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Harvey, 2003 Neurobiology of antidepressant withdrawal


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#37 Henosis

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Posted 07 October 2016 - 06:35 PM

these journal articles both show that AD withdrawal partially caused by overexpression of NMDA receptors. Sure, it is light, and animal models, but would certainly explain if some people are getting help from NMDA antagonists like ketamine infusion, which I've been considering despite the expense.


https://www.ncbi.nlm...4625154/related

https://www.ncbi.nlm...ubmed/14625154/

Medication before problems: Took Paxil 60-100mg from 2003 to 2014 for OCD.
1) Last pill taken November 2014, horrendous withdrawal started six weeks later.

2) Re-instated successfully @ 20mg May 2015, but accompanied by severe anhedonia, loss of emotion, apathy, and fatigue

3) Switched to Prozac, Viibyrd, Zoloft, Nefazadone, Cymbalta, Nardil in attempt at abating WD symptoms while not re-introducing anhedonia. Each one either failed to relieve WD or brought back anhedonia (the serotonergic ones)

4) Re-stabilized on Paxil at 15mg

5) Tried augmenting Wellbutrin (only increased anxiety), Vyvanse/Adderall (works for anhedonia, but the crash is brutal) low-dose Zyprexa (bad rxn), low-dose abilify (no effect), cyproheptadine (precipitated withdrawal), mirtazapine (knocked me out), Tianpetine (no effect) in attempt at relieving anhedonia through boosting dopamine directly or indirectly through targeted serotonin receptor blockade)

6) Tapered down to 7.5mg as of October 2016. More energy, anhedonia/loss of emotions remains apart from short windows.

7) Attempted Nortriptaline to paxil trapper to boost motivation and reduce anhedonia (it acts like an NRI, with target serotonin blockade at the "bad" receptors)

8) Stopped Nortriptaline after increased anxiety, no effect on anhedonia, and increased withdrawal symptoms. Only positive was alleviating ADHD symptoms.

9) May 2017 - down to 3.5mg of Paxil (no other meds)

 


#38 Bobo32

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Posted 05 May 2017 - 02:29 AM

Dr. Harvey sent me this in correspondence:

I am very glad to see you are recovering from your own nasty experience. I find it especially interesting that you are showing this recovery using lamotrigine, which is a very effective inhibitor of glutamate release. Our studies have strongly implicated altered glutamatergic activity following antidepressant discontinuation/withdrawal, with especially overt activity at NMDA receptors acting to perpetuate the illness via a kindling-like action. One could even consider this to be a useful case report in support of the argument.


Hey alto,
I read what Dr. harvey said about glutamate dysregulation and how it could be the factor in withdrawal syndrome.
I am now 3 months into withdrawal and I improved in many ways except for tinnitus and pssd which manifests as soft glans syndrome. What do you think I should do? Is iamotrigine the answer ?
Thank you in advance for your help

2004-2007 paxil

2015- zoloft 3 months zyprexa 3 months lexapro 3 months xanax

Med free since Feb 28th 2017

Mostly experiencing PSSD - soft glans and difficulty maintaining erection

 


#39 Jennifer78

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Posted 17 May 2017 - 07:49 AM

This paper describes the neurological activity that leads to withdrawal syndrome. The authors conclude:

The distress that potentially accompanies antidepressant withdrawal has not always been sufficiently appreciated. As alluded to earlier, missed doses, abrupt dose reduction, or abrupt discontinuation of some antidepressants may be associated with an antidepressant discontinuation syndrome. Although the severity of withdrawal symptoms may vary with the type of antidepressant and between patients, all too often not enough emphasis is placed on the possible neurobiological effects and possible longer-term risks associated with inappropriate withdrawal or discontinuation.

As emphasized here, antidepressant discontinuation may involve a stress response accompanied by a set of specific biochemical responses that cause further neuronal dysfunction and that may compromise long-term outcome. This is not to say that clinicians should continue antidepressants indefinitely; it is, however, to emphasize that the decision to discontinue antidepressants should be made judiciously and on an individualized basis.


Biol Psychiatry. 2003 Nov 15;54(10):1105-17.
Neurobiology of antidepressant withdrawal: implications for the longitudinal outcome of depression.
Harvey BH, McEwen BS, Stein DJ.


Source

Division of Pharmacology, School of Pharmacy, Potchefstroom University for Christian Higher Education, Potchefstroom, South Africa.

Abstract at http://www.ncbi.nlm....thdrawal harvey Full text here.

Inappropriate discontinuation of drug treatment and noncompliance are a leading cause of long-term morbidity during treatment of depression. Increasing evidence supports an association between depressive illness and disturbances in brain glutamate activity, nitric oxide synthesis, and gamma-amino butyric acid. Animal models also confirm that suppression of glutamate N-methyl-D-aspartate receptor activity or inhibition of the nitric oxide-cyclic guanosine monophosphate pathway, as well as increasing brain levels of gamma-amino butyric acid, may be key elements in antidepressant action. Imaging studies demonstrate, for the most part, decreased hippocampal volume in patients with depression, which may worsen with recurrent depressive episodes. Preclinical models link this potentially neurodegenerative pathology to continued stress-evoked synaptic remodeling, driven primarily by the release of glucocorticoids, glutamate, and nitric oxide. These stress-induced structural changes can be reversed by antidepressant treatment. In patients with depression, antidepressant withdrawal after chronic administration is associated with a stress response as well as functional and neurochemical changes. Preclinical data also show that antidepressant withdrawal evokes a behavioral stress response that is associated with increased hippocampal N-methyl-D-aspartate receptor density, with both responses dependent on N-methyl-D-aspartate receptor activation. Drawing from both clinical and preclinical studies, this article proposes a preliminary molecular perspective and hypothesis on the neuronal implications of adherence to and discontinuation of antidepressant medication.


I'm confused about this article. So do we heal from cold turkey or not? What's the point in going off meds if it's only going to make us worse in the long run?
Celexa 40mg stopped taking it 12-01-16
Abilify 10mg stopped 12-01-16
Wellbutrin XL currently taking
I have been on some type of meds for 15 years

#40 Altostrata

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Posted 24 May 2017 - 10:16 PM

 

Dr. Harvey sent me this in correspondence:
 

I am very glad to see you are recovering from your own nasty experience. I find it especially interesting that you are showing this recovery using lamotrigine, which is a very effective inhibitor of glutamate release. Our studies have strongly implicated altered glutamatergic activity following antidepressant discontinuation/withdrawal, with especially overt activity at NMDA receptors acting to perpetuate the illness via a kindling-like action. One could even consider this to be a useful case report in support of the argument.


Hey alto,
I read what Dr. harvey said about glutamate dysregulation and how it could be the factor in withdrawal syndrome.
I am now 3 months into withdrawal and I improved in many ways except for tinnitus and pssd which manifests as soft glans syndrome. What do you think I should do? Is iamotrigine the answer ?
Thank you in advance for your help

 

 

Bobo, you've improved after 3 months, that's a very promising rate of healing. It may take somewhat longer for all the symptoms to go away. We don't know of any definite way to cure those symptoms. Please let us know how you're doing in your Intro topic.

 

Jennifer -- This paper describes what might happen after inappropriate discontinuation

 

We know it's not good for your nervous system to go off psychiatric drugs suddenly. This paper describes why the potential neurological results might be. The research did not investigate the process of healing from this.


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#41 Bobo32

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Posted 25 May 2017 - 01:43 AM

alto still having the 

 

 

 

Dr. Harvey sent me this in correspondence:
 

I am very glad to see you are recovering from your own nasty experience. I find it especially interesting that you are showing this recovery using lamotrigine, which is a very effective inhibitor of glutamate release. Our studies have strongly implicated altered glutamatergic activity following antidepressant discontinuation/withdrawal, with especially overt activity at NMDA receptors acting to perpetuate the illness via a kindling-like action. One could even consider this to be a useful case report in support of the argument.


Hey alto,
I read what Dr. harvey said about glutamate dysregulation and how it could be the factor in withdrawal syndrome.
I am now 3 months into withdrawal and I improved in many ways except for tinnitus and pssd which manifests as soft glans syndrome. What do you think I should do? Is iamotrigine the answer ?
Thank you in advance for your help

 

 

Bobo, you've improved after 3 months, that's a very promising rate of healing. It may take somewhat longer for all the symptoms to go away. We don't know of any definite way to cure those symptoms. Please let us know how you're doing in your Intro topic.

 

Alto, is it possible that neuronal damage due to SSRIs is the reason for soft glans and PSSD? I dont know what to do for this symptom. Should I reinitiate and withdraw differently? I cut the lexapro pill in bits when I quit. Is it the reason I have this? 


2004-2007 paxil

2015- zoloft 3 months zyprexa 3 months lexapro 3 months xanax

Med free since Feb 28th 2017

Mostly experiencing PSSD - soft glans and difficulty maintaining erection

 


#42 Jennifer78

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Posted 25 May 2017 - 06:27 AM


 
Jennifer -- This paper describes what might happen after [color=#b22222]inappropriate discontinuation[/color

I did a cold turkey. So am I not going to recover mentally?
Celexa 40mg stopped taking it 12-01-16
Abilify 10mg stopped 12-01-16
Wellbutrin XL currently taking
I have been on some type of meds for 15 years