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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by Anna P. on August 23, 2000, at 12:19:44
Hello there,
Based on my medline research I can conclude that Reboxetine can be combined
effectively with SSRI's such as Prozac, Zoloft, Paxil, Exxexor or Serzon.
Posted by Sunnely on August 24, 2000, at 20:00:32
In reply to Reboxetine/SSRI combos, posted by Anna P. on August 23, 2000, at 12:19:44
> Hello there,
>
> Based on my medline research I can conclude that Reboxetine can be combined
> effectively with SSRI's such as Prozac, Zoloft, Paxil, Exxexor or Serzon.Hi Anna,
People with treatment-resistant depression (TRD) are probably the ones who will benefit more with the combination of reboxetine (Edronax, Vestra) + an SRI (serotonin reuptake inhibitor).
Some caution, however. Nefazodone (Serzone) is a marked inhibitor of the liver enzyme CYP3A4. Reboxetine is primarily metabolized by the liver enzyme CYP3A4. The combination of Serzone and reboxetine could lead to increased reboxetine blood level and side effects. Venlafaxine (Effexor) is both a serotonin reuptake inhibitor and norepinephrine reuptake inhibitor at lower and higher doses, respectively. Increasing doses of Effexor plus reboxetine even at the recommended therapeutic doses could lead to increased norepinephrine side effects (e.g., increased blood pressure, agitation, insomnia, etc.).
Fluoxetine (Prozac) moderately inhibits the liver enzyme CYP3A4 and has the potential to raise the blood level of reboxetine, although most likely not to the same degree as Serzone. Paroxetine (Paxil) and sertraline (Zoloft) have none or weak effect on CYP3A4 therefore, no significant effect on the reboxetine's metabolism and blood level is expected.
Among the SSRIs, citalopram (Celexa) is probably the top choice to combine with reboxetine for people with TRDs for at least 2 reasons. First (pharmacokinetic wise), Celexa has none or weak effect on CYP3A4, therefore no clinically significant effect on reboxetine's metabolism and blood level. Second, (pharmacodynamic wise), Celexa is the MOST selective serotonin reuptake inhibitor, while reboxetine is a selective norepinephrine or noradrenaline reuptake inhibitor (NARI). In effect, Celexa + reboxetine is like aggressively treating TRD by hitting both receptors (serotonin and norepinephrine) hard, simultaneously. Below is a recent report published in a psychiatric journal indicating the successful use of this combination in TRD patients, although small number (4 cases).
JMHO (Just my humble opinion).
Source:
Devarajan S, Dursun SM: Citalopram plus reboxetine in treatment-resistant depression (letter to editor). Canadian Journal of Psychiatry 2000;45:489-490.
Posted by Anna P. on August 25, 2000, at 0:49:15
In reply to Re: Reboxetine/SSRI combos, posted by Sunnely on August 24, 2000, at 20:00:32
> > Thank you Sunnely,
These are valuable info for me. I had big hopes for combining Serzone and Reboxetine. Now I'm concerned. How about Remeron?
I have a treatment resistant depression.Anna
Posted by SLS on August 25, 2000, at 7:36:04
In reply to Re: Reboxetine/SSRI combos/SUNNELY, posted by Anna P. on August 25, 2000, at 0:49:15
> > > Thank you Sunnely,
>
> These are valuable info for me. I had big hopes for combining Serzone and Reboxetine. Now I'm concerned. How about Remeron?
> I have a treatment resistant depression.
>
> Anna
Hi Anna.Substituting desipramine (Norpramin) for reboxetine might be an alternative. Like reboxetine, desipramine is a potent and selective NE reuptake inhibitor. Perhaps Sunnely can offer an evaluation of Serzone-desipramine interactions. I don't think they significantly interfere with each other's metabolisms.
- Scott
Posted by Sunnely on August 25, 2000, at 19:58:27
In reply to Re: Reboxetine/SSRI combos/SUNNELY, posted by SLS on August 25, 2000, at 7:36:04
> Substituting desipramine (Norpramin) for reboxetine might be an alternative. Like reboxetine, desipramine is a potent and selective NE reuptake inhibitor. Perhaps Sunnely can offer an evaluation of Serzone-desipramine interactions. I don't think they significantly interfere with each other's metabolisms.
>
>
> - ScottHi Scott,
Reboxetine (Edronax, Vestra) and desipramine (Norpramin) both act as norepinephrine reuptake inhibitor. Reboxetine is "cleaner" than desipramine, however. Desipramine, apart from inhibiting norepinephrine uptake, carries the extra baggage of blocking the muscarinic cholinergic receptors and alpha1-adrenergic receptors, which can result in unwanted side effects (e.g., blurred vision and drop in blood pressure, respectively).
Desipramine modestly increase the blood level of nefazodone under relevant steady-state dosing conditions. Nefazodone has been shown (in vitro) to be a potent inhibitor of the liver enzyme CYP3A4 and a weak inhibitor of CYP2D6. Desipramine is a model substrate for the liver enzyme CYP2D6. Nefazodone has been shown in an in vivo study to be at least 40 times less potent than fluoxetine (Prozac) in inhibiting the action of CYP2D6. The combined use of nefazodone (300 mg/day at steady state) and desipramine led to modest increase in desipramine blood level. This study also indicates that triazolodione and mCPP (meta-chlorophenylpiperazine), the principal metabolites of nefazodone, do not inhibit CYP2D6.
Final answer: No significant pharmacokinetic drug-drug interactions between nefazodone and desipramine.
Posted by Sunnely on August 25, 2000, at 20:45:20
In reply to Re: Reboxetine/SSRI combos/SUNNELY, posted by Anna P. on August 25, 2000, at 0:49:15
> > > Thank you Sunnely,
>
> These are valuable info for me. I had big hopes for combining Serzone and Reboxetine. Now I'm concerned. How about Remeron?
> I have a treatment resistant depression.
>
> AnnaI assume you meant Remeron (mirtazapine) and reboxetine in combination. Probably good augmenters to each other especially in treatment-resistant depression.
No significant pharmacokinetic drug-drug interactions involved with this combination. Mirtazapine is metabolized by CYP1A2, CYP2D6, and CYP3A4. In turn, it is a weak inhibitor of these liver enzymes (CYPs). As I have mentioned in my previous response, reboxetine is primarily metabolized by CYP3A4 therefore, expect no appreciable increase in reboxetine blood level when combined with Remeron.
Like Remeron, reboxetine does not interfere with the action of the cytochrome enzymes (CYPs), therefore expect no appreciable increase in Remeron blood level with this combination. Also, doubt any serious pharmacodynamic drug-drug interaction involved with this combination.
JMHO (Just my humble opinion).
Posted by SLS on August 26, 2000, at 11:42:23
In reply to Re: Reboxetine/SSRI combos/SUNNELY, posted by Sunnely on August 25, 2000, at 19:58:27
> Reboxetine (Edronax, Vestra) and desipramine (Norpramin) both act as norepinephrine reuptake inhibitor. Reboxetine is "cleaner" than desipramine, however. Desipramine, apart from inhibiting norepinephrine uptake, carries the extra baggage of blocking the muscarinic cholinergic receptors and alpha1-adrenergic receptors, which can result in unwanted side effects (e.g., blurred vision and drop in blood pressure, respectively).
Hi Sunnely.Your command of pharmacology continues to astound me.
I didn't know that desipramine blocked NE alpha-1 receptors. It seems to me that this might explain its purported effect to mitigate MAOI-tyramine pressor reactions. Are the other tricyclics similarly antagonistic to NE alpha-1 receptors?
- Scott
Posted by Anna P. on August 26, 2000, at 19:40:22
In reply to Re: Reboxetine/SSRI combos/SUNNELY » Anna P., posted by Sunnely on August 25, 2000, at 20:45:20
> > > > Thank you Sunnely and Scott.
I appreciate your suggestions. They are really helpful. I don't know much about pharmacology.
Unfortunately, I can't use Desipramine or Celexa anymore, as I've tried them in different combinations, and I've developed 100% tolerance - they are just sugar pills to me, and yes, this is possible.
I've tried:
Celexa 60 mg
Desipramine + Celexa
Desipramine + Ritalin
Celexa + Dexedrine
Celexa + RitalinI also won't respond anymore to Zoloft, Wellbutrin or Effexor.
My only hope is to try Reboxetine + Remeron. I really need to add serotonian medication to Reboxetine, as serotonin makes me more resistant to stress and prevents crying symptoms.
I'm currently on Rebox/Neurontin combo, but it isn't effective enough.Anna
> >
> >
Posted by Sigolene on August 27, 2000, at 7:07:19
In reply to Re: Reboxetine/SSRI combos/SUNNELY/Scott, posted by Anna P. on August 26, 2000, at 19:40:22
And what about a combination Rebox + Trazodone ?
I think this combination could be interesting in view of what has been said before.
Has someone experience with that ?Anyway, I'm interested in the results of your trial Ana. Could you inform us on this board ?
Sigolene.> > > > > Thank you Sunnely and Scott.
> I appreciate your suggestions. They are really helpful. I don't know much about pharmacology.
> Unfortunately, I can't use Desipramine or Celexa anymore, as I've tried them in different combinations, and I've developed 100% tolerance - they are just sugar pills to me, and yes, this is possible.
>
> I've tried:
> Celexa 60 mg
> Desipramine + Celexa
> Desipramine + Ritalin
> Celexa + Dexedrine
> Celexa + Ritalin
>
> I also won't respond anymore to Zoloft, Wellbutrin or Effexor.
> My only hope is to try Reboxetine + Remeron. I really need to add serotonian medication to Reboxetine, as serotonin makes me more resistant to stress and prevents crying symptoms.
> I'm currently on Rebox/Neurontin combo, but it isn't effective enough.
>
> Anna
> > >
> > >
Posted by drbosch on August 26, 2001, at 18:38:03
In reply to Re: Reboxetine/SSRI combos/SUNNELY/Scott, posted by Anna P. on August 26, 2000, at 19:40:22
It is, more the post part standard psychiatric protocol to treat "resistant depression" with Monoamine Oxidase Inhibitors" (MAO's) Aside from the "cheese effect" they are some of the most effects AD's available. There is a new one out that does not impart the cheese effect. And as you may know, Reboxetine is purported to greatly attenuate the cheese effect. I noted from your med list you hadn't tried an MAO. I've had two severe major episodes quicked off by chronic pain. The second I responded to nothing and the last step before ECT was Phenelezine (Nardil). It worked. That was 15 years ago. Since then I've done many other things to ameliorate my depression , and for the last ten years have been only on SSRI's which as a Dr. think they suck, especially Zoloft. So considered what I've suggested. Thanx
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