“Selective serotonin reuptake inhibitors, including fluoxetine, have an influence on blood count parameters.”

All antidepressant classes, including SSRIs, were associated with decreased white blood cell (WBC) count in both short-term and long-term cohorts. This suggests that antidepressants exhibit anti-inflammatory effects on a clinical immune marker, WBC count, which can persist over at least a 1-year timeframe.

Following SSRI treatment in MDD, the red blood cell (RBC) count, hematocrit, and red cell distribution width (RDW) significantly increased. Hemoglobin tended to increase, while MCV, MCH, and MCHC values decreased significantly. White blood cell count, neutrophil percentage, monocyte count, and monocyte and basophil percentages decreased significantly, whereas the percentage of lymphocytes significantly increased.

All antidepressant classes, including SSRIs, were associated with decreased white blood cell (WBC) count in the long-term cohorts. SSRI use was specifically associated with a decrease of 0.24 thousand cells/μL in neutrophil count in the 1-year cohort.

Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), is rarely associated with hematological side effects such as thrombocytopenia, which is a significant decline in platelet count. By depleting serotonin stores, SSRIs can impair platelet function, potentially leading to bleeding tendencies or, rarely, thrombocytopenia.

Drugs with the highest degree of serotonin reuptake inhibition, such as fluoxetine, paroxetine, and sertraline, are more frequently associated with abnormal bleeding and modifications of hemostasis markers, including decreased platelet aggregability and activity, and prolongation of bleeding time. However, some studies have reported no changes in platelet aggregation or coagulation parameters after fluoxetine or paroxetine use.

Fluoxetine has been reported to produce bruising, bleeding, and other hematologic disorders, including thrombocytopenia. The mechanism behind these adverse effects is the prevention of serotonin-induced amplification of platelet aggregation by fluoxetine, which reduces or depletes platelet serotonin stores.

A study investigating the effects of SSRIs on coagulation profile found a significant increase in bleeding time in patients receiving fluoxetine after 3 months of treatment, but this remained within the normal range. No significant differences were observed for clotting time, platelet count, prothrombin time, and partial thromboplastin time with kaolin.

Platelets also express the serotonin transporter. Therefore, when SSRIs are used, they result in decreased storage of serotonin in platelet dense granules. Platelet serotonin depletion leads to decreased platelet aggregation amplification and can potentially lead to increased bleeding in patients on SSRIs or other antidepressants.

The present study reveals a stimulatory effect of fluoxetine on eryptosis, the suicidal death of erythrocytes. The concentrations required to stimulate eryptosis are only moderately higher than the concentrations encountered in vivo. Thus, a stimulation of eryptosis is only expected at toxic dosages of fluoxetine or at a particular sensitivity of the erythrocytes.

This study provides quantitative real‐world evidence of the risk of thrombocytopenia by SSRIs and SNRIs marketed in Japan. The results suggest that the risk of thrombocytopenia by sertraline or fluvoxamine was comparable to that by paroxetine, leading to the revision of the sertraline PI as a regulatory safety measure.

Among SSRIs, sertraline and fluvoxamine showed a relatively higher point estimate of aHR > 1.0 (1.23 [95% confidence interval: 0.78-1.94] and 1.48 [0.87-2.51], respectively). The results suggest that the risk of thrombocytopenia by sertraline or fluvoxamine was comparable to that by paroxetine, known as having the risk of thrombocytopenia, leading to the revision of the sertraline package insert as a regulatory safety measure.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) intake were associated with lower hemoglobin level (β = -0.11; p = .01).

There have been rare reports of altered platelet function and/or abnormal results from laboratory studies in patients taking fluoxetine, with some reports of abnormal bleeding. The mechanism behind these adverse effects is the prevention of serotonin-induced amplification of platelet aggregation by fluoxetine, which reduces or depletes platelet serotonin stores.

A critical literature examination reveals very low certainty of evidence on potential SSRI effect on platelet functions, with findings often inconsistent even when similar methods are used, likely due to differences in study design, patient characteristics, SSRI type and dose, and uncontrolled confounding factors.

The risk of thrombocytopenia associated with SSRIs is generally low, but it can occur within the first few months of treatment or after a dose increase. Common SSRIs that may cause this side effect include fluoxetine, sertraline, paroxetine, and escitalopram.

Investigators examined the relationship between the long-term use of proton pump inhibitors, oral anticoagulants, antidepressants, antiplatelets and nonsteroidal anti-inflammatory drugs and the risk of iron deficiency anemia among 1,210 adult patients. Although there were no significant associations between antidepressants, antiplatelets and nonsteroidal anti-inflammatory drugs, the investigators found that the use of proton pump inhibitors and oral anticoagulants were associated with the risk of iron deficiency anemia.

The evidence clearly shows that routine blood tests are not necessary for patients taking SSRIs, unlike some other psychiatric medications such as valproate which requires complete blood counts. Clinical monitoring for therapeutic response and side effects remains the cornerstone of appropriate SSRI management.

Complete blood count (CBC) parameters and inflammatory ratios should also be examined, as SSRI treatment can impact these values. The following CBC parameters may be affected by Prozac treatment: Red blood cell (RBC) count, Hematocrit, Red cell distribution width (RDW), Hemoglobin, Mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), Mean corpuscular hemoglobin concentration (MCHC), White blood cell count, Neutrophil percentage, Monocyte count, Monocyte and basophil percentages, Lymphocyte percentage, Neutrophil-to-lymphocyte ratio (NLR), Monocyte-to-lymphocyte ratio (MLR), Platelet count, Platelet-to-lymphocyte ratio (PLR).

A case study describes a patient who developed leukopenia (WBC 3.04x10^9/L) without neutropenia after starting citalopram, an SSRI. Repeat blood tests showed continued low WBC, and later, with sertraline, WBC fell to 2.83x10^9/L. This highlights that some antidepressants can decrease white blood cell counts.

A 59-year-old woman presented with moderate neutropenia detected in a routine blood test, with 1300 neutrophils. After ruling out other causes, fluoxetine was progressively withdrawn, and a blood test two months later showed 4100 neutrophils, with the rest of the parameters normal, suggesting fluoxetine-induced neutropenia.

Regarding the complete blood count, the most important results that were obtained were related to HCT, MCV, MCHC and Mono. HCT and MCV increased during the withdrawal period, whereas MCHC and Mono decreased during the same period. The study concluded that the use of fluoxetine in dogs is safe, and does not seem to change any parameter that could affect the behavior of the animal.