The findings of this review suggest that painful physical symptoms may be an important part of the depressive syndrome. Although the relationship between depression and painful physical symptoms is not yet fully understood, findings suggest that diagnosis and treatment of depression should involve investigating and treating the full spectrum of symptoms (emotional and physical). Further research in psychiatric and generalist settings is needed to elucidate the relationship between depression and painful physical symptoms as experienced by patients and at the clinical level.

SUMMARYRetigabine (RTG; international nonproprietary name)/ ezogabine (EZG; North American adopted name), a firstin-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.

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.

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.

Next-day residual effects of single evening doses of 3 mg eszopiclone, 7.5 mg zopiclone and placebo were assessed in a randomised, 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 to11.5 hours post-dose commencing 15 min after awakening. Night-time 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 endpoint, mean CTT tracking error averaged from 7.5-9.5 hours postdose, however a pre-specified post hoc parametric analysis of reciprocal-transformed data favoured eszopiclone over racemic zopiclone (P=0.026).