Efficacy and Tolerability of Gabapentin in Adults with Sleep Disturbance in Medical Illness: A Systematic Review and Meta-analysis

Increasing evidence suggests an association between insomnia and cardiovascular disease. We performed a systematic review with meta-analysis of all the available prospective studies that investigated the association between insomnia and risk of developing and/or dying from cardiovascular disease. Systematic review and meta-analysis of prospective cohort studies. We conducted an electronic literature search through MedLine, Embase, Google Scholar, Web of Science, The Cochrane Library and bibliographies of retrieved articles up to December 2011. Studies were included if they were prospective, had assessment of insomnia or sleep complaints at baseline, evaluated subjects free of cardiovascular disease at baseline and measured the association between insomnia and risk of developing and/or dying from cardiovascular disease. After the review process 13 prospective studies were included in the final analysis. These studies included 122,501 subjects followed for a time ranging from three to 20 years. A total of 6332 cardiovascular events occurred during the follow-up. Insomnia was assessed through questionnaire and defined as either difficulty of initiating or maintaining sleep or presence of restless, disturbed nights. The cumulative analysis for all the studies under a random-effects model showed that insomnia determined an increased risk (+45%) of developing or dying from cardiovascular disease during the follow-up (relative risk 1.45, 95% confidence interval 1.29-1.62; p < 0.00001), with no evidence of heterogeneity across the studies (I 2: 19%; p = 0.14). Insomnia is associated with an increased risk of developing and/or dying from cardiovascular disease.

Pain is the most disturbing symptom of diabetic peripheral neuropathy. As many as 45% of patients with diabetes mellitus develop peripheral neuropathies. To evaluate the effect of gabapentin monotherapy on pain associated with diabetic peripheral neuropathy. Randomized, double-blind, placebo-controlled, 8-week trial conducted between July 1996 and March 1997. Outpatient clinics at 20 sites. The 165 patients enrolled had a 1- to 5-year history of pain attributed to diabetic neuropathy and a minimum 40-mm pain score on the Short-Form McGill Pain Questionnaire visual analogue scale. Gabapentin (titrated from 900 to 3600 mg/d or maximum tolerated dosage) or placebo. The primary efficacy measure was daily pain severity as measured on an 11-point Likert scale (0, no pain; 10, worst possible pain). Secondary measures included sleep interference scores, the Short-Form McGill Pain Questionnaire scores, Patient Global Impression of Change and Clinical Global Impression of Change, the Short Form-36 Quality of Life Questionnaire scores, and the Profile of Mood States results. Eighty-four patients received gabapentin and 70 (83%) completed the study; 81 received placebo and 65 (80%) completed the study. By intent-to-treat analysis, gabapentin-treated patients' mean daily pain score at the study end point (baseline, 6.4; end point, 3.9; n = 82) was significantly lower (P<.001) compared with the placebo-treated patients' end-point score (baseline, 6.5; end point, 5.1; n = 80). All secondary outcome measures of pain were significantly better in the gabapentin group than in the placebo group. Additional statistically significant differences favoring gabapentin treatment were observed in measures of quality of life (Short Form-36 Quality of Life Questionnaire and Profile of Mood States). Adverse events experienced significantly more frequently in the gabapentin group were dizziness (20 [24%] in the gabapentin group vs 4 [4.9%] in the control group; P<.001) and somnolence (19 [23%] in the gabapentin group vs 5 [6%] in the control group; P = .003). Confusion was also more frequent in the gabapentin group (7 [8%] vs 1 [1.2%]; P = .06). Gabapentin monotherapy appears to be efficacious for the treatment of pain and sleep interference associated with diabetic peripheral neuropathy and exhibits positive effects on mood and quality of life.

Increasingly, there is a need in both research and clinical practice to document and quantify sleep and waking behaviors in a comprehensive manner. The Pittsburgh Sleep Diary (PghSD) is an instrument with separate components to be completed at bedtime and waketime. Bedtime components relate to the events of the day preceding the sleep, waketime components to the sleep period just completed. Two-week PghSD data is presented from 234 different subjects, comprising 96 healthy young middle-aged controls, 37 older men, 44 older women, 29 young adult controls and 28 sleep disorders patients in order to demonstrate the usefulness, validity and reliability of various measures from the instrument. Comparisons are made with polysomnographic and actigraphic sleep measures, as well as personality and circadian type questionnaires. The instrument was shown to have sensitivity in detecting differences due to weekends, age, gender, personality and circadian type, and validity in agreeing with actigraphic estimates of sleep timing and quality. Over a 12-31 month delay, PghSD measures of both sleep timing and sleep quality showed correlations between 0.56 and 0.81 (n = 39, P < 0.001).