Role of Depression “Risk Gene” Questioned
It has long been thought that one’s genetic makeup combines with stressors to cause depression, but for many years there was little data to support this hypothesis. This changed in a 2003 paper by Caspi and colleagues, which strongly supported the idea that variation in the serotonin transporter gene, when combined with stressors, drastically influences the rate of depression (Caspi A et al., Science 2003;301:386-389). By itself, this variation did not predispose participants to depression. But people with one short allele of “serotonin transporter linked polymorphic region” (5-HTTLPR) were more likely to become depressed in the face of stressful life events, and people with two short alleles were even more so. These results supported the popular serotonin theory of depression, since short alleles decrease the production of the serotonin transporter, leading, presumably, to faulty regulation of serotonin in the synapses. Intrigued by such findings, other scientists attempted to replicate them. A new meta-analysis examined the results of 14 such studies, and found that the short allele result was apparently a chance finding. In fact, only four studies supported the link between the short allele and depressive response to life events, whereas two found opposite results (long allele was linked to depressive response to life events), with others finding no consistent link between 5-HTTLPR and depressive response to stress. When the studies were combined, there was no link between the 5-HTTLPR genotype and responding to stressors with depression. (Risch et al., JAMA 2009;301:2462-2471).
TCPR’s Take: Several studies were excluded from the meta-analysis because their measurements were not directly comparable to the original Caspi et al. paper; this could have biased the findings somewhat. However, such exclusions happen in most meta-analyses and are unlikely to have altered the results significantly. Given the complexity of our genetic makeup and the frequent failure to replicate psychiatric genetics findings, it is likely wise to wait for consistent replication when a “risk gene” is identified.
Restricting Drug Samples May Reduce Costs
Drug samples are a staple of pharmaceutical marketing. The drug industry argues, quite logically, that samples are useful to treat patients who lack the funds to purchase medications. Yet some reformers have called for drug samples to be banned, an idea that has received a decidedly mixed reception. A small body of research has investigated the topic of drug samples, including a recent study that examined changes in prescriptions when samples of brandname statins, levothyroxine, and SSRIs were removed from an internal medicine clinic in Iowa. Over the 180-day period in which samples were removed, generic prescriptions increased by 23% for statins, 10% for SSRIs, and 3% for levothyroxine (Miesner AR et al., Arch Intern Med 2009;169:1241-1242). In another study, a university-based internal medicine clinic moved, leaving its sample closet inaccessible for nine months. During this time, the rate of generic prescribing for uninsured patients increased from 12% to 30%, though there was no change in generic prescribing for Medicaid patients (Miller DP et al., South Med J 2008;101:888-893).
Surprisingly, drug samples are more often given to insured Americans than to the uninsured or poor (Cutrona SL et al., Am J Public Health 2008;98:284-289). In that case, drug samples also tend to increase costs for patients who receive them (Alexander GC et al., Med Care; 46:394-402); when patients receive a sample, they often remain on that more expensive drug once the sample expires rather than switching to a less expensive generic drug. Samples probably produce overall cost savings only if they will be given indefinitely to patients who have no coverage for prescriptions and cannot afford to pay out of pocket for generic drugs.
TCPR’s Take: The combined results of these studies suggest that clinicians should be wary of drug samples and consider carefully whether they are actually helping to reduce costs for patients.
N-Acetylcysteine Effective For Trichotillomania
Trichotillomania (TTM) is an impulse control disorder in which patients feel that they can relieve tension by pulling out hair from different parts of their bodies. While sharing some features with obsessive compulsive disorder, DSM-IV-TR does not officially classify it as a type of OCD. The pharmacological treatment of trichotillomania has often frustrated patients and clinicians alike. Clomipramine has outperformed placebo, but its benefits appear to diminish substantially after discontinuation and SSRIs have failed to beat placebo across four trials (Bloch MH et al., Biol Psychiatry 2007;62:839-846). A recent study compared an amino acid (N-acetylcysteine, or NAC) to placebo. Why NAC? Because NAC is converted to cysteine, which reduces synaptic release of glutamate. Some research has implied that repetitive behaviors like TTM my be caused by excessive glutamate, providing a biochemical rationale for a trial of NAC for TTM. Of the 50 enrolled patients, most had at least one comorbid condition, including depression (28%), an anxiety disorder (28%), or another impulse control disorder such as compulsive skin picking (36%). About half were taking other psychotropic medications, and maintained their dose of these drugs during the study. Participants took 1200 mg/day of NAC for six weeks (or matching placebo), then increased dosage to 2400 mg daily for the remaining six weeks. Patients on NAC outperformed placebo patients on all trichotillomania measures by a quite large effect size. 44% of NAC patients experienced a 50% or greater drop in trichotillomania symptom rating scores compared to zero patients on placebo. NAC did not improve depression or anxiety scores more than placebo. Remarkably, no patients on NAC reported any side effects (Grant JE et al., Arch Gen Psychiatry 2009;66:756-763), though NAC may worsen asthma.
TCPR’s Take: NAC can be found at many health food stores and is cheaper than most prescription medications. The very promising safety and efficacy profile demonstrated in this study provides much needed hope to patients and clinicians alike, though replication is needed. Also keep in mind that habit reversal therapy (a form of behavior therapy), has demonstrated efficacy for trichotillomania.