Important role of modern depot preparations such as Risperidone ISM® (Okedi®) in multimodal schizophrenia therapy

24.10.2023 13:32

Schizophrenia is a severe, chronic mental illness that can significantly and permanently impair the functioning and quality of life of those affected [1]. To minimize the negative effects of the illness, treatment should be multimodal and tailored to the needs of the patient [2,3]. As part of the symposium "From hospital to home: How can innovations in long-acting injectable antipsychotics shape schizophrenia treatment?" at the 2023 European College of Neuropsychopharmacology (ECNP) Congress, supported by ROVI GmbH, top-class international experts addressed the role of depot antipsychotics in multimodal schizophrenia therapy.

The depot formulation Risperidone ISM® received special attention because, due to its special pharmacokinetics, it can already be used in the context of inpatient decongestion [4,5] and thus enables a smooth transition to long-term outpatient treatment.

Patients with schizophrenia require personalized and integrated treatment strategies

"Recovery is a lifelong process for schizophrenia patients," said Prof. Dr. Dr. Silvana Galderisi, head of the emergency room of the Department of Mental Health at the Luigi Vanvitelli University of Campania and former EPA President, citing the testimony of a patient. It should be understood as symptomatic and functional remission, which includes holistic aspects, such as a lifestyle perceived as meaningful and fulfilling and a positive self-perception [6]. Recovery-oriented therapy must include integrated and personalized interventions, such as psychoeducation, cognitive behavioral therapy, or supported work [2,3]. Clinical stability is an important prerequisite for participation in non-pharmacological treatment programs [7], which is why long-term and consistent treatment with antipsychotics is so important, Galderisi emphasized. Given poor treatment adherence and high relapse rates [8,9], coordinated transition from inpatient to outpatient care and continuous, needs-based treatment are of utmost importance. The longer patients remain untreated—and every relapse must be taken into account—the worse the prognosis [10]. Therefore, the treatment of schizophrenia patients should be considered long-term from the outset, with fast-acting and long-lasting depot medications with a simple treatment regimen being advantageous [8]. According to Galderisi, a corresponding treatment plan can usually be decided and implemented even for acutely ill patients.

Patients can expect effective treatment suggestions and shared decision-making from their treating psychiatrists

It is now widely known and repeatedly proven that the use of depot antipsychotics, especially second-generation ones, achieves better results in terms of relapse prevention, rehospitalization rates, and mortality risk [11,12], stated Prof. Dr. Stephan Heres, Head of the Department of Psychiatry and Psychotherapy at the kbo-Isar-Amper-Klinikum in Munich and Professor at the Technical University of Munich. Furthermore, new data show that a proactive approach—that is, switching to a depot medication without prior adherence problems or a psychiatric emergency—is associated with significantly lower rehospitalization rates [13]. "A depot medication can and should always be considered when antipsychotic therapy is indicated," concluded Heres. Another study shows that relapses occur more frequently and, above all, more quickly after discontinuation of oral antipsychotic medication compared to depot medications [14]. Following a planned or arbitrary discontinuation of a long-acting antipsychotic, there is therefore more time to notice a deterioration and intervene if necessary. At the same time, it is essential for long-term patient satisfaction with treatment that treatment decisions are made in cooperation with those affected. In this regard, actual practice still falls short of both patients' expectations and the self-perception of treating physicians [15]. Furthermore, it is important and sensible, even in the context of inpatient treatment, to involve patients' caregivers and relatives more closely from the outset. This does not happen automatically, but must be actively encouraged, also to avoid a breakdown in social contacts of mentally ill people as a result of hospital stays [16].

Depot formulation Risperidone ISM® – constant therapeutic plasma levels and effective D2 receptor occupancy

"Treatment adherence is the Achilles' heel of oral antipsychotic therapy," states biologist and chemist Dr. Eric Snoeck. The expert in pharmacokinetic and pharmacodynamic modeling emphasized that in patients treated with oral risperidone, with poor adherence, meaning only 25–50% of the medication was taken correctly, more than half of the patients did not have therapeutic plasma levels, thus preventing effective D2 dopamine receptor occupancy [17,18]. Accordingly, the risk of relapse, rehospitalization, and even suicide attempt is increased in non-adherent versus adherent patients [19]. Depot preparations could offer advantages in cases of adherence problems, with the rapid achievement and sustained maintenance of therapeutic drug levels over the entire treatment interval, as well as minimal accumulation of the drug over multiple doses, being important pharmacokinetic quality parameters. For the depot preparation Risperidone ISM®, a patient-based pharmacokinetic study demonstrated that therapeutic plasma levels and a steady state comparable to oral administration are achieved after the first injection and without oral supplementation or loading dose and are maintained over a period of 4 weeks [4]. Using a population pharmacokinetic model, it has now been further demonstrated that drug accumulation with repeated administration of Risperidone ISM® is minimal [20] and that both dose escalation from 75 mg to 100 mg and de-escalation are easily possible [21]. Continuation or resumption of treatment after delayed or missed doses is just as easy, as steady state is restored with the injection [21]. Modeling results further demonstrated more reliable D2 receptor occupancy with Risperidone ISM® compared to oral administration in cases of moderate or poor adherence, and also compared to monthly intramuscular injections of paliperidone palmitate – especially during the first four months of treatment [20].

Conclusion

Depot antipsychotics can play an important role in personalized, integrated schizophrenia therapy, as they ensure consistent and reliable antipsychotic effects and promote patient clinical stability [8,22], which is often required for participation in non-pharmacological interventions. Proactive use of a depot antipsychotic before adherence problems or a psychiatric emergency arise can have a positive impact on prognosis [13], with a collaborative treatment decision significantly influencing patient satisfaction [15]. The depot formulation Risperidone ISM® is characterized by favorable pharmacokinetic properties [4] and a simple initiation and conversion regimen [5], allowing early use in the context of de-updating and improving patient acceptance.
could improve.

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