At the Blood–Brain barrier (BBB), the superfamily of ATP-binding cassette (ABC) transporters includes the ABCB1 subfamily corresponding to P-glycoprotein (P-gp), the ABCC subfamilies of multidrug resistance-associated proteins (MRPs), and the ABCG2 subfamily corresponding to breast cancer resistance protein (BCRP). These efflux transporters are located mainly in the endothelial cells forming the BBB and prevent the entry of xenobiotics into the brain. Since psychotropics act on target sites of the central nervous system (CNS) in the brain, it is very important to know these transporters' roles at the BBB and to determine the brain drug concentrations at the targeted sites of the CNS. However, there is little information on human brain concentrations of psychotropics. Recent studies have demonstrated that brain concentrations of many psychotropics are significantly higher in P-gp-knockout mice than in wild-type mice. This result implies that P-gp may be a key player in the regulation of brain psychotropic pharmacokinetics and possibly causes the P-gp-mediated drug interaction at the BBB. In this review, we discuss the current findings concerning the role of drug transporters on the concentrations of psychotropics in the brain and summarize the available in vivo studies related to psychotropics.
Purpose: Accurate evaluation of medication adherence is important; however, no simple evaluation scale that is applicable to patients with bipolar disorder has been established in Japan. In this study, we prepared a modified Japanese version of a self-rating scale for medication adherence in the field of psychiatry, the Brief Evaluation of Medication Influences and Beliefs (BEMIB), and investigated its reliability and validity. Methods: Forty-one patients with bipolar disorder who visited several facilities, including Nagoya University Hospital, from April 2006 to August 2006 and from April 2009 to July 2009 underwent medication adherence evaluations using the Japanese versions of BEMIB and the Drug Attitude Inventory-10 Questionnaire (DAI-10). Results: The Cronbach α coefficient of the Japanese version of BEMIB was 0.73. Four-week test-retest reliability coefficients of each item and the BEMIB total score were 0.39-0.68 (p < 0.05) and the intra-class correlation coefficient was 0.63 (95% CI = 0.33-0.75, p < 0.001). In addition, a significant positive correlation was observed between the BEMIB and DAI-10 total scores (Pearson's correlation coefficient = 0.39, p < 0.001), showing that the concurrent validity was sufficient. Discussion: The Japanese version of BEMIB modified for patients with bipolar disorder is sufficiently reliable and valid. We suggest that this simple evaluation scale of medication adherence in patients with bipolar disorder is applicable in routine medical practice.
To investigate the plasma levels of prolactin during treatment with aripiprazole and their relationship to extrapyramidal symptoms (EPS), the levels of prolactin were measured and episodes of EPS were reviewed in 129 inpatients treated with aripiprazole or olanzapine. The mean level of prolactin in the aripiprazole group was significantly lower than that in the olanzapine group (male: 2.5 vs. 23.5; female: 5.8 vs. 38.4 ng/mL, p < 0.01). In the male aripiprazole subjects, a significant negative correlation between prolactin levels and the dosage was found (p < 0.01) and, at some (but not all) dosages, extrapyramidal symptoms occurred in the subjects with the lowest prolactin levels. These results suggest that aripiprazole could act as a “net antagonist” in the nigrostriatal pathway, and that the development of EPS may be associated with lower prolactin levels in male subjects. Simultaneously, aripiprazole acts as a strong dose-dependent “net agonist” in the tuberoinfundibular pathway, and causes severe hypoprolactinemia that may be associated with adverse events in aripiprazole monotherapy.
Patients with BPD are characterized by a pervasive pattern of instability in affect regulation, impulse control, interpersonal relationships, and self-image. The efficacy of fluvoxamine and lamotrigine for affective instability in patients with BPD has been shown in controlled studies. However, no study has evaluated the effectiveness and safety of lamotrigine for treating irritability in adolescent patients with BPD in Japan. Here, we report the case of a patient with BPD whose condition improved after lamotrigine administration. Lamotrigine could be effective and safe for treating BPD-associated affective instability. However, large-scale controlled studies are needed to confirm our findings.
Hyponatremia and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are recognized as serious side effects of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs). As elderly patients are easily predisposed to hyponatremia due to multiple factors, the use of SSRIs or SNRIs may be more likely to aggravate hyponatremia. We report the case of an elderly patient who developed hyponatremia most likely related to SIADH induced by duloxetine, an SNRI. Symptoms of hyponatremia emerged after treatment initiation and resolved with conservative care following discontinuation of duloxetine. Severe hyponatremia, serum hypoosmolality, urine osmolality, and measurable levels of plasma antidiuretic hormone suggested SIADH. Multiple factors, such as physical comorbidities and conditions, and drug interactions, might be associated with hyponatremia. Older patients receiving SNRIs or SSRIs should be closely monitored for clinical and laboratory evidence of hyponatremia.