How SSRI work in withdrawal


Neurons in the brain use both electrical and chemical signals to work.  When a neuron is stimulated, it fires electrically.  This stimulates the release of neurotransmitters at the end of the neuron.  These chemicals flow in the gap between neurons until they bind to receptors on another neuron.  Once enough neurotransmitters have attached to the next neuron, it stimulates that neuron to fire electrically, and the process continues.  SSRI affect the chemical part of this process.  Chemically, SSRI mimic the neurotransmitter Serotonin on one side of the molecule, but are different, otherwise.  When it binds to a receptor, instead of activating that receptor, it blocks it.  These receptors absorb excess Serotonin and store it in the neuron.  By blocking the absorption of Serotonin, more of this neurotransmitter stays in the gap between neurons.  The theory is that having more Serotonin available to stimulate new neurons improves mood.

As receptors that are stimulated by Serotonin are blocked, less of the neurotransmitter is absorbed back into neurons.  The brain responds to this lack of stored Serotonin by creating new networks of neurons in an attempt to reestablish the old state of function.  These new receptors are in turn blocked by the SSRI.  As the process continues, the dosage of an SSRI prescription may be increased to counteract the brain’s attempts to restore the old functional state.  Patients refer to this as “poop out”.  It’s similar to the tolerance that other drug users experience.  The difference is that most illegal drugs act on a wide range of neurotransmitters, whereas SSRI target Serotonin specifically.

In withdrawal, the blocking action of the SSRI is removed, and the excess networks of neurons are able to absorb Serotonin again.  Since the brain has been trying to balance against reduced absorption capacity, the result is over absorption.  Serotonin is closely linked to emotions and mood.  The over absorption of Serotonin can lead to extreme fluctuations in mood and even create symptoms in the patient that mimic serious mental illnesses.  Psychosis, anxiety, fear, and even suicidal thoughts are not uncommon.  It takes a long time for the brain to re balance to the new amount of Serotonin.  The brain once again rewires itself and reduces its capacity to absorb Serotonin.  During this rewiring, moods and emotions can fluctuate.  Many patients withdrawaling from an SSRI report that their mood can be different from day to day.  This most likely reflects the fluctuations in available Serotonin.

Serotonin doesn’t just exist in the brain.  There are neuron like cells throughout the body.  Some have described the neurons in the gut as a belly brain.  They’re not as organized as the neurons in the brain and serve different purposes, but the analogy is fairly accurate.  Serotonin is produced in the gut and migrates to the brain where it is used as a neurotransmitter.  The same Serotonin balancing process that occurs in the brain happens in other parts of the body.  SSRI withdrawal can have impacts on many parts of the body.  Along with mood fluctuations, it can cause muscle twitching, stomach aches, gastrointestinal problems.  The effect of blocking Serotonin in the gut may also be linked to weight gain, which is a very common side effect of SSRI use.

SSRI withdrawal can present symptoms that are very close to other diseases.  Doctors who see these symptoms often misdiagnose withdrawal as a new illness or the re emergence of an existing illness.  The diagnostic problem is one of scale.  Anxiety, fear, anger, and even psychosis are present in all human emotions to a small degree.  In withdrawal, these emotions become unnaturally amplified.  An event that would normally produce mild anxiety produces debilitating anxiety in withdrawal.  It’s not until the brain has completed balancing for the new state of Serotonin absorption and release that emotions once again return to the normal baseline.  This problem is further complicated in patients who have pre existing conditions that affect these emotions.  Often, doctors will prescribe new drugs that compound the problems of withdrawal.  Instead of allowing the brain to balance itself, a new chemical is introduced, with new effects and changes to the brain.  Introducing new changes to the brain while it is trying to deal with existing changes can cause a spiral of new symptoms and diagnoses that put the patient on a tract to taking a cocktail of drugs, each meant to treat the effects of the previous drug.

The safest way to stop taking an SSRI is to do so very slowly.  By slowly weaning off an SSRI, the brain has enough time to consolidate the changes in Serotonin absorption and production.  Instead of absorbing the majority of Serotonin in a short time, the brain has the opportunity to deactivate the excess receptors that cause a lack of available Serotonin.  Most doctors and drug manufacturers recommend reducing SSRI dosages by large amounts.  Most tapering schedules only last a month or two.  This time frame is too short for the brain to adjust.  It took a long time for neurons to extend themselves into new areas in the attempt to absorb Serotonin.  Likewise, it takes a long time for the brain to change the structure of neurons so that the old functional state is achieved.  The tapering period doesn’t have to last as long as the original treatment, but it does need to be longer than most recommendations.  10% reductions in dosage each 4-6 weeks is usually sufficient to allow the brain to adjust slowly.  For example, a patient taking 40mg/day would reduce to 36mg/day in the first month, then 32.4mg/day in the second month, continuing to reduce 10% from the last dose.  It’s difficult to measure pills to this granularity, but being as precise as possible is important to reducing withdrawal symptoms.

15 Responses to “How SSRI work in withdrawal”

  1. mindy Says:

    Hello, Thank you for this article I have been on Paxil for 16 years,, and was fine for a long time I think about a year ago it poooped out.. I am on a five month weaning program down to 10 mg now.. I feel so awful at times… brain fogginess so bad, terrible anxiety, crying dread…. it helps to know i am not alone in this… can you please keep in touch with me at ***************,.. so i dont feel alone.. I hate hate hate this more then anything in the world… and just want to feel myself again.. thanks so much mindy.

    • npanth Says:

      Withdrawal can be a very challenging time, especially after years of SSRI use. Emotions seem uncontrollable at times. It’s not a linear process to get better, it seems to go up and down. Being part of a community helps a lot. Try, there are a lot of people there who have experienced the same thing and have good advice on how to cope with the symptoms.

  2. Serontin withdrawal | My2shoppe Says:

    […] How SSRI work in withdrawal « James Heaney […]

  3. carrotshead Says:

    Thanks for your information.
    Now I’m wean off Lexapro for about 1 week.
    So terrible experiencing lightheaded, dizziness, vertigo also weight gain now


    • npanth Says:

      Good luck weaning. If the symptoms become unmanageable, try slowing down your weaning schedule. Many doctors recommend very fast weaning schedules which some people can’t tolerate. I’ve found that I have to wait until I stabilize after each drop before I attempt another reduction. I understand the desire to be off the drug as soon as possible, but a very slow weaning schedule will improve quality of life, and you’ll get off, eventually 🙂

      • carrotshead Says:

        I’ve been on Lexapro 20 mg for about 6 months and start cut off to 15 mg for 2 weeks, 10 mg for 2 weeks and 5 mg on the last 2 weeks. My emotion is now alright but for physical I dealing with Lightheadedness 😥

        But very glad found your blog. I love your blog and will be the one of your followers 😀

        P.S. Sorry for confusing english skill. I’m Thai (asian) and not good at english. I’ll do my best 😀

  4. silver account Says:

    The linkage of serotonin to depression has been known for the past five years. From numerous studies, the most concrete evidence of this connection is the decreased concentration of serotonin metabolites like 5-HIAA (5-hydroxyindole acetic acid) in the cerebrospinal fluid and brain tissues of depressed people. If depression, as suggested, is a result of decreased levels of serotonin in the brain, pharmaceutical agents that can reverse this effect should be helpful in treating depressed patients. Therefore, the primary targets of various antidepressant medications are serotonin transports of the brain. Since serotonin is activated when released by neurons into the synapse, antidepressants function at the synapse to enhance serotonin activity. Normally, serotonin’s actions in the synapse are terminated by its being taken back into the neuron then releases it at which point “it is either recycled for reuse as a transmitter or broken down into its metabolic by products and transported out of the brain.” As a result, antidepressants work to increase serotonin levels at the synapse by blocking serotonin reuptake (2) .

    • shiraj.ks9 Says:

      hii ths is shriraj …npath…dear my symptoms became manageable thnks for ur help….my libido however is fluctuating….sumtyms its gud sumtyms poor.. erection not full……but i can say libido us not zero soo ….i guess its all process of recovery isnt…

  5. Sean Says:

    Wow, nice to hear some honesty about these drugs! Everyone has been telling me that they’re long out of my system but I knew they weren’t!!

    I came off the SSRI’s very slowly slower than recommended and still have had very bad withdrawal symptoms, I’m off them for coming on 9 months now and am still experiencing symptoms any idea how much time it takes I know its how long is a piece of string sorta thing but just wondering if you had any idea? I’m still experiencing twitching and mood swings and find normal situations difficult and I feel it’s all down to the withdrawal symptoms.

    • npanth Says:

      I think that the body and brain adjust to the absence of an SSRI at the same rate as the slow taper method that a lot of sites recommend. They advise to drop the drug dose by 10% every 4-6 weeks. On that method, it would take about a year to taper off 10mg/day. I think that stopping cold turkey from 10mg/day would also take about a year of recovery time. The difference between cold turkey and slow taper is the severity of the symptoms during recovery. I know that a year sounds like a very long time when you’re experiencing symptoms minute by minute. It’s not as long as it sounds when you read it, though. The symptoms get easier to manage over time, and they diminish over time, too.

  6. T. de Vreugd Says:

    Reblogged this on groundzerox.

  7. mary Says:

    now, to get this info to all medical professionals to inform patients BEFORE getting on them!! great article, thanks!

  8. joanna taylor-maynard Says:

    I’ll came off sertraline a year and the last two weeks feel like when I first started taking them and trying to adjust. Can’t sleep all of sudden and sweats anxiety terrible. Before this feeling the last few weeks I had that feeling I stuck in bubble looking out but that feeling gone before that i hated my husband and life and wanted to leave for no reason. Is this norm process. How long does it take hey. X

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