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Hypersensitivity and Kindling


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Hypersensitivity and Kindling   



What causes hypersensitivity? Some people may experience minor difficulty in stopping a psychiatric drug one time, but the next time they start and stop, the withdrawal symptoms are worse. For benzos, this can even include seizures due to a lowered seizure threshold (note: this is much more likely with a rapid or cold turkey benzo withdrawal). Stimulants and some antidepressants (such as Wellbutrin) also lower the seizure threshold. Repeated instances of going on and off drugs, adverse reactions, cold turkey, etc. seem to build neurological hypersensivity to drug and dosage changes, resulting in worsening adverse reactions, usually some form of activation.


In Altostrata's post One Theory of Antidepressant Withdrawal, she writes:



On 5/24/2011 at 10:59 PM, Altostrata said:

My guess is: The first phase of withdrawal, the acute phase, is the initial shock of withdrawal at the target receptors, with the most defined symptoms, such as brain zaps and nausea and possibly waves of unusually intense "depression" and "anxiety" -- actually, emotions generated by the neurological upset. Later, hyper-reactivity and autonomic instability take over. Often the autonomic instability causes wide hypersensitivity to drugs, supplements, and even foods.


A benzo works by increasing GABA. Long-term exposure to benzos causes GABA receptor down-regulation and glutamate receptor up-regulation. A slow and careful taper makes it easier for the receptors to return to their pre-benzo state. But when there's a history of prior withdrawal, hypersensitivity may result in increased neuro-excitability, creating worsening withdrawal symptoms upon dosage reduction.


If someone is dealing with antidepressant withdrawal in addition to benzo withdrawal, neurological hyper-reactivity may be even more intense. And with serotonin needed to release GABA and glutamate (see Serotonin as a Modulator of Glutamate- and GABA-Mediated Neurotransmission), the interplay of all of this neurotransmitter dysregulation can make hypersensitivity more likely. 


What is kindling? Kindling is a neurological reaction where repeated withdrawals cause hypersensitivity, then hyper-reaction when the same drug or a different drug is introduced. The kindling response is an exaggerated adverse reaction to the drug. 


You may be vulnerable to kindling if you have a history of repeated rapid taper or cold turkey withdrawal and / or a history of heavy or chronic alcohol use, especially binge drinking -- in effect, going on and off the drug, with hyper-reaction when the drug is taken again.  


Some short half-life benzos (such as Halcion) and z-drugs used for sleep may cause kindling because much of the drug is eliminated in between nightly doses. Over time, this traumatizes the nervous system with repeated exposure and withdrawal in between doses. The same may be true of the short half-life antidepressants, each successive drug dose causing a hyper-reaction. The same may also be true from skipping doses (for more, see How about taking my medication every other day to reduce my dosage?).


While this phenomenon has been documented in the scientific literature for benzodiazepines for a long time, any drug that effects the nervous system and causes dependency can have a traumatic impact on the nervous system when changes are made often and abruptly. Research is now also pointing to kindling in antidepressant use. In the article Expertise from outside the Academy: tapering off antidepressants, Dr. Mark Horowitz cites a study by Dr. Giovanni Fava:



Kindling: a phenomenon observed with illicit psychotropic medications may be relevant to antidepressants – whereby repeated rounds of trialling different medications, or stopping and starting medications makes withdrawal increasingly more difficult (Fava, 2020). (This may help explain why people who use a single antidepressant for a short period of time often do not experience difficulty in stopping, whereas those who have years of complex regimes often do.)


While the exact mechanism of kindling is unknown, some of the details on kindling have been written about in papers on alcohol withdrawal, which like benzodiazepines, affects GABA (here is one such paper - Kindling in Alcohol Withdrawal).


Here is an excellent explanation on the Benzodiazepine International Coalition website:  Benzo Kindling


For a much more thorough description of GABA and glutamate during benzo withdrawal, see What is happening in your brain?


Hopefully, more research will be published in the future regarding kindling in antidepressants, antipsychotics, drugs used as mood stabilizers, and drugs for pain. Kindling in antidepressants, for example, may involve the damage caused to the serotonin receptors by repeated on and off use of one or more of these types of drugs and the effect this has on the overall nervous system. 


A note on dopamine receptor supersensitivity:


If you've been exposed to neuroleptics (antipsychotics), you can become hypersensitive to endogenous dopamine (the dopamine your body makes naturally) when the drug's dopamine blockage is removed. As opposed to benzo and antidepressant withdrawal caused by down-regulation of receptors, dopamine receptor supersensitivity is caused by up-regulation. However, dopamine receptor supersensitivity is not kindling - the symptoms of dopamine supersensitivity can occur without additional introduction or reinstatement of a drug or substance. You may experience dopamine receptor supersensitivity after coming off only one neuroleptic but not experience kindling. For more on dopamine receptor supersensitivity, see:


Chouinard, 2017 Antipsychotic-Induced Dopamine Supersensitivity Psychosis: Pharmacology, Criteria, and Therapy


While dopamine supersensitivity psychosis is specifically a neuroleptic withdrawal symptom, switching neuroleptics or making abrupt dose changes to the same neuroleptic can also lead to kindling. So it's important for people tapering neuroleptics to taper slowly to decrease the chances of both dopamine receptor supersensitivity and kindling. 


A note on limbic or psychological kindling:


In this article on limbic (or psychological) kindling, the concept of being "hard-wired" for hypersensitivities is explored. If in addition to psychiatric drugs, you are also dealing with trauma, exposure to other drugs, pollutants, or chemicals, etc., you may already be in a state of chronic stress or what is also called the "flight or fight" state.  Whether this directly translates to kindling is not clear - it may be related to learned responses, especially for those who have a history of trauma. Either way, learning how to self-soothe and calm the limbic system can be very helpful. See Non-drug techniques to cope with emotional symptoms.


Steps to reduce the damage and mitigate hypersensitivity and kindling:



Edited by Shep
added information on skipping doses

Drug free May 22, 2015 after 30 years of neuroleptics, benzos, z-drugs, so-called "anti"-depressants, and amphetamines 


My Success Story:  Shep's Success: "Leaving Plato's Cave"


And what is good, Phaedrus, and what is not good — need we ask anyone to tell us these things? ~ Zen and the Art of Motorcycle Maintenance

I am not a medical professional and this is not medical advice, but simply information based on my own experience, as well as other members who have survived these drugs.


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