4.1. Pharmacotherapy

Antipsychotics are a standard treatment for PDD, effectively managing symptoms. Case studies demonstrate that the antidepressant olanzapine may reduce psychotic symptoms induced by drug addiction. Dopamine antagonists have also demonstrated effectiveness in decreasing drug addiction. Research has shown that psychotic symptoms are associated with changes in brain chemistry. Antipsychotic medications restore the brain's natural chemical balance, reducing or eliminating psychotic symptoms. Medications may require weeks to work. Conventional antipsychotics are dopamine antagonists and target one of five subtypes of dopamine receptors in the brain. Dopamine 2 (D2) receptor antagonism in the mesolimbic tract improves hallucinations and delusions, but the conventional antipsychotic blockade of all D2 receptors causes other problems. Antagonizing D2 receptors in the mesocortical dopamine pathway worsens negative symptoms including avolition, anhedonia, alogia, and affective flattening. Atypical antipsychotics antagonize serotonin 5HT2A receptors as well as D2 antagonism seen with conventional antipsychotics. Serotonin affects dopamine differently in each of the four pathways. In the nigrostriatal pathway, serotonin antagonism increases dopamine release, resulting in fewer reports of movement disorders. Serotonin antagonism in the tuberoinfundibular pathway eliminates serotonin's ability to increase prolactin levels, mitigating the effect of two blockades in this pathway. In the mesocortical pathway, where serotonin 2A receptors predominate, antagonizing serotonin increases dopamine. This is thought to be responsible for improved cognition, affection, and motivation seen with antipsychotics. Weak serotonin 2A antagonism in the mesolimbic tract cannot reverse dopamine antagonism; D2 receptors remain blocked, and hallucinations and delusions decrease. Pharmacotherapy remains the main effective treatment for PDD.
