Aggregating research on lithium's serotonergic activity

[utaninja]

Three cases of SS with Venlafaxine and Lithium-
Adan-Manes J, Novalbos J, López-Rodríguez R, et al.: Lithium and venlafaxine interaction: a case of serotonin syndrome. J Clin Pharm Ther 2006; 31:397–400 Crossref, Medline, Google Scholar
Mekler G, Woggon B: A case of serotonin syndrome caused by venlafaxine and lithium. Pharmacopsychiatry 1997; 30:272–273 Crossref, Medline, Google Scholar
Torre LE, Menon R, Power BM: Prolonged serotonin toxicity with proserotonergic drugs in the intensive care unit. Crit Care Resusc 2009; 11:272–275 Medline, Google Scholar

This goes into quite a few sources relating to this
https://www.nature.com/articles/1395366

“Lithium is known to increase serotonin levels in the cerebrospinal fluid by inducing serotonin synthesis and is supported by animal studies where is enhances the serotonin toxicity” https://neuro.psychiatryonline.org/doi/full/10.1176/appi.neuropsych.11080196#:~:text=Lithium%20and%20venlafaxine%20combination%20has,is%20enhances%20the%20serotonin%20toxicity.

“Lithium appears to act, in some ways, as a direct serotonin agonist. Among lithium’s complex pharmacology is evidence that it enhances serotonergic activity either through increased biosynthesis of serotonin or by receptor adaptation (Lenox et al 1995).”
https://www.biologicalpsychiatryjournal.com/article/S0006-3223(98)00161-9/pdf

Although geriatric patients may be more sensitive to side effects of lithium in combination with the SSRIs, the combination has generally been well-tolerated. There have, however, been a number of case reports of serotonin syndrome associated with the addition of lithium to an SSRI. Sobanski et al (1997) recently reported that the addition of lithium 400 mg/day to paroxetine 30 mg/day produced a serotonin syndrome in a 59-year-old woman that resolved when the dose of paroxetine was reduced to 10 mg/day. Similarly, Ohman and Spigset (1993) described a nonfatal serotonin syndrome with the combination of lithium and fluvoxamine. Although serious drug interactions between lithium and SSRIs, such as serotonin syndrome, appear uncommon, the risk is not negligible.
https://www.biologicalpsychiatryjournal.com/article/S0006-3223(98)00161-9/pdf

“Lithium has the ability to increase the release of serotonin from pre-synaptic terminals; therefore, caution is needed when using lithium together with SSRIs and venlafaxine, because of the risk of serotonin toxicity.”
https://www.cambridge.org/core/journals/advances-in-psychiatric-treatment/article/new-drugs-old-problems-revisiting-pharmacological-management-of-treatmentresistant-depression/D44091E25F9537B93CD6F4580F340645

I wanted to also note this study - https://journals.lww.com/intclinpsychopharm/abstract/2000/15040/efficacy,_safety_and_tolerability_of_combined.2.aspx