Antipsychotic Medications for Schizophrenia

Classification and Mechanism of Action

Antipsychotic medications are classified into two main groups: first-generation (typical/conventional) antipsychotics, which work as dopamine D2 receptor antagonists, and second-generation (atypical) antipsychotics, which have serotonin-dopamine antagonist activity, with second-generation antipsychotics like aripiprazol being the first-line choice due to their better metabolic side effect profile 1, 2
First-generation antipsychotics, such as haloperidol, have a high potency and are less likely to cause sedation but more likely to cause extrapyramidal symptoms 2
Second-generation antipsychotics, such as amisulpride, olanzapine, risperidone, and quetiapine, work as serotonin-dopamine receptor antagonists with various receptor affinities 2
Aripiprazol has partial agonist activity at the dopamine receptor, distinguishing it pharmacologically 2
Aripiprazol has a better metabolic profile with a low risk of weight gain and minimal impact on prolactin levels 1

The American Academy of Child and Adolescent Psychiatry recommends starting with monotherapy of a single atypical antipsychotic as the first-line choice 1
Aripiprazol is recommended as a first-line choice due to its superior metabolic profile 1
Agents with high anticholinergic properties should be avoided as they can impair cognitive function 1
Therapeutic doses should be given for at least 4-6 weeks to assess efficacy 1, 3

The distinction between first-generation and second-generation antipsychotics is not a clear category from a pharmacological or clinical perspective and should not be used to guide psychotropic choice 2
Treatment selection should be based on the individual drug's pharmacodynamic profile, side effect profile, and patient-specific factors 2
Both typical and atypical antipsychotics carry an increased risk of sudden cardiac death, with a dose-dependent effect 2
Approximately 70% of patients require long-term treatment to control symptoms 1
Long-acting injectable formulations are valuable for adherence 1
Patients with a first episode should receive maintenance psychopharmacological treatment for 1-2 years after the initial episode 3

Before starting antipsychotics, measure BMI, waist circumference, blood pressure, HbA1c, glucose, lipids, prolactin, liver function, urea, and electrolytes, as well as complete blood count and EKG 1
Follow-up monitoring should include glucose at 4 weeks after initiation, BMI, waist circumference, and blood pressure weekly for 6 weeks, and all parameters repeated after 3 months and then annually 1