DOPAMINERGIC DYSFUNCTION IN NEUROPSYCHIATRIC DISORDERS AND THE EFFECT OF CARIPRAZINE IN THEIR TREATMENT
Csehi Réka
János Szentágothai Neurosciences
Dr. Bereczki Dániel
SE, Genomikai Medicina és Ritka Betegségek Intézete
2024-10-28 14:00:00
Klinikai idegtudományok
Dr. Molnár Mária Judit
Dr. Balogh Lívia
Dr. Álmos Péter Zoltán
Dr. Purebl György
Dr. Tamás Gertrúd
Dr. Kapás István
The HD study was the first one ever to investigate the effectiveness of cariprazine in this patient population. It was a 12-week, open-label, single arm, retrospective, observational study with 15 enrolled patients. Cognitive symptoms were evaluated using the ACE and the Cognitive Examination of the UHDRS, both of which revealed the effectiveness of cariprazine. Behavioural/mood symptoms were examined using the BDI and the Behavioural Examination of the UHDRS - again, cariprazine proved to be efficacious in the alleviation of these symptoms as well. Strikingly, cariprazine did not only improve cognitive and behavioural/mood symptoms, but also the motor symptoms, as measured by the Motor Examination of the UHDRS, with the positive effect being driven by the vast majority of the single items.
In addition to the HD study, a systematic review of the available cariprazine case reports was conducted, which was the first one to do so. In fact, generally, there are not many systematic reviews of case reports investigating the real-world effectiveness and safety of psychiatric compounds. The systematic review synthesised, analysed and evaluated information from 38 cases. In addition to the approved indications (i.e., schizophrenia, depressive and manic/episodes associated with bipolar disorder and MDD as adjunctive therapy), it included patients with disorders that have not been investigated before in relation to cariprazine, especially not in clinical trials. These included SUD (yielding abstinence in most cases), Wernicke-Korsakoff syndrome (reducing psychotic, cognitive and negative symptoms and improving psychosocial functioning), OCD (reducing OCD symptoms completely) and borderline personality disorder (reduction in affective symptoms, and completely resolving hostility and impulsivity).
Taken together, cariprazine seems to be a promising treatment option for the treatment of various disorders, including HD. The uniqueness of cariprazine lies in its partial agonist activity at D3 receptors to which it binds with high affinity - even higher than endogenous dopamine, making it the only approved antipsychotic to occupy the D3 receptors in the presence of dopamine in vivo. Therefore, cariprazine can achieve the effects associated with D3 receptors (i.e., cognitive, negative, and affective symptom-reduction). In summary, the findings imply that cariprazine could alleviate the most troublesome symptoms from patient functioning point-of-view, which are cognitive, negative, and affective symptoms. However, the efficacy cariprazine needs to be established in these indications as well, by conducting studies with more rigorous design to be able to draw causality.
