GABA is the most abundant inhibitory neurotransmitter in the brain. In simple words, benzos increase the activity of GABA, which basically slows down the brain and produces a calming effect. Alcohol does the same thing with GABA (among other pharmacological processes). People get terrible withdrawal from benzos when taken a long time much the same reason alcohol can cause bad withdrawal, but benzos are much more potent and can cause worse withdrawal symptoms like seizures when stopped abruptly.
Mechanisms of action. Anyone struggling to get off their benzodiazepines will be aware that the drugs have profound effects on the mind and body apart from the therapeutic actions. Directly or indirectly, benzodiazepines in fact influence almost every aspect of brain function. For those interested to know how and why, a short explanation follows of the mechanisms through which benzodiazepines are able to exert such widespread effects.
All benzodiazepines act by enhancing the actions of a natural brain chemical, GABA (gamma-aminobutyric acid). GABA is a neurotransmitter, an agent which transmits messages from one brain cell (neuron) to another. The message that GABA transmits is an inhibitory one: it tells the neurons that it contacts to slow down or stop firing. Since about 40% of the millions of neurons all over the brain respond to GABA, this means that GABA has a general quietening influence on the brain: it is in some ways the body's natural hypnotic and tranquilliser. This natural action of GABA is augmented by benzodiazepines which thus exert an extra (often excessive) inhibitory influence on neurons (Fig. 1).
The way in which GABA sends its inhibitory message is by a clever electronic device. Its reaction with special sites (GABA-receptors) on the outside of the receiving neuron opens a channel, allowing negatively charged particles (chloride ions) to pass to the inside of the neuron. These negative ions "supercharge" the neuron making it less responsive to other neurotransmitters which would normally excite it. Benzodiazepines also react at their own special sites (benzodiazepine receptors), situated actually on the GABA-receptor. Combination of a benzodiazepine at this site acts as a booster to the actions of GABA, allowing more chloride ions to enter the neuron, making it even more resistant to excitation. Various subtypes of benzodiazepine receptors have slightly different actions. One subtype (alpha 1) is responsible for sedative effects, another (alpha 2) for anti-anxiety effects, and both alpha 1 and alpha 2, as well as alpha 5, for anticonvulsant effects. All benzodiazepines combine, to a greater or lesser extent, with all these subtypes and all enhance GABA activity in the brain.
As a consequence of the enhancement of GABA's inhibitory activity caused by benzodiazepines, the brain's output of excitatory neurotransmitters, including norepinephrine (noradrenaline), serotonin, acetyl choline and dopamine, is reduced. Such excitatory neurotransmitters are necessary for normal alertness, memory, muscle tone and co-ordination, emotional responses, endocrine gland secretions, heart rate and blood pressure control and a host of other functions, all of which may be impaired by benzodiazepines. Other benzodiazepine receptors, not linked to GABA, are present in the kidney, colon, blood cells and adrenal cortex and these may also be affected by some benzodiazepines. These direct and indirect actions are responsible for the well-known adverse effects of dosage with benzodiazepines.
The problem with benzos is they only mask the problem. Its like taking a pain killer for an open wound rather than properly caring for it. They dont work on the area of the brain thought to even cause anxiety and depressive disorders. In time there presence causes tolerance which is a neurological change to over come the drugs effects. The process of these changes getting back to normal is what causes the withdrawal symptoms. Most experts agree that in the end all they do is aggravate anxiety disorders because they indirectly inhibit the chemicals we need to stay calm. Drugs like ads work on the areas of the brain thought to actually cause these disorders and are a much better solution for the problem.
I think I've asked you this before Joe, but it was a long time ago and I forgot what you said. What do fellow benzo-bashers say about other drugs for epilepsy like Neurontin, Lamictal, Trileptal, etc? I definitely found them helpful in preventing what I guess you could call "over-firing" symptoms. They helped prevent racing thoughts and spasms and helped me during panic-attacks. Even though they couldn't fully stop panic attacks, I found it easier to rationalize through an attack. There were some moments were Klonopin wouldn't help me and those could. It's almost like the DP could be somewhat controlled during anxiety attacks. Just inetersted. I'm not trying anything but if your expert opinion sees them as benign I could potentially see their use somehwere down the line.
I think most of the anti-seizure drugs are fairly benign but I dont shit about them and I think you know Im no expert. I believe very strongly about the serotonin theory tho and an drug which slows down the brain, which includes anti-seizure meds, I believe is working against you. It simply slows the output of the chemical we need to stay calm(serotonin). I know youve said youve tried ads and they are ineffective but have you ever tried them solo without the klonopin or with the use of an adjunct boosting drug like pindolol or buspar? I believe those who have the hardest time getting on them are the ones that need them the most. The levels are so low and you have to go thru alot of mental hell to get them where they are supposed to be. I used Paxil for 4 months while on 3 mg of Klonopin and it was completely ineffective. I believe it was because of the near comatose state my brain was in. Now off all depressants, Ive gotten almost an immediate response. I do believe tho my serotonin levels were already on their way up from the lexapro I was taking.
I think there is a lot more to it than just serotonin levels. I was on only ADs about a year and a half before ever going on klonopin. I found only Remeron really helpful for my panic disorder and depression. However, in some ways it seemed to make my DP worse. In retrospect I was a lot better on only ADs. My cognitive abilities were much better. However, I was really depressed but at least I still had feelings. Once I got on Klonopin, I seemed to care a lot less about a lot of things and wasn't that depressed...for a while.
I disagree. I truly believe this is strictly a serotonin issue. Serotonin is in theory the neurotransmitter related to our perception of reality. If a person takes ectasy, it forces all the serotonin out of the cells(which damages them) and brings about a feeling of complete..ecstasy. Not only that, in alot of people it causes a temporary perceptual shift. It can go either way. I believe dp is nothing more than an imbalance of serotonin which screws up our healthy perception. In our case its a depletion. Most people here have anxiety, depression, memory and concentration difficulty, blunted emotions, which are all related to low serotonin levels.
You got it! Most of the "experts" believe in the klono-ssri combo...I dont. I think they work against each other. As Ive said before, its like trying to make progress shoveling water up hill.
Maybe in your experience the serotonin theory holds true but if that were true, there would probably be a lot more people getting 'fixed' here on SSRIs alone. Perception of reality may be most attributed to serotonin but it is definitely not limited to that. The 'old antipsychotics' weren't serotonin antagonists but rather dopamine antagonists. The newer 'atypical antipsychotics' are half serotonin/half dopamine. Attention/memory/concentration are as much related, if not more related to norepinephrine and dopamine. The brain is complicated and so is DP/DR.
Did you have severe muscle problems during your c/t from klonopin. My muscles are always hurting in some way. They are either tense, throbbing, tingling, burning etc..Did you have these and did they eventually go away for you?
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