Bibliography
Relating to SSRI-induced Serotonin DepletionTM

PLATELETS AND WHOLE BLOOD

“Platelets contain approximately 99% of whole blood serotonin…”
Teodor T. et al. Selective Serotonin Reuptake Inhibitors (SSRIs): Measurement of Effect on Platelet Function Transl Res. 2008 March ; 151(3): 168–172
“Serotonin stored in platelets represents more than 99% of the total serotonin concentration in the human body.”
Renoux C. et al. Association of Selective Serotonin Reuptake Inhibitors With the Risk for Spontaneous Intracranial Hemorrhage JAMA Neurol. 2017;74(2):173-180

DEPLETION AT ONE WEEK

Platelets are depleted of serotonin within the first week, …”
Dall, M. et al. An Association Between Selective Serotonin Reuptake Inhibitor Use and Serious Upper Gastrointestinal Bleeding Clinical Gastroenterology and Hepatology 2009;7:1314 –1321
“In addition, we found a particularly high risk associated with recent start of SSRI therapy. Platelets are depleted of serotonin within the firstweek …”
Dall, M. et al. An Association Between Selective Serotonin Reuptake Inhibitor Use and Serious Upper Gastrointestinal Bleeding Clinical Gastroenterology and Hepatology 2009;7:1314 –1321

DEPLETION AT TWO WEEKS

“Intraplatelet serotonin concentrations are decreased by up to 80% within 2 weeks after initiation of an SA (serotonergic agent [SSRI]).”
Schultz, J. et al. Serotonergic agents increase the incidence of gastrointestinal bleeds in patients with continuous-flow left ventricular assist devices The J of Heart and Lung Transplantation, Vol 35, No 6, June2016

DEPLETION AT THREE WEEKS

“After 3 weeks of treatment (with fluoxetine) … the platelet 5-HT content was significantly reduced by about 90% of its original level.”
Wagner, A. et al. Effects of fl uoxetine treatment of platelet 3H-imipramine binding, 5-HT uptake and 5-HT content in major depressive disorder Journal of Affective Disorders Volume 20, Issue 2, October 1990,Pages 101-113

DEPLETION BEYOND THREE WEEKS

“Depending on the dose and type of medication (SSRI), the platelet 5-HT (serotonin) level can drop to undetectable levels.”
Maurer-Spurej. E. The influence of selective serotonin reuptake inhibitors on human platelet serotonin Thromb Haemost 2004; 91: 119–28
“…serotonin enhances platelet activation induced by adenosine diphosphate and thrombin, and SSRIs can deplete serotonin (induce ahyposerotonergic condition) in platelets by up to 95 %.”
Gagne, J. et al. Selective Serotonin Reuptake Inhibitor Use and Perioperative Bleeding and Mortality in Patients Undergoing Coronary Artery Bypass Grafting: A Cohort Study An International Journal of MedicalToxicology and Drug Experience; Vol. 38, Iss. 11, (Nov 2015): 1075-1082

Additional Information relating to SSRI-induced Serotonin DepletionTM

“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
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) inplatelets,”
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