Vitamin E and Cognitive Function in Women
Vitamin E, recommended variously for preventing cardiovascular disease, Alzheimer’s disease, and tardive dyskinesia, has taken quite a drubbing in recent years. Recent results from Harvard’s Women’s Health Study have put another nail in its coffin. In the cognitive portion of this study, over 6,000 women were randomly assigned to treatment with either vitamine E, 600 IU every other day (3,184 subjects), or placebo (3,193 subjects). All women were given a series of basic cognitive tests 6, 8, and 10 years after starting treatment.
No differences between treatment groups were seen in either global cognitive scores or scores on individual items at any of the three times points tested. The research group also conducted 15 secondary analyses, three of which showed modest benefits of vitamin E in certain subpopulations of women (such as women with low serum levels of vitamin E) but the investigators admitted these findings could have occur by chance alone (Kang et al., Arch Intern Med 2006; 166:2462- 2468).
TCPR’s Take: This is the latest controlled trial showing that vitamin E supplementation is ineffective for preventing memory decline. Other studies have reported that vitamin E actually poses a health hazard, by increasing the risk of heart failure and all-cause mortality in patients taking 400 IU or greater (Boothby LA et al, Ann Pharmacother 2005;39(12):2073-80). Bottom line: We recommend that patients get their vitamin E the old-fashioned way by eating nuts and green leafy vegetables. Vitamin E supplements are good for the dietary supplement industry but probably useless and possibly harmful for everybody else.
POST-TRAUMATIC STRESS DISORDER
Common PTSD Drug Doesn’t Really Help
Guanfacine is an alpha-2 agonists approved for the treatment of hypertension, but commonly prescribed for posttraumatic stress disorder. Like clonidine, another alpha-2 agonist, guanfacine is believed to decrease norepinephrine release from noradrenergic neurons during states of heightened arousal. In the first randomized, controlled trial of an alpha-2 agonist for PTSD, guanfacine (average dose 2.4 mg QD) was no more effective at reducing symptoms of PTSD than placebo. In addition, the drug was associated with significantly higher reports of adverse effects, including somnolence, lightheadedness, and dry mouth (Neylan et al., Am J Psychiatry 2006;163:2186-2188).
TCPR’s Take: While we don’t suggest ditching a potential treatment based on a single study, the onus is now on the research community to provide solid evidence that alpha-2 agonists are helpful for PTSD. On the bright side, prazosin, an antihypertensive with a slightly different mechanism of action (alpha-1 blockade) has been shown effective for symptoms of PTSD in controlled trials (Raskind MA, Biol Psychiatry 2006;Oct 25, epub, available online).
A Cure for Amphetamine Dependence?
We have no effective treatment for severe amphetamine dependence. Now, a study from Finland points to an obvious candidate treatment for those meeting DSM-IV criteria for intravenous amphetamine dependence. Patients were randomly assigned to Abilify (aripiprazole–15 mg/day), Concerta (methylphenidate controlled release–54 mg/day) or placebo for 20 weeks. Why was Abilify included? Because it is a partial dopamine agonist and therefore theoretically might decrease craving for the dopamine-stimulating effects of speed. The comparable agent in the world of opiates is Suboxone, a partial opiate agonist.
The results were so significant at a planned interim analysis, the study was terminated early. Patients taking Abilify were nearly four times more likely to have amphetamine-positive urine screens than placebo, while those taking Concerta were less than half as likely to have a positive urine screen (Tiihonen et al., Am J Psychiatry 2007; 164:160-162).
TCPR’s Take: Yes, we know what you’re thinking: What’s the point of getting speed addicts hooked on another form of speed? There are obvious advantages to Concerta: it’s legal, it’s an oral medication, and it poses no risk of spreading bloodborne diseases such as HIV or hepatitis. Nonetheless, let’s hope that researchers can someday find a more convincing “cure” for amphetamine addiction.
Curb Your Enthusiasm!
Recently, the FDA approved the Amplichip CYP450 Test (from Roche Diagnostics), which is a device allowing laboratories to quickly find out whether your patient metabolizes drugs too slowly or too quickly. Theoretically, poor metabolizers (PMs) should be given lower doses of P450-metabolized SSRIs, such as Prozac and Paxil, whereas ultra-rapid metabolizers should be given higher-than-normal doses.
Recently, the Centers for Disease Control funded researchers to review the literature on this issue. The final 145-page report concluded that P450 testing is definitely not ready for prime-time. Most of the studies have relied on giving healthy volunteers a single dose of an SSRI in order to measure the effect of P450 genotype status on serum levels. Studies of depressed populations, however, have led to wildly inconsistent results, and no firm conclusions can be drawn.
By far the best way to prescribe SSRIs, according to the team, is to choose an agent that is not significantly metabolized by the P450 system, which would include Celexa, Lexapro, or Zoloft (Download report from http://www.ahrq.gov/clinic/tp/cyp450tp.htm).
TCPR’s Take: It’s hard to argue with the report’s conclusions. In general, it’s reasonable to restrict P450 testing to our “challenging” patients, such as those who have not responded to multiple medications or those who report intolerable side effects to miniscule doses.