There's a word of warning after research on monkeys finds that an SSRI antidepressant may alter brain architecture if taken by those who aren't really depressed.
There is new reason to be cautious about using popular antidepressants in people who are not really depressed.
For the first time, research has shown that a widely used antidepressant may cause subtle changes in brain structure and function when taken by those who are not depressed. The drug is sertraline. It is most commonly known as Zoloft and is present in 16 other generic forms in Australia.
There has been long debate about the effect such drugs can have on the architecture of the brain. While the changes it induces in the depressed brain are regarded as advantageous, researchers wanted to know what happens in the brains of those who are not depressed. They wanted to know because these drugs are commonly used for other conditions such as anxiety, bulimia, hot flushes, obsessive-compulsive disorder, post-traumatic stress disorder, stroke recovery and sexual dysfunction
Their study revealed the drugs can have unexpected and unwanted effects.
Published in the journal Neuropharmacology, their results showed the drugs reduced the volume of two important regions of the brain. The first was the anterior cingulate cortex, the part of the brain that controls and regulates mood. The other was the hippocampus where the registration and consolidation of memory takes place.The authors noted that depressed people have previously been shown to have smaller volumes of these two regions compared to non-depressed people.
The drug used in this trial is a SSRI, a selective serotonin reuptake inhibitor, and experts say other drugs in this class work on the same mechanism and chemistry and would likely have the same effect.
Of the estimated two million Australians who are using antidepressants, most would be taking an SSRI. Consumption of antidepressants is very high in Australia; in 2013, an OECD survey showed that out of 33 countries, it was the second biggest user per head, after Iceland.
Rather than using the drug in people, the new study used primates.
"It's a thoroughly impressive study, " says Philip Mitchell, Scientia professor and head of the School of Psychiatry at the University of New South Wales. He says changes in brain architecture with antidepressants are notoriously difficult to study because there are so many variables. Sample sizes can be small, people have different underlying illnesses, types of depression can vary, as can treatments, collection methods and the interpretation of results.
By using primates, he says this study managed to look at the issue "in a neat way" by excluding many variables. It used monkeys which have brain structures and functions similar to humans. While the extrapolation from the primate model of depression to humans is not perfect, this is widely accepted in the research community. He notes the monkeys with depression showed show similar structural brain changes to those seen in humans with chronic depression, such as a reduction in the size of hippocampus.
For the study middle-aged female monkeys were chosen because depression is nearly twice as common in women and antidepressants are most commonly used in women aged 40 to 59. In the first 18 months phase of the study, the monkeys were fed a diet that replicated a typical American diet. During this time, their depressive behaviour was recorded. For the next 18 months, they were divided into two groups. One group received sertraline in daily doses comparable to those taken by humans. This was equivalent to humans taking the drug for five years.
The other group received a placebo.
Afterwards, MRI imaging revealed that in depressed monkeys the drug significantly increased the volume of the anterior cingulate cortex.In the non-depressed monkeys it decreased this and the hippocampus.
"This is the first time this has been clearly shown and it should raise caution but not alarm, " says Mitchell, who is also a professorial fellow at The Black Dog Institute. "Sure it is not in humans, but it has tantalising possibilities. It is throwing up the possibility that these drugs may be doing different things in people who are not depressed."
"Perhaps we should be a bit more cautious than we are at the moment, about who we use antidepressants for. We need more research."
He notes, however, that SSRI's have been in use for some 25 years and there is no evidence of brain damage or a negative impact on intellectual capacity. But the caution here is about subtle changes. International collaborative research, published in June this year, concluded that brain damage is caused by persistent depression rather than being a predisposing factor for it.
Published in Molecular Psychiatry, it involved scans of 9000 people and proved recurrent depression shrinks the hippocampus. As a single episode does not, it raises an argument for early identification of the more severe persistent or recurrent cases. Experts noted the hippocampus was a regenerative area of the brain and the effects of depression were reversible with appropriate treatment.