Do SSRIs cause osteoporosis?
A recent issue of Archives of Internal Medicine contained two articles suggesting that SSRIs may result in loss of bone density in the elderly. One study was a longitudinal trial, in which 2722 elderly women (average age, 78.5 years) were periodically examined over a 2 year period. Women on SSRIs lost double the bone density of those either on tricyclics or on no antidepressants (Diem SJ et al., 2007;167(12):1240-1245). The other study focused on 5995 elderly men, and was of cross sectional design, examining bone density measurements and antidepressant usage at a single time point. Men on SSRIs had 4-6% lower bone density than men on no antidepressants (Haney EM et al., 2007;167(12):1240-1245). Both studies controlled for a number of other factors related to osteoporosis, such as physical activity, smoking, and diet.
TCPR’s Take: The main limitation of these findings is that they did not control for the specific effects of depression itself on bone density. Patients on SSRIs are usually depressed, and depression itself has been associated with osteoporosis. On the other hand, the studies did try to control for the presumed mechanisms by which depression may lead to low bone density (such as lack of exercise, poor diet, and smoking). The bottom line is that you need to warn your elderly patients about this potential side effect, even though the findings are still preliminary.
Lyrica (pregabalin) is approved for fibromyalgia
Fibromyalgia is a condition characterized by at least 3 months of widespread pain (both above and below the waist and on both sides of the body) and by the presence of at least 11 tender points (these are the official American College of Rheumatology criteria). There are no diagnostic tests for fibromyalgia, and it is a diagnosis of exclusion. Recently, the FDA announced approval for Lyrica (pregabalin, the “cousin” of Neurontin, or gabapentin) for the treatment of fibromyalgia, based on two double-blind placebo-controlled trials involving 1800 patients. Effective doses ranged from 300 to 450 mg/day.
TCPR’s Take: We have not yet seen the data upon which the FDA’s approval was based, although a brief summary of some of this data is presented on the Pfizer website, in their updated Lyrica product insert (http://www.pfizer.com/ pfizer/download/uspi_lyrica.pdf). The key questions will be whether Lyrica does better than tricyclics or SNRIs, both of which are effective in fibromyalgia (though neither class has FDA approval). Lyrica has a fairly negative side effect profile, including high rates of sedation and dizziness, and has some abuse liability, being classified in the same DEA schedule as cough suppressants with codeine.
Meta-analysis shows no difference between SSRIs and bupropion
Clinical lore has it that SSRIs are preferable to bupropion for depressed patients who present with anxiety and insomnia. Papakostas and colleagues tested this assumption by obtaining patient data from 10 studies funded by GlaxoSmithKline (makers of brand name Wellbutrin) over the years. Analyzing results involving 2122 patients with major depression, the authors found no differences in overall efficacy between the two classes, with the exception of a marginal advantage in the Hamilton Anxiety Scale for women, but not men. How marginal was the benefit? The SSRI anxiety scale response rate was 63.8% vs. bupropion’s 58.8%. Since the authors reviewed 64 different outcome measures, this difference was highly likely to occur by chance alone (Papakostas GI, et al., Int Clin Psychopharmacology July 2007;22(4):226-229.)
TCPR’s Take: While this data implies that Wellbutrin is just as effective for anxious depression as the SSRIs, all of the trials were sponsored by GSK, meaning that they were presumably designed in order to make bupropion look good. The authors did not discuss this possibility, presumably because they all have dozens of industry relationships and because two of the authors are GSK employees.