Antidepressants do little for mild cases: study

WASHINGTON, 06 jan 2010– Patients with mild or moderate depression may benefit little from antidepressant medications and may be better treated with alternatives, researchers said Tuesday.

A group of researchers combined data from six studies involving 718 adult outpatients who ranged from mildly to very severely depressed according to the Hamilton Depression Rating Scale.

Their study, which sought to compare the benefits of commonly prescribed antidepressants (ADM) compared to placebos, was published in the Journal of the American Medical Association.

The authors, led by Jay Fournier of the University of Pennsylvania, Philadelphia, found that the effect of antidepressants varied considerably, depending on the severity of the symptoms.

"True drug effects (an advantage of ADM over placebo) were nonexistent to negligible among depressed patients with mild, moderate and even severe baseline symptoms, whereas they were large for patients with very severe symptoms," they wrote.

Most studies on antidepressants -- currently the standard treatment for major depressive disorders -- focus on the impact of the drugs on patients considered to be severely depressed, but there remains scant evidence on their effect for patients with less severe depression.

Advertisements for these drugs to clinicians or the general public omit this feature, the researchers noted.

The majority of patients receiving antidepressants in clinical practice have depression measures below the high level of symptom severity they found necessary for the drugs to have a meaningful impact, according to the study.

"Prescribers, policymakers and consumers may not be aware that the efficacy of medications largely has been established on the basis of studies that have included only those individuals with more severe forms of depression," the authors wrote.

"Efforts should be made to clarify to clinicians and prospective patients that whereas antidepressant medications can have a substantial effect with more severe depressions, there is little evidence to suggest that they produce specific pharmacological benefit for the majority of patients with less severe acute depression."

ACP Offers Guidelines on Second-Generation Antidepressants

23 nov 2008--The American College of Physicians has released clinical practice guidelines on using second-generation antidepressants to treat the spectrum of depressive disorders in adults.

The guidelines, which appear in Annals of Internal Medicine, derive from an analysis of nearly 30 years' worth of published research on 12 drugs: bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine.

The principal recommendations follow:

• Since all of the drugs are about equally effective, consider adverse-effect profiles, costs, and patient preferences when choosing among them.
  
• Assess the patient's status regularly, beginning within 2 weeks after starting therapy.
  
• Modify treatment if there's no response within 2 months.
  
• Successful treatments of first episodes of major depression should continue for about 6 months; patients with a history of two or more episodes should undergo treatment for much longer periods.
  

LINK(S):

Annals of Internal Medicine guidelines (Free)

Genes Tied to Bad Reactions to Antidepressant Drug

By BENEDICT CAREY
Variations in two genes may increase the likelihood that a person will report suicidal thoughts after taking an antidepressant, researchers reported yesterday. The finding could help doctors develop tests to predict which patients will do well on such medications and which will react badly.
The authors of the study, which was released to reporters yesterday and will appear in The American Journal of Psychiatry on Monday, said that the findings were preliminary and would need to be verified by further testing.
The study focused on reactions to only one drug, Celexa from Forest Laboratories, and found no link between the gene variations and dangerous behavior like suicide attempts.
This distinction is critical, because doctors do not know whether people who report thoughts of ending their lives are at increased risk to act on them. The one patient in the study who attempted suicide consistently denied having any suicidal thoughts.
The findings come at a time when psychiatrists, regulators and some former patients are locked in a furious debate about the risks of antidepressant drugs, which include products like Prozac from Eli Lilly and Zoloft from Pfizer. In recent years, health regulators have required that drug makers post strong warnings on antidepressant labels, saying that some young patients may be at increased risk of suicidal thoughts and behavior.
Some psychiatrists say the warnings have scared off patients who would benefit from the drugs — based largely on reports of suicidal thinking, which may not increase the risk of suicide itself.
“What I would say is that this study is a wake-up call, that we may have the opportunity to use genomic tests to guide personalized care for depression,” said Dr. Thomas Insel, director of the National Institute of Mental Health, which helped finance the study.
But Dr. Insel added that the genetic test “is not yet ready for prime time.”
The researchers used data from a large government-financed depression study that included more than 4,000 adult patients. They found that about 6 percent of these patients reported having thoughts of suicide after taking the drug, usually within the first few weeks of starting treatment.
They then analyzed blood samples from 120 of those who reported the suicidal thoughts, looking to see whether variations in certain genes were especially common in them.
The scientists found that 36 percent of the patients who had markers for two gene variations reported suicidal thoughts — a more than 10-fold risk compared with those with neither of the gene markers.
These patients were also far less likely to recover taking the drug. Both markers were in genes that affect how the brain processes a chemical messenger called glutamate, which works to activate neurons.
If genetic tests are developed, “they could add to the whole clinical picture,” said Dr. Francis McMahon, chief of the genetics and mood disorders unit of the National Institute of Mental Health and the senior author of the study.
“If a patient tells me he thinks his life is not worth living, or I know he’s at risk of having that reaction, I’m going to monitor him more closely or treat him differently,” Dr. McMahon said.
The researchers searched for links to 68 genes in the patients’ blood samples that might influence mood states, but these are clearly not the only genes that could be involved in the emergence of suicidal thoughts.
Many of the patients who reported a sudden urge to end their lives did not have either of the gene variations found to put people at high risk.