pregabalin and Mood-Disorders

There have been substantial advances in the pharmacotherapy of fibromyalgia (FM), which have occurred in parallel with advances in our understanding of the pathophysiology of FM in the past several years. Consortia of researchers have established a core set of symptom domains, which constitute the condition of FM, including pain, fatigue, sleep and mood disturbance and cognitive dysfunction, which significantly impact a patient's overall well-being and ability to function. Outcome measures, which assess these domains, both singly and in composite format, are showing increasing reliability to discriminate between the treatment and placebo arms in clinical trials of emerging therapies, which are targeting the pathophysiologic mechanisms of FM. Several different medications, including the serotonin and norepinephrine reuptake inhibitors, duloxetine and milnacipran, and the α(2)δ modulator, pregabalin, have been approved by the Food and Drug Administration (FDA) for the management of FM, based on their clinically meaningful and durable effect on pain in monotherapy trials. They also have been shown to beneficially effect patient global impression of change, function and variably other key symptom domains, such as fatigue, sleep disturbance and cognition. Other medicines, although they have not gone through the formal approval process, have also shown efficacy in multiple domains of FM. Although combination trials have generally not yet been performed, the combined use of medicines with complementary mechanisms of action is rational, and, when done with appropriate caution, will likely be shown to be safe and well tolerated. Adjunctive therapy with medicines targeted at specific symptom domains, such as sleep, as well as treatments aimed at common co-morbid conditions, such as irritable bowel syndrome, or disease states, such as rheumatoid arthritis, should be considered for the purpose of reducing the patient's overall symptom burden. Current therapies neither completely treat FM symptoms nor benefit all patients; thus, further research on new therapies with different mechanisms and side-effect profiles is needed.

Topics: Analgesics; Chronic Pain; Clinical Trials as Topic; Cognition Disorders; Cyclopropanes; Duloxetine Hydrochloride; Fatigue; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Milnacipran; Mood Disorders; Pain Management; Pregabalin; Selective Serotonin Reuptake Inhibitors; Sleep Wake Disorders; Syndrome; Thiophenes; Treatment Outcome

The aims of the present study were to investigate the main demographic and clinical characteristics, comorbidity patterns, use in association and tolerability of pregabalin in a sample of patients with affective disorders, and to compare demographic and clinical variables of the groups divided, according to the treatment pregabalin was associated with.. One hundred and fourteen consecutive outpatients, with anxiety and/or depressive disorders with or without comorbidity, were started on pregabalin, assessed and interviewed and their demographic data, associated therapy, tolerability and side effects collected over an observational period of 6 months.. The most frequent primary diagnoses were mood disorders (49.1%) and generalized anxiety disorder (21.9%). The most commonly associated treatments were antidepressants (66.7%) and mood stabilizers (15.8%). The most frequent side effects were sedation (3.4%), dizziness (0.9%), nausea (0.9%), diarrhea (0.9%), cough (0.9%) and peripheral edema (0.9%). When patients were divided according to the co-treatments, subgroups differed in terms of prescription of benzodiazepines (χ(2) = 15.25, df = 6, p = 0.013, phi = 0.37), with the most frequent use of these molecules in patients co-treated with tricyclic antidepressants and minor use in the selective serotonin reuptake inhibitors group.. Differences in the co-administration of benzodiazepines might suggest a stronger anxiolytic effect when pregabalin is combined with specific psychotropic drugs (e.g., SSRIs).

Topics: Adult; Aged; Anticonvulsants; Antidepressive Agents; Anxiety Disorders; Benzodiazepines; Depressive Disorder; Drug Therapy, Combination; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Mood Disorders; Outpatients; Pregabalin; Prospective Studies

Chronic pain is associated with a range of other problems, including disturbed sleep, depression, anxiety, fatigue, reduced quality of life, and an inability to work or socialise. We investigated whether good symptom control of pain (using definitions of moderate and substantial benefit) is associated with improvement in other symptoms. Individual patient data from four randomised trials in fibromyalgia (2575 patients) lasting 8-14weeks were used to calculate percentage pain reduction for each completing patient (1858), divided into one of five groups according to pain reduction, irrespective of treatment: substantial benefit - 50% pain reduction; moderate - 30% to <50%; minimal - 15% to <30%; marginal - 0% to <15%; worse - <0% (increased pain intensity). We then calculated change from baseline to end of trial for measures of fatigue, function, sleep, depression, anxiety, ability to work, general health status, and quality-adjusted life year (QALY) gain over a 12-month period. Substantial and moderate pain intensity reductions were associated with statistically significant reduction from baseline by end of trial in all measures, with values by trial end at or approaching normative values. Substantial pain intensity reduction resulted in 0.11 QALYs gained, and moderate pain intensity reduction in 0.07 QALYs gained over a 12-month period. Substantial and moderate pain intensity reduction predicts broad beneficial outcomes and improved quality of life that do not occur without pain relief. Pain intensity reduction is a simple and effective predictor of which patients should continue treatment, and which should discontinue and try an alternative therapy.

Topics: Activities of Daily Living; Adult; Analgesics; Fatigue Syndrome, Chronic; Female; Fibromyalgia; gamma-Aminobutyric Acid; Health Status; Humans; Male; Mood Disorders; Outcome Assessment, Health Care; Pain Measurement; Pain Threshold; Pregabalin; Quality of Life; Severity of Illness Index; Sick Leave; Stress, Psychological; Treatment Outcome

This study was designed to assess the efficacy and safety of pregabalin-a novel alpha(2)-delta ligand with analgesic, anxiolytic, and anticonvulsant activity-for treating neuropathic pain in patients with post-herpetic neuralgia (PHN). Two hundred and thirty-eight patients were randomised into this multicentre, doubleblind, placebo-controlled trial to receive 150 (n=81), 300 mg/day (n=76) pregabalin, or placebo (n=81) for 8 weeks. Among the exclusion criteria was failure to respond to previous treatment for PHN with gabapentin at doses > or =1200 mg/day. Endpoint mean pain scores were significantly reduced in patients receiving 150 or 300 mg/day pregabalin compared with placebo. Efficacy was observed as early as week 1 and was maintained throughout the study. Significantly more patients in both pregabalin groups (150 mg, 26%; 300 mg, 28%) were responders (> or =50% decrease in mean pain score from baseline to endpoint) than in the placebo group (10%). Additionally, by week 1 and for the study's duration, 150 and 300 mg/day pregabalin significantly reduced weekly mean sleep interference scores. More pregabalin-treated patients than placebo-treated patients reported that they were 'much improved' or 'very much improved'. Health-related quality-of-life (HRQoL) measurements using the SF-36 Health Survey demonstrated improvement in the mental health domain for both pregabalin dosages, and bodily pain and vitality domains were improved in the 300 mg/day group. The most frequent adverse events were dizziness, somnolence, peripheral oedema, headache, and dry mouth. Pregabalin efficaciously treated the neuropathic pain of PHN. Additionally, pregabalin was associated with decreased sleep interference and significant improvements in HRQoL measures.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Female; gamma-Aminobutyric Acid; Herpes Zoster; Humans; Male; Middle Aged; Mood Disorders; Neuralgia; Pain Measurement; Placebos; Pregabalin; Quality of Life; Sleep Wake Disorders; Treatment Outcome

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

Pregabalin is a treatment option for patients with persistent neuropathic pain. Its use has been associated with changes in mood and the development of depression and/or suicidal ideation.. Case presentations were reviewed of five patients reporting changes in mood, depression and suicidal ideation from the first 50 (approximately) patients commenced on pregabalin at the clinic.. Although these patients had a history of depression, their mood had been stable before commencing pregabalin. Soon after commencement they reported changes in mood, and development of depression and/or suicidal ideation, which improved with dose reduction or cessation of pregabalin. Ultimately, all five patients ceased pregabalin treatment. Suicidal ideation is a recognised adverse effect of pregabalin. Patients should be warned of and monitored for deterioration in mood.

Topics: Analgesics; Depression; Humans; Mood Disorders; Neuralgia; Pregabalin; Risk Factors; Suicidal Ideation; Surveys and Questionnaires