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Zhong L, Yue Y, Liu X, Chen H, Qian Y, Tang W, Chen B, Yuan Y, Shao H. The effects of six antidepressants on electrolytes, hepatic and renal functions, and glycolipid metabolism in patients with major depressive disorder. J Affect Disord 2025; 380:734-741. [PMID: 40169121 DOI: 10.1016/j.jad.2025.03.172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 03/26/2025] [Accepted: 03/29/2025] [Indexed: 04/03/2025]
Abstract
BACKGROUND Most antidepressants with similar pharmacological characteristics exhibit comparable therapeutic efficacy but differ in side effects. Therefore, we used a retrospective design to compare biochemical changes induced by six antidepressants and identify differences among them. METHODS Case records from 1706 hospitalized patients with major depressive disorder (MDD) receiving antidepressant monotherapy were divided into six groups based on the specific antidepressants used: paroxetine, sertraline, fluoxetine, escitalopram, venlafaxine, and duloxetine. Electrolytes, hepatic and renal functions, body weight, and glycolipid metabolism were assessed at baseline and 2 weeks post-antidepressant initiation. Paired analysis was used for comparing the changes prior to and after administration within each group, and analysis of covariance was used for evaluating the distinctions among the six groups. RESULTS After 2 weeks of treatment, significant decreases in serum sodium and chloride levels were observed with venlafaxine, duloxetine, and fluoxetine, while potassium, phosphorus, and carbon dioxide concentrations tended to increase across all six antidepressants. In terms of hepatic indicators, these antidepressants significantly elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (GGT) levels, with duloxetine showing the most pronounced changes from baseline, while decreasing total and direct bilirubin. Sertraline effectively reduced uric acid, although changes in renal indicators were mild with other antidepressants. Notably, these antidepressants were associated with an unfavorable lipid profile, particularly elevated triglycerides and cholesterol, but they lowered blood glucose during the acute phase. LIMITATION Residual confounding may indirectly influence the retrospective outcomes. CONCLUSION Early biochemical changes can distinguish differences among antidepressants and guide individualized medication.
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Affiliation(s)
- Lingjun Zhong
- Department of Pharmacy, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Yingying Yue
- Department of Psychiatry and Psychosomatics, Zhongda Hospital, School of Medicine, Jiangsu Provincial Key Laboratory of Brain Science and Medicine, Southeast University, Nanjing, China
| | - Xiaoyun Liu
- Department of Psychiatry and Psychosomatics, Zhongda Hospital, School of Medicine, Jiangsu Provincial Key Laboratory of Brain Science and Medicine, Southeast University, Nanjing, China
| | - Hualing Chen
- Department of Biostatistics, School of Public Health, Southeast University, Nanjing, China
| | - Yongkang Qian
- Department of Biostatistics, School of Public Health, Southeast University, Nanjing, China
| | - Wei Tang
- Department of Pharmacy, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Bingwei Chen
- Department of Biostatistics, School of Public Health, Southeast University, Nanjing, China.
| | - Yonggui Yuan
- Department of Psychiatry and Psychosomatics, Zhongda Hospital, School of Medicine, Jiangsu Provincial Key Laboratory of Brain Science and Medicine, Southeast University, Nanjing, China.
| | - Hua Shao
- Department of Pharmacy, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
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Sugunan S, K P L, Menon B. Vortioxetine-associated syndrome of inappropriate ADH secretion. BMJ Case Rep 2025; 18:e262735. [PMID: 40010753 DOI: 10.1136/bcr-2024-262735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/28/2025] Open
Abstract
This case report presents the first documented instance of vortioxetine-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH) in India. Vortioxetine, a newer antidepressant, was prescribed to an elderly male in his 80s with major depressive disorder, in combination with mirtazapine. Despite initial improvement in mood, he developed hyponatraemia, a rare but serious side effect possibly linked to vortioxetine's serotonergic action. The patient exhibited symptoms such as giddiness and confusion, prompting the discontinuation of vortioxetine and initiation of corrective treatment. His condition improved, with sodium levels returning to normal while he was maintained on mirtazapine alone. This case underscores vortioxetine's potential to induce SIADH, highlighting the need for careful monitoring and the consideration of alternative antidepressants in vulnerable populations.
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Affiliation(s)
- Sreedevi Sugunan
- Psychiatry, Amrita Institute of Medical Sciences, Kochi, Kerala, India
| | - Lakshmi K P
- Psychiatry, Amrita Institute of Medical Sciences, Kochi, Kerala, India
| | - Bindu Menon
- Psychiatry, Amrita Institute of Medical Sciences, Kochi, Kerala, India
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Djukic M, Grewe J, Kunz O, Gross O, Nau R. Hyponatremia in geriatric patients. Z Gerontol Geriatr 2025; 58:40-45. [PMID: 39143233 DOI: 10.1007/s00391-024-02342-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 07/21/2024] [Indexed: 08/16/2024]
Abstract
Hyponatremia is the most frequent electrolyte imbalance in geriatric medicine. Causes of hyponatremia were retrospectively analyzed in all in-patients treated in 2016 (N = 2267, 1564 women, 703 men, mean age ± standard deviation 81.9 ± 7.6 years). Any form of hyponatremia on admission, during the stay or on discharge was noted in 308 patients (13.6%, 231 women, 77 men; mean age ± standard deviation 83.1 ± 7.3 years, p = 0.009 vs. age of all patients). Women had a higher probability of developing hyponatremia compared to men (p = 0.019), 131 patients were hypovolemic, and dyspnea as an indicator of hypervolemia was noted in 71 patients.Only 12 patients suffering from hyponatremia (3.9%) did not receive any of the potentially sodium-lowering drugs assessed (diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, antidepressants, neuroleptics, nonsteroidal antirheumatics, carbamazepine, oxcarbazepine). The median number of drugs per patient potentially lowering the plasma sodium level was 3 and the maximum number was 7.Hypovolemic hyponatremia and the syndrome of inadequate antidiuretic hormone secretion were the most important causes of hyponatremia. Adverse drug effects were the main origins of both conditions. In patients with hyponatremia the drug load influencing plasma sodium level should be minimized, thiazide diuretics should be avoided and older individuals should receive a diet with sufficient salt content.
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Affiliation(s)
- Marija Djukic
- Department of Neuropathology, University Medicine Göttingen, Georg-August-University Göttingen, 37075, Göttingen, Germany
- Department of Geriatrics, Protestant Hospital Göttingen-Weende, An der Lutter 24, 37075, Göttingen, Germany
| | - Jeannine Grewe
- Department of Neuropathology, University Medicine Göttingen, Georg-August-University Göttingen, 37075, Göttingen, Germany
| | - Olga Kunz
- Amedes MVZ for Laboratory Medicine, Medical Microbiology and Infectiology, 37077, Göttingen, Germany
| | - Oliver Gross
- Department of Nephrology and Rheumatology, University Medicine Göttingen, Georg-August-University Göttingen, 37075, Göttingen, Germany
| | - Roland Nau
- Department of Neuropathology, University Medicine Göttingen, Georg-August-University Göttingen, 37075, Göttingen, Germany.
- Department of Geriatrics, Protestant Hospital Göttingen-Weende, An der Lutter 24, 37075, Göttingen, Germany.
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Lane NE, Bai L, Seitz DP, Juurlink DN, Paterson JM, Guan J, Stukel TA. Hyponatremia-associated hospital visits are not reduced by early electrolyte testing in older adults starting antidepressants. J Am Geriatr Soc 2024; 72:1770-1780. [PMID: 38662854 DOI: 10.1111/jgs.18930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 03/21/2024] [Accepted: 03/29/2024] [Indexed: 06/19/2024]
Abstract
BACKGROUND Clinical practice guidelines recommend early serum electrolyte monitoring when starting antidepressants in older adults due to the increased risk of hyponatremia. It is unclear whether this monitoring improves outcomes. METHODS Population-based, retrospective cohort study of Ontario adults aged ≥66 years who initiated therapy with a selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI) between April 1, 2013, and January 31, 2020. The index date was the date of the first such prescription, and the exposure of interest was serum electrolyte measurement during the subsequent 7 days. The primary outcome was any emergency department or hospital admission with hyponatremia within 8-60 days of antidepressant initiation. Poisson regression models compared individuals who had versus did not have their serum electrolytes tested in the week following SSRI/SNRI initiation, weighting by propensity score-based overlap weights. RESULTS Among the 420,085 patients aged ≥66 years initiating treatment with an SSRI/SNRI, 26,808 (6.4%) had serum electrolytes measured in the subsequent 7 days and 6109 (1.5%) subsequently presented to hospital with hyponatremia. The time from drug initiation to hospitalization varied (median 29, interquartile range [IQR] 17-44 days), and the median sodium concentration measured in the community (136, IQR 133-138 mmol/L) was marginally higher than those at the time of hospitalization (132, IQR 130-134 mmol/L). Patients who underwent electrolyte testing in the week following SSRI/SNRI treatment were more likely to attend an emergency department (ED) or hospital with hyponatremia within 8-60 days relative to those who did not (relative risk = 2.31, 95% confidence interval: 2.16-2.46). CONCLUSIONS Testing serum electrolytes in the week after starting an SSRI/SNRI is not associated with a reduced risk of a hospital visit with hyponatremia. These findings do not support current guidelines recommending routine electrolyte monitoring.
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Affiliation(s)
- Natasha E Lane
- Division of Geriatric Medicine, University of Toronto, Toronto, Ontario, Canada
- ICES, Toronto, Ontario, Canada
| | - Li Bai
- ICES, Toronto, Ontario, Canada
| | - Dallas P Seitz
- Department of Psychiatry and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - David N Juurlink
- ICES, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- Division of General Internal Medicine, Sunnybrook, Toronto, Ontario, Canada
- Division of Clinical Pharmacology and Toxicology, Sunnybrook, Toronto, Ontario, Canada
| | - J Michael Paterson
- ICES, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | | | - Therese A Stukel
- ICES, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
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Gheysens T, Van Den Eede F, De Picker L. The risk of antidepressant-induced hyponatremia: A meta-analysis of antidepressant classes and compounds. Eur Psychiatry 2024; 67:e20. [PMID: 38403888 PMCID: PMC10966618 DOI: 10.1192/j.eurpsy.2024.11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 09/13/2023] [Accepted: 02/08/2024] [Indexed: 02/27/2024] Open
Abstract
BACKGROUND Hyponatremia (hypoNa) is a potentially serious adverse event of antidepressant treatment. Previous research suggests the risk of drug-induced hyponatremia differs between antidepressants. This meta-analysis sought to determine the risk of antidepressant-induced hypoNa, stratified by different compounds and classes. METHODS A PRISMA-compliant systematic search of Web of Science and PubMed databases was performed from inception until Jan 5, 2023, for original studies reporting incidences or risks of hypoNa in adults using antidepressants. We modelled random-effects meta-analyses to compute overall event rates and odds ratios of any and clinically relevant hypoNa for each compound and class, and ran head-to-head comparisons based on hypoNa event rates. We conducted subgroup analyses for geriatric populations and sodium cut-off value. The study is registered with PROSPERO, CRD42021269801. RESULTS We included 39 studies (n = 8,175,111). Exposure to antidepressants was associated with significantly increased odds of hypoNa (k = 7 studies, OR = 3.160 (95%CI 1.911-5.225)). The highest event rates were found for SNRIs (7.44%), SSRIs (5.59%), and TCAs (2.66%); the lowest for mirtazapine (1.02%) and trazodone (0.89%). Compared to SSRIs, SNRIs were significantly more likely (k = 10, OR = 1.292 (1.120 - 1.491), p < 0.001) and mirtazapine significantly less likely (k = 9, OR = 0.607 (0.385 - 0.957), p = 0.032) to be associated with hypoNa. CONCLUSION Our meta-analysis demonstrated that, while no antidepressant can be considered completely risk-free, for hypoNa-prone patients mirtazapine should be considered the treatment of choice and SNRIs should be prescribed more cautiously than SSRIs and TCAs.
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Affiliation(s)
- Tim Gheysens
- Collaborative Antwerp Psychiatric Research Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Scientific Initiative of Neuropsychiatric and Psychopharmacological Studies, University Psychiatric Centre Campus Duffel, Duffel, Belgium
| | - Filip Van Den Eede
- Collaborative Antwerp Psychiatric Research Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Department of Psychiatry, Antwerp University Hospital, Edegem (Antwerp), Belgium
| | - Livia De Picker
- Collaborative Antwerp Psychiatric Research Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Scientific Initiative of Neuropsychiatric and Psychopharmacological Studies, University Psychiatric Centre Campus Duffel, Duffel, Belgium
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Inoue M, Nakai K, Tanaka S, Mitsuiki K, Tokumoto M, Tsuruya K, Kitazono T, Nakano T. Prevalence of hyponatremia and associated factors in patients with chronic kidney disease: the Fukuoka Kidney Disease Registry (FKR) study. Clin Exp Nephrol 2023; 27:1023-1031. [PMID: 37642786 DOI: 10.1007/s10157-023-02395-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 08/11/2023] [Indexed: 08/31/2023]
Abstract
BACKGROUND Hyponatremia is a common and important electrolyte disorder. However, the prevalence and factors associated with hyponatremia in patients with chronic kidney disease (CKD) are unknown. METHODS We studied the factors associated with hyponatremia (< 135 mEq/L) in CKD patients registered in the Fukuoka Kidney Disease Registry (FKR) study using a logistic regression model variable selected using the variable reduction method. RESULTS We analyzed the baseline characteristics of 4367 participants with CKD (age, 64 ± 16 years; male, 56.1%). Hyponatremia was detected in 2.0% of the patients at baseline, and multivariate logistic analysis showed that the independent factors for hyponatremia were body mass index (odds ratio [OR] 0.91; 95% confidence interval [CI] 0.85-0.97), prescription of benzodiazepine (OR 2.31; 95% CI 1.39-3.86), blood hemoglobin level (OR 0.76; 95% CI 0.65-0.88), and serum C-reactive protein level (OR 1.27; 95% CI 1.04-1.54). CONCLUSION The cross-sectional analysis using baseline data from the FKR study revealed independent factors associated with hyponatremia in patients with decreased kidney function. Longitudinal analyses of the FKR cohort are needed to evaluate the effects of these factors on the prognosis of hyponatremia in patients with CKD.
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Affiliation(s)
- Megumi Inoue
- Division of Nephrology and Dialysis Center, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan
| | - Kentaro Nakai
- Division of Nephrology and Dialysis Center, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan
| | - Shigeru Tanaka
- Department of Medicine and Clinical Science, Graduated School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 8128582, Japan
| | - Koji Mitsuiki
- Division of Nephrology and Dialysis Center, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan
| | - Masanori Tokumoto
- Division of Nephrology and Dialysis Center, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan
| | - Kazuhiko Tsuruya
- Department of Nephrology, Nara Medical University, Kashihara, Japan
| | - Takanari Kitazono
- Department of Medicine and Clinical Science, Graduated School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 8128582, Japan
| | - Toshiaki Nakano
- Department of Medicine and Clinical Science, Graduated School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 8128582, Japan.
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Muacevic A, Adler JR, Gutlapalli SD, Prakash K, Swarnakari KM, Bai M, Manoharan MP, Raja R, Desai A, Desai DM, Arcia Franchini AP. Poststroke Depression, An Underrated Clinical Dilemma: 2022. Cureus 2022; 14:e32948. [PMID: 36712776 PMCID: PMC9879592 DOI: 10.7759/cureus.32948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Accepted: 12/25/2022] [Indexed: 12/28/2022] Open
Abstract
It is known that the majority of patients are prone to develop depression following a stroke. Several biological factors, including the disruption of the hypothalamic and adrenal axis and changes in cortisol and interleukin 6 (IL6), are said to have an essential role in its development. Magnetic resonance imaging (MRI) scans point toward white matter lesions and lacunar infarcts as the primary pathological culprit. People affected by poststroke depression (PSD) are more likely to commit suicide or develop another ischemic event after the initial episode, which can likely increase the mortality related to PSD and stroke. Selective serotonin reuptake inhibitors (SSRIs) are the mainstay of treatment for PSD. However, it has a poor safety profile and is not very productive, making the use of SSRIs controversial, and further studies are required to prove its benefits concerning PSD. This literature review discusses the importance of PSD, how it impacts the quality of life of people affected by stroke, and its treatment.
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Kim GH. Pathophysiology of Drug-Induced Hyponatremia. J Clin Med 2022; 11:jcm11195810. [PMID: 36233678 PMCID: PMC9572915 DOI: 10.3390/jcm11195810] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 09/26/2022] [Accepted: 09/28/2022] [Indexed: 11/16/2022] Open
Abstract
Drug-induced hyponatremia caused by renal water retention is mainly due to syndrome of inappropriate antidiuresis (SIAD). SIAD can be grouped into syndrome of inappropriate antidiuretic hormone secretion (SIADH) and nephrogenic syndrome of inappropriate antidiuresis (NSIAD). The former is characterized by uncontrolled hypersecretion of arginine vasopressin (AVP), and the latter is produced by intrarenal activation for water reabsorption and characterized by suppressed plasma AVP levels. Desmopressin is useful for the treatment of diabetes insipidus because of its selective binding to vasopressin V2 receptor (V2R), but it can induce hyponatremia when prescribed for nocturnal polyuria in older patients. Oxytocin also acts as a V2R agonist and can produce hyponatremia when used to induce labor or abortion. In current clinical practice, psychotropic agents, anticancer chemotherapeutic agents, and thiazide diuretics are the major causes of drug-induced hyponatremia. Among these, vincristine and ifosfamide were associated with sustained plasma AVP levels and are thought to cause SIADH. However, others including antipsychotics, antidepressants, anticonvulsants, cyclophosphamide, and thiazide diuretics may induce hyponatremia by intrarenal mechanisms for aquaporin-2 (AQP2) upregulation, compatible with NSIAD. In these cases, plasma AVP levels are suppressed by negative feedback. In rat inner medullary collecting duct cells, haloperidol, sertraline, carbamazepine, and cyclophosphamide upregulated V2R mRNA and increased cAMP production in the absence of vasopressin. The resultant AQP2 upregulation was blocked by a V2R antagonist tolvaptan or protein kinase A (PKA) inhibitors, suggestive of the activation of V2R-cAMP-PKA signaling. Hydrochlorothiazide can also upregulate AQP2 in the collecting duct without vasopressin, either directly or via the prostaglandin E2 pathway. In brief, nephrogenic antidiuresis, or NSIAD, is the major mechanism for drug-induced hyponatremia. The associations between pharmacogenetic variants and drug-induced hyponatremia is an area of ongoing research.
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Affiliation(s)
- Gheun-Ho Kim
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul 04763, Korea
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Sidhom E, O’Brien JT, Butcher AJ, Smith HL, Mallucci GR, Underwood BR. Targeting the Unfolded Protein Response as a Disease-Modifying Pathway in Dementia. Int J Mol Sci 2022; 23:2021. [PMID: 35216136 PMCID: PMC8877151 DOI: 10.3390/ijms23042021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 01/19/2022] [Accepted: 01/26/2022] [Indexed: 01/27/2023] Open
Abstract
Dementia is a global medical and societal challenge; it has devastating personal, social and economic costs, which will increase rapidly as the world's population ages. Despite this, there are no disease-modifying treatments for dementia; current therapy modestly improves symptoms but does not change the outcome. Therefore, new treatments are urgently needed-particularly any that can slow down the disease's progression. Many of the neurodegenerative diseases that lead to dementia are characterised by common pathological responses to abnormal protein production and misfolding in brain cells, raising the possibility of the broad application of therapeutics that target these common processes. The unfolded protein response (UPR) is one such mechanism. The UPR is a highly conserved cellular stress response to abnormal protein folding and is widely dysregulated in neurodegenerative diseases. In this review, we describe the basic machinery of the UPR, as well as the evidence for its overactivation and pathogenicity in dementia, and for the marked neuroprotective effects of its therapeutic manipulation in murine models of these disorders. We discuss drugs identified as potential UPR-modifying therapeutic agents-in particular the licensed antidepressant trazodone-and we review epidemiological and trial data from their use in human populations. Finally, we explore future directions for investigating the potential benefit of using trazodone or similar UPR-modulating compounds for disease modification in patients with dementia.
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Affiliation(s)
- Emad Sidhom
- Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, UK; (E.S.); (A.J.B.); (H.L.S.); (G.R.M.)
- Department of Clinical Neurosciences, UK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK
- Cambridgeshire and Peterborough NHS Foundation Trust, Windsor Research Unit, Fulbourn Hospital, Cambridge CB21 5EF, UK
- Gnodde Goldman Sachs Translational Neuroscience Unit, Windsor Research Unit, University of Cambridge, Cambridge CB2 1TN, UK
| | - John T. O’Brien
- Department of Psychiatry, University of Cambridge, Herchel Smith Building, Forvie Site, Cambridge CB2 0SZ, UK;
| | - Adrian J. Butcher
- Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, UK; (E.S.); (A.J.B.); (H.L.S.); (G.R.M.)
- Department of Clinical Neurosciences, UK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK
| | - Heather L. Smith
- Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, UK; (E.S.); (A.J.B.); (H.L.S.); (G.R.M.)
- Department of Clinical Neurosciences, UK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK
| | - Giovanna R. Mallucci
- Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, UK; (E.S.); (A.J.B.); (H.L.S.); (G.R.M.)
- Department of Clinical Neurosciences, UK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK
| | - Benjamin R. Underwood
- Cambridgeshire and Peterborough NHS Foundation Trust, Windsor Research Unit, Fulbourn Hospital, Cambridge CB21 5EF, UK
- Gnodde Goldman Sachs Translational Neuroscience Unit, Windsor Research Unit, University of Cambridge, Cambridge CB2 1TN, UK
- Department of Psychiatry, University of Cambridge, Herchel Smith Building, Forvie Site, Cambridge CB2 0SZ, UK;
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10
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Pinkhasov A, Xiong G, Bourgeois JA, Heinrich TW, Huang H, Coriolan S, Annamalai A, Mangal JP, Frankel S, Lang M, Raj YP, Dandois M, Barth K, Stewart AL, Rado J, Pesek J, Sanders A, Spearman-McCarthy EV, Gagliardi J, Fiedorowicz JG. Management of SIADH-related hyponatremia due to psychotropic medications - An expert consensus from the Association of Medicine and Psychiatry. J Psychosom Res 2021; 151:110654. [PMID: 34739943 PMCID: PMC10911096 DOI: 10.1016/j.jpsychores.2021.110654] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 10/03/2021] [Accepted: 10/22/2021] [Indexed: 11/21/2022]
Abstract
OBJECTIVE Hyponatremia is the most common electrolyte imbalance encountered in clinical practice and is associated with negative healthcare outcomes and cost. SIADH is thought to account for one third of all hyponatremia cases and is typically an insidious process. Psychotropic medications are commonly implicated in the etiology of drug induced SIADH. There is limited guidance for clinicians on management of psychotropic-induced SIADH. METHODS After an extensive review of the existing literature, clinical-educators from the Association of Medicine and Psychiatry developed expert consensus recommendations for management of psychotropic-induced SIADH. A risk score was proposed based on risk factors for SIADH to guide clinical decision-making. RESULTS SSRIs, SNRIs, antipsychotics, carbamazepine, and oxcarbazepine have moderate to high level of evidence demonstrating their association with SIADH. Evaluation for an avoidance of medications that cause hyponatremia is particularly important. Substitution with medication that is less likely to cause SIADH should be considered when appropriate. We propose an algorithmic approach to monitoring hyponatremia with SIADH and corresponding treatment depending on symptom severity. CONCLUSIONS The proposed algorithm can help clinicians in determining whether psychotropic medication should be stopped, reduced or substituted where SIADH is suspected with recommendations for sodium (Na+) monitoring. These recommendations preserve a role for clinical judgment in the management of hyponatremia with consideration of the risks and benefits, which may be particularly relevant for complex patients that present with medical and psychiatric comorbidities. Further studies are needed to determine whether baseline and serial Na+ monitoring reduces morbidity and mortality.
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Affiliation(s)
- Aaron Pinkhasov
- Department of Psychiatry, NYU Langone Hospital-Long Island, NY, United States of America; Psychiatry and Medicine, NYULI - SOM, NY, United States of America.
| | - Glen Xiong
- University of California at Davis, CA, United States of America
| | - James A Bourgeois
- Psychiatry, Baylor Scott & White Health, TX, United States of America
| | - Thomas W Heinrich
- Psychiatry and Behavioral Medicine and Family and Community Medicine, Medical College of Wisconsin, WI, United States of America
| | - Heather Huang
- Psychiatry and Internal Medicine, University of WI, WI, United States of America
| | - Shanice Coriolan
- NYU Langone Hospital - Long Island, NY, United States of America
| | - Aniyizhai Annamalai
- Psychiatry and Internal Medicine, Yale School of Medicine, CT, United States of America
| | - Jed P Mangal
- Psychiatry, Uniformed Services University of the Health Sciences, MD, United States of America
| | - Steven Frankel
- Psychiatry, University of Minnesota Medical School, MN, United States of America; Psychiatry, UCSF, Medical School, University of Minnesota, MN, United States of America
| | - Michael Lang
- Internal Medicine and Psychiatry, Brody School of Medicine at East Carolina University, NC, United States of America
| | - Y Pritham Raj
- Depts of Internal Medicine & Psychiatry, Oregon Health & Science University, United States of America
| | | | - Kelly Barth
- Psychiatry and Internal Medicine, Medical University of South Carolina, SC, United States of America
| | - Anne Louise Stewart
- Consultation-Liaison Psychiatry, University of Texas Southwestern, TX, United States of America
| | - Jeffrey Rado
- Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, IL, United States of America
| | - Justin Pesek
- Baylor Scott & White Health, TX, United States of America
| | - Aaron Sanders
- Baylor Scott & White Health, TX, United States of America
| | - E Vanessa Spearman-McCarthy
- Internal Medicine and Psychiatry, Medical College of Georgia, Augusta University, GA, United States of America
| | - Jane Gagliardi
- Psychiatry and Behavioral Sciences, Duke University School of Medicine, NC, United States of America
| | - Jess G Fiedorowicz
- Mental Health, The Ottawa Hospital, ON, Canada; Ottawa Hospital Research Institute, Department of Psychiatry, School of Epidemiology and Public Health, ON, Canada; University of Ottawa, and uOttawa Brain and Mind Research Institute, ON, Canada
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11
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Brender R, Mulsant BH, Blumberger DM. An update on antidepressant pharmacotherapy in late-life depression. Expert Opin Pharmacother 2021; 22:1909-1917. [PMID: 33910422 DOI: 10.1080/14656566.2021.1921736] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Introduction: Clinically important depressive symptoms that occur in adults over age 60 are often termed late-life depression (LLD). LLD poses challenges for treating clinicians in both detection and treatment. Antidepressants are the most common first-line treatment approach. Older adults are at an increased risk of adverse effects because of polypharmacy.Areas covered: This article summarizes the challenges and approaches when using pharmacotherapy in LLD with a focus on newer data that have become available during the last five years. While no new antidepressants have become available during this period, a review of the literature summarizes advances in the knowledge of the adverse effects associated with various antidepressants and on the potential contribution of pharmacogenetic tools when prescribing antidepressants to older patients.Expert opinion: During the past 5 years, most of the literature relevant to the pharmacotherapy of MDD in older patients has focused on adverse effects. In particular, the effects of antidepressants on cognition and bone are emerging as important areas for clinical attention and further investigation. There is also an emerging literature on the potential role of pharmacogenetic testing in patients with MDD, though recommendations for use in older adults await larger studies that demonstrate its efficacy and cost-effectiveness.
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Affiliation(s)
- Ram Brender
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Canada.,Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada
| | - Benoit H Mulsant
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada
| | - Daniel M Blumberger
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Canada.,Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada
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12
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Di Vincenzo JD, Siegel A, Lipsitz O, Ho R, Teopiz KM, Ng J, Lui LMW, Lin K, Cao B, Rodrigues NB, Gill H, McIntyre RS, Rosenblat JD. The effectiveness, safety and tolerability of ketamine for depression in adolescents and older adults: A systematic review. J Psychiatr Res 2021; 137:232-241. [PMID: 33706168 DOI: 10.1016/j.jpsychires.2021.02.058] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 01/22/2021] [Accepted: 02/20/2021] [Indexed: 12/23/2022]
Abstract
The majority of antidepressant medication trials have focused on adult populations (ages 18-65), with much less research in older and younger populations. Moreover, key differences in the efficacy and safety of antidepressants have been identified between these age groups. Ketamine has emerged as a promising new treatment for treatment resistant depression (TRD). The objective of this review is to summarize and synthesize the extant literature on the effectiveness, safety and tolerability of ketamine for depression in special age populations (age ≤18 and ≥ 60). Following PRISMA guidelines, a systematic review was performed, searching EMBASE, PsycInfo, and PubMed from inception through July 2020. Studies reporting the use of any ketamine formulation with variable routes of administration to treat clinically diagnosed depression in adolescents or older adults were included. Thirteen studies were included in the analysis and ten observed rapid (≤2 week latency) antidepressant effects following ketamine treatments, with better outcomes following larger, repeated doses, and in open-label rather than blinded settings. Two case reports in adolescents assessed measures of suicidal ideation and both found ketamine to effectuate rapid anti-suicidal effects. Ketamine appears to be safe and well-tolerated in adolescents and older adults. The small quantity, high heterogeneity, and generally low quality of available studies precludes statistical syntheses and significantly limits the strength of our conclusions. Preliminary proof-of-concept studies are promising, however, rigorously designed randomized controlled trials (RCTs) are still required to ascertain effectiveness, safety and tolerability in these groups.
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Affiliation(s)
- Joshua D Di Vincenzo
- Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst St, M5T 2S8, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Medical Sciences Building, 1 King's College Circle, ON, M5S 1A8, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada
| | - Ashley Siegel
- Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst St, M5T 2S8, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada
| | - Orly Lipsitz
- Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst St, M5T 2S8, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada
| | - Roger Ho
- Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 9, 119228, Singapore; Institute of Health Innovation and Technology (iHealthtech), National University of Singapore, MD6, 14 Medical Drive #14-01, 117599, Singapore
| | - Kayla M Teopiz
- Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst St, M5T 2S8, Toronto, ON, Canada
| | - Jason Ng
- Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst St, M5T 2S8, Toronto, ON, Canada
| | - Leanna M W Lui
- Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst St, M5T 2S8, Toronto, ON, Canada
| | - Kangguang Lin
- Department of Affective Disorders, The Affiliated Hospital of Guangzhou Medical University, Guangzhou (Guangzhou Huiai Hospital), China
| | - Bing Cao
- Key Laboratory of Cognition and Personality (SWU), Faculty of Psychology, Ministry of Education, Southwest University, Chongqing, 400715, PR China
| | - Nelson B Rodrigues
- Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst St, M5T 2S8, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada
| | - Hartej Gill
- Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst St, M5T 2S8, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Medical Sciences Building, 1 King's College Cir, M5S 1A8, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada
| | - Roger S McIntyre
- Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst St, M5T 2S8, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Medical Sciences Building, 1 King's College Circle, ON, M5S 1A8, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, 250 College Street, 8th Floor, M5T 1R8, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada
| | - Joshua D Rosenblat
- Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst St, M5T 2S8, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, 250 College Street, 8th Floor, M5T 1R8, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada.
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13
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Repeated fluoxetine treatment induces transient and long-term astrocytic plasticity in the medial prefrontal cortex of normal adult rats. Prog Neuropsychopharmacol Biol Psychiatry 2021; 107:110252. [PMID: 33484756 DOI: 10.1016/j.pnpbp.2021.110252] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Revised: 01/08/2021] [Accepted: 01/14/2021] [Indexed: 12/15/2022]
Abstract
Fluoxetine (Flx)-induced neuronal plasticity plays an important role in the effective treatment of depression and mood disorders. It is less understood whether repeated Flx treatment induces astrocytic plasticity that outlasts the presence of the drug in the body. We showed previously that Flx-induced neuronal plasticity in the medial prefrontal cortex (mPFC) persisted up to 20 days after the treatment. In this study, adult rats were subjected to a 15-day repeated Flx treatment at a daily dose of 20 mg/kg body weight. Astrocytic metabolites and markers were assessed in the mPFC at day 1 (d1) and day 20 (d20) after the treatment. Significant transient reductions in the concentrations of astrocytic metabolites taurine and myo-inositol and the expressions of glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP4) were observed in the mPFC of Flx-treated rats at d1, which recovered to the control levels at d20. Further, Flx treatment resulted in long-lasting changes in Kir4.1 expression in the mPFC, which remained downregulated at d20. The expression of 5-HT1A receptor in the mPFC of Flx-treated rats was downregulated at d1 but became upregulated at d20. In summary, repeated Flx treatment induces both transient and long-term astrocytic plasticity in the mPFC of adult rats. The changes observed at d1 are consistent with disturbed water homeostasis and astrocytic de-maturation in the mPFC. The persistent changes in the expressions of Kir4.1 and 5-HT1A at d20, presumably of the astrocytic origin, might have contributed to the long-term neurotrophic effects of repeated Flx treatment in the mPFC.
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14
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Antidepressants and the Risk of Cardiovascular Events in Elderly Affected by Cardiovascular Disease: A Real-Life Investigation From Italy. J Clin Psychopharmacol 2020; 40:112-121. [PMID: 32134848 DOI: 10.1097/jcp.0000000000001189] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE The purpose of this study was to assess the possible relation between use of antidepressant (AD) drugs, that is, tricyclic ADs, selective serotonin reuptake inhibitors (SSRIs), and atypical ADs (AAs), and the risk of hospitalization for cardiovascular (CV) events among older patients with previous CV diseases. METHODS A nested case-control study was carried out among patients aged 65 years and older from 5 Italian health care territorial units who were discharged for CV disease during 2008 to 2010. The cohort was composed by 344,747 individuals, and of these, 97,739 (28%) experienced hospital admission for CV events (myocardial infarction, arrhythmia, stroke, heart failure) during follow-up (until 2014) and were included as cases. Up to 5 controls were randomly selected and matched to each. A conditional logistic regression was fitted to estimate the risk of CV events associated with ADs past or current use. A within-patient comparison was performed by the case-crossover design to account the effect of depression. FINDINGS Current users of SSRIs and AAs were at increased risk of CV events with odds ratios of 1.25 (95% confidence interval, 1.21-1.29) and 1.31 (1.25-1.37), respectively. An increased risk of arrhythmia and stroke was associated with current use of SSRIs and AAs, whereas an increased risk of heart failure was detected with current use of any ADs. The results were confirmed by the case-crossover approach. IMPLICATIONS Evidence that AD use is associated with an increased risk of CV events in accordance with specific mechanisms of action among older people with CV disease was added by this study.
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Oliver WD, D'Angelo R, Gonzales J, Wilson T, Millstein LS. Acute Severe Hyponatremia Induced by a Duloxetine Overdose in an Elderly Woman. Cureus 2020; 12:e10318. [PMID: 33052279 PMCID: PMC7546372 DOI: 10.7759/cureus.10318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
We report a case of acute severe hyponatremia within 24 hours after a duloxetine overdose. An 82-year-old woman presented to the ED after ingesting duloxetine and diltiazem. She became hemodynamically unstable due to the diltiazem overdose and was appropriately resuscitated. During hospitalization she experienced hyponatremia consistent with syndrome of inappropriate antidiuretic hormone (SIADH). Based on the observations we concluded there was a probable relationship between the hyponatremia and the duloxetine overdose. Clinicians should monitor patients’ electrolytes for acute disturbances after an overdose of duloxetine.
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Affiliation(s)
- Wesley D Oliver
- Emergency Medicine, University of Maryland Medical Center, Baltimore, USA
| | - Ryan D'Angelo
- Cardiology, Thomas Jefferson University Hospital, Philadelphia, USA
| | | | - Tracey Wilson
- Medical Intensive Care Unit, University of Maryland Medical Center, Baltimore, USA
| | - Leah S Millstein
- Internal Medicine - Pediatrics, University of Maryland School of Medicine, Baltimore, USA
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16
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Gibbons C, Garrahy A, Sheehan J, McQuaid SE, Hatunic M. Severe symptomatic hyponatremia secondary to fluoxetine. Ir J Med Sci 2020; 190:443-445. [PMID: 32671644 DOI: 10.1007/s11845-020-02314-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 07/11/2020] [Indexed: 10/23/2022]
Affiliation(s)
- Ciara Gibbons
- Department of Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Aoife Garrahy
- Department of Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland
| | - John Sheehan
- Department of Psychiatry, Mater Misericordiae University Hospital, Dublin, Ireland.,Medicine & Medical Specialties, UCD School of Medicine, University College Dublin, Dublin, Ireland
| | - Siobhan E McQuaid
- Department of Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland.,Medicine & Medical Specialties, UCD School of Medicine, University College Dublin, Dublin, Ireland
| | - Mensud Hatunic
- Department of Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland. .,Medicine & Medical Specialties, UCD School of Medicine, University College Dublin, Dublin, Ireland.
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17
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Pattanakuhar S, Kovindha A. Colonic obstruction in a tetraplegic patient: a common symptom from an uncommon cause. Spinal Cord Ser Cases 2020; 6:53. [PMID: 32601285 DOI: 10.1038/s41394-020-0305-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Revised: 06/17/2020] [Accepted: 06/17/2020] [Indexed: 11/09/2022] Open
Abstract
INTRODUCTION It is difficult to diagnose an acute abdomen condition in people with spinal cord injury due to abnormal sensation below the injured level and multiple co-morbidities. These issues can mislead the exact diagnosis and delay proper treatment. CASE PRESENTATION A 57-year-old male with C4 AIS C tetraplegia developed nausea and vomiting, abdominal distension and feeding intolerance. Serum electrolytes indicated severe hyponatremia. A provisional diagnosis of pseudo-gut obstruction was made. After the failure of 48 h of conservative treatment with a nasogastric and rectal tube, abdominal CT was performed and revealed sigmoid volvulus. CONCLUSIONS Due to the inconclusive clinical features and lack of subjective complaints, early use of CT scan or MRI is preferable in people with SCI who are suspected of an emergency intra-abdominal condition.
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Affiliation(s)
- Sintip Pattanakuhar
- Department of Rehabilitation Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
| | - Apichana Kovindha
- Department of Rehabilitation Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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18
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Song HG, Nahm FS. Oxcarbazepine for trigeminal neuralgia may induce lower extremity weakness: A case report. World J Clin Cases 2020; 8:922-927. [PMID: 32190628 PMCID: PMC7062623 DOI: 10.12998/wjcc.v8.i5.922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 01/22/2020] [Accepted: 02/11/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Although few studies have reported hyponatremia due to carbamazepine or oxcarbazepine in patients with epilepsy, no study has investigated cases of carbamazepine- or oxcarbazepine-induced hyponatremia or unsteady gait in patients with neuropathic pain. Herein, we report a case of oxcarbazepine-induced lower leg weakness in a patient with trigeminal neuralgia and summarize the diagnosis, treatment, and changes of clinical symptoms.
CASE SUMMARY A 78-year-old male with a history of lumbar spinal stenosis was admitted to the hospital after he experienced lancinating pain around his right cheek, eyes, and lip, and was diagnosed with trigeminal neuralgia at the right maxillary and mandibular branch. He was prescribed oxcarbazepine (600 mg/d), milnacipran (25 mg/d), and oxycodone/naloxone (20 mg/10 mg/d) for four years. Four years later, the patient experienced symptoms associated with spinal stenosis, including pain in the lower extremities and unsteady gait. His serum sodium level was 127 mmol/L. Assuming oxcarbazepine to be the cause of the hyponatremia, oxcarbazepine administration was put on hold and the patient was switched to topiramate. At subsequent visit, the patient’s serum sodium level had normalized to 143 mmol/L and his unsteady gait had improved.
CONCLUSION Oxcarbazepine-induced hyponatremia may cause lower extremity weakness and unsteady gait, which should be differentiated from those caused by spinal stenosis.
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Affiliation(s)
- Hyun-Gul Song
- Department of Anesthesiology and Pain Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul 07061, South Korea
| | - Francis Sahngun Nahm
- Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam 13620, South Korea
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19
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Grattagliano I, Mastronuzzi T, D'Ambrosio G. Hyponatremia associated with long-term medication use in the elderly: an analysis in general practice. J Prim Health Care 2019; 10:167-173. [PMID: 30068472 DOI: 10.1071/hc17084] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION The aim of this study is to determine the prevalence of hyponatremia, its association with long-term medication use and underlying chronic conditions, the rate of hospitalisation and death within 3 months from its discovery and its management in community-dwelling older people. METHODS One year of data for ~5635 patients aged >65 years was extracted from the databases of 19 general practitioners (GPs); 2569 (45.6%) were checked for hyponatremia. RESULTS Hyponatremia occurred in 205 (8.0%) of 2569 checked individuals: 78.5% (161/205) had hypertension, 31.2% (64/205) diabetes, 23.9% (49/205) chronic renal failure; 38.0% (78/205) received diuretics, 36.6% (75/205) renin-angiotensin system antagonists (ACE-I/ARB) and 9.8% (20/205) serotonin reuptake inhibitors. Drug consumption was higher in hyponatremic patients, although only diuretics, ACE-I/ARB, anti-arrhythmics and opioids were significantly associated with hyponatremia. The likelihood of hyponatremia trebled when four drugs were taken, and it was seven-fold higher with the use of six drugs. Hyponatremia was associated with a higher prevalence of chronic illnesses and higher rate of hospitalisation (13.7% vs 7.7%, P = 0.005) and death (3.9% vs 1.8%, P < 0.035). The use of at least one long-term medication was associated with hospitalisation or death in hyponatremic patients (10% vs 6.3%, P = 0.010). Less than 20% of hyponatremic patients had their sodium level checked again after 1 month. DISCUSSION Hyponatremia is not uncommon among community-living older patients, especially in patients taking medications potentially causing hyponatremia. Hyponatremic patients are likely to encounter more serious events, including hospitalisation and death. Targeted training of GPs is desirable to improve their practice.
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Affiliation(s)
| | - Tecla Mastronuzzi
- Italian College of General Practitioners and Primary Care, Bari, Italy
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Abstract
PURPOSE OF REVIEW We review non-pharmacological and pharmacological approaches to managing behavioral and psychological symptoms of dementia (BPSD). We examine methods for assessment and evidence for interventions, focusing on recent findings and innovations. Finally, we recommend an algorithm for management of BPSD. RECENT FINDINGS Training of formal caregivers is the most effective intervention for BPSD; other non-pharmacological interventions are also beneficial. Antidepressants and antipsychotics remain a mainstay of pharmacological treatment for BPSD. There is limited evidence supporting the use of stimulants, cognitive enhancers, dextromethorphan/quinidine, benzodiazepines, anticonvulsants, and pimavanserin. The management of BPSD is highly individualized. Following thorough assessment, the initial step is addressing contributing medical problems. Non-pharmacological interventions should be tried prior to pharmacological interventions. Antipsychotics should be prescribed only when behaviors pose a significant safety risk or if the person with dementia is very distressed. New approaches will be needed to address an increasing population of people with dementia.
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Duloxetine-Induced Hyponatremia in an Elderly Male Patient with Treatment-Refractory Major Depressive Disorder. Case Rep Psychiatry 2019; 2019:4109150. [PMID: 31214374 PMCID: PMC6535824 DOI: 10.1155/2019/4109150] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Revised: 04/12/2019] [Accepted: 04/28/2019] [Indexed: 01/22/2023] Open
Abstract
Several classes of antidepressants can induce syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH), thereby causing hyponatremia. Initial symptoms of hyponatremia include neuropsychiatric and gastrointestinal manifestations can mimic depression, especially in elderly people with multiple somatic complaints. Here we present a case of a 68-year-old man with treatment-refractory depression and general anxiety disorder who developed duloxetine-induced hyponatremia. His symptoms of hyponatremia including unsteady gait, dizziness, nausea, general malaise, and poor appetite subsided after discontinuing the offending medication. Our case illustrates that drug-induced SIADH and potential drug-drug interactions should be considered in elderly patients who develop hyponatremia following the initiation of antidepressants.
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Abstract
The prevalence of dementia is expected to rise with the aging of our population for decades to come. Neuropsychiatric symptoms of dementia, also known as behavioral and psychologic symptoms of dementia, are extremely common. Symptoms are most prevalent in the moderate stages of the disease, often increase with advancing disease stage, and often more than one symptom is present. These symptoms can cause a great deal of distress for patients and families, and take a toll on society as well. Evaluation and management can be challenging, with nonpharmacologic strategies recommended as first-line approach. There is growing evidence for specific pharmacologic strategies, but these come with significant risk, such that informed consent with the patient and surrogate decision maker is critical. In this chapter, we focus on general principles of etiology, assessment, and management, and then turn to individual symptoms of agitation, psychosis, apathy, sleep disturbance, and feeding and eating problems more specifically. Depression and anxiety are covered elsewhere in this text.
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Affiliation(s)
- Rebecca Radue
- Division of Geriatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; Geriatric Research, Education and Clinic Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, United States
| | - Art Walaszek
- Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States.
| | - Sanjay Asthana
- Division of Geriatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
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Abstract
BACKGROUND Fibromyalgia is a clinically defined chronic condition of unknown etiology characterised by chronic widespread pain, sleep disturbance, cognitive dysfunction, and fatigue. Many patients report high disability levels and poor quality of life. Drug therapy aims to reduce key symptoms, especially pain, and improve quality of life. The tetracyclic antidepressant, mirtazapine, may help by increasing serotonin and noradrenaline in the central nervous system (CNS). OBJECTIVES To assess the efficacy, tolerability and safety of the tetracyclic antidepressant, mirtazapine, compared with placebo or other active drug(s) in the treatment of fibromyalgia in adults. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, SCOPUS, the US National Institutes of Health, and the World Health Organization (WHO) International Clinical Trials Registry Platform for published and ongoing trials, and examined reference lists of reviewed articles, to 9 July 2018. SELECTION CRITERIA Randomised controlled trials (RCTs) of any formulation of mirtazapine against placebo, or any other active treatment of fibromyalgia, in adults. DATA COLLECTION AND ANALYSIS Two review authors independently extracted study characteristics, outcomes of efficacy, tolerability and safety, examined issues of study quality, and assessed risk of bias, resolving discrepancies by discussion. Primary outcomes were participant-reported pain relief (at least 50% or 30% pain reduction), Patient Global Impression of Change (PGIC; much or very much improved), safety (serious adverse events), and tolerability (adverse event withdrawal). Other outcomes were health-related quality of life (HRQoL) improved by 20% or more, fatigue, sleep problems, mean pain intensity, negative mood and particular adverse events. We used a random-effects model to calculate risk difference (RD), standardised mean difference (SMD), and numbers needed to treat. We assessed the evidence using GRADE and created a 'Summary of findings' table. MAIN RESULTS Three studies with 606 participants compared mirtazapine with placebo (but not other drugs) over seven to 13 weeks. Two studies were at unclear or high risk of bias in six or seven of eight domains. We judged the evidence for all outcomes to be low- or very low-quality because of poor study quality, indirectness, imprecision, risk of publication bias, and sometimes low numbers of events.There was no difference between mirtazapine and placebo for any primary outcome: participant-reported pain relief of 50% or greater (22% versus 16%; RD 0.05, 95% confidence interval (CI) -0.01 to 0.12; three studies with 591 participants; low-quality evidence); no data available for PGIC; only a single serious adverse event for evaluation of safety (RD -0.00, 95% CI -0.01 to 0.02; three studies with 606 participants; very low-quality evidence); and tolerability as frequency of dropouts due to adverse events (3% versus 2%; RD 0.00, 95% CI -0.02 to 0.03; three studies with 606 participants; low-quality evidence).Mirtazapine showed a clinically-relevant benefit compared to placebo for some secondary outcomes: participant-reported pain relief of 30% or greater (47% versus 34%; RD 0.13, 95% CI 0.05 to 0.21; number needed to treat for an additional beneficial outcome (NNTB) 8, 95% CI 5 to 20; three studies with 591 participants; low-quality evidence); participant-reported mean pain intensity (SMD -0.29, 95% CI -0.46 to -0.13; three studies with 591 participants; low-quality evidence); and participant-reported sleep problems (SMD -0.23, 95% CI -0.39 to -0.06; three studies with 573 participants; low-quality evidence). There was no benefit for improvement of participant-reported improvement of HRQoL of 20% or greater (58% versus 50%; RD 0.08, 95% CI -0.01 to 0.16; three studies with 586 participants; low-quality evidence); participant-reported fatigue (SMD -0.02, 95% CI -0.19 to 0.16; two studies with 533 participants; low-quality evidence); participant-reported negative mood (SMD -0.67, 95% CI -1.44 to 0.10; three studies with 588 participants; low-quality evidence); or withdrawals due to lack of efficacy (1.5% versus 0.1%; RD 0.01, 95% CI -0.01 to 0.02; three studies with 605 participants; very low-quality evidence).There was no difference between mirtazapine and placebo for participants reporting any adverse event (76% versus 59%; RD 0.12, 95 CI -0.01 to 0.26; three studies with 606 participants; low-quality evidence). There was a clinically-relevant harm with mirtazapine compared to placebo: in the number of participants with somnolence (42% versus 14%; RD 0.24, 95% CI 0.18 to 0.30; number needed to treat for an additional harmful outcome (NNTH) 5, 95% CI 3 to 6; three studies with 606 participants; low-quality evidence); weight gain (19% versus 1%; RD 0.17, 95% CI 0.11 to 0.23; NNTH 6, 95% CI 5 to 10; three studies with 606 participants; low-quality evidence); and elevated alanine aminotransferase (13% versus 2%; RD 0.13, 95% CI 0.04 to 0.22; NNTH 8, 95% CI 5 to 25; two studies with 566 participants; low-quality evidence). AUTHORS' CONCLUSIONS Studies demonstrated no benefit of mirtazapine over placebo for pain relief of 50% or greater, PGIC, improvement of HRQoL of 20% or greater, or reduction of fatigue or negative mood. Clinically-relevant benefits were shown for pain relief of 30% or greater, reduction of mean pain intensity, and sleep problems. Somnolence, weight gain, and elevated alanine aminotransferase were more frequent with mirtazapine than placebo. The quality of evidence was low or very low, with two of three studies of questionable quality and issues over indirectness and risk of publication bias. On balance, any potential benefits of mirtazapine in fibromyalgia were outweighed by its potential harms, though, a small minority of people with fibromyalgia might experience substantial symptom relief without clinically-relevant adverse events.
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Affiliation(s)
- Patrick Welsch
- Health Care Center for Pain Medicine and Mental Health, Saarbrücken, Germany
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Finsterer J. The SeLECT score is inappropriate to predict post-stroke epilepsy. Lancet Neurol 2018; 17:106-107. [PMID: 29413306 DOI: 10.1016/s1474-4422(17)30460-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 11/09/2017] [Indexed: 10/18/2022]
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Gylvin SH, Jørgensen CC, Fink-Jensen A, Gislason GH, Kehlet H. The Role of Psychiatric Diagnoses for Outcome After Hip and Knee Arthroplasty. J Arthroplasty 2017; 32:3611-3615. [PMID: 28800859 DOI: 10.1016/j.arth.2017.06.051] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Revised: 06/27/2017] [Accepted: 06/29/2017] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Surgical patients receiving psychopharmacologic treatment have been associated with adverse outcomes in total hip and knee arthroplasty (THA and TKA). The purpose of this study was to investigate whether a specific high-risk group of patients receiving psychopharmacologic treatment could be identified based upon a nationwide psychiatric diagnosis register. METHODS From 7 different orthopedic centers, 8288 THA and TKA patients were included from January 2010 to November 2012 of which 943 (11.4%) received psychopharmacologic treatment. Patients receiving preoperative psychopharmacologic treatment were divided into 2 groups based on the presence or absence of a psychiatric diagnosis in a nationwide administrative database and analyzed with respect to length of hospital stay (LOS >4 days) and 30- and 90-day readmissions using multivariable logistic regression models. RESULTS A total of 191 patients receiving psychopharmacologic treatment were registered with a psychiatric diagnosis while 752 patients received psychopharmacologic treatment without a registered psychiatric diagnosis. No significantly increased risk was found in patients with a preoperative registered psychiatric diagnosis compared to patients without, with regard to LOS >4 days (odds ratio [OR], 1.19; P = .51), 30-day readmission (OR, 0.56; P = .086), or 90-day readmission (OR, 0.81; P = .446), respectively. However, both groups had an increased risk of LOS >4 days and readmissions compared to a control population without psychopharmacologic treatment or any registered psychiatric diagnoses. CONCLUSION No further risk was found for psychopharmacologically treated THA/TKA patients with an additional hospital-related psychiatric diagnosis compared to patients without, suggesting that the psychopharmacologic treatment per se is an outcome risk factor independent of severity of the psychiatric disorder.
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Affiliation(s)
- Silas H Gylvin
- Section of Surgical Pathophysiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Lundbeck Foundation Centre for Fast-track Hip and Knee Arthroplasty, Copenhagen, Denmark
| | - Christoffer C Jørgensen
- Section of Surgical Pathophysiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Lundbeck Foundation Centre for Fast-track Hip and Knee Arthroplasty, Copenhagen, Denmark
| | - Anders Fink-Jensen
- Psychiatric Centre Copenhagen and Laboratory of Neuropsychiatry, University of Copenhagen, Copenhagen, Denmark
| | - Gunnar H Gislason
- Department of Cardiology, Herlev and Gentofte University Hospital, Hellerup, Denmark; The Danish Heart Foundation, Copenhagen, Denmark
| | - Henrik Kehlet
- Section of Surgical Pathophysiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Lundbeck Foundation Centre for Fast-track Hip and Knee Arthroplasty, Copenhagen, Denmark
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Filippatos TD, Makri A, Elisaf MS, Liamis G. Hyponatremia in the elderly: challenges and solutions. Clin Interv Aging 2017; 12:1957-1965. [PMID: 29180859 PMCID: PMC5694198 DOI: 10.2147/cia.s138535] [Citation(s) in RCA: 109] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Decreased serum sodium concentration is a rather frequent electrolyte disorder in the elderly population because of the presence of factors contributing to increased antidiuretic hormone, the frequent prescription of drugs associated with hyponatremia and also because of other mechanisms such as the “tea and toast” syndrome. The aim of this review is to present certain challenges in the evaluation and treatment of hyponatremia in the elderly population and provide practical solutions. Hyponatremia in elderly subjects is mainly caused by drugs (more frequently thiazides and antidepressants), the syndrome of inappropriate antidiuretic hormone secretion (SIAD) or endocrinopathies; however, hyponatremia is multifactorial in a significant proportion of patients. Special attention is needed in the elderly population to exclude endocrinopathies as a cause of hyponatremia before establishing the diagnosis of SIAD, which then requires a stepped diagnostic approach to reveal its underlying cause. The treatment of hyponatremia depends on the type of hyponatremia. Special attention is also needed to correct serum sodium levels at the appropriate rate, especially in chronic hyponatremia, in order to avoid the osmotic demyelination syndrome. In conclusion, both the evaluation and the treatment of hyponatremia pose many challenges in the elderly population.
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Affiliation(s)
- Theodosios D Filippatos
- Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece
| | - Andromachi Makri
- Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece
| | - Moses S Elisaf
- Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece
| | - George Liamis
- Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece
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Gandhi S, Shariff SZ, Al-Jaishi A, Reiss JP, Mamdani MM, Hackam DG, Li L, McArthur E, Weir MA, Garg AX. Second-Generation Antidepressants and Hyponatremia Risk: A Population-Based Cohort Study of Older Adults. Am J Kidney Dis 2016; 69:87-96. [PMID: 27773479 DOI: 10.1053/j.ajkd.2016.08.020] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2016] [Accepted: 08/04/2016] [Indexed: 01/14/2023]
Abstract
BACKGROUND Hyponatremia may occur after initiation of a second-generation antidepressant drug. However, the magnitude of this risk among older adults in routine care is not well characterized. STUDY DESIGN Retrospective, population-based, matched-cohort study. SETTING & PARTICIPANTS In Ontario, Canada, 2003 to 2012, we compared older adults with a mood or anxiety disorder who were dispensed 1 of 9 second-generation antidepressant drugs with matched adults with comparable indicators of baseline health who were not dispensed an antidepressant drug (n=138,246 per group). A similar comparison was made in a subpopulation with available laboratory data (n=4,186 per group). PREDICTOR Second-generation antidepressant prescription versus no antidepressant prescription. OUTCOMES The primary outcome was hospitalization with hyponatremia. A secondary outcome was hospitalization with both hyponatremia and delirium. MEASUREMENTS We assessed hospitalization with hyponatremia using a diagnosis code and, in the subpopulation, serum sodium values. We assessed hospitalization with hyponatremia and delirium using a combination of diagnosis codes. RESULTS Second-generation antidepressant use versus nonuse was associated with higher 30-day risk for hospitalization with hyponatremia (450/138,246 [0.33%] vs 84/138,246 [0.06%]; relative risk [RR], 5.46 [95% CI, 4.32-6.91]). This association was consistent in the subpopulation with serum sodium values (73/4,186 [1.74%] vs 18/4,186 [0.43%]; RR, 4.23 [95% CI, 2.50-7.19]; absolute risk increase, 1.31% [95% CI, 0.87%-1.75%]). Second-generation antidepressant use versus nonuse was also associated with higher 30-day risk for hospitalization with both hyponatremia and delirium (28/138,246 [0.02%] vs 7/138,246 [0.005%]; RR, 4.00 [95% CI, 1.75-9.16]). LIMITATIONS Measures of serum sodium could be ascertained in only a subpopulation. CONCLUSIONS Use of a second-generation antidepressant in routine care by older adults is associated with an approximate 5-fold increase in 30-day risk for hospitalization with hyponatremia compared to nonuse. However, the absolute increase in 30-day incidence is low.
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Affiliation(s)
- Sonja Gandhi
- Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada; Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada
| | - Salimah Z Shariff
- Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada; Institute for Clinical Evaluative Sciences, London, Ontario, Canada
| | - Ahmed Al-Jaishi
- Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada; Institute for Clinical Evaluative Sciences, London, Ontario, Canada
| | - Jeffrey P Reiss
- Department of Psychiatry, Western University, London, Ontario, Canada
| | - Muhammad M Mamdani
- Institute for Clinical Evaluative Sciences, London, Ontario, Canada; Keenan Research Centre in the Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada
| | - Daniel G Hackam
- Institute for Clinical Evaluative Sciences, London, Ontario, Canada; Division of Clinical Pharmacology, Department of Medicine, Western University, London, Ontario, Canada
| | - Lihua Li
- Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada; Institute for Clinical Evaluative Sciences, London, Ontario, Canada
| | - Eric McArthur
- Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada; Institute for Clinical Evaluative Sciences, London, Ontario, Canada
| | - Matthew A Weir
- Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada; Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada
| | - Amit X Garg
- Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada; Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada; Institute for Clinical Evaluative Sciences, London, Ontario, Canada.
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