Zoloft not helpful for subsyndromal symptoms in cancer patients
About 20% of patients with cancer develop major depression, and at least 60% present with significant symptoms of sadness and anxiety not severe enough to meet criteria for a DSM-4 disorder. While SSRIs have been shown effective for treating depression in cancer patients, it is less clear that they are helpful for subsyndromal symptoms. In this study, 189 patients with advanced cancer were randomized to receive either sertraline 50 mg/day or placebo. Researchers excluded patients with DSM-4 major depression from the trial, in order to test the effect of sertraline specifically on subsyndromal symptoms. At 4 and 8 weeks, there were no differences on any symptom measures between sertraline and plabo groups (Stockler MR, Lancet Oncol 2007 online June 4).
TCPR’s Take: This is a surprising and disappointing result. It implies that we should be more discriminating in who we offer SSRIs to. In cancer patients who do not meet clear DSM-4 criteria, we should focus more on treatments specific to symptoms, such as hypnotics for insomnia, benzodiazepines for anxiety, and stimulants for fatigue.
More evidence that antipsychotics are dangerous in dementia
In 2005, the FDA issued a health advisory saying that antipsychotics appear to increase the risk of death in elderly patients with dementia. That advisory was based on data from placebo-controlled trials of antipsychotics conducted by industry. Now, a new study based on a completely different, and much larger, dataset, appears to confirm these dangers. Researchers used comprehensive medical records available through Canada’s health system to identify all elderly patients treated for dementia from 1997 to 2002 in the province of Ontario. A total of 27,259 patient records were examined. The researchers found that after 30 days of taking atypical antipsychotics, patients had a mortality rate of 3.9%, while matched patients on no antipsychotics had a mortality rate of 2.7%, meaning that atypicals increased the risk of early death by a factor of 1.55. Researchers had enough data to compare conventional agents vs. atypicals, and found that conventionals were riskier than atypicals by a factor of about 1.25 (Gill SS et al., Ann Intern Med 2007;146:775-786).
TCPR’s Take: The relative risk looks large, but the absolute risk is only 1.2%, meaning that atypicals would cause roughly one excess death out of each 100 patients treated with atypicals. The question is whether this small risk is overshadowed by the quality-of-life benefit agitated patients derive from being on antipsychotics. Many would argue that antipsychotics are worth this risk.
Is divorce a risk factor for getting a stimulant prescription?
In a provocative study, rates of Ritalin prescriptions in Canada from 1994-2000 were compared with rates of divorce. The study focused on children ages 2-7, and found that in families that stayed intact during the study period, 3.3% of children were prescribed Ritalin. In families undergoing a divorce, this rate nearly doubled, to 6.1% (Strohschein LA, CMAJ 2007;176:1711-1714).
TCPR’s Take: This finding adds fuel to the fire in the ongoing debate about whether stimulants are inappropriately prescribed. Higher prescribing in divorcing families could simply reflect a genetic component of ADHD, in which parents of ADHD kids are genetically more impulsive or otherwise more vulnerable to divorce. Alternatively, divorce may cause so much disruption that children are more likely to be brought in to the psychiatrist and be evaluated, enhancing case-finding and leading to increased (but appropriate) prescriptions. The worst case scenario is that divorce causes otherwise healthy kids to misbehave, leading to inappropriate ritalin treatment as opposed to more appropriate psychosocial interventions. Choose your own interpretation!
Latest CATIE results: Atypicals no better than Trilafon for improving cognition
One of the final major questions that the NIMH-funded CATIE trials promised to answer was whether atypical antipsychotics are better at improving cognition in schizophrenia than conventional agents, as some smaller studies implied. Patients with schizophrenia were randomly assigned to double blind treatment with Trilafon, Risperdal, Zyprexa, Seroquel, or Geodon. The patients were given neurocognitive testing at baseline and after 2, 6, and 18 months of treatment. Comparing the two scores showed that all treatments produced small neurocognitive improvement, with no significant differences among treatments. However, after 18 months, Trilafon was superior to the other agents in some secondary measures (Keefe R et al., Arch Gen Psychiatry 2007;64:633-647).
TCPR’s Take: This finding is not terribly surprising. The earlier studies showing apparent cognitive superiority of some atypicals used high dose Haldol as the comparator conventional agent, which often requires the use of anticholinergics to quell extrapyramidal side effects. Anticholinergics can cause confusion, which always made Haldol look worse in these studies. This confounding artifact was not present in CATIE, because investigators chose Trilafon, a medium potency drug that rarely requires the addition of anticholinergics.