Confusing presentation of data leads to premature condemnation of black box warnings
Recall that in October of 2003, the FDA issued a public health advisory about the possibility that antidepressants cause suicidal ideation in children and adolescents. A year later, the agency asked drug-makers to add a black box warning about this issue to their package inserts. In an article in the American Journal of Psychiatry, researchers reported that suicide rates increased by 14% in 2004, the largest such increase since the Center for Disease Control (CDC) began tracking this in 1979. The authors conclude that the black box warning not only failed, but may have had the opposite effect from what was intended (Gibbons RD et al., Am J Psychiatry 2007;164:1356-1363).
TCPR’s Take: Unfortunately, the study reported the data in a confusing manner, leading many to conclude from the paper that a drop in SSRI prescriptions was correlated with this rise in suicides. In fact, there was no drop in SSRI prescriptions in 2004; that drop did not occur until 2005, and the paper did not report suicide rates for that year. As it turns out, soon after the article was published, the CDC released preliminary suicide figures for 2005, showing that the overall population suicide rate actually decreased by about 3% (they have not yet released age-specific figures). This has become something of an embarrassment for the American Journal, because it took the New York Times to clarify the meaning of the data – something the journal should have required of the authors during the peer review process. Compounding the controversy, three of the authors have significant conflicts of interest, most conspicuously the first author, who has testified in product liability trials for Wyeth Pharmaceuticals (i.e., he makes money to argue that antidepressants do not cause harm). At any rate, it is certainly too early to determine whether the black box warning “failed”; we have to wait for the CDC to provide its final 2005 numbers, which may not occur for several months.
Nice review of psychiatric uses of Mirapex (pramipexole)
Most psychiatrists have at least heard of pramipexole (Mirapex) by now, and many of us have actually prescribed it. The Journal of Clinical Psychiatry recently published a short and sweet review of its potential uses in psychiatry. The remarkable thing about this review is that the writer has no funding from Boehringer Ingelheim Pharmaceuticals or any other drug company, making it a trustworthy source of information (Aiken CB, J Clin Psychiatry 2007;68:1230-1236).
Pramipexole is FDA approved for Parkinson’s disease and restless leg syndrome (RLS), but three placebo controlled trials have shown that it can be helpful as monotherapy for major depression or adjunctive treatment for bipolar depression. Pramipexole is a dopamine agonist, mostly stimulating the D3 receptor in the mesolimbic area of the brain, i.e., the emotional area. It comes in multiple strengths, including 0.125 mg, 0.25 mg, 0.5 mg, 1 mg, and 1.5 mg tablets. If you want to give a try for patients with RLS or affective disorder, start at 0.25 mg QHS, and very gradually (about weekly) increase by 0.25 mg increments. Shoot for 0.25-0.75 mg in RLS, higher for depression (mean dose in the studies was 1.6 mg/day). Common side effects: nausea, headache, sedation. Rare side effects: pathological gambling, psychosis, and sleep attacks. No drug-drug interactions, and it is cleared entirely by the kidneys.
Exercise may be as effective as sertraline
Researchers randomly assigned 202 depressed older adults (average age, 53 years old, 75% women) to four conditions: supervised group exercise 3 times a week, at-home aerobic exercise (unsupervised), sertraline, 50-200 mg/day, or placebo. After 4 months of treatment, the remission rates were as follows: Supervised exercise, 45%; home-based exercise, 40%; sertraline, 47%; placebo, 31%. When the results of all the active treatments combined were compared to placebo, they were almost superior, with p = .057, close to the p = .05 threshold for statistical significance (Blumenthal JA et al., Psychosom Med 2007;69:587-596).
TCPR’s Take: In an earlier study, this same group of researchers found that supervised exercise led to a 47% remission rate, vs. a 56% remission rate on sertraline (difference not statistically significant). They replicated the study because the earlier study did not include a placebo group, making it unclear to what extent non-specific factors were at play for both treatments. Unfortunately, in this paper the authors chose not to separate out the different active treatments in their presentation of their statistical tests, making us wonder how robust the findings actually were. Nonetheless, prescribing an aerobics class to patients with mild to moderate depression appears to be a reasonable treatment strategy, and it provides obvious physical health benefits as well.