Are there different predictors of analgesic response between antidepressants and anticonvulsants in painful diabetic neuropathy?

BACKGROUND: To investigate baseline demographics and disease characteristics as predictors of the analgesic effect of duloxetine and pregabalin on diabetic peripheral neuropathic pain (DPNP). METHODS: Based on data from the COMBO-DN study, a multinational clinical trial in DPNP, the potential impact of baseline characteristics on pain relief after 8-week monotherapy with 60 mg/day duloxetine or 300 mg/day pregabalin was assessed using analyses of covariance. Subgroups of interest were characterized regarding their baseline characteristics and efficacy outcomes. RESULTS: A total of 804 patients were evaluated at baseline. A significant interaction with treatment was observed in the mood symptom subgroups with a larger pain reduction in duloxetine-treated patients having no mood symptoms [Hospital Anxiety and Depression Scale (HADS) depression or anxiety subscale score <11; -2.33 (duloxetine); -1.52 (pregabalin); p = 0.024]. There were no significant interactions between treatment for subgroups by age (<65 or ≥65 years), gender, baseline pain severity [Brief Pain Inventory Modified Short Form (BPI-MSF) average pain <6 or ≥6], diabetic neuropathy duration (≤2 or >2 years), baseline haemoglobin A1c (HbA1c) (<8% or ≥8%), presence of comorbidities and concomitant medication use. CONCLUSIONS: Our analyses suggest that the efficacy of duloxetine and pregabalin for initial 8-week treatment in DPNP was consistent across examined subgroups based on demographics and disease characteristics at baseline except for the presence of mood symptoms. Duloxetine treatment appeared to be particularly beneficial in DPNP patients having no mood symptoms.

Treatment and outcomes for patients with depression who are partial responders to SSRI treatment: post-hoc analysis findings from the FINDER European observational study.

BACKGROUND: Remission is the goal in depression, but in practice many patients only experience a partial response to treatment. We sought to determine the prevalence, management and subsequent outcomes of partial responder patients. METHODS: Patients enrolled in the naturalistic Factors Influencing Depression Endpoints Research (FINDER) study with the Hospital Anxiety and Depression Scale depression subscale (HADS-D) score >10 at baseline who received only SSRI(s) between 0 and 3 months comprised the study cohort (n=1147). Patients were categorized as remitters, partial responders or non-responders at 3 months and then followed up at 6 months. RESULTS: At 3 months, 29.4% of the study population were considered non-responders, 27.6% were partial responders, and 39.3% were remitters. Most partial responders at 3 months remained on the same SSRI for the next 3 months. Of the 247 partial responders at 3 months and remained on the same SSRI(s) between 3 and 6 months, 10.9% met criteria for non-response at 6 months, 32.4% remained partial responders, and 56.3% achieved remission. Quality of life outcomes for the partial responders were significantly worse than those in remission (p<0.05). LIMITATIONS: FINDER was an observational study; the current analysis was conducted post-hoc. Multivariable methods were not applied and findings are primarily descriptive and exploratory. CONCLUSIONS: Partial response is common and patients in partial response have a poorer quality of life than those achieving remission. Despite this, the majority of partial responders continue to take the same SSRI. Our findings underscore the importance of continuing to strive for remission.

Noradrenergic function in generalized anxiety disorder: impact of treatment with venlafaxine on the physiological and psychological responses to clonidine challenge.

Serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressants have evidence of efficacy in the treatment of generalized anxiety disorder (GAD); however, it is not clear whether there is an advantage over selective serotonin reuptake inhibitor (SSRI) medicines and there is limited evidence for noradrenergic dysfunction in GAD. We tested whether a dysfunctional alpha-2 adrenoceptor system is present in patients with GAD and the effects of SNRI treatment on this system. The method used was an infusion of clonidine (a selective alpha-2 adrenergic receptor agonist) on psychological and physiological outcomes in three subject groups: 10 untreated GAD patients, five SNRI-treated GAD patients and seven normal controls. The clonidine challenge elicited sedation, a rise in growth hormone, decrease in blood pressure, decline in saccadic eye movement (SEM) variables, and improvement in verbal fluency as anticipated in the 22 subjects examined. Lower cortisol levels were found in controls and higher blood pressure readings in GAD-treated subjects, as well as evidence that GAD-treated subjects had SEMs that were intermediate between control and GAD subjects' scores and have less clonidine-induced sedation. The implications of these findings with reference to the study hypothesis in this small study are discussed.

Cost-effectiveness of venlafaxine XL compared with diazepam in the treatment of generalised anxiety disorder in the United Kingdom.

This study used decision modelling to compare the cost-effectiveness of venlafaxine XL (Efexor XL) to that of diazepam to treat non-depressed patients suffering from generalised anxiety disorder (GAD), from the perspective of the United Kingdom's National Health Service (NHS). Starting treatment with venlafaxine XL instead of diazepam significantly increased the expected probability of being in remission by 83% at 6 months (from 16.8% to 30.7%), and the expected probability of relapsing at 6 months was decreased by 79% (from 16.9% to 3.5%). The expected 6-month NHS cost of using venlafaxine XL to treat GAD was estimated to be pounds sterling 353 compared to pounds sterling 311 with diazepam. Hence starting GAD treatment with venlafaxine XL (75 mg per day) instead of diazepam (5 mg three times per day) is clinically more effective and the cost-effective strategy for managing non-depressed patients suffering from GAD in the UK.

Bisoprolol alone and in combination with amlodipine or nifedipine in the treatment of chronic stable angina.

Beta-blockers and calcium antagonists are both effective monotherapy for stable angina. When symptoms persist, these two agents are commonly co-prescribed in the hope that this combination has added benefit compared with monotherapy alone. We investigated the additional efficacy of the calcium antagonists amlodipine and nifedipine when added to bisoprolol in patients with stable angina. Patients were randomised in a multicentre, single-blind study, with crossover of three treatments consisting of bisoprolol 10 mg once daily, bisoprolol plus nifedipine 20 mg twice daily, and bisoprolol plus amlodipine 5 mg once daily. Exercise tests were performed at the end of each four-week study period and the exercise time to onset of angina was assessed. A total of 198 patients from 17 centres were recruited of whom 147 were evaluable for efficacy. There were no statistically significant differences in exercise duration to onset of angina between any of the groups. The combination of bisoprolol plus nifedipine was least well tolerated. In summary, this study suggests there is little benefit in adding a calcium antagonist to bisoprolol in treating patients with stable angina.

Pharmacoeconomic analysis of antidepressants for major depressive disorder in the United Kingdom.

OBJECTIVE: To estimate the cost effectiveness of different classes of antidepressants in the UK National Health Service. DESIGN, PATIENTS AND INTERVENTIONS: The use of the serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (norepinephrine) reuptake inhibitor (SNRI) venlafaxine was compared with that of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) in patients with major depressive disorder (MDD). A meta-analysis determined the clinical success rate, and a decision tree was constructed by interviewing general practitioners and psychiatrists. Adding pharmacological and nonpharmacological treatment costs, meta-analytic rates were applied to the decision tree to calculate the expected cost and outcome for each drug. Cost effectiveness was determined using a composite measure of outcome [symptom-free days (SFD)]. MAIN OUTCOME MEASURES AND RESULTS: The meta-analysis included data from 44 studies on 4033 patients. The highest overall efficacy rate for outpatients with MDD was with venlafaxine use (73.7%), compared with 61.4% for SSRIs and 59.3% for TCAs. Treatment with venlafaxine yielded the lowest outpatient cost for a SFD (10.53 Pounds), compared with 13.23 Pounds for SSRIs and 15.52 Pounds for TCAs (1998 values). CONCLUSIONS: Using this economic model, venlafaxine appears to be a cost-effective treatment for outpatients with MDD in the UK.

Comparison of ramipril against atenolol in controlling mild-to-moderate hypertension.

This trial was a multicenter, double-blind, randomized, parallel-group, variable-dose study comparing ramipril with atenolol, and incorporating a 4-week run-in period on placebo. A total of 92 patients suffering from mild to moderate hypertension were randomized to the trial. Following a 4-week run-in period on placebo, newly diagnosed patients were only continued if their blood pressure remained within the defined range throughout the placebo run-in period. Known hypertensive patients who were safely switched to the trial therapy were only continued if their blood pressure was within the defined range at the end of this placebo washout period. An analysis of the data at baseline showed no statistical differences between treatment groups. Both systolic and diastolic blood pressures were significantly reduced from baseline in each group, but there were no differences between treatments. The study showed that ramipril and atenolol were both successful at reducing and controlling mild-to-moderate hypertension, but it showed no difference between treatments.