Psycho-Babble Medication Thread 1109960

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Re: 5 drugs better than ADs for bipolar disorder » Lamdage22

Posted by SLS on May 6, 2020, at 8:35:24

In reply to Re: 5 drugs better than ADs for bipolar disorder, posted by Lamdage22 on May 5, 2020, at 12:52:50

> Is really low dose Lamotrigine worth any shot? Like without cognitive side effects?

From what I have seen, it is unusual for someone to respond to less than 200 mg/day. It is logical to experiment and try taking 200-300 mg/day if you haven't already. See if you really do experience cognitive or memory impairments. I experienced memory problems during the first few weeks of treatment the first time I took Lamictal. You might want to keep this in mind.


- Scott

 

Re: 5 drugs better than ADs for bipolar disorder

Posted by Lamdage22 on May 6, 2020, at 10:01:19

In reply to Re: 5 drugs better than ADs for bipolar disorder » Hugh, posted by SLS on May 6, 2020, at 8:26:29

That is so awesome! Welcome back. I have taken Lamotrigine 200 in the past and I felt pretty stupid.

> I am currently taking Nardil 60 mg/day. It is helping. I have not felt this well since 1990.
>
> It took many weeks to recover from the exacerbation that Trintellix (vortioxetine) produced. It was excruciating.
>
> > Have SSRIs ever helped you?
>
> Not really. Maybe a little on Zoloft. I responded transiently to Effexor and Cymbalta.
>
> Currently:
>
> Nardil 60 mg/day
> Nortriptyline 100 mg/day
> Lamictal 300 mg/day
> Lithium 300 mg/day
>
>
> - Scott
>
>

 

Re: 5 drugs better than ADs for bipolar disorder » SLS

Posted by undopaminergic on May 6, 2020, at 10:46:14

In reply to Re: 5 drugs better than ADs for bipolar disorder » Hugh, posted by SLS on May 6, 2020, at 8:26:29

>
> I am currently taking Nardil 60 mg/day. It is helping. I have not felt this well since 1990.
>

Wow, that's amazing!

I have "only" been depressed since the end of 1999 myself, but I'm currently at my best for years. The "mood" disorder is gone, but I have residual symptoms in the form of apathy and cognitive impairment.

-undopaminergic

 

Re: 5 drugs better than ADs for bipolar disorder » undopaminergic

Posted by SLS on May 7, 2020, at 13:15:57

In reply to Re: 5 drugs better than ADs for bipolar disorder » SLS, posted by undopaminergic on May 6, 2020, at 10:46:14

> > I am currently taking Nardil 60 mg/day. It is helping. I have not felt this well since 1990.

>
> Wow, that's amazing!
>
> I have "only" been depressed since the end of 1999 myself, but I'm currently at my best for years. The "mood" disorder is gone

That's great!

> but I have residual symptoms in the form of apathy and cognitive impairment.

That sucks!

What are you taking that you feel is responsible for your remission?

It's early for me with Nardil. I hope it lasts. No guarantees, unfortunately.


- Scott

 

Re: 5 drugs better than ADs for bipolar disorder » SLS

Posted by undopaminergic on May 8, 2020, at 0:11:08

In reply to Re: 5 drugs better than ADs for bipolar disorder » undopaminergic, posted by SLS on May 7, 2020, at 13:15:57

>
> > but I have residual symptoms in the form of apathy and cognitive impairment.
>
> That sucks!
>
> What are you taking that you feel is responsible for your remission?
>

As far as I can tell, it may be due to trimipramine, but it seems to involve psychodynamic factors as well. Eg. as far as anxiety is concerned, it's the latter.

-undopaminergic

 

Re: 'safer' not 'better'?

Posted by linkadge on May 8, 2020, at 6:45:28

In reply to Re: 5 drugs better than ADs for bipolar disorder » SLS, posted by undopaminergic on May 8, 2020, at 0:11:08

I have some qualms with the notion that more mood stabilizer is the best option for bipolar depression. I feel that many psych patients are not treated as aggressively as they were in the past. The goal seems to be to 'stabilize' rather than restore.

Linkadge


 

Re: BPI and BPII very different

Posted by linkadge on May 8, 2020, at 6:49:53

In reply to Re: 5 drugs better than ADs for bipolar disorder » SLS, posted by undopaminergic on May 8, 2020, at 0:11:08

Another thing to mention is that, according to a recent (fairly large) genetic study, patients with BPII had more genetic overlap with MDD rather than BPI.

If this is the case, then the BP diagnosis could really be a hinderance to a proper recovery.

If I have 'BP' it is BPII. For me, mood stabilizers alone DO NOT WORK. If I got the BP diagnosis, I'm afraid I would be relegated to a treatment course that avoids antidepressants and/or stimulants.

Personally, I don't know how somebody would function on say lithium + olanzapine. I don't know how they would experience any pleasure at all. But, of course, we are all different.


Linkadge


 

Re: BPI and BPII very different

Posted by undopaminergic on May 8, 2020, at 7:30:35

In reply to Re: BPI and BPII very different, posted by linkadge on May 8, 2020, at 6:49:53

I agree that there is to much emphasis on stabilisation, as opposed to relief.

Also, the risk of a switch to mania from antidepressant treatment is exaggerated. I have never reacted that way, and I have BP 1.

Sure, memantine induced a condition more or less indistinguishable from mania, but that was only the acute effect of a drug, and it subsided promptly and completely upon discontinuation.

-undopaminergic

 

Re: BPI and BPII very different

Posted by linkadge on May 9, 2020, at 8:12:32

In reply to Re: BPI and BPII very different, posted by undopaminergic on May 8, 2020, at 7:30:35

Right, and doctors seem so afraid of making a 'mistake' that they undertreat and perhaps avoid effective treatments.

Examples of this include: not prescribing opiates for legitimate pain, not prescribing benzos (thinking that SSRIs are as effective for everybody), avoiding MAOIs, and treating bipolar depression by layering on more mood stabilizers.

Linkadge

 

Re: BPI and BPII very different

Posted by undopaminergic on May 9, 2020, at 9:57:32

In reply to Re: BPI and BPII very different, posted by linkadge on May 9, 2020, at 8:12:32

> Right, and doctors seem so afraid of making a 'mistake' that they undertreat and perhaps avoid effective treatments.
>
> Examples of this include: not prescribing opiates for legitimate pain, not prescribing benzos (thinking that SSRIs are as effective for everybody), avoiding MAOIs, and treating bipolar depression by layering on more mood stabilizers.
>
> Linkadge

That is all true, unfortunately. And for treatment-resistant conditions, doctors need to be willing to try all kinds of drugs, with or without an official indication for the condition. And not just follow official "guidelines", because *if* such treatments work, then the condition was not particularly "treatment-resistant" in the first place.

-undopaminergic

 

Re: 5 drugs better than ADs for bipolar disorder » SLS

Posted by Jadde on May 9, 2020, at 14:24:56

In reply to Re: 5 drugs better than ADs for bipolar disorder » Hugh, posted by SLS on May 6, 2020, at 8:26:29

> Hi.
>
> > Hi, sScott. I'm doing pretty well, considering. I hope you are, too.
> >
> > I know you've been helped by MAOIs.
>
> I am currently taking Nardil 60 mg/day. It is helping. I have not felt this well since 1990.
>
> It took many weeks to recover from the exacerbation that Trintellix (vortioxetine) produced. It was excruciating.
>
> > Have SSRIs ever helped you?
>
> Not really. Maybe a little on Zoloft. I responded transiently to Effexor and Cymbalta.
>
> Currently:
>
> Nardil 60 mg/day
> Nortriptyline 100 mg/day
> Lamictal 300 mg/day
> Lithium 300 mg/day
>
>
> - Scott
>
>

Hi Scott, I, too, am at 60mg of Nardil. Got down to 15mg with the intention of trialing Marplan, but was so miserable I had to go back to a full dose of Nardil. Strangely I had that one week of feeling great as soon as I increased back to 60mg. I was hoping it would last but it didnt. Guess Im going to wait it out again and see what comes. Anyway, so happy for you that you are feeling better.

Jade

 

Re: 'safer' not 'better'?

Posted by beckett2 on May 11, 2020, at 2:04:23

In reply to Re: 'safer' not 'better'?, posted by linkadge on May 8, 2020, at 6:45:28

> I have some qualms with the notion that more mood stabilizer is the best option for bipolar depression. I feel that many psych patients are not treated as aggressively as they were in the past. The goal seems to be to 'stabilize' rather than restore.
>
> Linkadge
>
>
>

For a number of years, my psychiatrist encouraged me to consider an AD. (My BPll depression was entrenched and monolithic.)

I refused and hewed to the opinion that, given time, Lamictal would be enough. Well, that did not happen, and so I tried Lexapro, and together with the Lamictal, the lights went on for the first time in maybe 8+ years.

Further contraindicated by some experts, a little Adderall was added. I haven't, knock on wood while there is still some available, been hypo.

 

Re: 'safer' not 'better'?

Posted by linkadge on May 12, 2020, at 7:01:53

In reply to Re: 'safer' not 'better'?, posted by beckett2 on May 11, 2020, at 2:04:23

The problem is that the genetic load of say bipolar vs. unipolar is not categorical. It is along a continuum.

Therefore saying categorically, that antidepressants should be avoided in 'bipolar' is not useful. Future research would look to uncover which of dozens (or hundreds) of genes influence the response to one drug or another.

I.e. you would need a subgroup analysis of 'bipolars' to see which respond to antidepressants. There are some studies that show that (at least for some bipolars) antidepressants can acts as mood stabilizers. I recall one head to head study of venlafaxine vs. lithium in bipolar II showed that venlafaxine was more effective and didn't lead to instability.

Linkadge

 

Re: 'safer' not 'better'?

Posted by undopaminergic on May 12, 2020, at 9:07:59

In reply to Re: 'safer' not 'better'?, posted by linkadge on May 12, 2020, at 7:01:53

>
> I.e. you would need a subgroup analysis of 'bipolars' to see which respond to antidepressants. There are some studies that show that (at least for some bipolars) antidepressants can acts as mood stabilizers.
>

Yeah, sertraline was powerfully anti-manic for me. Even just a 50 mg dose turned out to be a bit too much.

Stimulants can also be stabilising. To an important degree, they seem to reduce my risk of screwing up. I remain in self-control.

-undopaminergic

 

Re: 'safer' not 'better'? » undopaminergic

Posted by linkadge on May 12, 2020, at 11:38:55

In reply to Re: 'safer' not 'better'?, posted by undopaminergic on May 12, 2020, at 9:07:59

The SSRIs can enhance allopregnanolone (which increases GABA-a sensitivity) - perhaps providing mood stabilization.

When I take (low dose) Effexor, it 'stabilizes' me, but I end up quitting it because I just feel nothing at all.

Linkadge

 

Re: 'safer' not 'better'?

Posted by undopaminergic on May 12, 2020, at 11:59:18

In reply to Re: 'safer' not 'better'? » undopaminergic, posted by linkadge on May 12, 2020, at 11:38:55

> The SSRIs can enhance allopregnanolone (which increases GABA-a sensitivity) - perhaps providing mood stabilization.
>

I think it was the increased agonism at 5-HT2C receptors.

I don't necessarily think it was a mood-"stabilising" effect, rather than just "anti-manic". But at least it's no worse than anti-psychotics.

> When I take (low dose) Effexor, it 'stabilizes' me, but I end up quitting it because I just feel nothing at all.
>

I have that problem (feeling nothing) but I connect this with depersonalisation, which was aggravated permanently by reboxetine.

-undopaminergic

 

Re: 'safer' not 'better'?

Posted by SLS on May 12, 2020, at 21:00:29

In reply to Re: 'safer' not 'better'?, posted by undopaminergic on May 12, 2020, at 11:59:18

> > The SSRIs can enhance allopregnanolone (which increases GABA-a sensitivity) - perhaps providing mood stabilization.

That's very interesting. I think zuranolone is an analogue of allopregnanolone. It also increases GABA-A receptor sensitivity (positive allosteric modulator). I look forward to seeing more investigations of zuranolone for depression and bipolar depression.


- Scott

 

Re: 'safer' not 'better'? » SLS

Posted by linkadge on May 13, 2020, at 7:52:51

In reply to Re: 'safer' not 'better'?, posted by SLS on May 12, 2020, at 21:00:29

There seems to be evidence that gaba-a dysregulation is present in post-partum depression (and perhaps anxious, melancholic depression). However, only certain gaba subtypes are associated with mood regulation (as opposed to anticonvulsant, amnesic, muscle relaxant, and anxiolytic effects).

Reading up on CBD (also a positive allosteric modulator of GABA-a) it seems to increase the effects of the two gaba-a subtypes that are dysregulated in bipolar. I don't remember these off hand, but I believe one of them was the gamma subtype.

Some depression, however, is likely associated with a predominance of gaba (relative to glutamate). Gaba antagonists are generally considered 'stimulant' and 'pro-cognitive' (and there appears to be a gaba excess in certain disorders like Alzheimer's. Of course, too much gaba antagonism and you have a seizure.

Linkadge

 

Re: 'safer' not 'better'? » linkadge

Posted by SLS on May 13, 2020, at 18:43:08

In reply to Re: 'safer' not 'better'? » SLS, posted by linkadge on May 13, 2020, at 7:52:51

Wow, Linkadge! Great work. I like how much you are able to say in so few words. Very concise and efficient. Have you ever considered writing? I didn't know there were subtypes of the GABA-A receptor. Makes sense. How many are there?

Are you still feeling better?


- Scott

> There seems to be evidence that gaba-a dysregulation is present in post-partum depression (and perhaps anxious, melancholic depression). However, only certain gaba subtypes are associated with mood regulation (as opposed to anticonvulsant, amnesic, muscle relaxant, and anxiolytic effects).
>
> Reading up on CBD (also a positive allosteric modulator of GABA-a) it seems to increase the effects of the two gaba-a subtypes that are dysregulated in bipolar. I don't remember these off hand, but I believe one of them was the gamma subtype.
>
> Some depression, however, is likely associated with a predominance of gaba (relative to glutamate). Gaba antagonists are generally considered 'stimulant' and 'pro-cognitive' (and there appears to be a gaba excess in certain disorders like Alzheimer's. Of course, too much gaba antagonism and you have a seizure.
>
> Linkadge
>
>

 

Re: 'safer' not 'better'? » linkadge

Posted by SLS on May 13, 2020, at 21:05:14

In reply to Re: 'safer' not 'better'? » SLS, posted by linkadge on May 13, 2020, at 7:52:51

My first reaction to learning of the actions of zuranolone and brexanolone was to wonder if increasing GABA-A might quell the overactivity in the lateral habenula or the ventral tegmental area observed in depression. However, I found this:

https://stm.sciencemag.org/content/6/234/234ec76

https://science.sciencemag.org/content/344/6181/313.abstract?_ga=2.171616032.1625245966.1589419290-1749848103.1589419290


- Scott

 

Re: 'safer' not 'better'? » SLS

Posted by undopaminergic on May 14, 2020, at 2:31:46

In reply to Re: 'safer' not 'better'? » linkadge, posted by SLS on May 13, 2020, at 18:43:08

> Wow, Linkadge! Great work. I like how much you are able to say in so few words. Very concise and efficient. Have you ever considered writing? I didn't know there were subtypes of the GABA-A receptor.
>

Usually they are called "subunits". A single GABA-A receptor has multiple types of subunits. Meanwhile, GABA-A and -B are sub*types*. Furthermore, GABA-A is ionotropic, namely chloride ion channels, whereas GABA-B is metabotropic, that is acting via an intracellular "second messenger" molecule.

-undopaminergic

 

Re: 'safer' not 'better'? » SLS

Posted by undopaminergic on May 14, 2020, at 2:50:02

In reply to Re: 'safer' not 'better'? » linkadge, posted by SLS on May 13, 2020, at 21:05:14

> My first reaction to learning of the actions of zuranolone and brexanolone was to wonder if increasing GABA-A might quell the overactivity in the lateral habenula or the ventral tegmental area observed in depression. However, I found this:
>
> https://stm.sciencemag.org/content/6/234/234ec76
>
> https://science.sciencemag.org/content/344/6181/313.abstract?_ga=2.171616032.1625245966.1589419290-1749848103.1589419290
>

The part about hyperexcitable dopamine neurons in depression sounds confusing and hard to believe, because dopaminergic stimulants *ameliorate* depression and they *boost* the effects of VTA activity in the nucleus accumbens, and they helps against apathy.

On a slightly other note, this article seems to be about a mouse model of depression, which is hardly the same syndrome as in human depression.

-undopaminergic

 

Re: 'safer' not 'better'? » undopaminergic

Posted by linkadge on May 14, 2020, at 9:27:00

In reply to Re: 'safer' not 'better'? » SLS, posted by undopaminergic on May 14, 2020, at 2:31:46

>Usually they are called "subunits".

Pardon my lack of distinction. When I read medical abstracts I'm typically more concerned about the functional relevance and utility of the distinctions rather than specific definitions and classifications. I am desperate for some nugget of information that might make my life slightly more tolerable, but I rarely care about getting the exact terminology.

I have mainly read about this in reference to the differences in actions of various benzodiazepines or non-benzodiazepine sedatives. For example, some benzos have more anticonvulsant while others may be more amnesic, or sedative etc.

There has always been a 'gaba theory' of depression. However, the relative lack of antidepressant effect of benzodiazepines, barbiturates etc. has lead to some abandonment of the theory. However, the discrepancy might be in the non-specificity of these drugs towards gaba receptors. Some subtypes (or locations) might be pro-depressant, while others are antidepressant.

Many hormones act to increase or decrease GABA function. I believe progesterone is a positive modulator of GABA-a whereas DHEA is negative. This could, in part, explain the calming vs. stimulating qualities of the two compounds.


 

Re: 'safer' not 'better'?

Posted by linkadge on May 14, 2020, at 9:38:51

In reply to Re: 'safer' not 'better'? » SLS, posted by undopaminergic on May 14, 2020, at 2:50:02

>The part about hyperexcitable dopamine neurons in >depression sounds confusing and hard to believe, >because dopaminergic stimulants *ameliorate* >depression and they *boost* the effects of VTA >activity in the nucleus accumbens, and they helps >against apathy.

I have read that the firing patterns are important to the antidepressant effects of certain compounds. I.e. a lack of 'burst firing' being associated with depression. It may be dependant on the type of depression. In some instancess 5-ht2c antagonists (which increase burst firing) are antidepressant. In other cases 5-ht2c agonists are antidepressant (and anti-OCD). Likewise, some depression is associated with prefrontal dopamine hyperfunction and some with hypofunction.

Overactivation of the reward system can paradoxically produce depression. In mouse models, chronic stress is associated with a loss of inhibitory GABAergic function in the NAc. Restoring this inhibition of dopamine can reduce depression. It could be that in response to the pain of stress, the brain tries to offset this with increased reward.

I've been through many stressful times where I get reward from the thoughts associated with 'getting through the stress'. I.e. "things are going to be so much better once this is over". However, often when the stress is over, there is, in fact, no reward. The reward system is just activating to get me through a difficult time. One it's over it comes back down and tires to recalibrate towards new goals or rewards.

 

Re: 'safer' not 'better'?

Posted by undopaminergic on May 14, 2020, at 12:11:59

In reply to Re: 'safer' not 'better'? » undopaminergic, posted by linkadge on May 14, 2020, at 9:27:00

> >Usually they are called "subunits".
>
> Pardon my lack of distinction. When I read medical abstracts I'm typically more concerned about the functional relevance and utility of the distinctions rather than specific definitions and classifications.
>

Of course.

> I am desperate for some nugget of information that might make my life slightly more tolerable, but I rarely care about getting the exact terminology.
>

I find that I pick up on the terminology pretty easily, although I may not remember it for long.

> I have mainly read about this in reference to the differences in actions of various benzodiazepines or non-benzodiazepine sedatives. For example, some benzos have more anticonvulsant while others may be more amnesic, or sedative etc.
>

I did a lot of reading on Wikipedia, including the article about the receptor and a multitude of drugs that interact with them. Some were pretty interesting.

> There has always been a 'gaba theory' of depression.

I haven't heard of it. Anyway, that could cut both ways -- too much or too little GABA.

NMDA glutamate receptor antagonists, such as ketamine and memantine, tilt the balance in favour of GABA (and dopamine).

-undopaminergic


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