Randomized, placebo-controlled comparison of amitriptyline, duloxetine, and pregabalin in patients with chronic diabetic peripheral neuropathic pain: impact on pain, polysomnographic sleep, daytime functioning, and quality of life.

OBJECTIVE: Chronic diabetic peripheral neuropathic pain (DPNP) is difficult to treat, with treatment regimens often inadequate at controlling pain and limited by side effects and drug tolerance. Secondary parameters, such as quality of sleep and mood, may also be important for successful DPNP management. The objectives of this study were to compare the analgesic efficacy of pregabalin, amitriptyline, and duloxetine, and their effect on polysomnographic sleep, daytime functioning, and quality of life in patients with DPNP. RESEARCH DESIGN AND METHODS: This was a double-blind, randomized, parallel group investigation of type 1 and 2 diabetic subjects with DPNP. Each treatment group had a single-blind, 8-day, placebo run-in followed by 14 days of lower-dose and 14 days of higher-dose medication. At the end of each dose titration period, subjective pain, sleep, and daytime functioning were assessed during a 2-day residential period. RESULTS: All medications reduced pain when compared with placebo, but no one treatment was superior to any other. For sleep, pregabalin improved sleep continuity (P < 0.001), whereas duloxetine increased wake and reduced total sleep time (P < 0.01 and P < 0.001). Despite negative effects on sleep, duloxetine enhanced central nervous system arousal and performance on sensory motor tasks. There were no significant safety findings; however, there was a significantly higher number of adverse events in the pregabalin treatment group. CONCLUSIONS: There was no significant difference in analgesic efficacy between amitriptyline, duloxetine, and pregabalin. However, there were significant differences in the secondary parameters, which may be of relevance when deciding the optimal treatment for DPNP.

A Case of Propylthiouracil-Induced Hepatitis during Pregnancy.

A 32-year-old with no pre-existing liver disease was diagnosed with Graves' disease at week 4 of pregnancy. Thyroid-stimulating hormone was undetectable with elevated free thyroxine levels and positive thyroid receptor antibodies. She was started on a reducing regime of propylthiouracil (PTU). At week 20 in pregnancy, she became jaundiced. Initial bloods revealed: bilirubin 91 µmol/l, alanine aminotransferase 1,796 IU/l, alkaline phosphatase 200 IU/l, international normalized ratio 1.2, and albumin 33 g/l. A presumptive diagnosis of PTU-induced hepatitis was made. PTU was immediately discontinued and best supportive care instigated. Serum markers for autoimmune and viral hepatitis were negative, abdomen ultrasound, ferritin and caeruloplasmin were normal. Although her alanine aminotransferase began to fall, her bilirubin continued to rise, peaking at 378. Two weeks after PTU cessation she became thyrotoxic and was started on a reducing regime of carbimazole. Her thyroid function stabilized and liver function tests continued to improve with carbimazole stopped at week 32. Growth scans remained normal with delivery of a healthy baby at 38 weeks. This report highlights that good outcomes can be achieved in PTU-induced hepatitis in pregnancy. Patients on PTU should be warned of the potential risk of hepatic failure and advised to seek medical advice immediately if they develop jaundice.