Depression is well-known to comorbid with several psychiatric disorders. Many schizophrenics also suffer from depression in the course of their illness. Combined therapy of SSRI and tricyclic antidepressants were reported to have benefits in some depressed patients. Paroxetine, a potent CYP2D6 inhibitor, increases the blood levels of tricyclic antidepressant markedly, Using paroxetine, we tried this combined therapy in the treatment of depressive symptoms in 10 chronic schizophrenic inpatients and evaluated its efficacy and drug interactions between paroxetine and tricyclic antidepressants. The following results were obtained: 1) The mean score of Hamilton's Depression Rating Scale(HDRS) was reduced significantly after 6 weeks-trials of this combined therapy for the mild depressive symptoms in 10 chronic schizophrenics. In four patients, 50% or more reductions in the scores of HDRS were noticed at final evaluation. 2) Two among our 10 subjects experienced severe toxic behavioral problems. Anticholinergic crisis with toxic confusion due to high blood levels of tricyclics was fecund in one patient and the other showed rapid clinical deterioration in his psychotic symptoms such as delusion and hallucination without any consciousness alternation. 3) Baseline plasma levels of tricyclics before adding paroxetine were higher or than expected in our chronic schizophrenic subjects maintained with their antipsychotic medications. Several antipsychotics were also known as a potent CYF2D6 inhibitors and to increase the blood levels of tricyclics. Because the blood levels of tricyclics had already increased significantly by the use of antipsychotics, adding paroxetine to antipsychotics and tricyclic antidepressant In our subjects could increase the blood levels of tricyclics not so much as previously reported in the literatures.
Antidepressive Agents, Tricyclic ; Antipsychotic Agents ; Consciousness ; Cytochrome P-450 CYP2D6 ; Delusions ; Depression* ; Drug Interactions ; Hallucinations ; Humans ; Inpatients ; Paroxetine* ; Plasma ; Schizophrenia