A 5-Year Study of Lithium and Valproic Acid Drug Monitoring in Patients with Bipolar Disorders in an Italian Clinical Center

Abstract

Therapeutic drug monitoring (TDM) is an effective tool used to improve the pharmacological treatment in clinical practice, especially to detect subtherapeutic drug plasma concentration (Cp) in order to consider a change of dosage during treatment and reach its putative therapeutic range. In this study, we report the Cp values of lithium and valproic acid (VPA), alone and in combination, mostly in bipolar patients admitted to an Italian clinical center of the University of Pisa during the years 2016–2020, which include 12,294 samples of VPA, 7449 of lithium and 1118 of both in combination. Lithium and VPA are the most utilized drugs in treating bipolar disorders, and their TDM is strongly recommended by recent guidelines. In relation to lithium Cp monitoring, several studies have underlined that 0.5–0.8 mmol/L is the optimal range for chronic treatment, and below 0.4 mmol/L, it is unlikely to produce a clinical response. For VPA, the therapeutic range is 50–100 μg/mL and a linear correlation between Cp and clinical efficacy has been proposed, where below 50 μg/mL, the clinical efficacy of VPA has not been proven thus far. Toxic levels of both drugs were rarely found in our study, while a high percentage of patients, about one-third, had sub-therapeutic Cp during their treatments. In addition, in several cases of patients receiving multiple blood sampling, the initial subtherapeutic Cp changed only partially without reaching its therapeutic window. In relation to age, we found a higher percentage of lithium and VPA Cp values in range in the adolescents than in the adults and elderly groups. No differences were reported when analyzing the distribution of Cp values in males and females. In conclusion, this present study suggests that TDM is widely used by many specialists, but there is still a window of improvement for optimizing pharmacological treatments in clinical practice.

A 5-Year Study of Antiseizure Medications (ASMs) Monitoring in Patients with Neuropsychiatric Disorders in an Italian Clinical Center

“…However, its serious adverse effects impose a constant monitoring of patient’s conditions, including C(p) measuring [ 7 ]. VPA utilization has become a standard approach for treating particular categories of bipolar disorders, such as mixed states, rapid cycling, and with anxiety in comorbidity [ 40 ]. In addition, VPA can be also used in migraine; however, data of TDM for this medical condition are still missing, so we can assume that in our sample, it was less represented [ 41 ].…”

Therapeutic Drug Monitoring in Psychiatry: Enhancing Treatment Precision and Patient Outcomes

“…Different studies have shown that lithium monitoring is often underused, despite the existing recommendations [50,51], even though, in some instances, the importance of regular TDM has been acknowledged by clinicians, with promising results in terms of ADR prevalence [52]. In other cases, while TDM seems correctly used in terms of frequency, it does not induce the clinician to adjust lithium dosages in the case of suboptimal plasma levels, possibly due to concerns about ADRs [45,[53][54][55].…”

“…Despite its proven benefits, valproate TDM is still an underused or misused tool for the clinician: some studies show low frequency of monitoring, while others show that valproate levels are often found underdosed or at the lowest-end limits in patients with mood disorders, which could either indicate a low adherence to therapy, or the use of low dosages by clinicians for the treatment of psychiatric disorders [55,[65][66][67][68].…”

Pharmacological Strategies for Bipolar Disorders in Acute Phases and Chronic Management with a Special Focus on Lithium, Valproic Acid, and Atypical Antipsychotics

“…Considering that Lithium usually is administrated for many years or throughout the whole patient’s life, its harmful adverse effect on thyroid and kidney function has to be constantly monitored and it can be reduced through Lithium plasma monitoring [ 51 , 52 ]. Particularly, this latter adverse effect limits its use in patients with significant renal impairment.…”