RESUMO
Psychiatric disorders are usually treated with antipsychotic agents belonging to different pharmacological and chemical classes, the most recent ones collectively known as "third-generation antipsychotics", such as cariprazine, approved in 2015 for the treatment of patients affected by schizophrenia. For these patients, a frequent therapeutic drug monitoring (TDM) becomes essential to assess compliance and to optimise and personalise their therapy, also due to cariprazine interindividual variability and narrow therapeutic range. In this study, a bioanalytical method featuring miniaturised sampling and pretreatment was developed, based on volumetric absorptive microsampling (VAMS) for TDM of psychiatric patients under cariprazine treatment and compared to a reference method based on fluid plasma analysis. Minimally invasive whole blood VAMS was coupled to an original instrumental method based on ultra-high performance liquid chromatography hyphenated to mass spectrometry (UHPLC-MS). A feasible and streamlined, yet reliable VAMS pretreatment protocol was carefully optimised and the VAMS-UHPLC-MS methodology was validated with satisfactory results in terms of linearity (r2 > 0.9970 in the 1.5-100 ng/mL range), precision (%RSD < 11.7), extraction yield (> 90.0 %) and matrix effect (8.2 ≤ %RE ≤ 10.9). Finally, the microsampling approach coupled to UHPLC-MS was successfully applied to the TDM of psychiatric patients treated with cariprazine and compared with standard fluid plasma analysis, providing reliable quali-quantitative results, and proving to be readily applicable to the clinical practice in TDM programs as a useful alternative to cariprazine plasma analysis. This is the first report of a successful microsampling application, and in particular the first report of VAMS application, for the TDM of cariprazine.
RESUMO
BACKGROUND: In premenstrual syndrome, depressed mood in the luteal phase of the menstrual cycle is acknowledged, whereas the presence of symptoms of depression during the follicular phase remains in debate. METHODS: On the basis of prospective daily recording of the presence and severity of symptoms for at least two menstrual cycles, 43 women were diagnosed with Late Luteal Phase Dysphoric Disorder (LLPD) according to the criteria of the third edition revision of the Diagnostic and Statistical Manual of Mental Disorders. They were compared to a group of 85 women who showed no evidence of LLPD for two menstrual cycles. Structured psychiatric interviews were administered during the follicular phase. Only those subjects without Axis I disorders were subsequently included in the study. RESULTS: Those women with minor/moderate symptoms of depression had an odds of suffering from LLPD of 1.9 (95% CI=1.5-2.4, p<0.001) in relation to increasing severity of symptoms of depression at the total MADRS scale (1-point increase). The ORs of LLPD in relation to each dimension (1-point increase) of the emotional/affective, cognitive, and neurovegetative symptoms were 1.6 (95% CI=1.2-2.3, p=0.003), 2.8 (95% CI=0.9-8.5, p=0.077) and 3.3 (95% CI=1.9-5.9, p<0.001), respectively. LIMITATIONS: No hormonal changes that may be associated with symptoms of LLPD were determined in this study. CONCLUSIONS: LLPD is likely to represent a variant of a depressive disorder, where premenstrual psychobiological changes seem to exacerbate mild depressive symptoms and signs to which LLPD women are otherwise predisposed. This hypothesis opens new perspectives for prevention and of even treatment for LLPD. Further longitudinal studies with larger populations and evaluation of hormonal changes are needed to confirm these data.