placebo (8.53). CONCLUSIONS: The findings demonstrate substantive and sustained efficacy of PRM in primary insomnia patients treated with antihypertensive drugs. PRM appears to be safe for insomnia in patients with cardiovascular comorbidity.

Patient reported outcome data following influenza A (H1N1p) vaccination in the 2009-2010 season: web-based and telephone evaluation.

BACKGROUND: There has been worldwide interest in the safety of the pandemic influenza A (H1N1p) vaccines, although limited data are available from the vaccine recipients' perspective. This evaluation was designed to collect data from people who had received an influenza vaccination during the 2009-2010 season using a web-based data collection tool supplemented by telephone reporting (PROBE). METHODS: People scheduled to receive the influenza A (H1N1p) or seasonal influenza vaccines were recruited through media advertising and campaigns throughout the West of Scotland. Vaccine recipients participated in the evaluation by answering demographic and side effect questions using PROBE methodology on the day of the immunization, after 3 days, 8 days, 6 weeks, 12 weeks, and 26 weeks. RESULTS: A total of 1103 vaccine recipients including 134 young children (0-4 years) participated in the evaluation; 694 (63%) received H1N1p vaccine only, 135 (12%) seasonal vaccine only, 224 (20%) both H1N1p and seasonal vaccines, and 50 (5%) received H1N1p or seasonal vaccine with a non-influenza vaccine (eg, travel or pneumococcal). Overall, 42% of recipients reported experiencing a side effect after their baseline vaccination; the most commonly reported were general and arm side effects (>20%). Injection site discomfort/pain and flu-like symptoms were reported by 57% and 24% of recipients, respectively. A significantly higher proportion of the 960 H1N1p vaccine recipients experienced a side effect (44% vs 27%, P < 0.001) or injection site discomfort/pain (61% vs 26%, P < 0.001) than those receiving seasonal influenza vaccines. Female sex and H1N1p vaccination were associated with a significantly higher risk of injection site discomfort/pain, whereas the 70+ age group was associated with a significantly lower risk. H1N1p vaccine was well tolerated by children under 5 years with side effects reported at a similar frequency to that found in the total population. CONCLUSIONS: Safety and tolerability data from influenza vaccine recipients including young children (via parents/carers) can be effectively collected using an online questionnaire with a telephone option (PROBE). The influenza A (H1N1p) vaccine was well tolerated, but was associated with more local short-term reactions than the seasonal influenza vaccine.

Prolonged release melatonin in the treatment of primary insomnia: evaluation of the age cut-off for short- and long-term response.

OBJECTIVES: The authors recently reported on efficacy and safety of prolonged-release melatonin formulation (PRM; Circadin 2 mg) in elderly insomnia patients. The age cut-off for response to PRM and the long-term maintenance of efficacy and safety were further evaluated by looking at the total cohort (age 18-80 years) from that study and subsets of patients aged 18-54 and 55-80 years (for whom the drug is currently indicated). DESIGN: Randomised, double-blind, placebo controlled trial. SETTING: Multicentre, outpatients, primary care setting. METHODS: A total of 930 males and females aged 18-80 years with primary insomnia who reported mean nightly sleep latency (SL) >20 min were enrolled and 791 entered the active phase of the study. The study comprised a 2-week, single-blind placebo run-in period followed by 3 week's double-blind treatment with PRM or placebo, one tablet per day at 2 hours before bedtime. PRM patients continued whereas placebo completers were re-randomised 1:1 to PRM or placebo for 26 weeks followed by 2-weeks run-out on placebo. MAIN OUTCOME MEASURES: SL and other sleep variables derived from sleep diary, Pittsburgh Sleep Quality Index (PSQI), Quality of life (WHO-5), Clinical Global Impression of Improvement (CGI-I) and adverse effects, recorded each visit, withdrawal and rebound effects during run-out. RESULTS: In all, 746 patients completed the 3-week and 555 (421 PRM, 134 placebo) completed the 6-month period. The principal reason for drop-out was patient decision. At 3 weeks, significant differences in SL (diary, primary variable) in favour of PRM vs. placebo treatment were found for the 55-80-year group (-15.4 vs. -5.5 min, p = 0.014) but not the 18-80-year cut-off which included younger patients. Other variables (SL-PSQI, PSQI, WHO-5, CGI-I scores) improved significantly with PRM in the 18-80-year population, more so than in the 55-80-year age group. Improvements were maintained or enhanced over the 6-month period with no signs of tolerance. No withdrawal symptoms or rebound insomnia were detected. Most adverse events were mild with no significant differences between PRM and placebo groups in any safety outcome. CONCLUSIONS: The results demonstrate short- and long-term efficacy of PRM in insomnia patients aged 18-80 years, particularly those aged 55 and over. PRM was well-tolerated over the entire 6-month period with no rebound or withdrawal symptoms following discontinuation. Study Registry No: ClinicalTrials.gov ID: NCT00397189.