Antonius Loonen

Tardive dyskinesia and DRD3, HTR2A and HTR2C gene polymorphisms in Russian psychiatric inpatients from Siberia.

BACKGROUND Pharmacogenetics of tardive dyskinesia and dopamine D3 (DRD3), serotonin 2A (HTR2A), and 2C (HTR2C) receptors has been examined in various populations, but not in Russians. PURPOSE To investigate the association between orofaciolingual (TDof) and limb-truncal dyskinesias (TDlt) and Ser9Gly (DRD3), -1438G>A (HTR2A), and Cys23Ser (HTR2C) polymorphisms in Russian psychiatric inpatients from Tomsk, Siberia. METHODS In total, 146 subjects were included. Standard protocols were applied for genotyping. TDof and TDlt were assessed with AIMS items 1-4 and 5-7, respectively. Two-part model, logistic and log-normal regression analyses were applied to assess different variables (e.g., allele-carriership status, age, gender, and medication use). RESULTS TDlt, but not TDof, exhibited an association with Ser9Gly and Cys23Ser (with 9Gly and 23Ser alleles exhibiting opposite effects). However, -1438G>A was not associated with TDof and Dlt. CONCLUSIONS This is the first pharmacogenetic report on tardive dyskinesia in Russians. Subject to further replication, our findings extend and support the available data.

Lack of drug interactions between mirtazapine and risperidone in psychiatric patients: a pilot study.

An open-label, non-randomized, pilot study has been performed in inpatients in need of treatment with an antipsychotic (risperidone) and an antidepressant (mirtazapine) with the objective to preliminarily assess a possible pharmacokinetic interaction and the tolerability of this combination. A 1-4-week single drug treatment phase (risperidone 1-3 mg bid or mirtazapine 30 mg nocte) was followed by a 2-4-week combined drug treatment phase at unchanged doses. Twelve patients were enrolled, nine of whom were treated with risperidone in the single drug phase. Results of plasma level measurements are available for six patients and indicate that adding mirtazapine to risperidone does not alter steady-state plasma concentrations of risperidone and its 9-hydroxy metabolite. Data from one patient suggest that adding risperidone to mirtazapine does not result in clinically relevant changes in plasma concentrations of either compound. The combination was well tolerated and no major or relevant adverse events were observed. Adding risperidone to mirtazapine probably does not necessitate a change of the dosage of either drug, but more extensive investigations are needed.

Oral risperidone with lorazepam versus oral zuclopenthixol with lorazepam in the treatment of acute psychosis in emergency psychiatry: a prospective, comparative, open-label study

Acutely psychotic patients presenting as psychiatric emergencies with aggression or agitation are often administered conventional antipsychotics intramuscularly. However, patients view intramuscular administration as coercive, and conventional antipsychotics are often associated with adverse events. In this open study, consecutive adult patients presenting with an acute exacerbation of schizophrenia or other psychotic disorder were assigned to oral risperidone 2-6 mg/day (n = 48) or oral zuclopenthixol 20-50 mg/day (n = 27) for 7-14 days. Lorazepam (either oral or intramuscular) was administered to both groups as needed. Patients were assessed regularly until day 14 or discharge. Mean Positive And Negative Syndrome Scale (PANSS) aggression scores (sum of item scores on excitement, poor impulse control, hostility and uncooperativeness) decreased steadily and similarly in both groups; the mean changes from baseline were statistically significant at days 10 and 14 and at study end-point. The mean decrease at study end-point in the PANSS component score for hostility was statistically significant in the risperidone group, but not in the zuclopenthixol group. Social Dysfunction and Aggression Scale aggression scores and Clinical Global Impression scores decreased significantly and similarly in both groups. Overall, 18.7% of patients showed minor extrapyramidal symptoms during the study, but only 16.7% of risperidone-treated patients, compared to 59.3% of zuclopenthixol-treated patients, received anti-parkinsonian medication (p< 0.001). Lorazepam was administered to all of the patients assigned to risperidone and to 89% of those assigned to zuclopenthixol. Oral risperidone plus lorazepam is a convenient, effective and well-tolerated alternative to conventional antipsychotics for the treatment of acute psychosis in emergency psychiatry.

NMDA receptor genotypes associated with the vulnerability to develop dyskinesia

Dyskinesias are involuntary muscle movements that occur spontaneously in Huntingtons disease (HD) and after long-term treatments for Parkinsons disease (levodopa-induced dyskinesia; LID) or for schizophrenia (tardive dyskinesia, TD). Previous studies suggested that dyskinesias in these three conditions originate from different neuronal pathways that converge on overstimulation of the motor cortex. We hypothesized that the same variants of the N-methyl-D-aspartate receptor gene that were previously associated with the age of dyskinesia onset in HD were also associated with the vulnerability for TD and not LID. Genotyping patients with LID and TD revealed, however, that these two variants were dose-dependently associated with susceptibility to LID, but not TD. This suggested that LID, TD and HD might arise from the same neuronal pathways, but TD results from a different mechanism.

Missense polymorphisms in three oxidative-stress enzymes (GSTP1, SOD2, and GPX1) and dyskinesias in Russian psychiatric inpatients from Siberia

Neuronal degeneration due to oxidative stress (OS) has been proposed as a mechanism for tardive dyskinesia (TD) pathogenesis. Cellular defense mechanisms against OS may involve detoxification enzymes (e.g., glutathione peroxidase‐1, GPX1; superoxide dismutase‐2, SOD2 [also commonly known as MnSOD]; and glutathione S‐transferase P1, GSTP1). Several pharmacogenetic studies have examined TD and OS in different ethnic groups, but not in Russians. Here we report the association between orofaciolingual (TDof) and limb‐truncal dyskinesias (TDlt) and polymorphisms of GSTP1 (Ile105Val), MnSOD (Ala‐9Val), and GPX1 (Pro197Leu) genes in 146 Russian inpatients from Siberia. We applied AIMS instrument to rate dyskinesias. Two‐part model analyses, logistic and multivariate parametric regressions were applied to assess the effects of different variables (e.g., genotype, age, gender, and medication use). Our analyses do not suggest that Pro197Leu (GPX1) is associated with TD. However, our analyses suggest that the 105Val‐allele of Ile105Val (GSTP1) may be associated with a lower risk and a severity of TDof and TDlt and that Ile105Val pharmacogenetics may be different in Slavonic Caucasians from that in American Caucasians. Furthermore, we find evidence for an association between Ala‐9Val (MnSOD) and TDof, but not TDlt. Subject to further replication, our findings extend the available knowledge on the pharmacogenetics of TD and oxidative stress. Copyright

Practical recommendations for improvement of the physical health care of patients with severe mental illness

Health care for the physical health of patients with severe mental illness (SMI) needs to be improved. Therefore, we aimed to develop policy recommendations to improve this physical health care in the Netherlands based on consensus (general agreement) between the major stakeholders.

Skin disorders in chronic psychiatric illness.

Background  Chronic psychiatric patients are prone to develop skin diseases. However, epidemiological data are scarce.

Halopemide, a new psychotropic agent. Cerebral distribution and receptor interactions.

Halopemide is a new psychotropic agent, a structural analogue of the neuroleptics of the butyrophenone type but with different pharmacological and clinical properties. Preliminary clinical findings indicate that halopemide lacks the ability to induce parkinsonism and may be an effective drug in the treatment of psychosis characterized by autism, emotional withdrawal or apathy. Its pharmacological effects at a molecular level in comparison to structurally related neuroleptics and putative metabolites are reviewed.

A cross-sectional study of prescribing patterns in chronic psychiatric patients living in sheltered housing facilities

OBJECTIVE To analyze prescribing patterns of chronic psychiatric patients living in sheltered housing facilities, to identify the extent of polypharmacy and to estimate associated risks in this patient group. METHODS In a retrospective cross-sectional study the prescription data of 323 chronic psychiatric patients (average age 48.5 years) living in sheltered housing facilities in Rotterdam, The Netherlands, were analyzed. Prescription data were obtained from pharmacy-dispensing records. RESULTS Patients received on average 4.6 drugs (95% CI, 4.3-4.9). The most frequently prescribed drugs were as expected antipsychotics, benzodiazepines and antimuscarinic drugs. Overall 25% (n=81) of patients received two or more antipsychotic drugs. A high proportion of patients (38%, n=124) received one benzodiazepine, and 15% (n=50) received two or more benzodiazepines. CONCLUSION Patients in our study received a worryingly high number of drugs, and a quarter of the population was subject to antipsychotic polypharmacy. This increases the risk that drug-drug interactions, adverse drug reactions and noncompliance occur. Our study indicates potentially low quality of prescribing and shows the need for reviewing and special monitoring of pharmacotherapy in this patient group.

Substantial skin disorders in psychiatric illness coincide with diabetes and addiction

Background  Dermatological diseases in psychiatric patients are common; however, epidemiological data on this subject are scarce and to our knowledge integral studies of dermatological disease in psychiatric inpatients are not available yet.