Almost 23,000 patients prescribed both long-acting opioids versus anticonvulsants and tricyclics, used for pain, were followed, and total mortality, over and above overdose deaths, was assessed. The alternatives to opioids were mainly gabapentin, pregabalin, carbamazepine, and tricyclics, mainly Elavil. Doses of greater than 150 mg of Elavil were excluded. These patients were treated for noncancer pain, mainly low back pain.
The opioid treated group had 1-1/2 to 2 times excess mortality compared to the other groups. This mortality was seen mainly in the first 6 months. Two-thirds of the excess deaths were unrelated to unintentional overdose. One-half were cardiovascular. Patients being treated for palliative or end-of-life care were excluded.
The authors believe that the main cause may be the fact that opioids cause or worsen obstructive and central sleep apnea, and these patients have increased incidence of nocturnal arrhythmias, myocardial infarction, or sudden death. They further stated that for some individual patients, the therapeutic benefits of opioids may outweigh the increase in mortality risk.
In the same journal, a second study beginning on page 2459 by J.C. Ballantyne, MD, looked at the efficacy and tolerability of long-term treatment with opioids for chronic low back pain. Thirteen trials with almost 3500 patients were identified. At least half withdrew for adverse effects or lack of efficacy. There was “moderate quality evidence” that opioids reduce pain in the short-term but no evidence to support long-term use for low back pain.
According to a new phase III study, presented at the 2016 AAN Annual Meeting, biotin at a dose of 300 mg daily seemed to reduce the rate of disease progression in both primary and secondary progressive MS. About 13% of the patients also showed an improvement in EDSS or timed 25-foot walk at month 9, which was maintained at month 12, compared to no patient in the placebo arm.
A widely used preparation called Women’s Hair, Skin, & Nails contains biotin, selenium, and zinc. Biotin is available over-the-counter, but highest dose is 10 mg. Thus, an MS patient would need to swallow 30 pills a day at a cost of about $30 a month. Several of my patients have located compounding pharmacies who will prepare a 300 mg pill at a cost of $70 to $100 per month.
Other recent studies regarding supplements for MS have shown benefit using lipoic acid 1200 mg a day, proprionic acid 1 gram a day, and a probiotic preparation termed VSL#3, double strength sachets, 3600 billion CFU/day.
Older studies strongly support the use of vitamin D. Melatonin 10 mg 1 to 2 hours before bedtime has not been rigorously tested in MS patients but may have anti-inflammatory effects. Studies about omega-3 fish oils are conflicting, as are studies with statins.
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Four major conditions – diabetes, hypertension, hyperlipidemia, and ischemic disease – have potential adverse effects on mortality and quality of life. A study of 44,000 Canadians with MS and 221,000 controls was done to determine the incidence of these disorders.
Incidence of diabetes rose more steeply with age in the MS population. Hyperlipidemia, hypertension, and ischemic heart disease were similar combining all age groups, but incidence of heart disease was higher in the younger MS population. As expected, all disorders increased with age.
MS is more common in women than men, whereas the comorbidities by contrast are higher in men.
A possible explanation for the finding of detecting more diabetes and hyperlipidemia in the MS population may be more frequent health contacts for those with MS, leading to earlier diagnosis. Other explanations include physical inactivity after MS onset, and the fact that patients with MS are more likely to smoke, at least in Canada, and be overweight.
Further, these vascular comorbidities are associated with more rapid disability in MS.
Those of us who treat MS patients should take a more active role in screening for these disorders and not assume that our patients’ primary care physicians do so consistently.
See Neurology: Clinical Practice, 2016, volume 6, page 120-128. Lead author was Ruth Ann Marrie, MD.