Main Findings
depressive symptoms
ADVERSE EFFECTS, SECONDARY
In this first RCT to date comparing PIT with standard treatment, we found that PIT resulted in faster attainment of therapeutic TCA plasma concentrations without exposing patients to more severe adverse effects. Our analyses indicated a mean reduction of 5 days in time to attainment of therapeutic concentrations compared with usual treatment. This effect was primarily due to faster attainment of therapeutic nortriptyline concentrations, which showed a median reduction of 6 days compared with usual treatment. Based on these findings, we conclude that the DPWG guidelines can be effectively used to safely accelerate attainment of therapeutic TCA plasma concentrations.The difference between PIT and usual treatment can be explained by personalized initial dosages and bypassing of the buildup phase in the PIT group. The apparent difference between secondary (nortriptyline) and tertiary (clomipramine and imipramine) TCAs might be explained by metabolization pathways,To date, only 1 studyRegarding the secondary outcome measures, we found that faster attainment of therapeutic plasma concentrations did not translate into a significantly greater reduction in depressive symptoms or adverse effects. However, for adverse effects, we observed a different pattern in severity over time, suggesting that patients in the PIT group experienced gradually fewer and less severe adverse effects compared with those in the control group. In addition, it is clear that clinical outcome is influenced by many other biological and nonbiological factors in addition to antidepressant plasma concentrations.Most previous studies