By Shari Roan
Originally published by The Los Angeles Times, January 6, 2010

Only people with severe depression benefit from antidepressants, says research published in the Journal of the American Medical Assn. Others do better with non-medical approaches.

Antidepressant medications probably provide little or no benefit to people with mild or moderate depression, a new study has found. Rather, the mere act of seeing a doctor, discussing symptoms and learning about depression probably triggers the improvements many patients experience while on medication.

Only people with very severe depression receive additional benefits from drugs, said the senior author of the study, Robert J. DeRubeis, a University of Pennsylvania psychology professor. The research was released online Tuesday and will be published today in the Journal of the American Medical Assn.

Hundreds of studies have attested to the benefits of antidepressants over placebos, DeRubeis said. But many studies involve only participants with severe depression. Confusion arises, he said, “because there is a tendency to generalize the findings to mean that all depressed people benefit from medications.”

The current analysis attempted to quantify how much of antidepressants’ benefit is attributable to chemical effects on the brain and how much can be explained by other factors, such as visiting a doctor, taking action to feel better or merely the passage of time.

Researchers reviewed six randomized, placebo-controlled studies with a total of 718 patients who took either an antidepressant or placebo. The patients were adults with levels of depression ranging from mild to very severe based on the Hamilton Depression Rating Scale, a questionnaire widely used in depression research. The studies did not exclude patients who were likely to have a strong response to a placebo. Researchers then compared the patients’ depression scores at the beginning of treatment with those after at least six weeks of treatment.

The study found that the magnitude of the drugs’ benefit increased with the baseline level of depression. The effect of treatment was similar in people with mild, moderate and severe symptoms, regardless of whether they took an antidepressant or placebo. Only the people who rated very severe on the depression scale at the start of the study showed measurable improvements on antidepressants.

“There is no doubt that there are tremendous benefits from antidepressants, as our study showed,” DeRubeis said. “But this study helps us resolve, to some degree, the question of how much benefit people can expect from the medicines themselves when symptoms are not severe.”

Other research has also found that antidepressants are most effective for severe symptoms, said Dr. Philip Wang, deputy director of the National Institute of Mental Health. Though it could be that antidepressants don’t work well for mild to moderate depression, it’s also possible that people enrolled in antidepressant studies have robust placebo responses that mask some of the impact of the medication.

A severely depressed person who would probably benefit from antidepressants might have symptoms such as frequent weeping, feelings of guilt and sadness, thoughts that life is not worth living, problems sleeping, fatigue and withdrawal from normal activities, DeRubeis said.

Better antidepressants are needed for people with mild to moderate depression, Wang said, as is research on how to diagnose depression with tools, such as biomarkers, that could help personalize treatment.

Of the six studies in the current analysis, three involved selective serotonin reuptake inhibitors, or SSRIs, the most commonly used antidepressants, and three involved an older class of medications called tricyclics. Both classes are thought to be equally effective, although SSRIs are associated with fewer side effects.

One exception to the study findings, DeRubeis said, was people with dysthymia, or chronic, low-level depression. The analysis assessed severity of symptoms, not chronically, he said. Other studies have established that people with chronic depression, no matter how severe, tend to respond well to antidepressants while other treatment may be ineffective.

Study Finds Medication of Little Help to Patients with Mild to Moderate Depression

by Jon Hamilton
Originally published by www.npr.org July 1, 2009

Three new genetic studies are providing some tantalizing hints about what causes schizophrenia.

The studies, published in the journal Nature, identify sections of our genetic code in which small changes can affect a person’s risk for developing the disorder.

The studies found such changes in stretches of code involved in brain development, memory and the immune system.

The findings are important because schizophrenia has been so hard to study, says Kari Stefansson, CEO of the Icelandic company deCODE Genetics and an author of one of the studies. One reason is that schizophrenia doesn’t occur in animals.

“It’s a disease of thoughts and emotions,” Stefansson says, “the two functions of the brain that define us as a species and define us as individuals.”

Scientists have tried for decades to find differences between the brains of typical people and those with schizophrenia, but without much success. So Stefansson and a consortium of researchers from around the world decided to look for subtle differences in the genes of thousands of people. Some had schizophrenia; some didn’t.

One place the studies found a clue about what might be going wrong in the brains of people with schizophrenia was in a gene responsible for a protein called neurogranin, which can affect memory and thought.

“The neurogranin pathway could be one of the biochemical pathways that lead to this disturbance of thought,” Stefansson says.

But he says a more provocative finding is a genetic hot spot in a stretch of code that affects the immune system.

“It raises the question that somehow the tendency to develop schizophrenia may have something to do with infections of mothers during pregnancy.”

The idea is that some families carry a genetic variation that affects the way the immune system responds to infection, Stefansson says. If a mother gets the flu while she’s pregnant, this immune response may affect her child’s brain.

It’s also possible that the immune system is involved in schizophrenia in some other way, says Dr. Tom Insel, director of the National Institute of Mental Health, which helped fund the new studies.

He says the stretch of genetic code affecting immunity is pretty mysterious.

“In some ways it’s a little bit like the Bermuda Triangle of the human genome,” he says. “It’s an area with tremendous amounts of variability. And it’s an area where we often find variation that’s associated with many different disorders: diabetes, rheumatoid arthritis, Crohn’s disease.”

In those diseases, the immune system attacks the body’s own cells, a process that could also affect the brain. Researchers have suspected the immune system before, Insel says. Now, they’ll probably take a harder look.

Insel says he’s particularly intrigued by the finding that some genetic variations linked to schizophrenia are also linked to depression and bipolar disorder.

“It suggests, potentially, that when we’re talking about the genetic factors that contribute, what we’re really thinking about are genetic factors that contribute to how a brain gets built,” he says.

That would mean problems in the brain start very early in life, even though the symptoms of schizophrenia may not appear for decades.

One thing the genetic studies clearly show is just how many different systems in the brain may contribute to schizophrenia, says Harvard’s Dr. Pamela Sklar, an author of one of the studies.

“That’s a hopeful finding because the implication is that there may be more places to intervene,” she says, “if we understand the biology.”

Schizophrenia May Be Linked To Immune System