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One Dose of SSRI Antidepressant Changes Brain Connectivity In 3 Hours

According to new research, if you notice your antidepressant affecting you from the very first dose, it probably isn’t “all in your head” or necessarily an indication of hypomania. New research suggests that antidepressants actually change your brain’s activity within just a few hours of taking them. In other words, you could feel or think considerably different than you did within just a few hours of popping your first antidepressant pill.

Although this study doesn’t imply that everyone should feel an “effect” from their antidepressant after a few hours, but it does indicate that the pill will have already changed your neural connectivity within a few hours. Previously, mainstream belief was that antidepressants take at least a month before they build up enough to actually influence the brain (Read: Why antidepressants take so long to work). Most doctors still subscribe to the belief that antidepressants won’t have any effect until they’ve been taken for weeks. Clearly this new study debunks that old way of thinking.

How One Dose of An SSRI Antidepressant Changes The Brain In 3 Hours

The new research was published in the Cell Press Journal of Current Biology and lead by Max Planck from the Institute for Human Cognitive and Brain Sciences. The study detailed the fact that just one dose of an antidepressant can cause significant functional changes within the human brain. What was most interesting wasn’t necessarily that the antidepressant resulted in functional changes, but that certain areas of the brain exhibited increased connectivity, while the majority of the brain experienced a significant decrease.

The research: Brain scans pre-Celexa and post-Celexa

Research began with participants getting a brain scan prior to taking a single dose of the SSRI medication Citalopram (Celexa), and shortly after their dose. The brain scans showed significant differences in neural connections within the brain, just after 3 hours of the single dose Celexa. The process was pretty straightforward, but in order to make sure that a person’s thoughts and emotions weren’t influencing brain activity, they were instructed to not think of anything dramatic as this could potentially invoke changes in connectivity.

In the study, the participants had no prior history or diagnoses of depression. Therefore it cannot necessarily be assumed that the connectivity among non-depressed and those with major depression will be the same at baseline scans. It should also be noted that responses may also differ among those with major depression to SSRIs. The lead researcher stated that similar 3-D brain maps will need to be generated to study functional connectivity and how it is influenced by an SSRI (Selective Serotonin Reuptake Inhibitor) medication.

Results: Grey matter connectivity changes as a result of the SSRI

Researchers were able to create connection maps in 3-D that showed the degree of interconnectivity within grey matter. They noticed that when more serotonin was present in the brain as a result of SSRI (Citalopram) administration, changes in connectivity were noticeable. Although this finding isn’t too surprising, what took researchers by surprise was the fact that other areas of the brain such as the cerebellum and thalamus exhibited different activity.

The results of the study showed that taking an SSRI essentially reduces the amount of neural connectivity within the brain – with the notable exception of two specific parts: the cerebellum and the thalamus. The team of researchers observed decrease in connectivity throughout most areas of the brain. However, they did find that in the cerebellum and thalamus, the opposite effect occurred and connectivity actually increased.

  • Reduced connectivity: Taking an SSRI was found to reduce internal connectivity in most areas of the brain.
  • Increased connectivity: Despite reducing activity in most of the brain, taking an SSRI also resulted in increased connectivity in the cerebellum and thalamus.

This finding suggests that those who respond best to SSRIs may exhibit over-connectivity among certain brain regions. Over and under connectivity within the brain can be associated with various mental illnesses such as autism.

Antidepressants Reorganize Brain’s Functional Connectivity

The study author Julia Sacher stated that what they had observed among individuals with no prior antidepressant treatment is likely a marker of brain reorganization. Researchers believe that these findings could be beneficial in that brain scans may be used in the future to assess how well someone will respond to an SSRI treatment. It is also thought to be beneficial in understanding brain scan changes among those who fail to experience relief in depressive symptoms after they’ve been taking an SSRI.

Sacher was quoted as saying, “It was interesting to see two patterns that seemed to go in the opposite direction.” She continued by stating, “What was really surprising was that the entire brain would light up after only three hours.” They didn’t expect that to happen. A majority of people who take antidepressants don’t notice changes in their mood until they’ve been on a medication for a few weeks.

This finding also supports my idea that individuals who are very self-aware may notice changes in thinking, feeling, and side effects within the first day of taking their antidepressant. Since this study only documented changes in brain scans immediately after taking the drug, it is thought that further changes could happen over the course of long-term treatment. It is speculated that synapse remodeling may take place as serotonin levels increase and influence neighboring cells.

Researchers will not be able to detect all of these changes with current brain scan technology, but they believe that further changes could be tested with other methods. Additionally, further research is warranted to better understand why there was an increase in functional connectivity in the cerebellum and thalamus, and how the rest of the brain experienced a decrease.

It could be because the cerebellum’s pathways are heavily influenced by the neurotransmitter serotonin. This region of the brain is responsible for interacting with the spinal cord to process signals that have been relayed. It also is thought to interact with the thalamus by altering its signaling to the rest of the cortex. The goal of this research is to eventually come up with a template for doctors to determine who will respond to SSRIs and who would be better off without them.

Some people experience bad reactions when they take antidepressants; it is well known that antidepressants can cause depression and suicidality in some people. Each person has an individual response to a specific medication. What may benefit one person, may actually make another person feel drastically worse. Since the changes happen so sudden, this supports the idea that some people notice antidepressants work immediately.

Future Studies of Antidepressants / Depression with Brain Scans

In the future, there are several things researchers can hopefully determine with technology. I’ve made a list of bullet points of things that should be a priority for those with depression and/or those stuck taking antidepressants.

  1. Learn how brain heals after withdrawal from an antidepressant: It is known that antidepressant withdrawal can be long lasting. It would be worth studying how conducting a gradual taper may result in different brain changes when compared with “cold turkey” withdrawals. In fact, studying the brains of individuals after quitting a medication “cold turkey” may be beneficial.
  2. How long it takes brain function to return to homeostasis: After withdrawal how long before the brain returns to homeostatic functioning. Does it ever return? Does it take years before function returns? Does the dose and the duration for which the medication was taken have any effect? This would be useful to know so that we could preach the truth instead of doctors telling patients that they should feel better after a few days of withdrawal. This may also allow us to devise methods that help speed up healing after antidepressant usage.
  3. Whether certain brain changes are linked to specific side effects: Changes in brain scans may reflect certain antidepressant side effects that people experience while taking a medication. Researchers may be able to one day pinpoint side effects from medications as being a result of functional changes in specific areas of the brain.
  4. Whether antidepressants create permanent changes for some people: Do some antidepressants end up permanently altering brain activity? Some people who take a drug for a long period of time and “never feel the same” since taking that medication may argue that antidepressants have caused permanent changes. Although the changes are unlikely to be permanent, it may take awhile before the brain returns to homeostasis following withdrawal.
  5. Relationship between dosage and connectivity: Is there some sort of relationship between the dosage of SSRI and the changes in connectivity? Could a greater dose result in amplified changes or more significant initial changes? Would a lower dose not have as significant of an effect?
  6. Differences in brain scans among various SSRIs: It should also be mentioned that the research cannot conclude whether these changes will be reflected with other SSRIs. For this study Citalopram was used, which is an SSRI, but it has a different pharmacological profile than other drugs. The question remains whether other SSRIs will result in different brain scan effects.
  7. How other types of antidepressants affect connectivity: There are many other types of antidepressants besides SSRIs. Other classes include SNRIs, atypicals, tricyclics, and MAOIs. It may be worth investigating how other classes of medications may result in different connectivity alterations.
  8. How other psychotropic drugs affect connectivity: It would be interesting to see how other drugs affect connectivity. Other notable drugs that could be studied include antipsychotics and benzodiazepines. Some may be interested in studying effects of illicit drugs, sleeping pills, and stimulants.

Study author Julia Sacher agrees that other drugs in addition to antidepressants should eventually be studied as well. This will continue to improve our (relatively primitive) understanding of how antidepressants are affecting the brain, and the speed at which they make changes. It should be mentioned that this study was conducted on an independent basis without funding from any pharmaceutical company.  Who knows, maybe brain scans will one day be used in tandem with blood tests for depression for highly accurate treatments and to verify favorable outcomes with specific medications and/or therapies.

  • Source: http://www.cell.com/current-biology/abstract/S0960-9822%2814%2901037-9

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{ 2 comments… add one }
  • Sharon Jenkins May 18, 2016, 10:22 pm

    May this also apply in reverse, as in when reducing the dose? My 20 year old son is severely autistic, high anxiety, OCD and epileptic. It has been agreed to try and reduce/withdraw all psychotropic meds. We are currently tapering off fluoxetine with the understanding that the half-life is a few weeks. Each time we have reduced by 5mg we have seen an extreme outburst of mania and aggression within 24 hours. It could be a complete coincidence but this blog has made me think again.

  • Kathlynn September 5, 2015, 8:35 am

    I’m on 10mg of citalopram, and I could totally feel a change in my brain on the first day I took it. It felt like my brain was being shored up, more supports added. Things felt stronger. Made it hard to sleep, since I was told to take at night, in case it caused drowsiness. By the 3rd day I was seeing a drastic drop in anxiety symptoms. (I had really high anxiety, but only Dysthymia level depression (rather then a MDE)). I don’t know how I would manage without it now.

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