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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 12 of 12. This is the beginning of the thread.
Posted by John Doughboy on May 10, 2008, at 18:04:51
Hi, I'm new to this board and this is my first post, but I've been lurking (reading) on and off for a couple years.
Basically, I have OCD and clinical depression. I'm 99% certain of this diagnosis; I'm sure I'm not bipolar,psychotic,manic or anything like that.
I take 100mg Zoloft (sertraline) for OCD.
The Zoloft works great for the OCD,but like many people on SSRI's, it flattens my moods and it doesn't help with my depression and might even make it worse. Getting off the Zoloft or lessening the dosage isn't really an option because the OCD would want me to bang my head against the wall.
What should I add to help with my depression? I'm thinking I have some kind of dopamine and/or norepinephrine problem in addition to the serotonin problem. How do I know if this is more a norepinephrine or dopamine related depression? They both sound similiar to me,ie related to motivation and energy.
Adderall really helps the motivation problems, but it only works for like a week and then it just totally poops out, no matter how high I raise the dose. Provigal just keeps me awake.(I haven't tried methylphenidate in a while, but I assume it will just poop out like the amphetamines).
I tried Effexor 150 mg instead of the Zoloft, but I only took it for like two weeks because it seemed to flatten my mood even more than Zoloft. I know Effexor inhibits sertonin reuptake more strongly than norepinephrine; does 150 mg have an appreciable effect on NE at that dose?
So basically I'm considering these options:
1. Stop the Zoloft and take Effexor 150mg instead and trying to tough it out for four to six weeks
2. Adding Wellbutrin 300mg to the Zoloft
3. Trying another SSRI (I highly doubt this will help)
Can anyone give me some advice as to what to take to help with the anhedonia and lack of energy? How can you tell if it's more dopamine or norepinephrine related? I also take an ACE inhibitor for high blood pressure, would that have any effect on the depression?
Any suggestions WHATSOEVER would be greatly appreciated. Just taking a shower and brushing for teeth seems like a monumental task.
Thank you...
Posted by bleauberry on May 10, 2008, at 20:13:34
In reply to Zolft helps OCD but doesn't help depression, posted by John Doughboy on May 10, 2008, at 18:04:51
I agree with you that it sounds like a norepinephrine and/or dopamine component that is missing. The difficult part is finding out what drug is going to work for that. There are many, but it is the exact mechanism, not the general assumption of what the drug does, that determines whether it works for any particular person or not. There is no predicting.
The most common choice would be wellbutrin. It made me profoundly worse when added to zoloft, but for other people it works fabulous. Other drugs that in my opinion should be on your radar screen are...
Adderall again except this time add Memantine to it to prevent the tolerance.
Zyprexa
Risperdal
Abilify
Nortriptyline
Desipramine
Duloxetine 30mg added to zoloft, but starting with custom doses of 1/4 capsules (not a common mixture, but at other forums it has been done with good results)
PramipexoleMailorder from overseas:
Trivastal
Adrafinil
MilnacipranNatural arena:
Tyrosine (natural precursor to norepinephrine and dopamine)All of these interact with norepinephrine and dopamine, but in varying mechanisms.
No matter what you try, be prepared to move on and try something else on the list if the first couple or three choices prove negative for you in some way. Keep the chin up and the eye on the goal.
While you mentioned effexor, it does have some norepinephrine and dopamine mechanisms at higher doses, but I just don't like that idea at this point. Zoloft is working for OCD. Half the battle is already won. I would keep that victory and don't mess with it. You may never get it back if you let it go. Happens a lot. Keep zoloft steady and add other things to it. Just my opinions.
Posted by John Doughboy on May 10, 2008, at 22:33:10
In reply to Re: Zolft helps OCD but doesn't help depression, posted by bleauberry on May 10, 2008, at 20:13:34
First of all, thank you for the response. This med stuff is extremely frustrating and it's good to know others have been through the same (or at least know what I'm talking about).
Some other comments...
I completely understand what you are saying about sticking with the Zoloft because I already know it works in the OCD aspect, but I've tried Effexor and I know it helps the OCD aspect as well. I know it has norepinephrine effects at higher doses,but what is considered a dose that has appreciable NE effects? Like how much would you have to take to get effects on NE similiar to a common dose of NE specific TCA (ie desipramine). If I can get good NE effects at 150 (but no higher), I would really like to try it.
And about my stimulant tolerance. It's not a QUANTITATIVE tolerance like I need more after awhile to get the same effects, it's like a QUALITATIVE tolerance where is just doesn't work, at any dose. (The stimulating mood elevation turns into pure agitation.)
Posted by Phillipa on May 11, 2008, at 12:15:54
In reply to Re: Zolft helps OCD but doesn't help depression, posted by John Doughboy on May 10, 2008, at 22:33:10
Very unscientific answer have you considered luvox for OCD? It really almost eliminated it in me and in the beginning at high doses really woke me up even with benzos. Love Phillipa
Posted by johnj on May 11, 2008, at 12:58:33
In reply to Re: Zolft helps OCD but doesn't help depression, posted by John Doughboy on May 10, 2008, at 22:33:10
You may want to look at pristiq. I believe it works on NE at lower doses than effexor. Just a thought.
johnj
Posted by John Doughboy on May 11, 2008, at 16:03:28
In reply to Re: Zolft helps OCD but doesn't help depression » John Doughboy, posted by johnj on May 11, 2008, at 12:58:33
I don't think Effexor (or Prestiq) is going to be my choice because I don't want more serotonin reuptake inhibition than I'm getting now on Zoloft at 100 mg. To get anything noticeable in the norepinephrine department, I would have to get even more serotonin because of venlafaxine's fixed serotonin/norepinephrine ratio. (Drugs with more than one AD mechanism of action might be convenient,but are hard to fine tune compared to two selective drugs.)
And trying Luvox: it's just another SSRI. To me all SSRI are more or less the same; they all are extremely selective for serotonin and bind to exactly the same pre-synaptic 5H-T sites-only differences are in widely varying halflifes and slighlty different metabolic pathyway
So it seems my only practical choice is adding on Wellbutrin XL (it's a shame that amineptine is no longer on the market).
Posted by John Doughboy on May 11, 2008, at 16:37:55
In reply to Re: Zolft helps OCD but doesn't help depression, posted by John Doughboy on May 10, 2008, at 22:33:10
Okay,I've pretty much decided I will add Wellbutrin XL 300mg to Zoloft 100mg.
If the bupropion doesn't work for some reason, I want to start researching other meds that also have primarily NE and/or DA activity with mood enhancing properties. (With the sertonin orgy over the last twenty years, they seem dificult to find.)
Please help with my list by adding these chemicals. They don't have to be improved for any certain conditions (antidepressants, stimulants, narcolepsy meds, Parkinson's meds , "smart drugs",anything...)
I only ask that they can be prescribed by any P-Doc in the U.S. or are still on the market overseas and easily be ordered over the internet.
Please help-the only ones I can think of are the amphetamines and methylpnenidate and that other ADD med Stattera (a selective NRI) , and some very nasty tricyclic AD's that are relatively NE specific.
Posted by undopaminergic on May 12, 2008, at 0:56:04
In reply to What are some dopameric and/or noradrengeric med?, posted by John Doughboy on May 11, 2008, at 16:37:55
>
> Please help-the only ones I can think of are the amphetamines and methylpnenidate and that other ADD med Stattera (a selective NRI) , and some very nasty tricyclic AD's that are relatively NE specific.
>Atomoxetine (Strattera) and reboxetine (Edronax) are highly selective noradrenaline (NA) reuptake inhibitors. These can be used to test the role of NA.
There are no selective dopamine (DA) reuptake inhibitors, except certain research compounds and the discontinued amineptine. The closest you can get within the range of clinically available drugs is methylphenidate (MPH) - including dextromethylphenidate (Focalin). Although modafinil has relatively better selectivity for DA over NA in comparison with MPH, it's less potent. MPH and amphetamines (AMPH) are substantially different in their mode of action, so what applies to AMPH is not necessarily true for MPH. For example, AMPH depletes neuronal stores of DA (and probably NA), whereas reuptake inhibitors, such as MPH (and cocaine), enhance them. In other words, DA reuptake inhibitors are worth trying - for comparison if nothing else.
Sulpiride (SLP) and amisulpride (ASLP) are DA D2-/D3-receptor antagonists with preferential affinity for presynaptic autoreceptors. DA autoreceptor blockade enhances DA release from nerve terminals into the synapse. The resulting stimulant effects of low doses of SLP or ASLP may be more powerful than those of MPH, although the combination of both is even better.
Another class of dopaminergic agents are the direct agonists. Long-term use of the ergot-derived ones are best avoided, due to the risk of serious adverse consequences, including cardiac valvulopathy. Clinically available non-ergot DA agonists are pramipexole, ropinirole, quinagolide, piribedil, and apomorphine. Of these, only apomorphine (derived from morphine) has any significant affinity to D1-subtype receptors; however, it has a very short half-life and is generally not used orally. Pramipexole has the highest affinity to D3-receptors, and may be the most anti-anhedonic of the dopamine agonists. Ropinirole is quite similar to pramipexole; both of them have been associated with compulsive gambling and hypersexuality. Piribedil has alpha2-adrenergic antagonist properties, which may be detrimental or beneficial depending on the details of your situation. Quinagolide is mainly used against hyperprolactinaemia, and its use in CNS disorders is not extensively explored. A problem with all the dopamine agonists under discussion is their preferential affinity for presynaptic DA receptors, the stimulation of which leads to reduced synthesis and release of DA; this is generally the opposite of the desired result, and may explain some of the adverse effects associatd with DA direct agonists, such as somnolence, sometimes of a very sudden onset.
Another class of drugs that may be of use for enhancing dopaminergic neurotransmission is MAO-inhibitors. Of the unselective MAOIs, tranylcypromine is likely to be the most appropriate, but only if you're prepared to avoid foods and drugs that are known to interact adversely with MAOIs. The selective MAO-B inhibitors selegiline and rasagiline have the advantage of a lower - often insignificant - potential for dangerous interactions with foods and drugs unless the recommended dose is exceeded; while the recommended doses of these drugs are unlikely to produce effects sufficient for your purposes, they may enhance the effects of stimulants, autoreceptor-blockers and DA precursors as well as rendering phenylalanine and phenylethylamine (PEA) effective as pharmacological agents.
The DA precursors are, of course, tyrosine and L-dopa. They are most useful when taken with peripheral inhibitors of aromatic amino acid decarboxylase (AADC) - of which carbidopa and benserazide are clinically relevant - in order to reduce peripheral side effects (e.g. nausea) and improve the availability of the DA precursor to the CNS; most preparations of L-dopa include a standard proportion of an AADC inhibitor.
Finally, some NMDA-antagonists, such as amantadine and especially memantine, can be useful to enhance dopaminergic neurotransmission - or so it would seem, based on their observed effects. These agents may have stimulant-like and anti-anhedonic effects of their own, but also appear to be useful for preventing tolerance to the beneficial effects of stimulants.
Posted by johnj on May 12, 2008, at 9:11:08
In reply to Effexor: nay? Wellbutrin:yay?, posted by John Doughboy on May 11, 2008, at 16:03:28
I could be wrong but I think Pristiq has more NE at lower levels than than effexor.
Posted by rgb on June 3, 2008, at 7:22:03
In reply to Re: What are some dopameric and/or noradrengeric med?, posted by undopaminergic on May 12, 2008, at 0:56:04
Sertraline is also somewhat dopaminergic; I seem to remember that its DAT affinity is roughly 1% of its SERT affinity. This doesn't sound all that bad (theoretically!) if you consider that SERT is saturated at low-ish doses and you don't need to nearly-saturate DAT.
With this in mind, I actually /increased/ my dose to 200mg and later to 300mg and on a few days even 400mg in an attempt to counter residual amotivation (don't try this at home.).
This even worked to some degree, though the increases felt more like a slight "awareness broadening" (5-HT2-esque) effect, no reinforcing/reward-type effect. Whatever it was, unfortunately I've mostly built tolerance to it and am mostly back in brain-fog-land. Go to 400mg permanently? (kidding ;)) My wild guess is that it's 5-HT2A downregulation; is there some way to counter this?
All of the above might be purely imaginary effects based on confirmation bias due to my neuroscience obsession, so take it with a major grain of salt please.
Posted by undopaminergic on June 3, 2008, at 9:55:35
In reply to Re: What are some dopameric and/or noradrengeric med? » undopaminergic, posted by rgb on June 3, 2008, at 7:22:03
> Sertraline is also somewhat dopaminergic; I seem to remember that its DAT affinity is roughly 1% of its SERT affinity. This doesn't sound all that bad (theoretically!) if you consider that SERT is saturated at low-ish doses and you don't need to nearly-saturate DAT.
>Well, 40 mg methylphenidate yields about 70% DAT inhibition, and it's really not sufficient in my experience. With sertraline even such a modest extent of inhibition is infeasible. If you can get methylphenidate, modafinil, cocaine, or one of the many less popular DAT inhbitors, there's no reason to attempt to exploit the weak DAT blockade of sertraline.
> With this in mind, I actually /increased/ my dose to 200mg and later to 300mg and on a few days even 400mg in an attempt to counter residual amotivation (don't try this at home.).
>
> This even worked to some degree, though the increases felt more like a slight "awareness broadening" (5-HT2-esque) effect, no reinforcing/reward-type effect. Whatever it was, unfortunately I've mostly built tolerance to it and am mostly back in brain-fog-land. Go to 400mg permanently? (kidding ;)) My wild guess is that it's 5-HT2A downregulation; is there some way to counter this?
>5-HT2A antagonists would probably counter it, but of course, the pharmacological effect of that would be equivalent to downregulation, until the antagonist is stopped, but at that point downregulation would again commence. There may be no way to eat the cake and have it too.
Posted by undopaminergic on June 3, 2008, at 12:57:45
In reply to Re: What are some dopameric and/or noradrengeric med? » undopaminergic, posted by rgb on June 3, 2008, at 7:22:03
>
> Whatever it was, unfortunately I've mostly built tolerance to it and am mostly back in brain-fog-land. Go to 400mg [of Zoloft/sertraline] permanently? (kidding ;))
>An alternative to higher doses would be cautious introduction of a MAO-inhibitor, such as selegiline or moclobemide. An antidote to serotonergic toxicity - preferably cyproheptadine - should be available prior to initiating the experiment.
This is the end of the thread.
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