The levels of the tricyclic antidepressants can be raised by the
SSRIs, but the extent varies greatly, from 20% to 10-fold. Tricyclic
toxicity has been seen in a number of cases.
Tricyclics may increase the levels of citalopram and possibly
fluvoxamine, but the significance of this is unclear. There are several case reports of the
serotonin syndrome, following concurrent and even sequential use of the
SSRIs and
tricyclics.
The increased tricyclic antidepressant levels can be beneficial. However, it has been suggested that patients given fluoxetine should have their tricyclic dose reduced to a quarter. Similar recommendations have been made with
fluvoxamine (reduction in tricyclic dose to one-third) and sertraline. It would also seem prudent to consider a dosage reduction of the tricyclic if
paroxetine is added. Some suggest that a small initial dose of the SSRI should also be used. Patients taking any combination of tricyclic and SSRI should be monitored for adverse effects (e.g. dry mouth, sedation, confusion) with tricyclic levels monitored where possible. Note that the active
metabolite of fluoxetine has a
half-life of 7 to 15 days, and so any interaction may persist for some time after the fluoxetine is withdrawn, and may therefore occur on sequential use.