Antipsychotic new drug brexpiprazole in improving symptoms significantly better than placebo

A study published in September, "American Journal of Psychiatry," the multi-center randomized double-blind controlled study, Hofstra University, USA - North Shore Medical Christoph U. Correll et al found that, for patients with acute exacerbation of schizophrenia, 2mg / d and 4mg / d of new drugs brexpiprazole antipsychotic in terms of improvement of symptoms was significantly better than placebo and well tolerated.
Dr. Donald C. Goff, New York University Medical Center for the drug with the Journal commented, the following main points of Dr. Goff:
In this study, 2mg and 4mg of brexpiprazole valid and 0.5mg invalid. This study shows us the short-term efficacy of the drug compared to placebo, but the lack of an active control of the design makes it difficult to predict the market compared to other antipsychotics, brexpiprazole exactly what advantages or disadvantages. And, brexpiprazole turned out coincides with many of the existing second-generation antipsychotics patents expire, including aripiprazole (aripiprazole), and imitation will wind current and future health care budget tremendous impact.
Similar to aripiprazole, brexpiprazole also D2 receptor partial agonist. By the relatively weak endogenous dopamine D2 receptor activation effect, D2 partial agonist reduces the maximum delivery of the "ceiling", while lower activity levels increased D2 receptor. Above mechanism aimed at achieving a balance: D2 receptor by agonistic effect sufficient to prevent neural side effects (extrapyramidal reactions) and hyperprolactinemia, but also to avoid excessive D2 receptor activity; D2 receptor activity It can reduce the effects of high anti-psychotic drugs, and lead to certain related side effects.
As previously sink like a stone a D2 receptor partial agonist, bifeprunox, its intrinsic activity for the D2 receptor stronger than aripiprazole. The result is that antipsychotic efficacy of the drug in inferior currently being used, while D2 receptor agonist effect and cause nausea and vomiting. In fact, we can speculate, as D2 receptor agonists, anti-psychotic effects of aripiprazole may also be weaker than other antipsychotics; however, head to head comparison of the current evidence is still limited, as far as the efficacy of aripiprazole still in the middle ranks of the second-generation antipsychotics. Essentially, aripiprazole without causing hyperprolactinemia and extrapyramidal symptoms, but as a D2 receptor agonist symptoms, nausea, insomnia and would rather not appear in the early treatment of some patients.
D2 receptor internalization activity of dopamine itself is 100%, brexpiprazole 43%, aripiprazole was 61%, bifeprunox 84%. From this perspective, among aripiprazole and D2 receptor antagonist antipsychotics brexpiprazole ranked. The absence of other factors being equal, people can predict, brexpiprazole efficacy and extrapyramidal reactions / prolactin increased risk of the same center. However, unlike aripiprazole it is different, the higher brexpiprazole with 5-HT1a receptor affinity, the same as a partial agonist; and 5-HT2a and α1b and 2c receptor also has an affinity for the potential antagonistic effects. Compared to aripiprazole, brexpiprazole above properties more similar to other second-generation antipsychotics, which may be helpful for efficacy.
In this study, despite a relatively prominent placebo effect exists, but the efficacy of 2mg and 4mg brexpiprazole still conclusive, involving positive improvement in negative symptoms and overall outcome indicators. However, Similarly, the use of placebo-controlled design BEACON study, after six weeks of treatment brexpiprazole just 4mg / d was significantly better than placebo. Two studies of adverse reactions similar situations, such as 4mg group and moderately associated with weight gain, an increase of about six weeks 1kg, prolactin also increased slightly. Correll's study, 4mg / d group had akathisia ratio of 7.2%, while the figure in the placebo group was 2.2%; BEACON study, brexpiprazole no significant difference with placebo. brexpiprazole other forms of nerve incidence of adverse reactions similar to placebo, the researchers also affect the drug on cardiac function was not detected. brexpiprazole and changes in blood pressure has nothing to do, but for a period of eight days of dose titration may mask the true situation. Given the extent of extrapyramidal reactions and weight gain / prolactin elevation affected the study sample, the drug previously used the same effect will continue, we will medicine with existing drugs is difficult to compare directly.
In summary, as we learned from the CATIE study until more comparative data, especially randomized study comparing head to head emergence, it is difficult to determine in the market compared to the existing drugs, an anti-psychotic Advantages and disadvantages of how new drugs. A very appealing concept is that clinicians may be based on the sensitivity and efficacy requirements for adverse reactions in patients, from a range of different intrinsic activity of D2 receptor partial agonist be selected. After aripiprazole and D2 receptor antagonist treatment failure, patients will find brexpiprazole "just right"? There may be, but in the open aripiprazole and D2 receptor antagonist antipsychotics between the space occupied by brexpiprazole not necessarily wide to have clinical significance. Head to head comparison or clinical practice, brexpiprazole could come to the fore, we'll see.