Antipsychotic and Antiepileptic Drugs in Bipolar Disorder: The Importance of Therapeutic Drug Monitoring

Abstract

Bipolar disorder (BD) is a long-term illness with mood swings which are characterized by recurrent episodes of mania/hypomania and depression, with variable interpolations of relatively asymptomatic periods, called euthymic, in which, however, some psychopathological symptoms may persist. Although mood stabilizers, such as lithium, are the first-line treatment for the prevention of new BD episodes, combination therapy has become the standard of care for BD patients. Besides lithium, the use of a mood stabilizer along with an atypical antipsychotic is recommended in many patients. Recently, atypical antipsychotics (quetiapine, olanzapine, risperidone and aripiprazole) and antiepileptic agents (valproate, lamotrigine and oxcarbazepine) are increasingly used as mood stabilizers. To reduce side effects and optimize treatment it is important to perform accurate monitoring of drug blood levels in these patients, who are often treated with multiple drugs. Therapeutic drug monitoring (TDM) is in fact a powerful tool that, starting from clinical-chemical correlation data, allows to tailor-cut treatment to the specific needs of individual patients; hence the need to have reliable analytical methods available for the determination of plasma levels of drugs and their metabolites. Analyses of biological samples are mainly carried out using high-performance liquid chromatography (HPLC) coupled with different detectors, capillary electrophoresis and gas-chromatography. Various procedures are employed to remove biological interferences before analyzing the samples. This review focuses on currently available analytical TDM methods for atypical antipsychotics and antiepileptic agents used in the treatment of patients with bipolar disorder. Advantages and limitations of the various analytical methods will be reviewed and discussed, together with an evaluation of the role of TDM.

Amygdala and hippocampus volumes are differently affected by childhood trauma in patients with bipolar disorders and healthy controls

“…57 Moreover, we found differences in the lifetime use of antidepressants and antipsychotics. As expected from clinical practice, BP-I patients presented a lower lifetime use of antidepressants and a higher lifetime use of antipsychotics than BP-II patients, 58,59 except in the case of BP-II patients who presented childhood trauma. This could indirectly indicate a worse clinical course in BP-II patients presenting childhood trauma, as well documented in the literature.…”

Hippocampal subfield volumes in short‐ and long‐term lithium‐treated patients with bipolar I disorder

“…Therefore, it seems unlikely that other pharmacological treatments may have influenced our data. Although comparing drug‐free patients with those on lithium monotherapy would be scientifically ideal for minimizing confounding variables, the fact that most people with BP clinically require polypharmacotherapy to maintain mood stability does not make it feasible in the real word. Fourth, larger total hippocampal and subfield volumes in a long‐exposure group might be related to the osmotic effect of lithium and might not constitute a real neuroprotective action.…”

Development and validation of a reversed‐phase HPLC method for licarbazepine monitoring in serum of patients under oxcarbazepine treatment

“…Oxcarbazepine, a 10‐keto derivative of carbamazepine, is a new antiepileptic drug that has been registered in more than 50 countries worldwide since 1990 (Glauser, ) and is indicated in the monotherapy or adjunctive treatment of partial onset seizures in adults and children. Oxcarbazepine was synthesized in order to reduce the adverse effects of carbamazepine (Musenga, Saracino, Sani, & Raggi, ; Patsalos & Berry, ). Oxcarbazepine is rapidly and almost completely absorbed after oral administration and is reduced by a noninducible arylketone reductase to the mono‐hydroxy derivative, licarbazepine (May, Korn‐Merker, & Rambeck, ).…”