Optimisation of pharmacotherapy in psychiatry through therapeutic drug monitoring, molecular brain imaging and pharmacogenetic tests: focus on antipsychotics.

BACKGROUND: For psychotic disorders (i.e. schizophrenia), pharmacotherapy plays a key role in controlling acute and long-term symptoms. To find the optimal individual dose and dosage strategy, specialized tools are used. Three tools have been proven useful to personalize drug treatments: therapeutic drug monitoring (TDM) of drug levels, pharmacogenetic testing (PG), and molecular neuroimaging. METHODS: In these Guidelines, we provide an in-depth review of pharmacokinetics, pharmacodynamics, and pharmacogenetics for 50 antipsychotics. Over 30 international experts in psychiatry selected studies that have measured drug concentrations in the blood (TDM), gene polymorphisms of enzymes involved in drug metabolism, or receptor/transporter occupancies in the brain (positron emission tomography (PET)). RESULTS: Study results strongly support the use of TDM and the cytochrome P450 (CYP) genotyping and/or phenotyping to guide drug therapies. Evidence-based target ranges are available for titrating drug doses that are often supported by PET findings. CONCLUSION: All three tools discussed in these Guidelines are essential for drug treatment. TDM goes well beyond typical indications such as unclear compliance and polypharmacy. Despite its enormous potential to optimize treatment effects, minimize side effects and ultimately reduce the global burden of diseases, personalized drug treatment has not yet become the standard of care in psychiatry.

Use of pharmacological treatment for posttraumatic stress disorder: Analysis of a psychiatric population in Switzerland and comparison with international guidelines.

OBJECTIVES: Several international guidelines for the pharmacological treatment of posttraumatic stress disorder (PTSD) have been published. However, it is unclear whether clinicians use these procedures in their daily practice. We compared the psychopharmacological prescription patterns in a Swiss adult psychiatric center with international clinical guidelines at admission and discharge. METHODS: Retrospective chart review study between 2005 and 2015 of adult patients with PTSD and no other documented psychiatric comorbidity. RESULTS: Fifty-two outpatients and 21 inpatients were included; 47% had at least one psychopharmacological treatment at admission. Among them, 47% had one or several antidepressants, mainly escitalopram (31%, n=5) or citalopram. At discharge, 68% had at least one psychopharmacological treatment. Among them, 76% had at least one antidepressant, mainly escitalopram (34%, n=13) or mirtazapine (21%, n=8). They were compared to the guidelines of the Department of Veterans Affairs and Department of Defense (VA/DoD), showing 19% of the patients treated with antidepressants at admission were in agreement with the guidelines (sertraline, fluoxetine, paroxetine, venlafaxine), and 26% at discharge. In addition, we found prescriptions of benzodiazepines (62% at admission and 50% at discharge), antipsychotics (12% and 22%), Z-drugs (zolpidem, zopiclone: 15 and 40%) and a few pregabalin prescriptions (n=4). CONCLUSIONS: Clinicians in this study frequently prescribed antidepressants to treat PTSD, as recommended. However, most of the antidepressants used were not recommended in the VA/DoD guidelines. Benzodiazepines and Z-drugs remained widely used, although they are not recommended.

Tools for optimising pharmacotherapy in psychiatry (therapeutic drug monitoring, molecular brain imaging and pharmacogenetic tests): focus on antidepressants.

Objectives: More than 40 drugs are available to treat affective disorders. Individual selection of the optimal drug and dose is required to attain the highest possible efficacy and acceptable tolerability for every patient.Methods: This review, which includes more than 500 articles selected by 30 experts, combines relevant knowledge on studies investigating the pharmacokinetics, pharmacodynamics and pharmacogenetics of 33 antidepressant drugs and of 4 drugs approved for augmentation in cases of insufficient response to antidepressant monotherapy. Such studies typically measure drug concentrations in blood (i.e. therapeutic drug monitoring) and genotype relevant genetic polymorphisms of enzymes, transporters or receptors involved in drug metabolism or mechanism of action. Imaging studies, primarily positron emission tomography that relates drug concentrations in blood and radioligand binding, are considered to quantify target structure occupancy by the antidepressant drugs in vivo. Results: Evidence is given that in vivo imaging, therapeutic drug monitoring and genotyping and/or phenotyping of drug metabolising enzymes should be an integral part in the development of any new antidepressant drug.Conclusions: To guide antidepressant drug therapy in everyday practice, there are multiple indications such as uncertain adherence, polypharmacy, nonresponse and/or adverse reactions under therapeutically recommended doses, where therapeutic drug monitoring and cytochrome P450 genotyping and/or phenotyping should be applied as valid tools of precision medicine.

Detection of bacterial DNA in synovial fluid from horses with infectious synovitis.

Standard culturing techniques are often unrewarding in confirming diagnosis of synovial infection in the equine patient. Several human studies report the use of sensitive polymerase chain reaction (PCR) techniques for the detection of bacterial involvement in acute synovitis. However, successful extraction of bacterial DNA directly from clinical samples from horses without prior culture has not been reported yet. The goal of this study was to develop a sensitive and reliable method for molecular detection and identification of bacterial species in synovial fluid from horses with infectious synovitis. Synovial fluid samples from 6 horses with culture confirmed synovial infection were used for broad range 16S rRNA gene PCR. Synovial aspirates of 2 healthy horses were used as negative controls. Following extraction and purification of synovial fluid DNA, all samples were processed by touchdown PCR. Amplicons were detected by reverse line blot hybridisation and visualised with chemiluminescence. Pathogen-specific detection of 16S rRNA gene sequences was successful in all 6 synovial fluid samples. No bacterial DNA was detected in the aspirates from the negative control horses using touchdown PCR followed by 25 additional cycles of amplification. The identity of the pathogens was confirmed by DNA sequencing of the amplicons. It can be concluded that broad range 16S rRNA gene PCR followed by reverse line blot hybridisation is a promising technique for detection of bacterial DNA in synovial fluid samples. Further research should aim at the detection of bacterial DNA in synovial fluid samples suspected of infection but having negative culture results. When the 16S PCR proves to be reliable and more sensitive than standard culturing techniques, it may become a powerful tool in the diagnosis of synovial infection.

[Miotics and occlusion in the treatment of accommodative strabismus]. / Traitement par miotiques et occlusion du strabisme accommodatif.

Antisuppressive occlusion is an intermittent occlusion prescribed in order to eliminate suppression. This way, the system of vergences is reactivated which results in a stabilisation of the position of the eyes and reduces asthenopic complaints. Miotics are used to treat a recent or intermittent convergent squint. Miotics can equally be used to remove positive glasses and to reduce a visible postoperative recurrence.