Effective pharmacologic treatments for psychiatric disorders are available, but their effect is limited due to patients' genetic heterogeneity and low compliance-related to frequent adverse events.... Show moreEffective pharmacologic treatments for psychiatric disorders are available, but their effect is limited due to patients' genetic heterogeneity and low compliance-related to frequent adverse events. Only one third of patients respond to treatment and experience remission. Pharmacogenetics is a relatively young field which focusses on genetic analyses in the context of the metabolism and outcome of drug treatment. These genetic factors can, among other things, lead to differences in the activity of enzymes that metabolize drugs. Recently, a clinical guideline was authorized by the Dutch Clinical Psychiatric Association (NVvP) on the clinical use of pharmacogenetics in psychiatry. The main goal was to provide guidance, based on current evidence, on how to best use genotyping in clinical psychiatric practice. A systematic literature search was performed, and available publications were assessed using the GRADE methodology. General recommendations for psychiatric clinical practice were provided, and specific recommendations per medication were made available. This clinical guideline for caregivers prescribing psychotropic drugs is the product of a broad collaboration of professionals from different disciplines, making use of the information available at the Dutch Pharmacogenetics Working Group (DPWG) and the Clinical Pharmacogenetics Implementation Consortium (CPIC) so far. We summarize the relevant literature and all recommendations in this article. General recommendations are provided and also detailed recommendations per medication. In summary we advise to consider genotyping, when there are side effects or inefficacy for CYP2C19 and CYP2D6. When genotype information is available use this to select the right drug in the right dose for the right patient. Show less
Hebbrecht, K.; Giltay, E.J.; Birkenhager, T.K.; Sabbe, B.; Verwijk, E.; Obbels, J.; ... ; Diermen, L. van 2020
Objective The Montreal Cognitive Assessment (MoCA) is a sensitive and clinically practical test but its usefulness in measuring long-term cognitive effects of ECT is unclear. Using the MoCA, we... Show moreObjective The Montreal Cognitive Assessment (MoCA) is a sensitive and clinically practical test but its usefulness in measuring long-term cognitive effects of ECT is unclear. Using the MoCA, we investigated short- and long-term global cognitive change in ECT-treated patients with a Major Depressive Episode (MDE). Method We included 65 consecutive ECT-treated patients with MDE, in whom global cognitive functioning was assessed at baseline (T0); during ECT (before the third session; T1); and 1 week (T2), 3 months (T3), and 6 months (T4) after completion of the index course. Changes in MoCA (sub)scores were analyzed using linear mixed models and reliable change indices were computed to investigate individual changes in MoCA total scores. Results There was a significant effect of time on MoCA scores (F(4, 230.5) = 4.14,P = 0.003), with an improvement in global cognitive functioning from T3 compared to T1 and T2. At the individual level, 26% (n = 17) of patients showed a significantly worse cognitive functioning at T2 and 12% (n = 8) an improved cognitive functioning compared to T0. For T4, these percentages ameliorated to 8% and 18% respectively. Conclusion No persistent global cognitive impairment induced by ECT was found at the group level using the MoCA. At the individual level, however, there was clear heterogeneity in the effects of ECT on cognitive functioning. The MoCA is a suitable tool to monitor short- and long-term global cognitive functioning in ECT-treated patients with MDE but in younger patients, potential ceiling effects must be taken into account. Show less
Baeten, R.F.; Rossum, E.F.C. van; Rijke, Y.B. de; Sabbe, B.G.C.; Mast, R.C. van der; Belge, J.B.; ... ; Diermen, L. van 2020
Background: There is substantial evidence showing changes in hypothalamic pituitary adrenal (HPA)-axis ac-tivity in patients with major depressive disorder (MDD). Also, there seem to be differences... Show moreBackground: There is substantial evidence showing changes in hypothalamic pituitary adrenal (HPA)-axis ac-tivity in patients with major depressive disorder (MDD). Also, there seem to be differences in HPA-axis func-tioning between MDD subgroups. It is however unclear whether hair cortisol concentrations (HCC), which are a stable marker of long-term cortisol levels, are suitable as a biomarker for identifying subgroups in MDD. Methods: We were able to attain valid HCC from a scalp hair sample of sixty-two patients with a major de-pressive episode right before electroconvulsive therapy (ECT). HCC were our main biological outcome measure. We created subgroups using depression severity as defined by the Hamilton Depression Rating Scale, the pre-sence/absence of psychotic symptoms, the presence of melancholia as defined by the CORE and catatonia as defined by the Bush-Francis Catatonia Rating Scale. Results: Our analyses of the total group showed a median HCC of 4.4 pg/mg. We found patients with catatonia (N = 10) to have substantially higher median HCC (8.3 pg/mg) than patients without catatonia (3.8 pg/mg). Although presence of melancholia and depression severity were not significantly associated with HCC, more severe psychomotor agitation was associated with higher HCC. Pre-treatment HCC was not associated with ECT outcome. Strengths and limitations: A complicating factor in interpretation of our results was the large variability in HCC. This could be related to potential confounders such as cardiometabolic and other comorbidities, that were however addressed to the extent possible. Conclusions: HCC is a potential biomarker for MDD patients with severe agitation and/or catatonia. ClinicalTrials.gov: Identifier: NCT02562846. Show less
Diermen, L. van; Versyck, P.; Ameele, S. van den; Madani, Y.; Vermeulen, T.; Fransen, E.; ... ; Schrijvers, D. 2019
Objectives The presence of psychotic symptoms is an important predictor of responsiveness to electroconvulsive therapy (ECT). This study investigates whether a continuous severity measure, the... Show moreObjectives The presence of psychotic symptoms is an important predictor of responsiveness to electroconvulsive therapy (ECT). This study investigates whether a continuous severity measure, the Psychotic Depression Assessment Scale (PDAS), is a more accurate predictor. Methods Depression severity was assessed before and after the ECT course using the Montgomery-Asberg Depression Rating Scale (MADRS) in 31 patients with psychotic depression and 34 depressed patients without psychotic symptoms. Logistic regression models for MADRS response and remission were fitted, with either the PDAS total score or the dichotomous predictors "absence/presence of psychotic symptoms" as the independent variables. Age, episode duration, and treatment resistance were added as covariates. Results Both the asserted presence of psychotic symptoms and a higher PDAS total score reflected MADRS response (areas under the curve, 0.83 and 0.85, respectively), with MADRS remission also being predicted by the presence of psychotic symptoms and higher PDAS scores (areas under the curves, 0.86 and 0.84, respectively). Age was a contributor to these prediction models, with response and remission rates being highest in the older patients. Psychotic Depression Assessment Scale scores decreased significantly during ECT: at end point, 81.5% of the patients showed significant response and 63.9% had achieved remission. Conclusions The PDAS indeed accurately predicts response to and remission after ECT in (psychotic) depression and most pronouncedly so in older patients but seems to have no clear advantage over simply verifying the presence of psychotic symptoms. This could be the consequence of a ceiling effect, as ECT was extremely effective in patients with psychotic depression. ClinicalTrials.gov: Identifier: NCT02562846. Show less
