pregabalin and Disorders-of-Excessive-Somnolence

Pregabalin has demonstrated robust, rapid efficacy in reducing symptoms of generalized anxiety disorder (GAD) in 4 placebo-controlled clinical trials. The current study compared the efficacy and safety of pregabalin and venlafaxine in patients diagnosed with moderate to severe GAD.. The study was conducted from December 21, 1999, to July 31, 2001. Outpatients (N = 421) in primary care or psychiatry settings meeting DSM-IV criteria for GAD were randomly assigned to 6 weeks of double-blind treatment with pregabalin 400 or 600 mg/day, venlafaxine 75 mg/day, or placebo. The primary analysis was change in Hamilton Rating Scale for Anxiety (HAM-A) total score from baseline to last-observation-carried-forward (LOCF) endpoint. Secondary analyses included the change in HAM-A psychic (emotional) and somatic (physical) factor scores, significant improvement at week 1, and week 1 improvement sustained at every visit through endpoint.. Pregabalin at both dosages (400 mg/day, p = .008; 600 mg/day, p = .03) and venlafaxine (p = .03) produced significantly-greater improvement in HAM-A total score at LOCF endpoint than did placebo. Only the pregabalin 400-mg/day treatment group experienced significant improvement in all a priori primary and secondary efficacy measures. Pregabalin in both dosage treatment groups (400 mg/day, p < .01; 600 mg/day, p < .001) significantly improved HAM-A total score at week 1, with significant improvement through LOCF endpoint. Statistically significant improvement began at week 2 for venlafaxine. Discontinuation rates due to associated adverse events were greatest in the venlafaxine treatment group: venlafaxine, 20.4%; pregabalin 400 mg/day, 6.2%; pregabalin 600 mg/day, 13.6%; placebo, 9.9%.. Pregabalin was safe, well tolerated, and rapidly efficacious across the physical-somatic as well as the emotional symptoms of GAD in the majority of patients studied in primary care and psychiatric settings.

Topics: Adult; Anticonvulsants; Anxiety Disorders; Cyclohexanols; Disorders of Excessive Somnolence; Dizziness; Dose-Response Relationship, Drug; Double-Blind Method; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Placebos; Pregabalin; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Venlafaxine Hydrochloride

Donepezil, an oral acetylcholinesterase inhibitor, is used to treat Alzheimer's disease and reportedly attenuates opioid-induced sedation in patients with cancer pain. Neuropathic pain is often treated with gabapentinoids (pregabalin, gabapentin), but gabapentinoid-induced somnolence sometimes prevents patients from using these agents. We conducted a retrospective chart review of patients with neuropathic pain to examine whether donepezil is useful for gabapentinoid-induced somnolence. We investigated pain severity in 13 patients before and after taking gabapentinoids and donepezil, the degree of gabapentinoid-induced somnolence before and after starting donepezil, and gabapentinoid dose escalation after taking donepezil. Donepezil was started at 3-5 mg/day upon experiencing gabapentinoid-induced somnolence. Likert-scale scores for somnolence (0 = no somnolence; 4 = severe somnolence with stumbling) improved significantly after starting donepezil (before: 2.3 ± 0.9, after: 0.5 ± 0.7; Wilcoxon's signed-rank test, P < .05), resulting in gabapentinoid dose escalation (before: 796.2 ± 564.3 mg, after: 1409.6 ± 526.9 mg; P < .05), which significantly decreased pain intensity (before: 7.4 ± 1.2, after: 5.0 ± 1.3; P < .05). Donepezil could be an alternative to psychostimulants for gabapentinoid-induced somnolence. The analgesic effect of gabapentinoids remained uncompromised by donepezil, which could enhance the dose-dependent analgesic effect of gabapentinoids.

Topics: Adult; Aged; Aged, 80 and over; Amines; Cholinesterase Inhibitors; Cyclohexanecarboxylic Acids; Disorders of Excessive Somnolence; Donepezil; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Indans; Male; Middle Aged; Neuralgia; Pain Measurement; Piperidines; Pregabalin; Retrospective Studies

Pregabalin is a commonly used therapy currently recommended as first-line treatment for a number of neuropathic pain (NeP) conditions. Since licensure, a number of clinical trials of pregabalin in different NeP conditions have been completed from which additional data on safety and tolerability can be drawn. In this analysis, patient-level data from 31 randomized clinical trials of pregabalin in peripheral NeP sponsored by Pfizer were pooled and assessed for incidence of adverse events (AEs). Incidence by age, disease condition, and race, together with risk differences and time to onset and resolution of AEs, was assessed. In total, 7,510 patients were included: 4,884 on pregabalin (representing 805 patient-years treatment) and 2,626 on placebo. Pregabalin vs. placebo risk analysis identified 9 AEs with a risk difference, for which the lower limit of the 95% confidence interval (CI) was > 1%: dizziness (risk difference [95% CI]: (17.0 [15.4 to 18.6]), somnolence (10.8 [9.5 to 12.1]), peripheral edema (5.4 [4.3 to 6.4]), weight increase (4.7 [3.9 to 5.5]), dry mouth (2.9 [2.1 to 3.8]), constipation (2.3 [1.5 to 3.2]), blurred vision (2.2 [1.6 to 2.9]), balance disorder (2.0 [1.5 to 2.5]), and euphoric mood (1.6 [1.2 to 2.0]). The most common AEs, dizziness and somnolence, typically emerged within the first 1 to 2 weeks of treatment and resolved 1 to 2 weeks later, without resulting in cessation of treatment. The data from this review provide information, indicating which AEs may be expected in patients treated with pregabalin, and suggest that careful dose titration to the highest tolerable dose is the most appropriate approach in clinical practice.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics; Case-Control Studies; Constipation; Disorders of Excessive Somnolence; Dizziness; Edema; Female; Humans; Male; Middle Aged; Mood Disorders; Neuralgia; Postural Balance; Pregabalin; Sensation Disorders; Vision Disorders; Weight Gain; Young Adult

Evidence to support the use of pregabalin in combination with opioid analgesics for the treatment of cancer-related neuropathic pain is limited.. We carried out a retrospective investigation on patients hospitalized in our department with cancer-related neuropathic pain and under pregabalin treatment. Patients were divided into two groups: A group (= < 300 mg pregabalin daily) and B group (> 300 mg pregabalin daily). The two groups were compared in terms of a suite of factors (e. g., age starting and maimtenance dose of pregabaline, adverse effect).. Patient's age was significantly lower in the B group (> 300 mg pregabalin daily). Of the total number of patients involved in the study, 67% experienced mild and moderate somnolence.. In this retrospective investigation, we conclude that the younger cancer patients may need lager doses of pregabalin to relieve cancer-related neuropathic pain. In addition, the mild and moderate somnolence occurs frequently when pregabalin is administered with opioid analgesics for the treatment of cancer-related neuropathic pain.

Topics: Aged; Analgesics; Disorders of Excessive Somnolence; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Neoplasms; Neuralgia; Palliative Care; Pregabalin; Retrospective Studies