Provigil for the Masses?
Provigil (modafinil) is FDA approved for excessive sleepiness due to various causes. An ADHD indication was rejected because of its possible association with a single case of Stevens-Johnson syndrome. Nonetheless, Provigil enjoys wide use for off-label indications, including medication-associated fatigue, augmentation of antidepressants, and as a pick-me-up for the frazzled and exhausted 21st-century human. A group of researchers at Vanderbilt University has recently reported on the effects of Provigil on 12 healthy male volunteers aged 30 to 44. Patients were randomized to either three days of Provigil 400 mg/day or placebo. Provigil made subjects feel more energized, alert, and quick-witted than did placebo, but it also produced more anxiety and tension (Taneja I et al., J Clin Psychopharm Feb 2007;27(1):76-78). In a separate report on the same subjects, Provigil was associated with a nine-beat increase in heart rate, a seven-point increase in systolic blood pressure, and a five-point increase in diastolic blood pressure (Taneja I et al., Hypertension 2005;45:612).
TCPR’s Take: Provigil energizes but causes autonomic activation when given to nonfatigued volunteers. This could be hazardous for people with cardiac disease. Let patients know that there are hazards associated with sharing their Provigil with family or friends who seek a quick boost. Caffeine is probably safer.
Does “California Rocket Fuel” Work?
The combination of Effexor (venlafaxine) and Remeron (mirtazapine) has been dubbed “California Rocket Fuel” by Stephen Stahl (see page 290 of his Essential Psychopharmacology, 2nd Edition) because of the multiple ways the combination boosts various neurotransmitter systems. The STAR-D study found that this combination outperformed the MAOI Parnate (tranylcypromine), though the difference was not statistically significant (McGrath PJ et al., Am J Psychiatry 2006; 163(9): 1531-1541). Psychiatrists in Ireland recently reported on a series of 32 patients with refractory depression who were given this combination. The response rate, based on the Clinical Global Impression Scale, was 44% at four weeks and 50% at eight weeks. Most patients who responded were on Effexor XR at 225 mg/day or higher and Remeron 30 mg to 45 mg HS. In terms of side effects, 12% of patients reported moderate to severe weight gain and another 12% reported at least moderate sedation (Hannan N et al., J Psychopharm 2007;21(2):161-164).
TCPR’s Take: Since this is only a case series, it doesn’t prove the value of Effexor/ Remeron, but the combination is fairly well tolerated and certainly worth trying in patients who have not responded to anything else.
What Are the Stages of Grief?
A widely cited sequence of reactions following the death of a loved one includes: disbelief, yearning (for the loved one’s return), anger, depression/mourning, and acceptance. Researchers conducted a study aimed at empirically assessing whether these stages actually occur and, if so, in what order. A total of 233 bereaved individuals were interviewed over a 24-month period after a loved one’s death. Subjects were limited to those whose loved ones died of natural causes; the majority were widowed women in their 60s. The study found that the predominant initial reaction was not disbelief, but rather acceptance and yearning. Nonetheless, when researchers looked at when each reaction reached its peak, they found that the data fit the theory exactly, with reactions peaking in the sequence disbelief, yearning, anger, depression, and acceptance. All the negative grief reactions (i.e., all those other than acceptance) peaked at six months postloss and declined steadily thereafter (Maciejewski PK et al., JAMA 2007;297(7)716-723).
TCPR’s Take: This is an extraordinary study that will help us to inform our patients (and ourselves) about what to expect after a loved one dies. This also confirms the validity of the concept of “prolonged grief disorder,” defined as symptoms of grief lasting longer than six months post-loss.
Vyvanse Approved for ADHD
On February 23, the FDA approved Shire and New River’s Vyvanse (lisdexamfetamine dimesylate) for the treatment of ADHD in children. Vyvanse is the molecule dextroamphetamine (trade names Dexedrine and Dextrostat) attached to the amino acid lysine. After this inactive “pro-drug” is absorbed through the GI tract into the bloodstream, the liver hydrolyzes the molecule, cleaving off the lysine and producing the active drug d-amphetamine. This delivery system slows the release of d-amphetamine, so that the concentration peaks at 3.5 hours instead of 3 hours, which is when plain d-amphetamine reaches its maximum concentration (see Dexedrine prescribing information, accessed at http://www.fda.gov/cder/foi/label/2006/ 017078s040lbl.pdf). While classified as a Schedule II controlled substance as existing stimulants, Vyvanse produces no high if snorted, and a 100 mg dose made drug abusers less buzzed than a 40 mg dose of Dexedrine. However, at 150 mg of Vyvanse there were no differences between the two on the “drug likeability scale.” (See the manufacturer’s Web site at www.vyvanse.com.)
TCPR’s Take: Vyvanse is not in pharmacies yet, so it is too early to judge whether there are any clinical advantages. If it is truly less abusable, this would be its primary advantage. The cynic in TCPR notes that Vyvanse is timed to be marketed shortly before Adderall XR goes off patent. Since Shire makes both drugs, watch for shenanigans such as “shortages” of Adderall XR just as Vyvanse hits the shelves.