Conventionals: Not only cheaper than atypicals, but more effective?
The latest results from the CATIE trial indicate that treatment with Trilafon (perphenazine) is not only much cheaper than treatment with SGAs (second generation antipsychotics), but leads to superior overall quality of life for patients. It’s a little confusing, because Phase One results of CATIE seemed to endorse Zyprexa as the most effective drug, as measured by “time to discontinuation.” In this study, the outcome of interest was the score on the “QALY” (qualityadjusted life year), a survey that takes into account both health gains and health losses (mainly due to side effects). Thus, while patients in CATIE may have stayed on Zyprexa longer, their overall quality of lives were better on Trilafon (Rosenheck et al, Psychiatry 2006;163:2080-2089).
TCPR’s take: This is another ringing endorsement of the effectiveness of intermediate potency conventional antipsychotics, which likely incur a risk of TD somewhat higher than SGAs, but lower than high potency conventionals such as Haldol.
Should We Still use Atypicals for Alzheimer’s Disease?
Only after thinking long and hard about it, according to the long anticipated results from the CATIE-AD trial. In this study, 421 patients with Alzheimer’s Disease were randomized to double-blind treatment with Zyprexa (mean dose, 3.2 mg/day), Seroquel (34.1 mg/day), Risperdal (0.7 mg/day), or placebo. There were no significant differences between any of the treatments in time to discontinuation. Zyprexa and Risperdal were more effective in terms of reducing behavioral symptoms than placebo (Seroquel didn’t beat placebo on this, probably because the protocol led to its underdosing) but this advantage was offset by a higher incidence of side effects on atypicals, especially sedation and confusion (Schneider et al, N Engl J Med 2006;355:1525-1538).
TCPR’s take: Antipsychotics are likely to quell agitation in some patients with AD, but be hyper-aware of possible side effects and have a low threshold for switching to something else.
Suicidality and Antidepressants
Another study has been published on the controversial issue of whether antidepressants increase the risk of suicidality in children. Researchers found that suicide rates among children and adolescents were lowest in U.S. counties that had higher antidepressant prescription rates (Gibbons et al, Am J Psychiatry 2006;163:1898-1904).
TCPR’s Take: We’re not convinced that this finding contributes much to the debate. This was a retrospective, observational study, and the results are almost certainly confounded by the fact that counties with higher antidepressant prescribing rates have other qualities that could lead to lower suicide rates, such as generally more progressive attitudes about the treatment of mental illness. On the other hand, the original research prompting the black box warning was based on double blind randomized controlled trials, which is the best type of research in clinical science (Hammad et al, Arch Gen Psychiatry, 2006;63:332-339). It is clear from that study that antidepressants can cause a mild increase in suicidal ideation in children, but not actual suicide.
Acupuncture for depression? Not.
In the largest ever randomized controlled trial of acupuncture for depression, the treatment did no better than “nonspecific” needling; in fact, it did somewhat worse. A total of 151 patients with moderate depression were randomized to one of three groups: acupuncture specific to each patient’s depressive symptoms (the active group); acupuncture using a comparable number of points but without any connection to depressive symptoms (placebo); and waitlist. Both patients and acupuncturists were blinded to the identity of the intervention. At eight weeks, response rates were as follows: specific treatment, 22%; placebo, 39%; waitlist, 17% (Allen et al, J Clin Psychiatry 2006;67(11):1665- 1673).
TCPR’s take: In the discussion section, the authors try to salvage acupuncture’s reputation by arguing that the nonspecific needling may have inadvertently been the active treatment. We don’t buy it. We all know that placebos are “active,” but the aim of the study was to show that a specific treatment has a specific therapeutic action. Studies endorsing placebo are a dime a dozen and don’t help us decide between treatments.
It’s Official: Topamax doesn’t work for Bipolar Disorder
It’s been a bad, bad year for Topamax (topiramate). First, the results of four controlled trials of Topamax as monotherapy for mania showed that it outperforms placebo in only two ways: more paresthesia and more weight loss (Kushner et al, Bipolar Disorders 2006;8:15-27). The latest blow concerns a very common intervention in psychiatry: the addition of Topamax to lithium or Depakote as a way of augmenting their anti-manic actions. Who hasn’t tried this? Researchers randomly assigned 287 manic or mixed manic patients to either adjunctive Topamax (average dose 255 mg/day) or adjunctive placebo. After 12 weeks, there were no treatment differences in either the primary or secondary measures, though Topamax produced about 5 lbs. more weight loss than placebo (Chengappa et al, J Clin Psychiatry 2006;67(11):1698-1706).
TCPR’s take: Topamax now joins Neurontin (gabapentin) in the “Looks Good in Open Trials but Bombs in Controlled Trials” club. But might Topamax still enjoy plenty of off-label use as a weight loss agent in bipolar disorder? Definitely, but don’t expect insurance companies to pay for it.