Schizophrenia is a group of severe mental disorders of unknown etiology, with significant
abnormalities in cognitive, thinking, emotional, behavioral and other aspects of mental
activities, and can lead to significant occupational and social function damage. According to
the relevant data of the World Health Organization, among 135 diseases or health conditions
common to young people (aged 15-44), schizophrenia ranks eighth in the total disease burden,
accounting for 2.6% of the total disease burden. Statistics from developed countries show
that direct expenditure caused by schizophrenia accounts for 1.4% - 2.8% of total health
resource expenditure. At present, there is no relevant medical economic data in China, but it
is estimated that nearly 7 million people in China are suffering from schizophrenia, which
causes huge medical expenditure every year, and also causes labor loss of patients and their
families. Schizophrenia is still the main disease leading to mental disability at present
[1].
The clinical manifestations of schizophrenia include five dimensions: positive symptoms,
negative symptoms, cognitive symptoms, aggression and hostility, anxiety and depression. The
existing antipsychotics (including typical and atypical antipsychotics) have a positive
effect on positive symptoms, but have a poor effect on improving symptoms in other
dimensions. From the perspective of prognosis, patients with non positive symptoms as the
main clinical phase usually have poor prognosis. The existing evidence shows that one of the
main reasons for suicide of schizophrenic patients is long-term depressive symptoms, and
negative symptoms, depression and cognitive symptoms are important factors affecting the
treatment outcome of patients. The treatment of negative symptoms is one of the core problems
of schizophrenia at present, which still needs more exploration. At present, the treatment of
negative symptoms with second-generation antipsychotics and antidepressants has been
supported by some studies. However, due to the heterogeneity of antidepressants, a large
number of research results are difficult to reach a unified conclusion with high evidence
level. The current clinical experience believes that despite the lack of strong RCT research,
the new antidepressants are well tolerated and have less side effects, which supports the use
of new antidepressants in the treatment of depressive symptoms of schizophrenics.
The pathogenesis of schizophrenia is very complex. At present, the hypothesis of dopamine
dysfunction plays a major role in the neurobiochemical abnormalities of schizophrenia.
Carlsson et al put forward the hypothesis of dopamine neurodevelopmental defect, which
believes that the core symptoms of schizophrenia are cognitive decline and negative symptoms,
which is due to the lack of dopaminergic neurogenesis. In the initial state of the disease,
the patients' brain has insufficient dopaminergic nerve function. When the load of the middle
cerebral cortex pathway increases (puberty), it shows that the function of the dopaminergic
nerve pathway is insufficient, activating the feedback regulation pathway of brain
neurotransmitters, Compensatory release of dopamine leads to excessive activation of
dopaminergic neural pathway in the midbrain limbic system, causing positive symptoms. With
the further extension of the course of the disease and the development of the disease, this
dopamine compensation mechanism is still insufficient to compensate for the dopaminergic
neural function, which leads to long-term negative symptoms and cognitive dysfunction of
patients.
Agomelatine is a new type of antidepressant. Its pharmacological effect is realized by
activating melatonin receptor (MT1/MT2) and antagonizing 5-HT2C receptor. Agomelatine
antagonizes the 5-HT2C receptor and can specifically increase the concentration of
norepinephrine and dopamine in the prefrontal cortex, thereby producing antidepressant, anti
anxiety and other effects. At the same time, the activation of melatonin receptor in the
brain can resynchronize the circadian rhythm and biological rhythm of patients, and improve
sleep rhythm disorder and sleep phase disorder caused by various reasons. At the same time,
through the synergistic effect of melatonin receptor activation and 5-HT2C receptor
antagonism, it can regulate the steady-state balance of neurotransmitters in the brain,
especially between 5-HT and dopamine, and restore neural function. In addition, studies have
shown that agomeratine has a certain role in the regeneration of hippocampal neurons and the
remodeling of neural circuits [2]. An open and prospective study abroad included 27
schizophrenic patients with depressive symptoms who received a stable dose of antipsychotic
drugs combined with agomeratine. The results showed that after 6 weeks of acute treatment,
the depressive symptoms of the patients were significantly improved. At the same time,
negative symptoms, overall psychopathology and psychosocial performance also improved
significantly, while positive symptoms remained stable [3]. Subsequently, the research team
further analyzed the data, which showed that after 12 weeks of treatment with agomeratine (6
weeks of acute phase+6 weeks of stable phase), the cognitive function of patients was
improved (the changes in MCCB scores were statistically different). However, due to the lack
of control in the experimental design, the limitation of sample number and other reasons, the
research team believed that the improvement of cognitive function of patients lacked clinical
significance, It is suggested to carry out research with reasonable design for further
verification. In China, a single center, single blind, controlled study conducted by Jingzhou
Mental Health Center in Hubei Province included 102 chronic schizophrenic patients with
negative symptoms. They were randomly divided into the treatment group of argomepratin
combined with risperidone (52 cases) and the treatment group of risperidone alone (50 cases).
The results showed that argomepratin combined with risperidone could significantly improve
the negative symptoms of patients after 6 months of treatment, Improve the quality of life of
patients [4, 5].
The above clinical studies confirm that antipsychotic drugs combined with agomeratine are
safe and feasible for the treatment of schizophrenia. The combined treatment has a positive
effect in improving the negative symptoms and depressive symptoms of patients. Long term
treatment may have the effect of improving the cognitive function of patients. However, the
current clinical research sample size is small, the follow-up period is short, and the
selected patients are biased, resulting in a low level of evidence. In addition, existing
studies have not studied other events (such as all-cause readmission rate, suicide/self
mutilation events, etc.) and the overall medical burden of patients during the treatment
process, so it is difficult to form reliable evidence-based medical evidence to promote the
development of clinical treatment plans for schizophrenia.
To sum up, it is proposed to carry out this prospective, multicenter, real world study of
second-generation antipsychotic drugs combined with agomeratine for schizophrenia patients,
aiming to further analyze the overall benefits of the combined agomeratine regimen for
schizophrenia patients, and to study in detail the treatment responses of patients in the
real world, and specifically analyze the effectiveness and safety of the regimen, Grasp the
advantage target population and comprehensive disease burden of the program, accurately judge
the application principle and medical social benefits of the program, and ultimately promote
the development of clinical treatment program for schizophrenia.