The whole course treatment strategy of sulfapride has been jointly created by many experts in the field of psychiatry!

Schizophrenia is a severe and disabling mental illness that tends to occur in young and middle-aged people, and patients take thinking, emotional, cognitive, behavioral and other disorders as the main symptoms, which not only seriously reduces the quality of life of patients, affects life expectancy, but also causes economic burden
to patients' families and even society.
At present, schizophrenia is mainly based on drug treatment, among which second-generation antipsychotic drugs such as amsulpride have the advantages of simple administration and less adverse reactions than first-generation antipsychotics, and are mostly
used in clinical practice.
The following focuses on the clinical application
of amsulpride in the treatment of the whole course of the drug.

1 Acute phase treatment

1.
1 Application of the first patient

Most patients with first-onset schizophrenia have a shorter course of disease and a younger age, making them more
likely to achieve recovery and return to society.
These patients are often more sensitive and more effective to antipsychotics, but also more sensitive to treatment-related adverse effects, so clinicians need to weigh the possible benefits and adverse effects
of treatment drugs more carefully.
For patients with a first episode, the Harvard South Shore Psychiatric Residency Training Program Pharmacological Treatment Protocol for Schizophrenia and the Chinese Guidelines for the Prevention and Treatment of Schizophrenia both recommend amsulpride as a first-line drug
.

Amsulpride has a significant effect on the positive symptoms represented by hallucinatory delusions, the initial dose is 200~400 mg/d, and the dose is gradually increased to 600~1200 mg/d
within 1 week.
After reaching the target therapeutic dose, it should be continuously treated and observed for 6~8 weeks, and the efficacy and safety should be evaluated regularly, and the target therapeutic dose can be adjusted
appropriately according to the efficacy and adverse reactions.
For hospitalized, young, insomatic disease, or agitated patients, the titration may be accelerated appropriately or in combination with benzodiazepines at the time of initial therapy
.
The duration of combined benzodiazepines is generally no more than 2 weeks, and the dose is gradually reduced until the drug
is discontinued as the symptoms of agitation improve.

1.
2 Application in patients with relapse

Such patients have relatively low sensitivity in terms of drug efficacy and adverse effects, and can take a relatively aggressive approach to therapeutics such as starting therapeutic dose, target dose, and time to complete dose titration in order to control or alleviate clinical symptoms and behavioral problems
as soon as possible.
The WFSBP guidelines state that for people with recurrent and multiple episodes of schizophrenia, the level of evidence for amsulpride is A and the recommended level is 1
.
Meta-analysis also showed that amsulpride was second only to clozapine in efficacy and had a low
rate of treatment discontinuation.
In addition, patients with recurrent attacks often have depressive symptoms, and amsulpride has a therapeutic effect on depressive symptoms, so it is also suitable for the treatment of patients with schizophrenia accompanied by depressive symptoms
.

The starting dose of amsulpride is recommended to be 400~600 mg/d
.
According to the severity of the disease, the dose can be adjusted accordingly, such as the elderly and frail, accompanied by physical diseases or known sensitivity to adverse drug reactions, the starting dose is 400 mg, once a day, for hospitalized or agitated patients, generally from 600 mg/d or even higher dose, according to 200 mg + 400 mg twice a day, gradually increased to the therapeutic dose
within 1 week.
The target dose for most patients is 800~1000 mg/d, and the maximum dose is 1200 mg/d
.

2 Consolidation phase therapy

Effective dose consolidation therapy of amsulpride should be continued for at least 6 months to promote further improvement of symptoms in the acute phase and should not be reduced
.
Adverse reactions of drugs should be closely monitored during medication, often with extrapyramidal symptoms and elevated prolactin levels
.
Patients and their families should be informed of the harm of reducing or stopping the drug at will, so as to increase the patient's compliance with the drug and reduce the risk
of recurrence caused by insufficient dose.
Strengthen psychosocial support interventions to promote the recovery
of patients' social functioning.

3 Maintenance period treatment

Maintenance therapy with a dose of amisulpride effective during the continuation phase should be continued so as not to cause relapse
.
Continuously monitor adverse drug reactions during medication, and if the efficacy is stable and there are no intolerable adverse reactions, do not change the drug
as much as possible.
The duration of treatment depends on the individual patient, and patients with the first episode should be maintained for at least 2 years, and 2 or more episodes within 5 years should be maintained for
a long time.

4 Patients with predominantly negative symptoms

Negative symptoms are mainly manifested as decreased or absent mental function, including emotional flatness, poor speech, lack of will, anhedonic experience, and attention impairment
.
For patients with negative symptoms as the main manifestation, amsulpride also has a good effect
.
The recommended dose is less
than 400mg/day.
Based on the results of ESCAPE research in China, the effective therapeutic dose of recurrent patients with mainly negative symptoms is usually 400~600 mg/d
.

5 dressing change strategies

Patients with schizophrenia who do not respond well to other antipsychotic drugs or who cannot tolerate them may be considered for switching to amsulipride
.

Common clinical dressing change methods include three types
: immediate dressing change, cross-dressing change and overlapping combined dose reduction change.
The dressing change strategy should follow the principle of individualization and consider the pharmacokinetic characteristics
.
Immediately change the dressing that is to stop taking the original drug suddenly, symptoms may rebound and withdrawal reactions may occur, such as anxiety, insomnia, nausea and vomiting, muscle pain and even consciousness disorders, involuntary movement disorders, rebound akathisia, dystonia, Parkinson-like reactions, and even malignant syndrome
.
Therefore, immediate dressing changes are generally not recommended
.
Immediate dressing change is mainly suitable for acute or serious adverse reactions caused by the original drug such as agranulocytosis, severe electrocardiogram abnormalities
, etc.

Cross-tapering refers to a gradual reduction in the dose of the original drug used, while gradually increasing the dose of amisulpride to the target dose over a period of 1 week, with few adverse effects but may reduce the efficacy of the original drug during the reduction of the prodrug and the absence of amsulpride to the target dose
.
The overlapping combined dose reduction and change method refers to maintaining the dose of the original drug, while gradually increasing the dose of amsulpride until the target dose is reached, and overlapping the two drugs for 2~3 weeks, and then gradually reducing the dose
of the original drug.
Because the two drugs overlap for a period of time, it will not affect the efficacy, but may increase the risk of
drug interactions and adverse effects.
Amsulpride is less metabolized by the liver, and the risk of drug interactions during overlapping therapy is low
with overlap combination reduction.

In addition, clozapine and olanzapine have strong anticholinergic effect or multi-receptor effect of drugs, in order to prevent the rebound of anticholinergic effect during dressing, usually the entire dressing change time takes 2~4 weeks or longer, and short-term combination with benzodiazepines with sedative effect can reduce insomnia and anxiety and other symptoms
during the dressing change.

References

[1] YING Xiang, CHENG Tao, SHEN Xueqian, et al.
Correlation between serum concentration of amisulpride and adverse reactions, prolactin level and cognitive function in patients with schizophrenia[J].
China Modern Applied Pharmacy,2022,39(11):1464-1469.
)

[2] LIANG Ying, LIU Dengtang, SI Tianmei, et al.
Expert opinion on clinical application of amsulpride in the treatment of schizophrenia[J].
Chinese Journal of Mental Health,2017,31(06):425-431.
)