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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 20 of 20. This is the beginning of the thread.
Posted by satsumas on May 30, 2008, at 13:42:55
Hi friends,
I'm currently taking 300 effexor and am having a terrible time with the apathy, anhedonia, amotivation. Understand that mirapex, and other pro-dop. drugs can help, and i'm currently a few days into a Mirapex trial.
But it seems that there is also research that supports the idea of using low dose antipsychotics like Seroquel or Zyprexa to augment SSRI. Does anyone have experience with adding one of these drugs to their S/NRI, specifically, it's effects on apathy, amotivation, anhedonia, and the perception of having more/less "free will"?
And don't these drugs antagonize dopamine receptors as opposed to mirapex and other stimulants which are pro-DA? So what's the right strategy?
Posted by kieran2585 on May 30, 2008, at 14:06:02
In reply to Mirapex vs. Seroquel for SSRI-induced anhedonia, posted by satsumas on May 30, 2008, at 13:42:55
> Hi friends,
>
> I'm currently taking 300 effexor and am having a terrible time with the apathy, anhedonia, amotivation. Understand that mirapex, and other pro-dop. drugs can help, and i'm currently a few days into a Mirapex trial.
>
> But it seems that there is also research that supports the idea of using low dose antipsychotics like Seroquel or Zyprexa to augment SSRI. Does anyone have experience with adding one of these drugs to their S/NRI, specifically, it's effects on apathy, amotivation, anhedonia, and the perception of having more/less "free will"?
>
> And don't these drugs antagonize dopamine receptors as opposed to mirapex and other stimulants which are pro-DA? So what's the right strategy?i think that stimulation of the 5ht2a/c receptors is what causes ssri induced apathy, zyprexa blocks these receptors increasing cortical dopamine which should help with the apathy you are experiencing, the d2 antagonism is only active for a few hourse after taking a dose, usually while you are asleep, so i wouldnt worry about that too much
Posted by satsumas on May 30, 2008, at 14:42:51
In reply to Re: Mirapex vs. Seroquel for SSRI-induced anhedonia, posted by kieran2585 on May 30, 2008, at 14:06:02
thanks! is zyprexa the best drug for antagonizing that receptor? or are there others that work as well/better?
Posted by linkadge on May 30, 2008, at 16:32:11
In reply to Re: Mirapex vs. Seroquel for SSRI-induced anhedoni, posted by satsumas on May 30, 2008, at 14:42:51
>i think that stimulation of the 5ht2a/c >receptors is what causes ssri induced apathy, >zyprexa blocks these receptors increasing >cortical dopamine which should help with the >apathy you are experiencing, the d2 antagonism >is only active for a few hourse after taking a >dose, usually while you are asleep, so i wouldnt >worry about that too much
If you are referring to loose dissociation (or whatever) of the antipsychotic I don't think this has ever been demonstrated with zyprexa. Seroquel is supposedly better for this but I don't know.
The point is that the drug is going to antagonize 5-ht2a/c for as long as it will antagonize the dopamine receptors.
It is true that the 5-ht2a/c antagonism of zyprexa/seroquel will increase dopamine/norepinephrine release in certain areas of the brain, but a certain degree of that neurotransmitter is going to be blocked by the drug. Zyprexa has a long half life so you are still going to get dopamine antagonism during the day.
For SSRI anhedonia, I would not really recomend an AP at all. They can augment SSRI's for depression, but I don't think there is much research showing they improve anhedonia.
I'd first start by lowering the dose of the SSRI to the absolute lowest efective dose. Then perhaps augment with mirapex, mirtazapine, TCA, bupropion, folic acid, omega 3, etc.
I'd stay away from AP's, they're not worth the risks, unless you really need them.
Linkadge
Posted by satsumas on May 30, 2008, at 17:42:56
In reply to Re: Mirapex vs. Seroquel for SSRI-induced anhedoni, posted by linkadge on May 30, 2008, at 16:32:11
thanks, very helpful! from the research i did, it looks like remeron also possesses 5-ht2a/c antagonism, so it looks like that could be a possibility as well. i tried focalin with cymbalta last year, and it just sped me up and probably did improve motivation, but I felt like it wasn't "quite right" and didn't help me CHOOSE the right things to focus on...it just made me focus intensely on whatever i happened to be looking at.
it was like, "right chemical, wrong part of the brain".
Posted by linkadge on May 30, 2008, at 17:50:07
In reply to Re: Mirapex vs. Seroquel for SSRI-induced anhedoni » linkadge, posted by satsumas on May 30, 2008, at 17:42:56
Yes, unfortunately drugs are dirty somtimes. Somtimes the more drugs you take the less the brain behaves like it naturally might. Whenever you push it in one way (ying) somtimes it compromises the yang.
Anyhow, mirtazapine might be an option. I'd personally recomend trying mirapex first, since (if you are taking mirtazapine with cymbalta) that might be a bit too activating.
Remeron has a noradrenergic effect which can amplify that of cymbalta.
Take care,
Linkadge
Posted by satsumas on May 30, 2008, at 17:52:40
In reply to Re: Mirapex vs. Seroquel for SSRI-induced anhedoni, posted by linkadge on May 30, 2008, at 17:50:07
thanks...i'ma ctually on effexor 300 plus 0.5 3x daily mirapex. been trying mirapex for 5 days now, don't notice much except for sleepyness after I take it, but that seems to be gradually going away.
do you have any advice on the therapeutic dose? i do agree with you regarding the SSRI being as low as possible...i think once I give the mirapex a try at the right dose, i'm going to try tapering off effexor to as low of a dose as i can manage.
Posted by linkadge on May 30, 2008, at 18:02:33
In reply to Re: Mirapex vs. Seroquel for SSRI-induced anhedoni » linkadge, posted by satsumas on May 30, 2008, at 17:52:40
You might notice that the mirapex operates better on lower doses of effexor. Lower doses of effexor may allow mirapex to produce a more meaninful modulation of dopamine. SSRI's/SNRI's can squelch dopamine release.
Linkadge
Posted by satsumas on May 30, 2008, at 18:09:42
In reply to Re: Mirapex vs. Seroquel for SSRI-induced anhedoni, posted by linkadge on May 30, 2008, at 18:02:33
hmm good suggestion. though i thought mirapex as an agonist was essentially replacing dopamine.
you seem to know a lot about this stuff....have you ever used DL-phenylalanine to pump up dopamine? did it work?
Posted by linkadge on May 30, 2008, at 18:20:18
In reply to Re: Mirapex vs. Seroquel for SSRI-induced anhedoni » linkadge, posted by satsumas on May 30, 2008, at 18:09:42
Well mirapex works as a post synaptic and presynaptic dopamine receptor agonist. After prolonged administration of mirapex, the drug may can desensitize the inhibitory autoreceptor which can promote the release of dopamine.
I personally don't think the use of phenylalanine or tyrosine are all that great idea. The amino acid l-dopa is used in parkinsons to enhance dopamine synthesis but it actually worsens parkinsons over time by some sort of excitotoxic or pro-oxidant mechanism, ie it ends up killing off dopamine cells. This might happen with other dopamine precursors. High protein foods are probably better idea.
Aerobic exercise has also been down to increase the density and sensitivity of dopamine receptors. Supplements that enhance GDNF like vitamin D and omega-3 can also work to do the same thing. Nicotine also increases the expression of d3 receptors (its one of the only abusable drugs that appears to increase reward sensitivity over time). Thats entering theoretical grounds (and nicotine might not be good with effexor - on account of BP issues), but who knows.
Linkadge
Posted by satsumas on May 30, 2008, at 18:29:22
In reply to Re: Mirapex vs. Seroquel for SSRI-induced anhedoni, posted by linkadge on May 30, 2008, at 18:20:18
thanks...strange because i started smoking again last week after coming back up on to effexor (after experiencing 4 weeks of suicidal depression after coming off of emsam)...cravings for cigarettes went through the roof and i gave into them. now i'm half a pack a day :(
on emsam (which i was on before the effexor) i felt I had way more "free will", wasn't as addicted to the internet, and cigarettes were not rewarding at all (actually quit before the emsam, but tried smoking a few times and threw away the rest of the pack).
basically, the strategy in trying mirapex on top of effexor is to replicate the good parts of emsam (the pro-DA aspects) without feeling the incredible anxiety and obsessive thoughts I felt while on it (guess it didn't do much for serotonin).
also thinking about trying tianeptine instead of effexor, perhaps with mirapex. just can't stand how effexor makes me so emotionally blunted and affectless. sometimes i wonder if i should just go cold turkey on all ADs.
thanks again for your kind and helpful responses.
Posted by linkadge on May 30, 2008, at 18:56:06
In reply to Re: Mirapex vs. Seroquel for SSRI-induced anhedoni » linkadge, posted by satsumas on May 30, 2008, at 18:29:22
>thanks...strange because i started smoking again >last week after coming back up on to effexor
>(after experiencing 4 weeks of suicidal >depression after coming off of emsam)...cravings >for cigarettes went through the roof and i gave >into them. now i'm half a pack a day :(Some studies have shown SSRI's / SNRI's can increase cigarette cravings. Perhaps the brain is seeking to restore the release of dopamine squelched by the AD.
>on emsam (which i was on before the effexor) i >felt I had way more "free will", wasn't as >addicted to the internet, and cigarettes were >not rewarding at all (actually quit before the >emsam, but tried smoking a few times and threw >away the rest of the pack).
Hmm. Perhaps the selegiline has some sort of antiaddictive properties. I think it raises GDNF, which like ibogaine can help reduce cravings.
>basically, the strategy in trying mirapex on top >of effexor is to replicate the good parts of >emsam (the pro-DA aspects) without feeling the >incredible anxiety and obsessive thoughts I felt >while on it (guess it didn't do much for >serotonin).
That sounds reasonable.
>also thinking about trying tianeptine instead of >effexor, perhaps with mirapex. just can't stand >how effexor makes me so emotionally blunted and >affectless. sometimes i wonder if i should just >go cold turkey on all ADs.
Thats an option. I don't know how it will fair with the OCD, but its worth a try. Somtimes a drug holliday can really help. It doesn't mean you need to stay permantnly off meds, but somtimes a washout can re-reveal the problems which need to be adressed.
Certain supplements too allow people to get by with less medication.
Linakdge
Posted by Phillipa on May 30, 2008, at 23:56:33
In reply to Re: Mirapex vs. Seroquel for SSRI-induced anhedoni, posted by linkadge on May 30, 2008, at 17:50:07
Link so remeron and cymbalta would be more powerful than effexor and remeron the California Rocket Fuel. Now we need a new name for this combo. Phillipa
Posted by bulldog2 on May 31, 2008, at 15:44:36
In reply to Mirapex vs. Seroquel for SSRI-induced anhedonia, posted by satsumas on May 30, 2008, at 13:42:55
> Hi friends,
>
> I'm currently taking 300 effexor and am having a terrible time with the apathy, anhedonia, amotivation. Understand that mirapex, and other pro-dop. drugs can help, and i'm currently a few days into a Mirapex trial.
>
> But it seems that there is also research that supports the idea of using low dose antipsychotics like Seroquel or Zyprexa to augment SSRI. Does anyone have experience with adding one of these drugs to their S/NRI, specifically, it's effects on apathy, amotivation, anhedonia, and the perception of having more/less "free will"?
>
> And don't these drugs antagonize dopamine receptors as opposed to mirapex and other stimulants which are pro-DA? So what's the right strategy?Some do well with a stimulant such as adderall or ritalin. Some seem to like the new time released formulation of adderall which is called vyvanse.
Posted by bleauberry on May 31, 2008, at 20:25:55
In reply to Mirapex vs. Seroquel for SSRI-induced anhedonia, posted by satsumas on May 30, 2008, at 13:42:55
The mechanisms are not fully understood, but either a dopamine agonist or a dopamine antagonist can improve ssri apathy. Obviously mileage varies and what works for one is different than someone else. While it makes sense from an armchair that blocking dopamine receptors would worsen apathy, it isn't that simple or understood. My prozac apathy was improved about 70% when I added 5mg zyprexa.
I agree with Link that APs should be reserved for later trials, try other things first. Since you are already into mirapex, stay with that for a month or two. But if you come to a point where you are thinking of an AP, I personally would opt for zyprexa or abilify. Seroquel is just too much of an elephant dart for many of us.
Posted by satsumas on May 31, 2008, at 20:33:38
In reply to Re: Mirapex vs. Seroquel for SSRI-induced anhedonia, posted by bleauberry on May 31, 2008, at 20:25:55
thanks, bleu. did you have any side effects from sucha low dose of zyprexa? i'm guessing it's because it's affects at the 5-ht2a receptor are more prominant, and only at a higher dose does it antagonize dopamine receptors.
Posted by linkadge on June 3, 2008, at 10:14:37
In reply to Re: Mirapex vs. Seroquel for SSRI-induced anhedoni » bleauberry, posted by satsumas on May 31, 2008, at 20:33:38
As an atypical, zyprexa will block 5-ht2a/c receptors a little more strongly than dopamine receptors. It will antagonize dopamine receptors at any dose however. At lower doses this may or may not be prominent. Most people augment with as little as 2.5mg but many people still notice dopamine related
side effects at this dose.Metabolically, Zyprexa is bad news though. Lilly just paid a huge settlement for downplaying these side effects and pushing the drug for non-approved uses. The drug is diabetogenic. Even in the absence of significant weight gain it can still damage pancreatic cells which can lead to more problems long term.
Linkadge
Posted by undopaminergic on June 5, 2008, at 15:45:34
In reply to Re: Mirapex vs. Seroquel for SSRI-induced anhedoni » linkadge, posted by satsumas on May 30, 2008, at 18:29:22
> thanks...strange because i started smoking again last week after coming back up on to effexor (after experiencing 4 weeks of suicidal depression after coming off of emsam)...cravings for cigarettes went through the roof and i gave into them. now i'm half a pack a day :(
>Have you considered replacing the cigarettes with nicotine chewing gum? I've never been a smoker, but lately I've been trying out 2 mg nicotine gum with a fruity flavour - so far, there has been no distinct benefits, but you would probably have better results as you apparently respond well to nicotine.
Posted by undopaminergic on June 5, 2008, at 16:16:27
In reply to Re: Mirapex vs. Seroquel for SSRI-induced anhedoni, posted by linkadge on May 30, 2008, at 16:32:11
>
> For SSRI anhedonia, I would not really recomend an AP at all. They can augment SSRI's for depression, but I don't think there is much research showing they improve anhedonia.
>While they may not do much for anhedonia, low doses of sulpiride and amisulpride can have powerful effects against apathy, quite possibly including SSRI-induced apathy. Sulpiride was a more powerful stimulant than methylphenidate for me until its effects dissipated, and its side-effects were non-existent.
Aripiprazole (Abilify) is another antipsychotic that may be stimulating and effective against apathy, but some people experience the opposite.
Pimozide is a stimulating antipsychotic as well, but it's not as safe as the agents mentioned above, so its use requires more caution.
Most other antipsychotics - especially the atypicals - are likely to be sedating - especially quetiapine (Seroquel), which is popular as a sleep aid.
> I'd stay away from AP's, they're not worth the risks, unless you really need them.
>This is an overgeneralisation. Most, if not all, drugs and supplements are associated with certain risks. Depending on the choice of AP and dose, the risks are not higher- and can be lower - than with many antidepressants, stimulants, and other classes of medicines.
Posted by linkadge on June 5, 2008, at 19:16:28
In reply to Re: Mirapex vs. Seroquel for SSRI-induced anhedoni, posted by undopaminergic on June 5, 2008, at 16:16:27
>This is an overgeneralisation. Most, if not all, >drugs and supplements are associated with >certain risks. Depending on the choice of AP and >dose, the risks are not higher- and can be >lower - than with many antidepressants, >stimulants, and other classes of medicines.
I don't know. Sure there are risks to all psychiatric drugs, but I tend to think of the AP's as generally a little nastier. AP's are about the only class of psychiatric meds which doctors admit to potentially causing irriversable neurological complications.
My argument is that there are likely better drugs to augment with for depression.
In the past antipsychotics were rarely used for augmentation agents unless the depression was psychotic or very agitated. Even then, the AP was generally tapered after the AD effect kicked in. Newer AP's are used more these days because of the atypical profile, but these effects can probably be replicated much more safely with other agents.
Just don't unnecessarily get caught up in dirty psychopharmacholgy. We are still in an aftermath of Lilly unethical offlable Zyprexa scam. Doctors still use it even though there are equally/more effective agumentation agents.
Linkadge
This is the end of the thread.
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