The efficacy of the addition of lithium to an established course of antidepressant treatment can be explained by a synergistic effect of the two drugs on central 5-HT neurotransmission. In the present study we investigated the effect of lithium addition on the 5-HT concentration in plasma and platelets and the concentration of 5-HIAA. Thirty-nine depressed inpatients who fulfilled the DSM-IV criteria for major depressive disorder and who did not respond to monotherapy with either imipramine or fluvoxamine participated in this study. Concentration of 5-HT in both plasma and platelets did not change significantly during lithium addition. The 5-HT ratio (plasma concentration/platelet concentration) shows a small non-significant increase after 3 weeks lithium addition. The mean concentration of 5-HIAA shows a significant increase during lithium addition; with no difference between the imipramine and the fluvoxamine sample. The increments in 5-HIAA concentration during lithium addition are indicative of an increased 5-HT turnover.

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Keywords Lithium addition, Major depression, Plasma 5-HIAA, Plasma 5-HT, Platelet 5-HT
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Birkenhäger, T.K., van den Broek, W.W., Fekkes, D., Mulder, P.G.H., Moleman, P., & Bruijn, J.A.. (2007). Lithium addition in antidepressant-resistant depression: Effects on platelet 5-HT, plasma 5-HT and plasma 5-HIAA concentration. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 31(5), 1084–1088. doi:10.1016/j.pnpbp.2007.03.012