Post hoc analysis of pregabalin vs. non-pregabalin treatment in patients with cancer-related neuropathic pain: better pain relief, sleep and physical health

BACKGROUND AND PURPOSE: A previous study of cancer-related neuropathic pain (NP) found that a 10-fold increase in pregabalin (PGB) use increased patients' satisfaction with treatment. Further research of PGB vs. non-pregabalin (non-PGB) treatment was carried out to assess if the use of more specific NP-targeting drugs, such as PGB, in combined therapy, in patients with cancer-related NP, provides better health outcomes. PATIENTS AND METHODS: Post hoc analysis of PGB- vs. non- PGB-treated patients in a 2-month epidemiological, prospective, multicentre study to assess NP prevalence and management in cancer pain patients visiting radiotherapy oncologic units. Patients undertook the Brief Pain Inventory (BPI), Hospital Anxiety and Depression Scale (HADS), the Medical Outcomes Sleep Scale (MOS-Sleep) and the short form (SF-12) Health Survey. RESULTS: A total of 273 patients with no previous PGB treatment: 162 were treated with PGB polytherapy and 111 with other treatments. At 8 weeks, satisfaction with treatment was 92.6% (PGB) vs. 78.9% (non-PGB), p=0.0024, and benzodiazepine use 37.8% (non-PGB) vs. 19.8% (PGB), p=0.0009. The decreases in BPI total pain intensity and total interference with activities and in MOS overall sleep problems index were significantly larger in the PGB group. CONCLUSIONS: The addition of more specific NP-targeting drugs to usual treatment, such as PGB, in NP cancer patients provides more satisfaction with treatment and better outcomes in terms of pain intensity, interference with activities and sleep than treatments without specific NP-targeting drugs. Anxiolytic profile of PGB could allow for less use of benzodiazepines (AU)

Amlodipine reduces predicted risk of coronary heart disease in high-risk patients with hypertension in Spain (The CORONARIA Study).

We evaluated the efficacy and safety of amlodipine besylate alone or in combination with other antihypertensive agents in high-risk hypertensive patients in Spanish primary care. In this 1-year, open-label, prospective cohort study, 7468 patients were treated with amlodipine 5 - 10 mg as a monotherapy or as an add-on therapy to attain blood pressure control (target of < 140/90 mmHg or, in patients with conditions such as diabetes or chronic kidney disease, < 130/85 mmHg). At 12 months, the primary outcome (change from baseline in predicted 10-year coronary heart disease risk) was -8.6%, down from 24.7% at baseline (relative risk reduction, 31.6%). Change in blood pressure from baseline (162.5/95.3 mmHg) was -26.7/-14.6 mmHg, and 38.6% of patients achieved their blood pressure target. In summary, significant reductions in predicted coronary heart disease risk and blood pressure were observed with amlodipine both as a monotherapy and as an add-on therapy. Amlodipine was well tolerated and compliance with treatment was good.

[Drug regimens in patients with medication-resistant epilepsy in neurology and epilepsy outpatient departments in Spain]. / Pautas terapéuticas en el paciente con epilepsia farmacorresistente en consultas ambulatorias de neurología y epilepsia en España.

INTRODUCTION: About 30% of epileptic patients suffer from drug-resistant epilepsy (DRE). Quality of life is worse and costs are higher than in controlled epilepsy. One of the aims of the LINCE study was to assess the prevalence of DRE in epilepsy-specialized and general neurology clinics in Spain and the clinical management of these patients in routine clinical practice. PATIENTS AND METHODS: Cross-sectional, retrospective study to evaluate clinical prevalence and cost of DRE in Spain. Every participant neurologist assessed the percentage of DRE among the first 40 patients with diagnosed epilepsy seen. Patients of both sexes, older than 18 years were recruited. Their treatment before and after DRE diagnosis was analyzed. RESULTS: DRE prevalence in Spain is 22.7% (36% in epilepsy-specialized and 18.5% in neurology clinics; p < 0.0001), with no differences between genders. More than 50% of these patients have hardly achieved a secondary education and only 44% are employed. The most frequent drugs used after DRE diagnosis are lamotrigine (33.5%), levetiracetam (32.4%), carbamazepine (31.9%) and topiramate (25.8%) in various combinations, but the highest efficacy (equal or more than 50% seizures reduction) is obtained with pregabaline (53.1%), oxcarbazepine (50.6%) and levetiracetam (49.5%) and topiramate (48%). CONCLUSIONS: 22.7% of epileptic outpatients in Spain are diagnosed with DRE in clinics of neurology. These will require certain social interventions and greater use of health resources, including treatment with more appropriate AEDs. Pregabaline, oxcarbazepine, levetiracetam and topiramate are among the most effective AEDs in this type of patients.

A 6-month prospective, observational, naturalistic, uncontrolled study to evaluate the effectiveness and tolerability of oral ziprasidone in patients with schizophrenia.

This multicenter, uncontrolled, naturalistic study evaluated the effectiveness and tolerability of 6 months of treatment with ziprasidone in 1266 patients with a diagnosis of schizophrenia. The percentage of responders (at least 30% reduction in PANSS total score) in the primary analysis sample (n=1022) was 47.3% (95% CI 44.2-50.4) at the end of the study. Patients showed a significant and clinically relevant reduction in the PANSS total, positive, negative and general psychopathology subscales scores (effect size of 1.60, 1.83, 0.62 and 1.40 respectively). Overall, 453 (35.8%) patients withdrew from the study; 9.3% withdrew owing to adverse events. Ziprasidone doses greater than 120 mg/day were associated with a lower risk of discontinuation for any cause (OR 0.46, 95% CI 0.33-0.65) Ziprasidone was well tolerated. Most common side effects were: insomnia, somnolence and nervousness. The effectiveness and tolerability of ziprasidone in clinical practice are consistent to those previously shown in the more restricted and homogeneous populations of clinical trials.

Effects of gabapentin on the motor response to levodopa: a double-blind, placebo-controlled, crossover study in patients with complicated Parkinson disease.

BACKGROUND: Motor fluctuations and dyskinesias affect many parkinsonian patients chronically treated with levodopa. Imbalance between gabaergic direct and indirect striatopallidal pathways may originate them. Manipulating GABA neurotransmission may be effective in the treatment of these patients. Gabapentin is an antiepileptic drug that increases the synthesis and release of GABA. Previous studies suggest that gabapentin may be useful in Parkinson disease (PD). OBJECTIVE: To know the effects of gabapentin on the motor response to levodopa in PD patients with motor complications. DESIGN: A randomized double-blind, placebo-controlled, cross-over trial with four weeks of treatment. SETTING: A tertiary referral center. PARTICIPANTS: Twenty subjects with PD and motor fluctuations and dyskinesias on stable antiparkinsonian treatment, took gabapentin up to a maximum dose of 2.400 mg/d in three doses and placebo. METHODS: Three levodopa challenges were performed: at the beginning of the study and at the end of each period of treatment (4 weeks). Basal (off) and best (on) motor status were assessed by the UPDRS III. Latency to peak effect, magnitude of motor response (difference between "on" and "off" scores in the UPDRS III), duration of motor response and severity and duration of dyskinesias after each levodopa challenge were assessed. Patients' diaries were administered. RESULTS: : Fifteen patients completed the study. A significant improvement in the basal UPDRS III resulting in a significant reduction in the magnitude of the motor response after gabapentin was obtained (P < 0.001). No other changes were observed, either on pharmacological parameters or in levodopa-induced dyskinesias. Number of daily hours spent in "on," "on with dyskinesias" and "off" also remained unchanged. Tolerance was good, dizziness being the most common side effect. CONCLUSION: Gabapentin improved parkinsonian symptoms (basal UPDRS III and magnitude of the motor response) following levodopa. This improvement was not reflected in the daily motor situation of patients. Dyskinesias remained unchanged. Gabapentin was well tolerated. Further studies are needed to know the impact of these results in the long-term.

Effects of atorvastatin on glucose homeostasis, postprandial triglyceride response and C-reactive protein in subjects with impaired fasting glucose.

AIMS: To investigate the effects of atorvastatin on glucose homeostasis, the basal and postprandial lipid profiles and the CRP levels (C reactive protein) in subjects with impaired fasting glucose (IFG). METHODS: Thirty-three subjects (22 men and 11 women) were included in our study. All displayed an IFG (fasting plasma glucose between 6.1 and 7.0 mmol/l) on at least two occasions during the last 6 months prior the study. They were randomly assigned to receive either 40 mg atorvastatin/day (n=16) or placebo (n=17) over 16 weeks, in a double-blind design. Before and after the end of the study all participants underwent on three consecutive days: a 75-g oral glucose tolerance test, a frequent sampling intravenous glucose tolerance test with Minimal Model analysis and a meal tolerance test (glucose, insulin and triglycerides). CRP was measured before and after the treatment period. RESULTS: CRP decreased significantly in the atorvastatin-treated group compared with the placebo group (percent change respect initial values; -42.3 %[-21.5 to - 63.1] and -9.6%[15.0 to -34.0], respectively, p<0.01). Atorvastatin treatment did not produce any change in oral glucose tolerance categories or induce any change in glucose and insulin response in OGTT. The statin produced a trend towards a significant improvement in insulin sensitivity as expressed by a change in Si from baseline to the end of treatment. Atorvastatin reduced the postprandial response of triglycerides to the meal test compared with placebo (19-26 % across the meal test, p<0.05) correlating with the amelioration observed in Si (-0.34, p<0.05; percentage changes). CONCLUSION: Our results suggest that the use of statins in subjects with IFG seems to include other potentially beneficial actions in addition to their cholesterol-lowering effects.

Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study.

OBJECTIVE: To assess the effects of gabapentin on sensory and motor symptoms in patients with restless legs syndrome (RLS). METHODS: Patients with RLS (22 idiopathic, 2 secondary to iron deficiency) were randomized and treated for 6 weeks with either gabapentin or placebo. After a 1-week washout they crossed over to the alternative treatment for 6 weeks. Patients were rated at baseline and at scheduled intervals by the RLS Rating Scale, Clinical Global Impression, pain analogue scale, and Pittsburgh Sleep Quality Index. At the end of each treatment period, all-night polysomnography was performed. RESULTS: Compared to placebo, gabapentin was associated with reduced symptoms on all rating scales. In addition, sleep studies showed a significantly reduced periodic leg movements during sleep (PLMS) index and improved sleep architecture (increased total sleep time, sleep efficiency, and slow wave sleep, and decreased stage 1 sleep). Patients whose symptoms included pain benefited most from gabapentin. The mean effective dosage at the end of the 6-week treatment period was 1,855 mg, although therapeutic effects were already observed at the end of week 4 (1,391 mg). CONCLUSIONS: Gabapentin improves sensory and motor symptoms in RLS and also improves sleep architecture and PLMS.

Allelic polymorphism -491A/T in apo E gene modulates the lipid-lowering response in combined hyperlipidemia treatment.

BACKGROUND: Combined hyperlipidemia (CHL) is one of the dyslipidemias more frequently found in clinical practice, and lipid-lowering drugs are often necessary in its management. Some genetic loci have been associated with CHL expression, and some studies have shown modulation of drugs efficiency in the treatment of dyslipidemias by genetic polymorphisms. We have investigated whether common polymorphisms and mutations in the apolipoprotein (apo) E, lipoprotein lipase (LPL), and apo CIII genes influence atorvastatin or bezafibrate responses in patients with CHL. DESIGN: One hundred and sixteen subjects participating in the ATOMIX study (Atorvastatin in Mixed dyslipidemia) were randomized to treatment with either atorvastatin or bezafibrate. Apolipoprotein E genotype and common -491A/T and -219T/G polymorphisms in the apo E gene promoter region, Sst I polymorphism in the apo CIII gene (3238C/G), and D9N and N291S common mutations in the LPL gene were determined by polymerase chain reaction (PCR) and restriction enzyme digestion. RESULTS: Statistical analysis showed the influence of the -491A/T polymorphism in atorvastatin and bezafibrate treatments. Subjects carrying the -491T allele showed an increased LDL-cholesterol-lowering effect with atorvastatin compared with -491T allele noncarriers (-35% vs. -27%, P = 0.037). Subjects carrying the -491T allele, when on bezafibrate treatment, showed a lower triglyceride reduction compared with -491T allele noncarriers (-23% vs. -39%, P = 0.05). CONCLUSIONS: In our study, the -491A/T polymorphism in the apo E gene promoter region modulated the lipid-lowering efficiency of atorvastatin and bezafibrate in CHL patients. Such influence might explain some of the interindividual response variabilities observed for the two drugs, and could help in CHL management.

Chitotriosidase genotype and serum activity in subjects with combined hyperlipidemia: effect of the lipid-lowering agents, atorvastatin and bezafibrate.

Chitotriosidase, an enzyme involved in the degradation of chitin-containing pathogens with unclear function in humans, has been proposed as a marker of lipid accumulation in macrophages in different lipid-storage diseases, including atherosclerosis. To evaluate (1) if lipid-lowering treatment could modify serum chitotriosidase activity and (2) be useful in monitoring lipid-lowering treatment, we have analyzed this enzyme activity in the participants in the Atozvastatin Versus Bezafibrate in Mixed Hyperlipidemia (ATOMIX) study, a double-blind, comparative, and randomized study comparing the efficacy of atorvastatin and bezafibrate in mixed hyperlipidemia. Because a common genetic deficiency of chitotriosidase modifies serum quitotriosidase activity, this genetic variation was also studied. Seven subjects of 116 (6.03%) were homozygous, and 46 (39.6%) were heterozygous for the defective allele. Mean serum quitotriosidase activity correlated with allele dosage, as it was found to be of 0, 59.8 +/- 52.6 and 81.2 +/- 41.6 nmol/mL/h, in homozygotes for the defective allele, heterozygotes, and homozygotes for the wild-type allele, respectively (P =.0011 for the difference between the last 2 groups). However, this enzyme activity was not found to correlate with lipid levels before and after treatment with either atorvastatin or bezafibrate, and neither with the intensity of the lipid lowering. These results do not support the use of serum chitotriosidase activity as a biologic marker of atherosclerotic plaque modification related to hypolipidemic treatment.

Efficacy and Safety of Quinapril 40mg Once Daily as Monotherapy for Patients with Poorly Controlled Hypertension : The EUREKA Study.

OBJECTIVE: We assessed the efficacy and safety of quinapril 40mg once daily for treating essential hypertension in patients with poorly controlled hypertension who were using other angiotensin-converting enzyme (ACE) inhibitors, or in those who needed to take more than one tablet a day of the ACE inhibitor to lower blood pressure, or in those who needed to start antihypertensive therapy with maximum doses of other drugs because of the severity of hypertension. DESIGN: Prospective, observational, noncomparative, open-label. METHODS: A total of 6082 patients of both genders, aged ≥40 years, received a single daily oral dose of quinapril 40mg for a period of 8 weeks. The primary end-point parameter of efficacy was the percentage of patients with adequate control of blood pressure, which was defined as systolic blood pressure (SBP) ≤140mm Hg and diastolic blood pressure (DBP) ≤90mm Hg. For the diabetic group the definition was 130/85mm Hg. Tolerability and safety of antihypertensive drugs was assessed by physical examination and detection of adverse effects potentially related to antihypertensive medication. RESULTS: At the end of the 8-week treatment period with quinapril, adequate control of DBP, SBP and both was found in 90, 56 and 54% of patients, respectively, with a mean difference of 25mm Hg for SBP and of 15mm Hg for DBP as compared with baseline. In hypertensive patients with diabetes mellitus (n = 1269) and in patients previously treated with other ACE inhibitors (n = 2083), quinapril therapy was also associated with statistically significant decreases in mean DBP and SBP (p < 0.0001). A total of 42 adverse events were recorded. No patient failed to complete the study because of adverse events. CONCLUSIONS: Quinapril 40mg significantly lowered blood pressure, achieving adequate control of DBP in up to 90% of patients with moderate essential hypertension previously unsuccessfully controlled.