Bibliography page 2 of 2, relating to
SSRI-Induced Serotonin Depletion™
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“In line with this hypothesis, acute SSRI administration causes a well documented reduction in serotonergic neuron firing, and numerous clinical studies report that hyposerotonergic states (that is, low cerebrospinal fluid levels of the 5-HT [serotonin] metabolite 5-HIAA) correlate with increased impulsive and violent behavior. Because hyposerotonergic states are associated with increased impulsivity and aggressive behavior, and because pediatric populations have increased rates of suicidal ideation and impulsivity during the first month of SSRI treatment, it is plausible that the acute negative effects of SSRIs could be a result of the 5-HT1AR-mediated decrease in serotonergic output during acute treatment.”
Rahn, K. et al. The role of 5-HT1A receptors in mediating acute negative effects of antidepressants: implications in pediatric depression Citation: Transl Psychiatry (2015) 5, e563; doi:10.1038/tp.2015.57
“Thus, early SSRI treatment produces a hyposerotonergic state, known to cause agitation.”
Geller B. KA et al. A Useful Theory on SSRI-Induced Suicidality in Children and Teenagers Transl Psychiatry 2015 May 5
“The SSRIs in therapeutic doses consistently deplete serotonin (induce a hyposerotonergic condition) after several weeks of treatment.”
Dalton S. et al. Use of Selective Serotonin Reuptake Inhibitors and Risk of Upper Gastrointestinal Tract Bleeding Arch Intern Med. 2003;163(1):59-64
“At therapeutic doses fluoxetine and other selective serotonin reuptake inhibitors have consistently been shown to block this reuptake of serotonin by platelets leading to a depletion of serotonin (induce a hyposerotonergic condition) after several weeks of treatment.”
De Abajo, F. et al. Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study BMJ VOLUME 319 23 Oct. 1999
“SSRI-induced UGIH (upper GI Hemorrhage) may occur through SSRI-induced inhibition of serotonin reuptake by platelets, leading to depletion of serotonin (induction of a hyposerotonergic condition) after several weeks of treatment.’
Loke Y. et al. Metanalysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs Aliment Pharmacol Ther 27, 31-40
“Although a causal relationship between abnormal bleeding and SSRIs is unclear, impaired platelet aggregation may result from platelet serotonin depletion (SSRI-induced hyposerotonergic condition) and, thus, contribute to GI bleeding.”
Yuan Y. et al. Selective serotonin reuptake inhibitors and risk of upper GI bleeding: confusion or confounding? Am J Med. 2006 Sep;119(9):719-27
These actions have been related to the important depletion (induction of a hyposerotonergic condition) these drugs produce in the platelet serotonin content,
Abojo, F. et al. Risk of Upper Gastrointestinal Tract Bleeding Associated With Selective Serotonin Reuptake Inhibitors and Venlafaxine Therapy Interaction With Nonsteroidal Anti-inflammatory Drugs and Effect of Acid-Suppressing Agents Arch Gen Psychiatry. 2008;65(7):795-803
“Selective serotonin reuptake inhibitors (SSRIs) have been associated with serotonin depletion (hyposerotonergic condition induction) in platelets,”
Abojo, F. et al. Risk of Upper Gastrointestinal Tract Bleeding Associated With Selective Serotonin Reuptake Inhibitors and Venlafaxine Therapy Interaction With Nonsteroidal Anti-inflammatory Drugs and Effect of Acid-Suppressing Agents Arch Gen Psychiatry. 2008;65(7):795-803
“Serotonin potentiates platelet aggregation. Selective serotonin reuptake inhibitors decrease serotonin uptake from the blood by platelets. Because platelets do not synthesize serotonin, these inhibitors decrease the amount of serotonin (induce a hyposerotonergic condition) in platelets.”
Walraven C. et al. Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort study BMJ Vold 323 22 Sep. 2001
“Platelets do not synthesize their own serotonin and therefore rely on reuptake of serotonin from the plasma, a process that is blocked by SSRIs. Analyses comparing the blood of patients on and off SSRI treatment have shown the former to have significantly lower concentrations of platelet serotonin (induce a hyposerotonergic condition).
Quinn G. et al. Effect of Selective Serotonin Reuptake Inhibitors on Bleeding Risk in Patients with Atrial Fibrillation Taking Warfarin Am J Cardiol. 2014 August 15; 114(4): 583–586.