Clinical Research
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Year 2025, Volume: 7 Issue: 3, 697 - 702, 09.09.2025
https://doi.org/10.37990/medr.1716257

Abstract

References

  • Phillips ML, Kupfer DJ. Bipolar disorder diagnosis: challenges and future directions. Lancet. 2013;381:1663-71.
  • Müller-Oerlinghausen B, Berghöfer A, Bauer M. Bipolar disorder. Lancet. 2002;359:241-7.
  • Merikangas KR, Jin R, He JP, et al. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry. 2011;68:241-51.
  • Price AL, Marzani-Nissen GR. Bipolar disorders: a review. American family physician. 2012;85:483-93.
  • Karaytuğ MO, Tamam L, Demirkol ME, Namli Z. Treatment compliance and related factors in patients with bipolar disorder. Arşiv Kaynak Tarama Dergisi. 2022;31:21-7.
  • Baldessarini RJ, Tondo L, Vázquez GH. Pharmacological treatment of adult bipolar disorder. Mol Psychiatry. 2019;24:198-217.
  • Macritchie K, Geddes JR, Scott J, et al. Valproate for acute mood episodes in bipolar disorder. Cochrane Database Syst Rev. 2003;CD004052.
  • Yatham LN, Kennedy SH, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20:97-170.
  • Chen YCB, Liang CS, Wang LJ, et al. Comparative effectiveness of valproic acid in different serum concentrations for maintenance treatment of bipolar disorder: a retrospective cohort study using target trial emulation framework. EClinicalMedicine. 2022;54:101678.
  • Lin WW, Jiao Z, Wang CL, et al. Population pharmacokinetics of valproic acid in adult Chinese epileptic patients and its application in an individualized dosage regimen. Ther Drug Monit. 2015;37:76-83.
  • Goodwin GM, Haddad PM, Ferrier IN, et al. Evidence-based guide- lines for treating bipolar disorder: revised third edition recommen- dations from the British Association for Psychopharmacology. JPsychopharmacol. 2016;30:495-553.
  • Bipolar disorder: assessment and management (CG185). London: NICE; 2018.
  • Grunze H, Vieta E, Goodwin GM, et al. The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2012 on the long-term treatment of bipolar disorder. World J Biol Psychiatry. 2013;14:154-219.
  • Gugler R, von Unruh GE. Clinical pharmacokinetics of valproic acid. Clin Pharmacokinet. 1980;5:67-83.
  • Hermida J, Tutor JC. A theoretical method for normalizing total serum valproic acid concentration in hypoalbuminemic patients. J Pharmacol Sci. 2005;97:489-93.
  • Abdi H. Coefficient of variation. In: Salkind N, Ed., Encyclopedia of Research Design. Thousand Oaks, CA: Sage. 2010.
  • Keck PE, Bowden CL, Meinhold JM, et al. Relationship between serum valproate and lithium levels and efficacy and tolerability in bipolar maintenance therapy. Int J Psychiatry Clin Pract. 2005;9:271-7.
  • Paholpak S, Jaikasemwong S, Roumcharoenkiat A, et al. Clinical outcome of valproate maintenance treatment in bipolar I disorder at Srinagarind Hospital. J Med Assoc Thai. 2014;97:431-8.
  • Carli M, Risaliti E, Francomano M, et al. A 5-year study of lithium and valproic acid drug monitoring in patients with bipolar disorders in an Italian clinical center. Pharmaceuticals. 2022;15:105.
  • American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Virginia: American Psychiatric Association, 2013. https://doi.org/10.1176/appi.books.9780890425596
  • Slyepchenko A, Frey BN, Lafer B, et al. Increased illness burden in women with comorbid bipolar and premenstrual dysphoric disorder: data from 1 099 women from STEP‐BD study. Acta Psychiatr Scand. 2017;136:473-82.
  • Menculini G, Steardo Jr L, Sciarma T, et al. Sex differences in bipolar disorders: impact on psychopathological features and treatment response. Front Psychiatry. 2022;13:926594.
  • Wu J, Li J, Jing W, et al. Valproic acid-induced encephalopathy: a review of clinical features, risk factors, diagnosis, and treatment. Epilepsy Behav. 2021;120:107967.
  • Ma P, Shang S, Huang Y, et al. Joint use of population pharmacokinetics and machine learning for prediction of valproic acid plasma concentration in elderly epileptic patients. Eur J Pharm Sci. 2024;201:106876.
  • Bukh JD, Andersen PK, Kessing LV. Rates and predictors of remission, recurrence and conversion to bipolar disorder after the first lifetime episode of depression–a prospective 5-year follow-up study. Psychol Med. 2016;46:1151-61.
  • Gitlin M, Frye MA. Maintenance therapies in bipolar disorders. Bipolar disorders. 2012;14:51-65.
  • Berk M, Kapczinski F, Andreazza AC, et al. Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev. 2011;35:804-17.
  • Patsalos PN, Spencer EP, Berry DJ. Therapeutic drug monitoring of antiepileptic drugs in epilepsy: a 2018 update. Ther Drug Monit. 2018;40:526-48.
  • Tseng YJ, Huang SY, Kuo CH, et al. Safety range of free valproic acid serum concentration in adult patients. PLoS One. 2020;15:e0238201.

The Effect of Individual Valproic Acid and Albumin Variation on the Risk of Episodes in Patients with Bipolar Disorder

Year 2025, Volume: 7 Issue: 3, 697 - 702, 09.09.2025
https://doi.org/10.37990/medr.1716257

Abstract

Aim: This study aimed to investigate the association between the coefficient of variation (CV%) of valproic acid (VPA) and albumin levels and mood episode status in patients with bipolar disorder who maintained therapeutic VPA concentrations.
Material and Method: Patients diagnosed with bipolar disorder who had been under follow-up for at least two years between 2018 and 2023 were retrospectively analyzed. Inclusion criteria required at least three annual measurements of simultaneous serum VPA and albumin levels, with VPA consistently within the therapeutic range (45–100 µg/mL). Patients were categorized based on episode occurrence. Mean values, standard deviation (SD), and CV% were calculated for VPA and albumin levels.
Results: A total of 90 patients with bipolar disorder were included, with 45 experiencing episodes and 45 remaining episode-free. The mean of the last six albumin measurements was significantly lower in the episode group (t=–2.688, p=0.009). While the CV% of total VPA levels did not differ significantly between groups, the CV% of albumin-adjusted VPA levels was significantly higher in the episode group (z=–2.005, p=0.045). Episode frequency showed a statistically significant but weak positive correlation with both normalized SD (r=0.281, p=0.007) and normalized CV% (r=0.260, p=0.013).
Conclusion: This study found that individuals with bipolar disorder who experienced episodes had significantly lower serum albumin levels, and that albumin-adjusted VPA fluctuations showed a weak but positive correlation with episode occurrence. Prioritizing the CV% of albumin-adjusted VPA measurements may play a significant role in monitoring episode risk in patients with bipolar disorder.

Ethical Statement

Ethical approval for the study was granted by the Non-Interventional Clinical Research Ethics Committee of Adıyaman University (Approval No: 2023/3-20, dated 14 November 2023), and all procedures adhered to the ethical standards outlined in the Declaration of Helsinki.

Supporting Institution

No

Thanks

The authors wish to acknowledge Ayşe Vlok for her support in the linguistic revision and refinement of the manuscript.

References

  • Phillips ML, Kupfer DJ. Bipolar disorder diagnosis: challenges and future directions. Lancet. 2013;381:1663-71.
  • Müller-Oerlinghausen B, Berghöfer A, Bauer M. Bipolar disorder. Lancet. 2002;359:241-7.
  • Merikangas KR, Jin R, He JP, et al. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry. 2011;68:241-51.
  • Price AL, Marzani-Nissen GR. Bipolar disorders: a review. American family physician. 2012;85:483-93.
  • Karaytuğ MO, Tamam L, Demirkol ME, Namli Z. Treatment compliance and related factors in patients with bipolar disorder. Arşiv Kaynak Tarama Dergisi. 2022;31:21-7.
  • Baldessarini RJ, Tondo L, Vázquez GH. Pharmacological treatment of adult bipolar disorder. Mol Psychiatry. 2019;24:198-217.
  • Macritchie K, Geddes JR, Scott J, et al. Valproate for acute mood episodes in bipolar disorder. Cochrane Database Syst Rev. 2003;CD004052.
  • Yatham LN, Kennedy SH, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20:97-170.
  • Chen YCB, Liang CS, Wang LJ, et al. Comparative effectiveness of valproic acid in different serum concentrations for maintenance treatment of bipolar disorder: a retrospective cohort study using target trial emulation framework. EClinicalMedicine. 2022;54:101678.
  • Lin WW, Jiao Z, Wang CL, et al. Population pharmacokinetics of valproic acid in adult Chinese epileptic patients and its application in an individualized dosage regimen. Ther Drug Monit. 2015;37:76-83.
  • Goodwin GM, Haddad PM, Ferrier IN, et al. Evidence-based guide- lines for treating bipolar disorder: revised third edition recommen- dations from the British Association for Psychopharmacology. JPsychopharmacol. 2016;30:495-553.
  • Bipolar disorder: assessment and management (CG185). London: NICE; 2018.
  • Grunze H, Vieta E, Goodwin GM, et al. The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2012 on the long-term treatment of bipolar disorder. World J Biol Psychiatry. 2013;14:154-219.
  • Gugler R, von Unruh GE. Clinical pharmacokinetics of valproic acid. Clin Pharmacokinet. 1980;5:67-83.
  • Hermida J, Tutor JC. A theoretical method for normalizing total serum valproic acid concentration in hypoalbuminemic patients. J Pharmacol Sci. 2005;97:489-93.
  • Abdi H. Coefficient of variation. In: Salkind N, Ed., Encyclopedia of Research Design. Thousand Oaks, CA: Sage. 2010.
  • Keck PE, Bowden CL, Meinhold JM, et al. Relationship between serum valproate and lithium levels and efficacy and tolerability in bipolar maintenance therapy. Int J Psychiatry Clin Pract. 2005;9:271-7.
  • Paholpak S, Jaikasemwong S, Roumcharoenkiat A, et al. Clinical outcome of valproate maintenance treatment in bipolar I disorder at Srinagarind Hospital. J Med Assoc Thai. 2014;97:431-8.
  • Carli M, Risaliti E, Francomano M, et al. A 5-year study of lithium and valproic acid drug monitoring in patients with bipolar disorders in an Italian clinical center. Pharmaceuticals. 2022;15:105.
  • American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Virginia: American Psychiatric Association, 2013. https://doi.org/10.1176/appi.books.9780890425596
  • Slyepchenko A, Frey BN, Lafer B, et al. Increased illness burden in women with comorbid bipolar and premenstrual dysphoric disorder: data from 1 099 women from STEP‐BD study. Acta Psychiatr Scand. 2017;136:473-82.
  • Menculini G, Steardo Jr L, Sciarma T, et al. Sex differences in bipolar disorders: impact on psychopathological features and treatment response. Front Psychiatry. 2022;13:926594.
  • Wu J, Li J, Jing W, et al. Valproic acid-induced encephalopathy: a review of clinical features, risk factors, diagnosis, and treatment. Epilepsy Behav. 2021;120:107967.
  • Ma P, Shang S, Huang Y, et al. Joint use of population pharmacokinetics and machine learning for prediction of valproic acid plasma concentration in elderly epileptic patients. Eur J Pharm Sci. 2024;201:106876.
  • Bukh JD, Andersen PK, Kessing LV. Rates and predictors of remission, recurrence and conversion to bipolar disorder after the first lifetime episode of depression–a prospective 5-year follow-up study. Psychol Med. 2016;46:1151-61.
  • Gitlin M, Frye MA. Maintenance therapies in bipolar disorders. Bipolar disorders. 2012;14:51-65.
  • Berk M, Kapczinski F, Andreazza AC, et al. Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev. 2011;35:804-17.
  • Patsalos PN, Spencer EP, Berry DJ. Therapeutic drug monitoring of antiepileptic drugs in epilepsy: a 2018 update. Ther Drug Monit. 2018;40:526-48.
  • Tseng YJ, Huang SY, Kuo CH, et al. Safety range of free valproic acid serum concentration in adult patients. PLoS One. 2020;15:e0238201.
There are 29 citations in total.

Details

Primary Language English
Subjects Psychiatry
Journal Section Original Articles
Authors

Şeyma Sehlikoğlu 0000-0002-9512-713X

Esra Göçer 0000-0003-0764-7715

Saniye Başak Oktay 0000-0002-3427-9893

Publication Date September 9, 2025
Submission Date June 9, 2025
Acceptance Date June 30, 2025
Published in Issue Year 2025 Volume: 7 Issue: 3

Cite

AMA Sehlikoğlu Ş, Göçer E, Başak Oktay S. The Effect of Individual Valproic Acid and Albumin Variation on the Risk of Episodes in Patients with Bipolar Disorder. Med Records. September 2025;7(3):697-702. doi:10.37990/medr.1716257

17741

Chief Editors

MD, Professor. Zülal Öner
İzmir Bakırçay University, Department of Anatomy, İzmir, Türkiye

Assoc. Prof. Deniz Şenol
Düzce University, Department of Anatomy, Düzce, Türkiye

Editors
Assoc. Prof. Serkan Öner
İzmir Bakırçay University, Department of Radiology, İzmir, Türkiye
 
E-mail: medrecsjournal@gmail.com

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