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Keywords:

  • bupropion;
  • escitalopram;
  • platelet count;
  • venlafaxine

Abstract

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. REFERENCES

The objective of the present study was to evaluate changes in platelet counts on three different kinds of antidepressant. All subjects (n = 131) in their drug-naïve state had been diagnosed with depression. Escitalopram (n = 42), venlafaxine (n = 50) and bupropion (n = 39) were prescribed, and platelet count was measured before and after 1 month of treatment and compared. Decrease in platelet count on escitalopram was significant, while the others were not. These findings suggest that escitalopram may be associated with decreased platelet count, and bupropion is less likely to exert an influence on platelet count.

IT IS WELL known that depression and antidepressants affect platelets. Neurons and platelets share similar serotonin (5-hydroxytryptamine, 5-HT) profiles, so the changes in 5-HT2A receptor and 5-HT transporter (5-HTT) on the surface of platelets can act as a surrogate biomarker for depression.1 Selective serotonin re-uptake inhibitors (SSRI) have inhibitory effects on 5-HTT and 5-HT receptors of platelets, thereby diminishing platelet aggregation.2 There have been many reports of SSRI causing reductions in platelet count and sometimes resulting in thrombocytopenia.3–6 Therefore, bleeding can be a complex result of altered platelet aggregation and reduced platelet count. Whether antidepressants that have less of a serotonergic effect also have a smaller effect on platelets, however, remains questionable. Platelets also have α2-adrenoreceptors, and an increase in the number of platelet α2-adrenoreceptors is associated with thrombosis.7 Noradrenergic drugs have an influence on platelets, but there are fewer reports on them compared to SSRI.

In this study, we compared the change in platelet count on escitalopram, venlafaxine and bupropion, as representative of SSRI; serotonin and noradrenaline re-uptake inhibitors (SNRI); and noradrenaline and dopamine re-uptake inhibitors (NDRI), respectively.

METHODS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. REFERENCES

The study involved a retrospective review of patients who were admitted to Yeouido St Mary's Hospital between 1 January 2005 and 31 August 2011. All patients were diagnosed with depressive disorders according to DSM-IV and did not have any other psychiatric or physical disorder. We selected patients who had been prescribed either escitalopram, venlafaxine or bupropion without any other kinds of antidepressants, mood stabilizers or antipsychotics.

A total of 131 patients (escitalopram, n = 42; venlafaxine, n = 50; bupropion, n = 39) were enrolled in the study. We reviewed patient demographics and laboratory data and compared the three groups using repeated-measures anova. We then applied multiple comparisons during post-hoc analysis. spss 18.0 (SPSS, Chicago, IL, USA) was used for statistical analysis.

RESULTS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. REFERENCES

There were no significant differences with regard to demographics and clinical characteristics (Table 1). The changes in platelet count were different among the three antidepressant groups (P < 0.001) and the platelet count for the escitalopram group was significantly greater compared to both the venlafaxine and bupropion groups. For the escitalopram group, there was a significant change in platelet count (246.2 ± 55.7 × 109/L vs 235.9 ± 57.0 × 109/L, P = 0.011). For the venlafaxine and bupropion groups, there were no significant changes (Table 2), but venlafaxine might have the ability to decrease platelet count (253.0 ± 47.8 × 109/L vs 249.6 ± 44.8 × 109/L, P = 0.068).

Table 1.  Subject characteristics vs antidepressant
VariablesEscitalopram (n = 42)Venlafaxine (n = 50)Bupropion (n = 39)P
  • Checked on 28th hospital day. BMI, body mass index; GAF, Global Assessment of Functioning; NA, not applicable.

Sex, n (%)    
 Female28 (66.7)31 (62.0)23 (59.0)0.376
Age (years)44.4 ± 13.643.5 ± 14.539.5 ± 13.20.088
Diagnosis, n (%)    
 Major depressive disorder31 (73.8)38 (74.0)27 (69.2)0.138
 Dysthymic disorder3 (7.1)5 (10.0)5 (12.8)0.145
 Depressive disorder not otherwise specified8 (19.0)7 (16.0 )7 (17.9)0.379
Baseline BMI (kg/m2)23.3 ± 4.022.8 ± 3.223.2 ± 2.40.144
Dose range (mg/day)10–20150–225150–300NA
Mean dose (mg/day)15.5 ± 4.3175.8 ± 34.6191.1 ± 90.0NA
Concomitance of medications, n (%)    
 Benzodiazepines40 (95.2)45 (90.0)37 (94.9)0.402
 Beta-blocker5 (11.9)10 (20.0)5 (12.8)0.083
Duration of admission (days)36.1 ± 12.433.7 ± 5.131.1 ± 10.90.195
Baseline GAF33.4 ± 18.234.6 ± 8.440.2 ± 11.80.076
Table 2.  Change in platelet count (×109/L) vs antidepressant
 Before treatment1 month of treatmentP
  • anova and post-hoc analysis (P < 0.001 [a < b,c]).

Escitaloprama246.2 ± 55.7235.9 ± 57.00.011
Venlafaxineb253.0 ± 47.8249.6 ± 44.80.068
Bupropionc250.9 ± 53.8249.1 ± 52.40.441

In all groups, patient age, initial Global Assessment of Functioning score, dose range and degree of decrease in platelet count did not correlate. There was no thrombocytopenia (platelet count <130 × 109/L) and no clinical event related to hematological change in any group.

DISCUSSION

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. REFERENCES

The present results show that escitalopram can decrease platelet count and that venlafaxine has a tendency toward decreased platelet count, while bupropion does not. The degree of serotonergic properties and the change in platelet count could be correlated. Escitalopram is a potent highly selective 5-HT re-uptake inhibitor, while bupropion lacks serotonergic properties. Venlafaxine is generally known to inhibit 5-HT selectively at low doses, and both 5-HT and noradrenaline at high doses.8 In this study, the dosage range of venlafaxine was only 150–225 mg/day and there was no correlation between that dose range and decrease in platelet count. As a result, we did not observe lower dose effects of venlafaxine on platelet count.

Depressed patients tend to have elevated platelet counts, and increased numbers of binding sites for procoagulatory factors on the surface.9 It has been shown that inhibition of 5-HT re-uptake by SSRI reduces platelet 5-HT levels, which leads to diminished release of 5-HT from platelets on activation, and decreases platelet aggregation.5 In the case of escitalopram, there was a report that it normalized mean platelet volume, which had been increased in patients with depression,10 and it also appears to inhibit platelet aggregation induced by adenosine diphosphate and collagen.11

Moreover, thrombocytopenia induced by antidepressants has been reported.3,4,12 It is believed that drugs that have an affinity with the surface of platelets can induce immune mechanisms via drug-dependent anti-platelet antibodies. Antibodies that recognize an epitope on the platelet glycoprotein complex (GPIb/IX, GPV, GPIIb/IIIa) have been bound by antidepressants.13 Decreases in platelet count are thought to occur as a complex result of serotonergic, noradrenergic inhibition and drug-dependent immune activation.

In general, decreased platelet counts induced by SSRI are not associated with severe bleeding such as thrombocytopenia. This can be attributed to the wide normal ranges for platelet count. Potential adverse effects of the combination of non-steroidal anti-inflammatory drugs and anti-platelet agents, however, should be considered. Another concern is that the individuals who have underlying platelet disorders and low platelet count or a history of unexplained bruising should be treated with non-serotonergic drug such as bupropion. In these cases when SSRI are prescribed, more careful monitoring should be conducted.

The main limitations of this study were the retrospective design and the low number of subjects. Also, we could assess only complete blood count performed as a routine test 1 month after admission. Another concern was that the correlation between the change in severity of depressive symptoms and platelet count was not evaluated owing to the lack of standard rating scales in the medical records.

Despite such limitations, this study excluded the possible effects of underlying physical illnesses, other concomitant medication use and inter-individual dietary differences in a closed ward setting. And considering that the hematological side-effects of psychiatric drugs occur often at the start of treatment,6 platelet count after 1 month of antidepressant use may be informative.

Large prospective studies using various platelet indicators are needed, and potential individual factors that may be associated with platelet disturbance on antidepressants should be examined.

ACKNOWLEDGMENT

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. REFERENCES

This research was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A102065).

REFERENCES

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. REFERENCES
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