Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study

Bruce J Kirenga; Levicatus Mugenyi; Marina Sánchez-Rico; Henry Kyobe; Winters Muttamba; Raymond Mugume; Eliya Mwesigwa; Ezra Kalimo; Vicky Nyombi; Ivan Segawa; Loryndah Olive Namakula; Rogers Sekibira; Wilberforce Kabweru; Rosemary Byanyima; Hellen Aanyu; Pauline Byakika-Kibwika; Henry G Mwebesa; Nicolas Hoertel; William Bazeyo

doi:10.1038/s41380-023-02004-3

Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study

Bruce J Kirenga^*, Levicatus Mugenyi, Marina Sánchez-Rico, Henry Kyobe, Winters Muttamba, Raymond Mugume, Eliya Mwesigwa, Ezra Kalimo, Vicky Nyombi, Ivan Segawa, Loryndah Olive Namakula, Rogers Sekibira, Wilberforce Kabweru, Rosemary Byanyima, Hellen Aanyu, Pauline Byakika-Kibwika, Henry G Mwebesa, Nicolas Hoertel, William Bazeyo

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Prior research suggests that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) used for the treatment of obsessive-compulsive disorder and major depressive disorder, could be repurposed against COVID-19. We undertook a prospective interventional open-label cohort study to evaluate the efficacy and tolerability of fluvoxamine among inpatients with laboratory-confirmed COVID-19 in Uganda. The main outcome was all-cause mortality. Secondary outcomes were hospital discharge and complete symptom resolution. We included 316 patients, of whom 94 received fluvoxamine in addition to standard care [median age, 60 years (IQR = 37.0); women, 52.2%]. Fluvoxamine use was significantly associated with reduced mortality [AHR = 0.32; 95% CI = 0.19–0.53; p < 0.001, NNT = 4.46] and with increased complete symptom resolution [AOR = 2.56; 95% CI = 1.53–5.51; p < 0.001, NNT = 4.44]. Sensitivity analyses yielded similar results. These effects did not significantly differ by clinical characteristic, including vaccination status. Among the 161 survivors, fluvoxamine was not significantly associated with time to hospital discharge [AHR 0.81, 95% CI (0.54–1.23), p = 0.32]. There was a trend toward greater side effects with fluvoxamine (7.45% versus 3.15%; SMD = 0.21; χ² = 3.46, p = 0.06), most of which were light or mild in severity and none of which were serious. One hundred mg of fluvoxamine prescribed twice daily for 10 days was well tolerated and significantly associated with reduced mortality and with increased complete symptom resolution, without a significant increase in time to hospital discharge, among inpatients with COVID-19. Large-scale randomized trials are urgently needed to confirm these findings, especially for low- and middle-income countries, where access to vaccines and approved treatments against COVID-19 is limited.

Original language	English
Number of pages	8
Journal	Molecular Psychiatry
DOIs	https://doi.org/10.1038/s41380-023-02004-3
Publication status	Published - 3 Mar 2023

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Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study (dataset)
Muttamba, W. (Creator), GitHub, 2023
https://github.com/mlsrico/fluvoxamine_uganda
Dataset: Software

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Kirenga, B. J., Mugenyi, L., Sánchez-Rico, M., Kyobe, H., Muttamba, W., Mugume, R., Mwesigwa, E., Kalimo, E., Nyombi, V., Segawa, I., Namakula, L. O., Sekibira, R., Kabweru, W., Byanyima, R., Aanyu, H., Byakika-Kibwika, P., Mwebesa, H. G., Hoertel, N., & Bazeyo, W. (2023). Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study. Molecular Psychiatry. https://doi.org/10.1038/s41380-023-02004-3

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title = "Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study",

abstract = "Prior research suggests that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) used for the treatment of obsessive-compulsive disorder and major depressive disorder, could be repurposed against COVID-19. We undertook a prospective interventional open-label cohort study to evaluate the efficacy and tolerability of fluvoxamine among inpatients with laboratory-confirmed COVID-19 in Uganda. The main outcome was all-cause mortality. Secondary outcomes were hospital discharge and complete symptom resolution. We included 316 patients, of whom 94 received fluvoxamine in addition to standard care [median age, 60 years (IQR = 37.0); women, 52.2%]. Fluvoxamine use was significantly associated with reduced mortality [AHR = 0.32; 95% CI = 0.19–0.53; p < 0.001, NNT = 4.46] and with increased complete symptom resolution [AOR = 2.56; 95% CI = 1.53–5.51; p < 0.001, NNT = 4.44]. Sensitivity analyses yielded similar results. These effects did not significantly differ by clinical characteristic, including vaccination status. Among the 161 survivors, fluvoxamine was not significantly associated with time to hospital discharge [AHR 0.81, 95% CI (0.54–1.23), p = 0.32]. There was a trend toward greater side effects with fluvoxamine (7.45% versus 3.15%; SMD = 0.21; χ2 = 3.46, p = 0.06), most of which were light or mild in severity and none of which were serious. One hundred mg of fluvoxamine prescribed twice daily for 10 days was well tolerated and significantly associated with reduced mortality and with increased complete symptom resolution, without a significant increase in time to hospital discharge, among inpatients with COVID-19. Large-scale randomized trials are urgently needed to confirm these findings, especially for low- and middle-income countries, where access to vaccines and approved treatments against COVID-19 is limited.",

author = "Kirenga, {Bruce J} and Levicatus Mugenyi and Marina S{\'a}nchez-Rico and Henry Kyobe and Winters Muttamba and Raymond Mugume and Eliya Mwesigwa and Ezra Kalimo and Vicky Nyombi and Ivan Segawa and Namakula, {Loryndah Olive} and Rogers Sekibira and Wilberforce Kabweru and Rosemary Byanyima and Hellen Aanyu and Pauline Byakika-Kibwika and Mwebesa, {Henry G} and Nicolas Hoertel and William Bazeyo",

note = "Funding: We acknowledge the funding support from the Government of the Republic of Uganda through the Makerere University Research and Innovations Fund (Mak-RIF).",

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doi = "10.1038/s41380-023-02004-3",

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Kirenga, BJ, Mugenyi, L, Sánchez-Rico, M, Kyobe, H, Muttamba, W, Mugume, R, Mwesigwa, E, Kalimo, E, Nyombi, V, Segawa, I, Namakula, LO, Sekibira, R, Kabweru, W, Byanyima, R, Aanyu, H, Byakika-Kibwika, P, Mwebesa, HG, Hoertel, N & Bazeyo, W 2023, 'Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study', Molecular Psychiatry. https://doi.org/10.1038/s41380-023-02004-3

TY - JOUR

T1 - Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda

T2 - a prospective interventional open-label cohort study

AU - Kirenga, Bruce J

AU - Mugenyi, Levicatus

AU - Sánchez-Rico, Marina

AU - Kyobe, Henry

AU - Muttamba, Winters

AU - Mugume, Raymond

AU - Mwesigwa, Eliya

AU - Kalimo, Ezra

AU - Nyombi, Vicky

AU - Segawa, Ivan

AU - Namakula, Loryndah Olive

AU - Sekibira, Rogers

AU - Kabweru, Wilberforce

AU - Byanyima, Rosemary

AU - Aanyu, Hellen

AU - Byakika-Kibwika, Pauline

AU - Mwebesa, Henry G

AU - Hoertel, Nicolas

AU - Bazeyo, William

N1 - Funding: We acknowledge the funding support from the Government of the Republic of Uganda through the Makerere University Research and Innovations Fund (Mak-RIF).

PY - 2023/3/3

Y1 - 2023/3/3

N2 - Prior research suggests that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) used for the treatment of obsessive-compulsive disorder and major depressive disorder, could be repurposed against COVID-19. We undertook a prospective interventional open-label cohort study to evaluate the efficacy and tolerability of fluvoxamine among inpatients with laboratory-confirmed COVID-19 in Uganda. The main outcome was all-cause mortality. Secondary outcomes were hospital discharge and complete symptom resolution. We included 316 patients, of whom 94 received fluvoxamine in addition to standard care [median age, 60 years (IQR = 37.0); women, 52.2%]. Fluvoxamine use was significantly associated with reduced mortality [AHR = 0.32; 95% CI = 0.19–0.53; p < 0.001, NNT = 4.46] and with increased complete symptom resolution [AOR = 2.56; 95% CI = 1.53–5.51; p < 0.001, NNT = 4.44]. Sensitivity analyses yielded similar results. These effects did not significantly differ by clinical characteristic, including vaccination status. Among the 161 survivors, fluvoxamine was not significantly associated with time to hospital discharge [AHR 0.81, 95% CI (0.54–1.23), p = 0.32]. There was a trend toward greater side effects with fluvoxamine (7.45% versus 3.15%; SMD = 0.21; χ2 = 3.46, p = 0.06), most of which were light or mild in severity and none of which were serious. One hundred mg of fluvoxamine prescribed twice daily for 10 days was well tolerated and significantly associated with reduced mortality and with increased complete symptom resolution, without a significant increase in time to hospital discharge, among inpatients with COVID-19. Large-scale randomized trials are urgently needed to confirm these findings, especially for low- and middle-income countries, where access to vaccines and approved treatments against COVID-19 is limited.

AB - Prior research suggests that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) used for the treatment of obsessive-compulsive disorder and major depressive disorder, could be repurposed against COVID-19. We undertook a prospective interventional open-label cohort study to evaluate the efficacy and tolerability of fluvoxamine among inpatients with laboratory-confirmed COVID-19 in Uganda. The main outcome was all-cause mortality. Secondary outcomes were hospital discharge and complete symptom resolution. We included 316 patients, of whom 94 received fluvoxamine in addition to standard care [median age, 60 years (IQR = 37.0); women, 52.2%]. Fluvoxamine use was significantly associated with reduced mortality [AHR = 0.32; 95% CI = 0.19–0.53; p < 0.001, NNT = 4.46] and with increased complete symptom resolution [AOR = 2.56; 95% CI = 1.53–5.51; p < 0.001, NNT = 4.44]. Sensitivity analyses yielded similar results. These effects did not significantly differ by clinical characteristic, including vaccination status. Among the 161 survivors, fluvoxamine was not significantly associated with time to hospital discharge [AHR 0.81, 95% CI (0.54–1.23), p = 0.32]. There was a trend toward greater side effects with fluvoxamine (7.45% versus 3.15%; SMD = 0.21; χ2 = 3.46, p = 0.06), most of which were light or mild in severity and none of which were serious. One hundred mg of fluvoxamine prescribed twice daily for 10 days was well tolerated and significantly associated with reduced mortality and with increased complete symptom resolution, without a significant increase in time to hospital discharge, among inpatients with COVID-19. Large-scale randomized trials are urgently needed to confirm these findings, especially for low- and middle-income countries, where access to vaccines and approved treatments against COVID-19 is limited.

U2 - 10.1038/s41380-023-02004-3

DO - 10.1038/s41380-023-02004-3

M3 - Article

SN - 1359-4184

JO - Molecular Psychiatry

JF - Molecular Psychiatry

ER -

Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study

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Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study (dataset)

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