Inconsistent results regarding the risk of relapse and better subjective outcomes of previous antipsychotic dose reduction trials in patients with remitted psychosis have not been verified using therapeutic drug monitoring (TDM). This study examined plasma drug concentrations of a dose-tapering trial which exhibited the potential of successful maintenance under lower antipsychotic dosages.

A 2-year open-label randomized prospective trial recruited remitted patients to undergo guided antipsychotic tapering. Blood samples were collected at baseline, annually, and after each dose reduction. Plasma aripiprazole/dehydroaripiprazole concentrations were determined using LC–MS/MS. The relationship between the dose and serum drug levels was examined using Spearman's correlation. Divided at 120 ng/mL, relapse rate, global function, quality of life, and psychopathology were compared between high- and low- drug level groups.

A total of 126 blood samples were collected, after excluding13 samples due of non-adherence. The correlation coefficients between dosage and drug level were 0.853 (aripiprazole) and 0.864 (dehydroaripiprazole), and the dose and concentration plots were parallel along the tapering trajectories, except patients with non-adherence. The concentration-to-dose ratio of aripiprazole in this cohort, 17.79 ± 7.23 ng/mL/mg, was higher than that in Caucasian populations. No significant differences were observed in the clinical outcomes between the high- and low-level groups. Remarkably, 12 of 15 patients maintained remission at plasma aripiprazole concentrations of <120 ng/mL.

The lower-than-expected doses reached in our antipsychotic tapering trial were substantiated to provide adequate prophylactic effects by TDM results in a subset of patients treated with aripiprazole, even considering the differences in pharmacogenomics between ethnicities.

Although clozapine is the most efficacious medication for treatment-refractory schizophrenia, not all patients will have an adequate response. Optimising clozapine dose using therapeutic drug monitoring could therefore maximise response.

Using individual patient data, we undertook a receiver operating characteristic (ROC) curve analysis to determine an optimal therapeutic range for clozapine levels to guide clinical practice.

We conducted a systematic review of PubMed, PsycINFO and Embase for studies that provided individual participant level data on clozapine levels and response. These data were analysed using ROC curves to determine the prediction performance of plasma clozapine levels for treatment response.

We included data on 294 individual participants from nine studies. ROC analysis yielded an area under the curve of 0.612. The clozapine level at the point of optimal diagnostic benefit was 372 ng/mL; at this level, the response sensitivity was 57.3%, and specificity 65.7%. The interquartile range for treatment response was 223–558 ng/mL. There was no improvement in ROC performance with mixed models including patient gender, age or length of trial. Clozapine dose and clozapine concentration to dose ratio did not provide significantly meaningful prediction of response to clozapine.

Clozapine dose should be optimised based on clozapine therapeutic levels. We found that a range between 250 and 550 ng/mL could be recommended, while noting that a level of >350 ng/mL is the most optimal for response. Although some patients may not respond without clozapine levels >550 ng/mL, the benefits should be weighed against the increased risk of adverse drug reactions.

Despite the widespread use of long-acting injectable (LAI) antipsychotics in schizophrenia and other disorders, there is a lack of longitudinal studies evaluating prescription trends and the usefulness of therapeutic drug monitoring (TDM) to inform dosing. Indeed, LAI prescription varies greatly among different areas of the world and over the years.

Assess trends in LAI prescription in 2013-2020 at the Psychiatry Department of Bozen, Italy, and (2) analyze the correlation between dose of prescribed LAIs and blood levels measured via TDM.

Parametric statistics.

LAIs were administered to 471 patients (x̅ age±SD=47.2±16.3 years; 56.3% men). The pie chart shows LAI treatment duration, i.e., from 1 to 7 consecutive years. The most used LAIs were haloperidol in 2013-2104 (26.5-31.8%) and paliperidone in 2015-2020 (22.5-25.7%). Dose adjustments were rather frequent, whereas the switch between LAI, due to moderate-to-side effects or unsatisfactory improvement of clinical status, was infrequent (41 cases/8 years). LAI interruption for the same reasons or non-compliance was even more infrequent (10 cases), but in 8 cases it happened for opposite reasons, i.e., achievement of patients’ stabilization and good compliance. The Table shows doses and plasma levels of LAIs. Correlations between doses and plasma levels were: haloperidol: r=-0.037, p=0.620; paliperidone: r=0.290; p=0.000; risperidone: r=0.219, p=0.006; fluphenazine r=0.358, p=0.000; aripiprazole: r=-0.051, p=0.610; olanzapine: r=-0.090, p=0.634.

Haloperidol and paliperidone were the most used LAIs. Drug prescription trends and doses were stable over time. A significant positive correlation between dose and plasma level was found for paliperidone, fluphenazine, and aripiprazole.

No significant relationships.

Clinical relapses in schizophrenia remain a frequent event. Long-acting injectable (LAI) antipsychotics enhance adherence, but low blood levels can sometimes be observed despite an adequate posology. Nonetheless, the evaluation of this parameter is uncommon in clinical practice.

To explore the potential advantages of therapeutic drug monitoring (TDM) of LAIs as a predictor of relapse in clinically stable outpatients with schizophrenia.

44 individuals who had reached the pharmacokinetic steady state of LAI treatment (paliperidone, olanzapine, aripiprazole) underwent an anamnestic and psychopathological assessment. LAI blood levels were measured using liquid chromatography-mass spectrometry and classified as “in range” or “under range” according to the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) guideline values. Individuals who relapsed during the one-year follow-up were compared to non-relapsers (Fisher’s exact test, χ2 or Mann-Whitney U). An exploratory binary logistic regression tested the role of other possible relevant predictors of relapse.

No differences were observed in baseline use of mood stabilisers (p=0.211), antidepressants (p=0.530), or prescribed LAI (p=0.563). Other comparisons are presented in the table: among these variables, in-range LAI levels were the only significant predictor of relapse (F=5.95, p=0.015; OR 0.04, 95%CI 0.02-0.56).

TDM of LAIs may optimise the clinical management of schizophrenia by highlighting a suboptimal dosage and a consequent higher relapse risk. Large-scale, drug-specific assessments are needed to confirm these findings.

No significant relationships.

No significant relationships.

Mycobacterium kansasii is a nontuberculous mycobacterium that causes infection associated with past or current tuberculosis disease. Clinical syndromes and radiological findings are mostly indistinguishable from that of Mycobacterium tuberculosis, thus requiring microbiological confirmation.

We report a case of a 44-year-old man diagnosed with schizophrenia and Mycobacterium kansasii infection.

Case report and non-systematic narrative review from PubMed.

Case report: Patient with schizophrenia who was admitted at the inpatient unit presenting psychotic exacerbation with high levels of excitement. Risperidone 6 mg/day and valproate 500 mg/day were initiated. He was also diagnosed with a M. kansasii lung infection, with radiological findings of past tuberculosis disease. Before the microbiological confirmation, it was necessary to start rifampicin, requiring an increase in doses of both psychotropic drugs. Review: (1)Comorbidity of mycobacterial infections and schizophrenia. Several studies have shown that people with severe mental illness have higher rates of tuberculosis compared with the general population. Although the relationship between tuberculosis and M. Kansasii infection is known, few literature is available with regard to the association of M. Kansasii and schizophrenia. (2)Interactions between antipsychotics and mood stabilizers with rifampicin. Rifampicin is mainly metabolized by CYP3A4 and transported by P-glycoprotein. Add-on with rifampicin have been reported to reduce clozapine and olanzapine plasma levels (despite both are metabolized by CYP1A2), reduce haloperidol and risperidone levels (possible role of P-glycoprotein in this interaction), as well as for valproate.

Treatment of comorbid infections in people with schizophrenia remains a challenge. Antibiotics used to treat mycobacterial infections can modify the pharmacokinetic of psychotropic drugs.

No significant relationships.

Routine therapeutic drug monitoring in clozapine therapy has previously not been considered justifiable. Using observational data, the clinical utility of annual clozapine assay monitoring is explored within a large mental health trust.

After the introduction of routine monitoring, the rate of clozapine assays rose to 2.3 per patient per year, with a consistent reduction in high-risk clozapine assays (<0.1 mg/L or >1.0 mg/L or any result more than 24 months old). High-risk assays are associated with a mortality rate of 31.6 deaths per 1000 patients, more than twice that of those within the target range (0.35–0.60 mg/L and conducted within the past 12 months) (P = 0.048).

Routine clozapine assay monitoring has significant clinical utility. Our simple but targeted approach can be readily implemented to reduce the number of patients with high-risk clozapine assay levels, potentially reduce all-cause mortality and provide optimal treatment for those with treatment-resistant schizophrenia.