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BrianOCD

Do Benzos Help Rebuild Serotonin?

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I've been reluctant to restart my benzo but I'm getting increasingly desperate.  I'm aware Benzos mechanism of action slows all the chemicals down.

My question is by eliminating the excessive worry and ruminations, can benzos potentially rebuild your serotonin system.  I can tell now I'm extremely deficient.  I'm waiting on Cymbalta to start acting but it's clearly been a slow process...

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I'm not sure how to interpret this article. Maybe someone else can step in...

https://www.ncbi.nlm.nih.gov/pubmed/5064914

Evidently benzodiazepines do interact with the serotonin system, but I'm just not sure how to make sense of this article.  

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Well that article seems to say it generally reduces serotonin and norepinephrine which I thought was the case.

But what I'm wondering is about the therapeutic effects of Benzos.  Like in the long run will they inevitably increase serotonin / dopamine levels in the brain by shutting off anxiety, worries, ruminations which obviously deplete serotonin / dopamine ...

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1 hour ago, BrianOCD said:

Well that article seems to say it generally reduces serotonin and norepinephrine which I thought was the case.

But what I'm wondering is about the therapeutic effects of Benzos.  Like in the long run will they inevitably increase serotonin / dopamine levels in the brain by shutting off anxiety, worries, ruminations which obviously deplete serotonin / dopamine ...

I believe benzodiazepines do increase dopamine, and it has something to do with stimulation of the α1 subunit of the GABAA receptor, but I can't recall or find where I read this... I don't know about serotonin though...

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6 hours ago, BrianOCD said:

\Like in the long run will they inevitably increase serotonin / dopamine levels in the brain by shutting off anxiety, worries, ruminations which obviously deplete serotonin / dopamine ...

It doesn't really work like that.  

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On 10/24/2018 at 9:43 PM, BrianOCD said:

Well that article seems to say it generally reduces serotonin and norepinephrine which I thought was the case.

But what I'm wondering is about the therapeutic effects of Benzos.  Like in the long run will they inevitably increase serotonin / dopamine levels in the brain by shutting off anxiety, worries, ruminations which obviously deplete serotonin / dopamine ...

I am in no ways educated enough to talk about benzo's mechanism of action or anything like that, but I really don't think that's how benzos work. A lot of people aren't truly sure how a lot of psych drugs work. Try not to obsess about this "serotonin" deficiency, since it is probably not true at all. You must wait until your Cymbalta begins to work, and the only drugs that I know of that increase/release serotonin immediately are illicit ones.

Also I believe I read somewhere about Klonopin decreasing serotonin over time, while I think Xanax increased it? Again, I have no credentials to speak on this, so don't take that as fact or even slightly true. This is pure speculation.

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Benzos work primarily on GABA.  Just because the anxiety relief from benzos makes your depression better doesn't mean that serotonin has anything to do with it.  There's something like a dozen different chemical imbalances that can result in more or less the same experience of depression. 

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16 hours ago, Velvet Elvis said:

Benzos work primarily on GABA.  Just because the anxiety relief from benzos makes your depression better doesn't mean that serotonin has anything to do with it.  There's something like a dozen different chemical imbalances that can result in more or less the same experience of depression. 

I Understand what you're saying.

My question was does it indirectly help serotonin rebuild since anxiety, obsessions, etc....all tend to wear down serotonin in the long run.

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13 hours ago, BrianOCD said:

I Understand what you're saying.

My question was does it indirectly help serotonin rebuild since anxiety, obsessions, etc....all tend to wear down serotonin in the long run.

From what I have read, no. Some benzos such as Klonopin are known to decrease serotonin. A lot of benzos can actually cause depression. Although I do think if being on a benzo rids you of your anxiety/panic/obsessions, then yes, your serotonin levels MIGHT increase due to being happier. But that is just a guess, a highly uneducated one. For the most part, I wouldn't seek out benzos in hopes of it directly or indirectly increasing serotonin levels.

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14 hours ago, icygrave said:

From what I have read, no. Some benzos such as Klonopin are known to decrease serotonin. A lot of benzos can actually cause depression. Although I do think if being on a benzo rids you of your anxiety/panic/obsessions, then yes, your serotonin levels MIGHT increase due to being happier. But that is just a guess, a highly uneducated one. For the most part, I wouldn't seek out benzos in hopes of it directly or indirectly increasing serotonin levels.

Generally I've always felt better with Ativan...but the withdrawals....oh how I remember them....

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I've recently started to get breakthrough depression.  Wondering if my Ativan could be at fault (3mg/day, prn).  I'm trying to taper off of it now.  It's difficult.  I find myself using Benedryl to manage my anxiety... poorly.

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20 hours ago, Inanlae said:

I've recently started to get breakthrough depression.  Wondering if my Ativan could be at fault (3mg/day, prn).  I'm trying to taper off of it now.  It's difficult.  I find myself using Benedryl to manage my anxiety... poorly.

Benadryl is OK short term but in the long term it and many other anticholinergic drugs have been linked to dementia, so it is not a drug to take all the time.

https://www.health.harvard.edu/blog/common-anticholinergic-drugs-like-benadryl-linked-increased-dementia-risk-201501287667

"Common anticholinergic drugs like Benadryl linked to increased dementia risk. In a report published in JAMA Internal Medicine, researchers offers compelling evidence of a link between long-term use of anticholinergic medications like Benadryl and dementia. The ACT results add to mounting evidence that anticholinergics aren’t drugs to take long-term if you want to keep a clear head, and keep your head clear into old age. The body’s production of acetylcholine diminishes with age, so blocking its effects can deliver a double whammy to older people. It’s not surprising that problems with short-term memory, reasoning, and confusion lead the list of side effects of anticholinergic drugs, which also include drowsiness, dry mouth, urine retention, and constipation.

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I'm taking Ativan right now to give my mood a boost and relieve my severe anhedonia. That's all I'm getting from it, really. I get kind of a euphoria for 6 or so hours from .5 mg. Just got a panic attack from it today, I guess that's how it kicks in. Could someone with an understanding of pharmokinetics please explain how it's relieving the depression, as well as suggest some dedicated antidepressants (preferably as augments for nortriptyline) that do the same thing? 

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22 hours ago, Schlep said:

I'm taking Ativan right now to give my mood a boost and relieve my severe anhedonia. That's all I'm getting from it, really. I get kind of a euphoria for 6 or so hours from .5 mg. Just got a panic attack from it today, I guess that's how it kicks in. Could someone with an understanding of pharmokinetics please explain how it's relieving the depression, as well as suggest some dedicated antidepressants (preferably as augments for nortriptyline) that do the same thing? 

I'm getting pretty desperate myself, I have to go back to taking ATivan which I struggled and resisted against for the same reasons.  Anhedonia, mood, and stress.

I believe it does give a dopamine boost.

Edited by BrianOCD
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Yes, I believe low dopamine is my problem. Do you have links to any evidence verifying that Ativan boosts dopamine?

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12 hours ago, Schlep said:

Yes, I believe low dopamine is my problem. Do you have links to any evidence verifying that Ativan boosts dopamine?

This is a link about the addictive properties of benzos, but it does specifically mention their ability to increase dopaminergic firing, but I don't believe they increase dopamine levels.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871668/

Quote

Here we show that benzodiazepines increase firing of dopamine neurons of the ventral tegmental area through the positive modulation of GABAA recpetors in nearby interneurons. Such disinhibition, which relies on α1-containing GABAARs expressed in these cells, triggers drug-evoked synaptic plasticity in excitatory afferents onto dopamine neurons and underlies drug reinforcement.

Basically, by means of stimulating the benzodiazepine site of GABAA receptors containing α1 subunits, they increases dopaminergic firing. There are some benzos that have more and some with less binding to this subunit, so some produce more and some produce less effects caused by binding to this subunit (sedation, dependence, anticonvulsant activity, and amnesia).

Btw, I didn't post the link about addictive properties to deter anyone from benzo use, it was just the only link I could find that cited the mechanism of action that I was looking for.

Edited by mikl_pls
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1 hour ago, mikl_pls said:

Basically, by means of stimulating the benzodiazepine site of GABAA receptors containing α1 subunits, they increases dopaminergic firing. There are some benzos that have more and some with less binding to this subunit, so some produce more and some produce less effects caused by binding to this subunit (sedation, dependence, anticonvulsant activity, and amnesia).

Btw, I didn't post the link about addictive properties to deter anyone from benzo use, it was just the only link I could find that cited the mechanism of action that I was looking for.

Yes, but are there any antidepressents or augmentations that work similarly? 

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4 hours ago, Schlep said:

Yes, but are there any antidepressents or augmentations that work similarly? 

Not with the same mechanism of action as the benzos, but plenty that boost dopamine in other ways.

As far as antidepressants go, there are several options.

  • Wellbutrin is an NDRI (norepinephrine-dopamine reuptake inhibitor), which mainly works on dopamine I believe, while also being a nicotinic acetylcholine receptor antagonist for several receptors. It is a weak NDRI, but an NDRI nonetheless. It tends to exacerbate anxiety in those who have anxiety already, but in some people it may quell anxiety, particularly in those with ADHD symptoms.
  • Any antidepressant that has NRI (norepinephrine reuptake inhibition) qualities will also increase dopamine in the prefrontal cortex. This includes SNRIs, the tricyclics (especially the secondary amines, namely desipramine, nortriptyline, and protriptyline), the tetracyclics amoxapine and maprotiline, and the selective NRI, Strattera.
  • MAOIs nonselectively boost monoamine levels in the brain, including but not limited to dopamine by way of inhibiting the breakdown of neurotransmitters (inhibiting monoamine oxidase [MAO], the enzyme that breaks down these neurotransmitters).
  • Any antidepressant with 5-HT2A/2C antagonism may boost dopamine, including trazodone, nefazodone, mirtazapine, and some of the tricyclics/tetracyclics (amoxapine, but amoxapine has dopamine antagonism properties).
  • Trintellix/Viibryd are SSRIs + 5-HT1A agonists, which produce downstream dopamine release.
    • Trintellix, specifically, is also a 5-HTantagonist, which also yields dopamine release.
  • Zoloft (an SSRI) has affinity for the DAT (the dopamine transporter) as an inhibitor comparable to Ritalin, meaning it is also a dopamine reuptake inhibitor (DRI).
    • However, theoretically, the increase in serotonin can counteract the increase in dopamine.

As far as augmentations go, there are also many options.

  • Stimulants
    • Methylphenidate (Ritalin, Metadate, Concerta, etc.)/dexmethylphenidate (Focalin) is a potent NDRI. Methylphenidate preferentially boosts dopamine, while dexmethylphenidate is about 50/50 I believe.
    • Adderall (mixed amphetamine salts)/dextroamphetamine/Vyvanse/other amphetamine products are potent NDRAs (norepinephrine-dopamine releasing agents) and NDRIs. They work in a different mechanism of action than methylphenidate, but produce the same end result.
  • Atypical antipsychotics
    • Abilify/Rexulti/Vraylar
      • By means of dopamine Dpartial agonism, it is believed that in a hypodopaminergic state, it will behave as a dopamine agonist at these receptors (is one theory).
      • Vraylar specifically has more affinity for D3 receptors, which is believed to have a pro-cognitive effect.
    • The above AAPs, plus the rest of the AAPs...
      • 5-HT2A antagonism yields dopamine release
      • 5-HT2C antagonism yields dopamine and norepinephrine release
        • Abilify is a 5-HT2C partial agonist, except when administered alongside a serotonergic antidepressant, when it behaves as a 5-HT2C antagonist
      • 5-HT1A partial agonism yields downstream dopamine release
        • Some AAPs are actually 5-HT1A antagonists, but at low affinity.
        • Zyprexa and Risperdal come to the tip of the tongue... but I can't remember if any others are.
      • However, most other AAPs are dopamine antagonists, so would need to pick an antipsychotic with higher or equal affinity for 5-HT1A/5-HT2A than for D2.
  • BuSpar
    • An anti-anxiety agent used alone or alongside antidepressants.
    • 5-HT1A partial agonism yields downstream dopamine release.
    • Presynaptic D2 autoreceptor antagonism in lower doses yields dopamine disinhibition = more dopamine release.
  • Augment with other antidepressants
Edited by mikl_pls
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Thanks, I'm going to look this over. I was just editing my previous post with another question: Can you think of any kind of chemical imbalances that could effect a benzo so that it could cause (or contribute to) anxiety?

Also, what do you think of supplements that effect dopamine? Are they safe to take with nortriptyline and Ativan?

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