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Re: prozac withdrawl-for Ami JackieJ

Posted by Sunnely on October 29, 2000, at 18:59:21

In reply to Re: prozac withdrawl-for Ami Ami, posted by JackieJ on October 27, 2000, at 13:14:49

> To Ami and All:
>
> I have been on prozac for 5 years. I am currently taking 40 mg per day in addition to 400 mg of wellbutrin. My doctor just yesterday dropped my dose of prozac from 40 to 30 mg. In 2 more weeks I will go from 30 to 20, in another 2 weeks, down to 10, and in 2 more weeks, no more prozac. Then he will INCREASE my wellbutrin from 400 mg per day to 600 mg per day. (He told me that just recently it is safe to go as high as 600 mg whereas 400 mg USED to be the max. I'm very scared of withdrawal symptoms from prozac and increased intake of wellbutrin. I can NOT live the way I did without the prozac. However, I'm sick of the sexual side effects after 5 years. And I am sick of the weight gain! Any input from all is appreciated. Please respond to my email address as well in case I can't find this site again. JackieJeckyl@aol.com

Hi JackieJ,

Could you ask your doctor where he got the information (reference) that it is "safe" to go as high as 600 mg/day with Wellbutrin? Would you be kind enough to post it here? I will be concerned about going up to 600 mg/day of Wellbutrin as this puts you on a really high risk for seizures (even with the use of the sustained-release or SR formulation). Not only that the use of higher doses of Wellbutrin i.e., greater than 450 mg/day, puts one at higher risk for seizures, in your case, the combined use of Prozac + Wellbutrin raises that risk even higher.

FYI, Wellbutrin (bupropion) and one of its active metabolites or daughter compounds (hydroxybupropion) are metabolized (broken down) by at least 3 liver enzymes namely CYP2B6, CYP3A4, and CYP2D6. More specifically, the parent compound (bupropion) is metabolized mainly by CYP2B6 and partly by CYP3A4, while the active metabolite (hydroxybupropion) is metabolized by CYP2D6. Prozac does not affect the action of CYP2B6 and modestly inhibits the action of CYP3A4. Therefore, it has a weak effect on the metabolism of the parent compound (bupropion). However, Prozac markedly inhibits the action of CYP2D6. Prozac's inhibiting action on this liver enzyme will then significantly inhibits the metabolism of the active metabolite (hydroxybupropion) causing an increase in its blood level. Since the metabolite, hydroxybupropion, has equal propensity to cause seizures as its parent compound, the rise in its blood level consequently raises one's risk for seizures. Even though your dose of Prozac is being gradually reduced, its inhibiting effect on the liver enzyme CYP2D6 will continue (although diminishing) for at least another 5-8 weeks after it is completely dicontinued. This is due to Prozac's very long half-life (the combined half-life of fluoxetine and norfluoxetine). I believe I read somewhere that the increase in blood level of hydroxybupropion can also cause a decrease in Wellbutrin's antidepressant effect. I am not certain about this, however.

Withdrawal symptoms from Prozac (if they ever occur) are usually milder than the other SSRIs with shorter half-lives. As mentioned above, Prozac has a very long half-life which acts as a "protective" mechanism from the occurrence of withdrawal. This is not to say that withdrawal symptoms will never occur if Prozac is abruptly discontinued.

The following is a general guideline to minimize the risk of seizures with the use of Wellbutrin as an antidepressant:

1. The dose should be carefully titrated (increased) to achieve the lowest effective dose.

2. Daily doses (if greater than 150 mg/day) are to be divided into at least every 6 to 8 hours interval.

3. The dose should not exceed 450 mg/day.

4. Any SINGLE dose should not exceed 150 mg.

5. The doses should not be given closer than every 6 hours.

6. Further dose increases should not occur any more frequently than every 3 days, and for no more than 100 mg.

7. Preferably, use the SR (Sustained Release) than the IR (Immediate Release) formulation.

8. The combined use of Wellbutrin (antidepressant) and Zyban (smoking cessation) is contraindicated. The generic name for both drugs is bupropion, manufactured by the same company.

References:

1. Benefits of new sustained-release bupropion: less-frequent dosing, fewer side effects. In: Psychoparmacology Update, November 1997.

2. Preskorn SH: Bupropion. Journal of Psychiatric Practice, January 2000.


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