ANTI DEPRESSANT DRUG BLOG

Research Reveals How Prozac Triggers New Brain Cell Growth

May 30, 2006

Experts have long suspected that one way antidepressants such as Prozac, Paxil and Zoloft dispel depression is by stimulating the growth of new brain cells.

Now, researchers say they’ve zeroed in on just how that happens.

“It was clear that this generation of new neurons is important for the action of antidepressants,” explained lead researcher Grigori Enikolopov, an associate professor at Cold Spring Harbor Laboratory in Cold Spring Harbor, N.Y.

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His team used a new mouse strain that made it easy to identify and track these early progenitor cells. The work “defines a cellular target for antidepressants,” Enikolopov said. “What has been known for 20, 30 years is that Prozac increases the level of serotonin [a neurotransmitter associated with good mood.]” But what wasn’t known was why Prozac takes three or four weeks to start working.

“Alcohol, Valium, they work immediately,” he says. “But these selective serotonin reuptake inhibitors, they need three or four weeks.”

“Three to four weeks is basically comparable, in our schedule, of the 28 to 30 days it takes to go from a stem cell to a neuron,” he pointed out.

Prozac first went on the market in 1987 in the United States as the first SSRI. These medications selectively target serotonin, inhibiting its reabsorption into the cell so there is more available.

Dennis Steindler, executive director of the McKnight Brain Institute at the University of Florida, Gainesville, applauded the Cold Spring work.

“The beauty of this study is, a new model has been generated,” he said.

“This study is in essence a ‘readout,’ a neurogenic readout, whereby using this [mouse] model, the Enikolopov group found exactly the cell that increases its rate of proliferation,” he said. “That leads to generating more neurons as a result of taking this drug.”

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Gene Influences Antidepressant Response

May 30, 2006

Whether depressed patients will respond to an antidepressant depends, in part, on which version of a gene they inherit, a study led by scientists at the National Institutes of Health (NIH) has discovered. Having two copies of one version of a gene that codes for a component of the brain’s mood-regulating system increased the odds of a favorable response to an antidepressant by up to 18 percent, compared to having two copies of the other, more common version.

Since the less common version was over 6 times more prevalent in white than in black patients — and fewer blacks responded — the researchers suggest that the gene may help to explain racial differences in the outcome of antidepressant treatment. The findings also add to evidence that the component, a receptor for the chemical messenger serotonin, plays a pivotal role in the mechanism of antidepressant action.

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Located on cells in the brain’s thinking center (cortex), the serotonin 2A receptor regulates circuits implicated in depression. Antidepressants, including citalopram, reduce the number of serotonin 2A receptors in animal cortex over the course of a few weeks — the same time-frame required for the drugs to work in humans — suggesting that the receptors are important in the drugs’ mechanism of action.

Everyone inherits two copies of the serotonin 2A receptor gene, one from each parent. A tiny glitch in the gene’s chemical sequence results in some people having an adenine (A) at the same point that other people have a guanine (G). So an individual can have gene types AA, AG or GG. Overall, the prevalence of the A version was 38 percent, compared to 62 percent for the G version in this sample. Fourteen percent had AA gene type, 43 percent AG and 43 percent GG. Since the site of variation is located in a stretch of genetic material with no known function, the researchers suspect that it may be just a marker for a still-undiscovered functional variation nearby in the gene.

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Antidepressants extend time to relapse in diabetics

May 30, 2006

Maintenance treatment with the antidepressant sertraline (Zoloft) after a first episode of depression has resolved extends the time to relapse in patients with diabetes, study results suggest. And sustained remission of depression is associated with improved control of blood sugar.

Depression is highly prevalent among patients with diabetes, Dr. Patrick J. Lustman, from Washington University School of Medicine in St. Louis, and colleagues note, and recurrence after initial successful treatment is common. Depression, in turn, is linked to increased morbidity and mortality among diabetics, they point out in the Archives of General Psychiatry for May.3

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The second phase of the trial included 152 diabetics from the first group who were successfully treated for depression. Seventy-nine were randomly assigned to continued Zoloft and 73 to placebo.

Zoloft was significantly more successful than placebo in prolonging the depression-free interval, report the investigators. Time to recurrence in one third of patients was 57 days in the placebo group and 226 days in the Zoloft group.

During the second phase of the trial, changes in HbA1c level — a marker of blood sugar control — did not differ between groups. However, HbA1c levels were significantly lower than baseline during depression-free periods, regardless of treatment.

According to Lustman’s group: “Vigilant monitoring of depression symptoms to prompt treatment augmentation or modification is required and may improve the picture.” They also suggest that psychotherapy may help provide more durable relief of depression.

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Anti-depressant stillbirth link

May 5, 2006

Use of a type of anti-depressant medication during pregnancy may increase the risk of a stillborn baby, research suggests.
A Canadian study of almost 5,000 mothers found those who used SSRIs were also more likely to have premature and low birth weight babies.

However experts said women should not stop taking medication without expert advice.

The study is published in the American Journal of Obstetrics and Gynaecology.

Pregnant women should continue taking their medication as normal

Charlotte Davies

The researchers, from the University of Ottawa, compared the health of babies born to 972 women taking SSRI anti-depressants with that of babies born to mothers who did not use anti-depressants.

SSRIs, or selective serotonin reuptake inhibitors work by increasing levels of the mood chemical serotonin in the brain. They include Prozac.

The researchers found women using the drugs were twice as likely to have a stillbirth. They were also almost twice as likely to have a low birth weight baby.

Almost 20% of women who used SSRIs gave birth prematurely, compared to 12% of those who did not use the drugs.

Babies born to women using SSRIs were also more likely to have seizures.

Benefits and risks

The researchers said women should be fully briefed about the potential risk of SSRIs before taking a decision about whether or not to use them.

Charlotte Davies, of Tommy’s, the baby charity said pregnant women could opt for other types of anti-depressant medication.

She said: “Whilst this study has found a correlation between SSRIs and pregnancy complications, it has in no way confirmed a clear causal effect between the two, so pregnant women should continue taking their medication as normal.

“Left untreated, the physical and psychological effects of depression can lead to problems during pregnancy.

“Sufferers of depression are far more likely to smoke, as well as lose their appetites and in extreme cases are more likely to attempt suicide, which can all have devastating effects on mother and baby.”

Other doubts

Previous research has also raised doubts about the safety of using SSRIs while pregnant.

Last year Danish and US scientists found use of the drugs in the first three months of pregnancy was linked to a 40% increased risk of birth defects such as cleft palate.

That research also suggested that use of SSRIs in pregnancy raised the risk of a premature birth.

In a separate study, Spanish research found that babies whose mothers used SSRIs are at risk of being born with withdrawal symptoms.

The Medicines and Healthcare products Regulatory Agency has warned doctors not to prescribe most SSRI drugs, apart from Prozac, to children.

This followed evidence that use of the drugs in young people might increase the risk of suicidal behaviour.

A spokesman for Eli Lilly, which manufactures, Prozac said the company had never promoted the use of the drug for pregnant or nursing mothers.

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May 5, 2006

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