A method to assess the dissipation of the [corrected] residual effects of [corrected] hypnotics: eszopiclone versus zopiclone.

Next-day residual effects of single evening doses of 3 mg of eszopiclone, 7.5 mg of zopiclone, and placebo were assessed in a randomized, double-blind, placebo-controlled, 3-way crossover study that used a mild sleep restriction protocol (sleep duration, 7 hours). During each period, 91 healthy volunteers spent 2 consecutive nights in the laboratory with time in bed restricted to 7 hours. Volunteers completed the Continuous Tracking Test, Critical Flicker Fusion task, Digit Symbol Substitution Test, N-back tasks, and Linear Analogue Rating Scales every half-hour from 7.5 to 11.5 hours after dose, commencing 15 minutes after awakening. Nighttime dosing of both eszopiclone (3 mg) and racemic zopiclone (7.5 mg) was associated with next-day performance impairment, and these residual effects dissipated over time. Eszopiclone did not differ from zopiclone on the primary end point, mean Continuous Tracking Test tracking error averaged from 7.5 to 9.5 hours after dose; however, a prespecified post hoc parametric analysis of reciprocal-transformed data favored eszopiclone over racemic zopiclone (P = 0.026).

The urinary safety profile and secondary renal effects of retigabine (ezogabine): a first-in-class antiepileptic drug that targets KCNQ (K(v)7) potassium channels.

Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; North American adopted name), a first-in-class antiepileptic drug (AED) that reduces neuronal excitability primarily by enhancing the activity of KCNQ2/3 (K(v)7.2/7.3) potassium channels, has recently been approved by the European Medicines Agency and the U.S. Food and Drug Administration as adjunctive therapy in adults with partial-onset seizures. Much of the RTG/EZG safety profile will be familiar to health care professionals who are experienced with the clinical use of AEDs. RTG/EZG, as a potassium channel opener, also has a pharmacologic effect on smooth muscle of the urinary bladder. Consequently, the adverse event (AE) profile of RTG/EZG includes a potential risk of effects on the urinary system. This review summarizes the urinary safety profile and any secondary renal effects of RTG/EZG using data from patients in the pivotal controlled trials and the overall phase 2/3 clinical development program. Urinary AEs were reported more frequently in patients receiving RTG/EZG compared with placebo, although most patients were able to continue with treatment. Specifically, there is an increased risk of urinary retention with RTG/EZG, with urinary hesitation representing the most frequently reported urinary retention-related AE. Potential secondary renal effects, which may be caused by an inability to empty the bladder, were evaluated. Crystals with a bilirubin-like appearance were detected in the urine of patients receiving RTG/EZG. Although investigations indicated that these crystals were not bilirubin, their composition remains undetermined. There was no causal association with urinary tract infections, and nephrolithiasis was uncommon. The reported clinical effects of RTG/EZG are consistent with its documented effects on bladder smooth muscle in preclinical studies. RTG/EZG should be used with caution in patients at risk of urinary retention.

A randomized, controlled trial of duloxetine alone vs. duloxetine plus a telephone intervention in the treatment of depression.

OBJECTIVE: We hypothesized that combining antidepressant medication with a standardized telephone adherence support intervention would lead to superior outcomes in the treatment of depression compared with antidepressant medication alone. METHOD: Patients with depression were randomized to receive the antidepressant duloxetine alone (DLX), or duloxetine plus a standardized telephone intervention (DLX+TI), for 12 weeks of open-label treatment. The primary outcome measure was remission (HAMD 17 total score 90% at every visit) in both groups. CONCLUSIONS: A telephone intervention in combination with antidepressant medication (duloxetine) did not improve depression outcomes compared with antidepressant alone in this clinical trial, perhaps due to high drug adherence in both treatment groups. Addition of a telephone intervention was, however, associated with increased reporting of AEs.

Factors influencing depression endpoints research (FINDER): study design and population characteristics.

Factors influencing outcomes of depression in clinical practice, especially health-related quality of life (HRQoL), are poorly understood. The Factors Influencing Depression Endpoints Research (FINDER) study is a European prospective, observational study designed to estimate the HRQoL of adults with a clinically diagnosed depressive episode at baseline, and 3 and 6 months after commencing antidepressant medication. We report here the study design and baseline patient characteristics. HRQoL was assessed by the 36-item Short-Form Health Survey (SF-36) and European Quality of Life-5 Dimensions (EQ-5D). Patient ratings on Hospital Anxiety and Depression Scale (HADS) and pain Visual Analogue Scale (VAS) were also obtained. Results (n=3468) showed that SF-36 mental component summary (mean 22.2) was more than two SDs below general population norms (mean 50.0) and one SD below clinical depression norms (mean 34.8); the physical component summary (mean 46.1) was similar to general population (mean 50.0) and clinical depression norms (mean 45.0). Mean EQ-5D scores were also lower than general population norms. Mean HADS-Depression and -Anxiety subscores were 12.3 and 13.0, respectively. Fifty-six percent of patients reported an overall pain VAS score of at least 30mm and 70% of these patients had no physical explanation for their pain. Further investigation into factors associated with HRQoL in depression after treatment initiation is warranted.

The importance of somatic symptoms in depression in primary care.

OBJECTIVE: Patients with depression present with psychological and somatic symptoms, including general aches and pains. In primary care, somatic symptoms often dominate. A review of the literature was conducted to ascertain the importance of somatic symptoms in depression in primary care. DATA SOURCES AND EXTRACTION: MEDLINE, EMBASE, and PsychLIT/PsychINFO databases (1985-January 2004) were searched for the terms depression, depressive, depressed AND physical, somatic, unexplained symptoms, complaints, problems; somatised, somatized symptoms; somatisation, somatization, somatoform, psychosomatic; pain; recognition, under-recognition; diagnosis, underdiagnosis; acknowledgment, under-acknowledgment; treatment, undertreatment AND primary care, ambulatory care; primary physician; office; general practice; attribution, re-attribution; and normalising, normalizing. Only English-language publications and abstracts were considered. STUDY SELECTION: More than 80 papers related to somatic symptoms in depression were identified using the content of their titles and abstracts. DATA SYNTHESIS: Approximately two thirds of patients with depression in primary care present with somatic symptoms. These patients are difficult to diagnose, feel an increased burden of disease, rely heavily on health care services, and are harder to treat. Patient and physician factors that prevent discussion of psychological symptoms during consultations must be overcome. CONCLUSIONS: Educational initiatives that raise awareness of somatic symptoms in depression and help patients to re-attribute these symptoms should help to improve the recognition of depression in primary care.

Quality of life outcomes among patients with depression after 6 months of starting treatment: results from FINDER.

BACKGROUND: Health-related quality of life (HRQoL) data in depression are limited. We studied the impact of antidepressant (AD) treatment on HRQoL outcomes in depressed patients and investigated factors associated with these outcomes in routine practice settings. METHODS: The Factors Influencing Depression Endpoints Research (FINDER) study was a 6-month, European, prospective, observational study, designed to estimate HRQoL in 3468 adult patients with a clinically diagnosed episode of depression at baseline and at 3 and 6-months after commencing AD treatment. HRQoL was assessed by the Medical Outcome Short-Form (36) Health Survey (SF-36) and European Quality of Life-5 Dimensions (EQ-5D). Regression analysis identified baseline and treatment variables independently and significantly associated with HRQoL outcomes. RESULTS: Most HRQoL improvement occurred within 3 months of starting treatment. Better HRQoL outcomes were strongly associated with fewer somatic symptoms at baseline, AD treatment taken and not switching within AD groups. Education and occupational status were also important. Depression variables (number of previous depressions and current episode duration) were consistently associated with worse HRQoL outcomes. Self-rated depression severity was associated with poorer outcomes on the SF-36 mental component only. LIMITATIONS: As this was an observational study, the important finding that between and within AD group switching impacted HRQoL will need to be investigated in more controlled settings. CONCLUSIONS: Receiving an AD treatment was associated with large improvements in HRQoL, but switching within AD groups was consistently associated with poorer outcomes. Somatic symptoms, including painful symptoms, are often present in depressed patients and appear to negatively impact HRQoL outcomes.