Total RSP concentration: the invisible helmsman of mental health
发布日期:
2025-07-21
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Total risperidone (i.e. the sum of risperidone and its active metabolite, 9-hydroxyrisperidone) is a key indicator to be monitored during antipsychotic treatment, as its blood concentration is closely related to efficacy and adverse effects [1]. The clinically recommended therapeutic window is 20–60 ng/mL; within this range, better symptom control is achieved, and the risk of extrapyramidal reactions and hyperprolactinaemia is reduced [1]. Due to the wide variation in metabolism caused by polymorphisms in the CYP2D6 gene, the first blood sample should be taken 3–5 days after therapy begins to determine trough concentrations. Follow-up samples should then be taken every 3–6 months during the maintenance period and at any time if adjustments to the dose are needed or if signs of inefficacy or toxicity appear [1].

01



Clinical challenges of total risperidone[2]



01
 Significant burden of adverse effects

High incidence: Across all populations studied, the incidence of adverse events (AEs) was significantly higher in patients treated with risperidone than in those given a placebo. For instance, 94% of risperidone-treated children with autism experienced an AE, compared to 70% of those in the placebo group.

Common adverse reactions include movement disorders (e.g. Parkinson's syndrome or an inability to sit still), metabolic abnormalities (e.g. weight gain or elevated blood glucose), cardiovascular problems (e.g. upright hypotension or a prolonged QT interval) and leukopenia.

Serious risk: There is an increased risk of cerebrovascular accidents (e.g. stroke) and death associated with the use of risperidone in patients with dementia.


02
The risks associated with use by children and adolescents are significant

Although FDA-approved indications are limited, over-the-counter use is common in clinics for conditions such as ADHD and OCD.

 The long-term effects are unknown as most studies had a short follow-up period of eight weeks or less, and did not assess long-term adverse effects such as decreased bone density, pituitary tumours and diabetes mellitus.

Weight and metabolic issues: pediatric patients are more likely to experience rapid weight gain, insulin resistance and hyperlipidemia, which can impact growth and development.


03
Contradiction between efficacy and individual differences

There is high fluctuation in efficacy: although risperidone is effective in treating positive symptoms, it has limited efficacy in improving negative symptoms and cognitive function, and some patients respond poorly.

The relationship between blood concentration and efficacy is complex. The therapeutic window is narrow, so therapeutic drug monitoring (TDM) is needed to optimize dosing, but its clinical prevalence is low.


04
Adherence and dosage form challenges

Poor adherence to oral formulations: around 50% of patients reduce or stop taking their medication due to side effects or inadequate symptom relief, which increases the risk of relapse.

Limitations of long-acting injectable (LAI) formulations: although these can improve adherence, obstacles include unclear initiation timing, the need for specialized training and low patient acceptance.


05
Limitations of medication in special populations

Alzheimer's patients: the pros and cons must be carefully considered due to the risk of death and cerebrovascular events.

People with hematological abnormalities are at risk of granulocyte deficiency and require regular blood count monitoring.

Conclusion

The clinical challenges associated with total risperidone use primarily concern safety, particularly with regard to metabolic and neurological adverse effects, risks to specific populations, differences in efficacy, and adherence management. Addressing these challenges will require individualized treatment, TDM-guided dosing, optimization of long-acting dosage forms and long-term follow-up studies.

02



The significance of total risperidone TDM[2,3]

01
Individualised dose adjustment:

Total risperidone TDM helps adjust the dose according to blood concentration. This is especially useful for patients with poor efficacy or significant adverse effects. By monitoring the concentration of the active fraction (total risperidone + 9-hydroxy risperidone), the dosage can be optimised and adverse effects reduced.

02
Alternative strategies for refractory schizophrenia:

For patients with refractory schizophrenia, TDM can support the use of higher-than-standard doses of risperidone/paliperidone as an alternative to multidrug combinations or switching to clozapine, while maintaining patient stability and reducing hospitalisation.

03
Guidance for children and adolescents:

Although the relationship between blood levels and dosage in children and adolescents is unclear, TDM can detect differences between individuals, prevent adverse effects (e.g. extrapyramidal reactions) and suggest a lower therapeutic concentration range than for adults.

04
Long-term pharmacokinetic monitoring:

TDM reveals long-term concentration patterns of risperidone and its metabolites (e.g. cumulative C/D ratios at 2 and 6 months), helping to identify pharmacokinetic abnormalities and optimise long-term treatment.

In conclusion, total risperidone TDM is an important tool for individualised treatment, the management of refractory cases and dosing in special populations (e.g. children and adolescents), improving safety and efficacy.



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Automated Therapeutic Drug Monitoring Platformfor Chemicals and Biologics


Total RSP concentration: the invisible helmsman of mental health
Total RSP concentration: the invisible helmsman of mental health
Total RSP concentration: the invisible helmsman of mental health


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