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Re: Reboxetine/SSRI combos

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.


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