Does Concerta augmentation of antidepressants work?
Psychostimulants are commonly added to antidepressants in order to augment their effects, but most of the clinical trials have been either open or small controlled trials. In what may be the largest trial done to date, these investigators (who received funding from Janssen-Ortho, the maker of Concerta) randomized 145 depressed patients, all of whom had failed at least one trial of an antidepressant, to either Concerta augmentation (n = 73) or placebo augmentation (n = 72). Concerta was started at 18 mg/day and was gradually increased, as needed, up to a maximum of 54 mg/day; the average final dose was 36.4 mg/day. The primary outcome measure was the MADRS depression scale score after 5 weeks. Results: There was no difference between Concerta and placebo on the MADRS scale, nor on any of the secondary outcome scales except for the Apathy Evaluation Scale, which showed a small improvement in favor of Concerta. Concerta also outperformed placebo on measures of fatigue early on, but at the 5 week endpoint, there was no significant benefit (Ravindran AV et al., J Clin Psychiatry 2008;69:87-94).
TCPR’s Take: Similar to earlier placebo-controlled trials of Provigil augmentation, it appears that Concerta augmentation doesn’t have an effect on the core symptoms of depression, but is somewhat helpful for apathy and fatigue. Whether this benefit is sufficient to outweigh the disadvantages of prescribing a stimulant (mild increase in heart rate and blood pressure, the hassles of prescribing a scheduled substance) is a judgement call for each clinician and each patient.
ANTIEPILEPTICS AND SUICIDE
Twice the risk of suicide when taking antiepileptics
The U.S. Food and Drug Administration (FDA) warned healthcare professionals that patients taking antiepileptic drugs (AEDs) have twice the risk of suicidal behavior or ideation compared with those taking placebo. A yet unpublished analysis of data from 199 placebo-controlled studies of 11 AEDs indicated that 0.43% of the AED group experienced suicidal behavior or ideation compared to 0.22% of the placebo group. In the 27,863 AED patients, there were 105 reports of suicidal symptoms and 4 completed suicides compared to 35 reports of suicidal symptoms and 0 suicides in the placebo group. This effect was seen in as little as 1 week, and the relative risk versus placebo was higher in epilepsy patients (RR= 3.6) than in psychiatric patients (RR= 1.6) (accessed online at http://www.fda.gov/cder/drug/ InfoSheets/HCP/antiepilepticsHCP.htm).
TCPR’s Take: It appears that AEDs roughly double the risk of suicidality as compared with placebo. However, the absolute risks are small, and the effect appears more likely in patients treated for epilepsy than for patients with psychiatric illness (although the FDA has yet to publish all the data required to compare these two populations). Given the small absolute risks, this finding likely won’t affect AED prescribing for bipolar disorder or epilepsy, but it encourages us to think twice before prescribing AEDs for less established off-label indications, like anxiety disorders.