Recommendations for Switching and Tapering Selected Antidepressants

The key principle is to minimize the complications of possible cytochrome P450 drug interactions between the two antidepressants during the crossover. Note that the patient may be on other drugs with which the new antidepressant may interact through the cytochrome system (e.g. - Coumadin, metoprolol), or in other ways. These interactions may result in a change in the potency of the other drugs, or of the new antidepressant. Consult our Cytochrome P450 Drug Interactions program. The following recommendations apply to typical, healthy, non-geriatric adults. For the elderly or infirm and smaller adolescents, consider using half the doses recommended.

FROM Fluoxetine TO Sertraline, Citalopram, Paroxetine, or Bupropion

STRATEGY

· Fluoxetine has a very long half-life (10 days or more), so it tapers itself and is associated with only rare discontinuation syndrome symptoms. If the patient is on 20 mg, it may be stopped without a taper. If on 40 or 60 mg, do a minimal taper by decreasing 20 mg a day over two or three days. The problem is that this residual fluoxetine stays around for 1-2 months and affects the other drugs.

· Sertraline and citalopram metabolism is strongly blocked by fluoxetine at two cytochromes, so with sertraline, start with 25 mg (50 mg every other day is usually OK) for a week and if no problems, go to 50 mg per day and follow the Followup protocol. For citalopram, start with 10 mg per day and increase to 20 mg after a week if tolerated.

· Paroxetine metabolism is strongly blocked by fluoxetine and fluoxetine metabolism is strongly blocked by paroxetine. In theory, therefore, this transition should be the most problem-prone, so be on the lookout. Begin with 5 or 10 mg of paroxetine and double the dose in a week if tolerated, and then do the Followup protocol.

· Bupropion metabolism is partly blocked by fluoxetine, and there have been reports of seizures in patients on the combination, presumably from elevating the level of bupropion. So, start with 100 mg of bupropion SR for the first two weeks and watch for the typical side effects. Then increase to 200 for two more weeks, then to 300 mg per day if tolerated.

FROMSertraline TO Citalopram, Paroxetine, or Bupropion

STRATEGY:

· Sertraline has a 2-3 day half-life due to the activity of a metabolite, so discontinuation symptoms are infrequent. Doses of 50 mg or less may be stopped without a taper. Doses above that may be tapered by 50 mg per day.

· Citalopram metabolism is strongly blocked by sertraline. So, start with 10 mg for the first week. By the second week, most of the sertraline should be gone, so you can proceed with the usual dose strategy from this point on.

· Paroxetine metabolism is only moderately blocked by sertraline. Still, it is reasonable to start with 10 mg for the first week, then go to the usual dosing strategy since by that time most of the sertraline will be gone.

· Bupropion metabolism is blocked moderately by sertraline. It seems reasonable to start with 100 mg for the first week, then go to the usual dosing strategy since by that time most of the sertraline will be gone.

FROM Citalopram TO Sertraline, Paroxetine, or Bupropion

STRATEGY:

· Citalopram has a half-life of about 35 hours. As such it might have some discontinuation side effects, so a conservative approach would be to taper it by 20 mg every other day when you are down to 20 mg, cut it to 10 mg before stopping.

· Sertraline metabolism is unaffected by citalopram so you can employ the usual dosage strategy.

· Paroxetine metabolism is minimally affected by citalopram so you can employ the usual dosage strategy. Paroxetine may slow the clearance of the citalopram so you could probably get away with doubling the speed of the taper of citalopram indicated above (i.e. - taper by 20 mg per day, etc.)

· Bupropion metabolism is minimally affected by citalopram so you can employ the usual dosage strategy.

FROM Paroxetine TO Sertraline, Citalopram, or Bupropion

STRATEGY:

· Paroxetine has complex non-linear metabolism but the net effect is that there is a short half-life and it is associated with the highest rate of discontinuation/withdrawal symptoms (dizziness, depressed mood, nausea, and confusion). Advise the patient of this possibility: otherwise the patient may conclude that the problem is due to the new medication being started. If the dose is 30 mg or higher, reduce by 10 mg every other day. If 20 mg, or when you get to 20 mg, try 4 days on 10 mg and then stop.

· Sertraline metabolism is moderately slowed by the residual paroxetine. Therefore, start with 25 mg of sertraline for the first week and then increase to 50 mg and use the regular dosing strategy from there.

· Citalopram and bupropion SR metabolism is markedly slowed by the residual paroxetine for the first week or two. Therefore, start with 10 mg of citalopram or 100 mg of bupropion SR for the first week (two weeks if the patient was on a high dose of paroxetine) and then increase in the regular dosing protocol.

FROM Bupropion TO Sertraline, Citalopram, or Paroxetine

STRATEGY:

· Bupropion SR has not been associated with any discontinuation syndrome. Nevertheless, it is reasonable to be conservative and taper by 100 mg or 150 mg every 2 or 3 days, depending on the patient's current dose.

· Bupropion does not affect the metabolism of any of the SSRIs, so the dosage strategy for starting the SSRI would be that described in the regular dosing protocol. The bupropion should be disappearing fast enough so that there is little risk from the fact that certain SSRIs can elevate bupropion levels.

FROM Buspirone (Buspar) TO SSRIs

STRATEGY:

· Buspirone has not been associated with any discontinuation syndrome and the manufacturer indicates it is OK to stop it without a taper. Nevertheless, it is reasonable to be conservative and taper it by 10 mg or 20 mg per day, depending on what is most convenient given the dose size the patient has available.

· Buspirone does not affect the metabolism of any SSRIs. Some SSRIs could raise buspirone levels, but it should be disappearing fast enough so there is little risk of any problems.