Neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug-resistant tuberculosis
Background: Cycloserine, or its structural analogue terizidone, has been associated with neuropsychiatric toxicity (psychosis, depression, and neuropathy). Prospective clinical data on the incidence of and risk factors for neuropsychiatric toxicity in TB patients treated with cycloserine are limited...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-04-01
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| Series: | International Journal of Infectious Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S120197122100206X |
| _version_ | 1818669398907420672 |
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| author | Richard Court Chad M. Centner Maxwell Chirehwa Lubbe Wiesner Paolo Denti Nihal de Vries Joseph Harding Tawanda Gumbo Gary Maartens Helen McIlleron |
| author_facet | Richard Court Chad M. Centner Maxwell Chirehwa Lubbe Wiesner Paolo Denti Nihal de Vries Joseph Harding Tawanda Gumbo Gary Maartens Helen McIlleron |
| author_sort | Richard Court |
| collection | DOAJ |
| description | Background: Cycloserine, or its structural analogue terizidone, has been associated with neuropsychiatric toxicity (psychosis, depression, and neuropathy). Prospective clinical data on the incidence of and risk factors for neuropsychiatric toxicity in TB patients treated with cycloserine are limited. Methods: A prospective evaluation of neuropsychiatric toxicity was performed using validated screening tools in patients with multidrug-resistant tuberculosis treated with terizidone. Cox proportional hazard modelling was performed to explore the effects of clinical variables and measures of cycloserine pharmacokinetics in plasma. Results: A total 144 participants were recruited: 86 were male and 58 were female; their median age was 35.7 years and 91 (63%) were HIV-infected. Fifty-five (38%) participants developed at least one neuropsychiatric event (30 cases per 100 person-months): 50 (35%) neuropathy, 14 (10%) depression, and 11 (8%) psychosis. Neuropathy was independently associated with cycloserine clearance ((adjusted hazard ratio 0.34 (aHR), P = 0.03)) and high-dose pyridoxine (200 mg vs 150 mg daily, aHR: 2.79, P = 0.01). Conclusions: A high incidence of early neuropsychiatric toxicity was observed in this cohort of patients treated with terizidone. Cycloserine clearance and higher doses of pyridoxine are associated with incident or worsening peripheral neuropathy. |
| first_indexed | 2024-12-17T06:51:35Z |
| format | Article |
| id | doaj.art-6ae1a1737cf54dba9bf642bea32b1e19 |
| institution | Directory Open Access Journal |
| issn | 1201-9712 |
| language | English |
| last_indexed | 2024-12-17T06:51:35Z |
| publishDate | 2021-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Infectious Diseases |
| spelling | doaj.art-6ae1a1737cf54dba9bf642bea32b1e192022-12-21T21:59:34ZengElsevierInternational Journal of Infectious Diseases1201-97122021-04-01105688694Neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug-resistant tuberculosisRichard Court0Chad M. Centner1Maxwell Chirehwa2Lubbe Wiesner3Paolo Denti4Nihal de Vries5Joseph Harding6Tawanda Gumbo7Gary Maartens8Helen McIlleron9Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa; Corresponding author at: Division of Clinical Pharmacology, K45 Old Main Building, Groote Schuur Hospital, Observatory, Cape Town, 7925, South Africa.Division of Medical Microbiology, University of Cape Town, Cape Town, South AfricaDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South AfricaDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South AfricaDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South AfricaBrooklyn Chest Hospital, Cape Town, South AfricaDP Marais Hospital, Cape Town, South AfricaQuantitative Preclinical and Clinical Sciences Department, Praedicare, Dallas, TX, USADivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa; Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa; Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South AfricaBackground: Cycloserine, or its structural analogue terizidone, has been associated with neuropsychiatric toxicity (psychosis, depression, and neuropathy). Prospective clinical data on the incidence of and risk factors for neuropsychiatric toxicity in TB patients treated with cycloserine are limited. Methods: A prospective evaluation of neuropsychiatric toxicity was performed using validated screening tools in patients with multidrug-resistant tuberculosis treated with terizidone. Cox proportional hazard modelling was performed to explore the effects of clinical variables and measures of cycloserine pharmacokinetics in plasma. Results: A total 144 participants were recruited: 86 were male and 58 were female; their median age was 35.7 years and 91 (63%) were HIV-infected. Fifty-five (38%) participants developed at least one neuropsychiatric event (30 cases per 100 person-months): 50 (35%) neuropathy, 14 (10%) depression, and 11 (8%) psychosis. Neuropathy was independently associated with cycloserine clearance ((adjusted hazard ratio 0.34 (aHR), P = 0.03)) and high-dose pyridoxine (200 mg vs 150 mg daily, aHR: 2.79, P = 0.01). Conclusions: A high incidence of early neuropsychiatric toxicity was observed in this cohort of patients treated with terizidone. Cycloserine clearance and higher doses of pyridoxine are associated with incident or worsening peripheral neuropathy.http://www.sciencedirect.com/science/article/pii/S120197122100206XCycloserineTerizidonePyridoxinePharmacokineticsNeuropathyNeuropsychiatric |
| spellingShingle | Richard Court Chad M. Centner Maxwell Chirehwa Lubbe Wiesner Paolo Denti Nihal de Vries Joseph Harding Tawanda Gumbo Gary Maartens Helen McIlleron Neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug-resistant tuberculosis International Journal of Infectious Diseases Cycloserine Terizidone Pyridoxine Pharmacokinetics Neuropathy Neuropsychiatric |
| title | Neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug-resistant tuberculosis |
| title_full | Neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug-resistant tuberculosis |
| title_fullStr | Neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug-resistant tuberculosis |
| title_full_unstemmed | Neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug-resistant tuberculosis |
| title_short | Neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug-resistant tuberculosis |
| title_sort | neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug resistant tuberculosis |
| topic | Cycloserine Terizidone Pyridoxine Pharmacokinetics Neuropathy Neuropsychiatric |
| url | http://www.sciencedirect.com/science/article/pii/S120197122100206X |
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