Response to tryptophan depletion in major depression treated with either cognitive therapy or selective serotonin reuptake inhibitor antidepressants

Mood sensitivity to rapid tryptophan depletion (RTD) has been demonstrated in patients treated with antidepressants that act preferentially on the serotonergic system. Depressed patients treated with bright-light therapy also show sensitivity to RTD, but those treated with electroconvulsive therapy or total sleep deprivation do not. Patients treated with an empirically supported psychotherapy have not been investigated for sensitivity to tryptophan depletion. This study compares the effects of RTD in patients treated with either selective serotonin re-uptake inhibitors (SSRIs) or cognitive therapy (CT). Twenty patients treated with either SSRIs or CT underwent both rapid tryptophan depletion and sham-depletion using a blinded crossover design. Depressive symptoms were assessed using a modified Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI). The differential change in depression scores across procedures between the groups was compared, and effect sizes were calculated. The differential worsening of mood for the SSRI group compared with the CT group was significant on the BDI. The effect size of the differential change was 1.6 for the BDI and .8 for the HDRS. Furthermore, the SSRI group experienced significant mood worsening during depletion compared with sham on both the HDRS and the BDI, whereas the CT group did not. The CT group was resistant to the effects of tryptophan depletion, but the SSRI group was not.