Review Question - QID 105687

This patient has been taking an antipsychotic medication. Risperidone is an atypical antipsychotic medication that primarily functions by blocking the dopamine-D2 receptor.

Psychotic features are associated with an excess of dopaminergic activity, therefore the preferred treatment is through a dopamine-receptor blockade. All antipsychotic medications block the dopamine-D2 receptor, but atypical antipsychotics also block serotonin (5-HT) receptors, resulting in decreased risk for extrapyramidal side effects. The latter is why the atypical antipsychotic medications are now preferred as the initial mode of treatment for psychosis. While each atypical antipsychotic has a specific adverse effect profile, as a whole, they can all cause weight gain and metabolic symptoms. Additionally, atypical antipsychotics have a weaker level of dopamine receptor blockade compared to that of 5-HT receptors. Said another way, atypical antipsychotics have a relatively weaker D2 receptor affinity as compared to 5-HT2 receptor affinity.

Kripke describes the use of risperidone in patients with schizophrenia in comparison to placebo. When based on disease-specific symptom scores for schizophrenia, risperidone has been found to improve symptoms compared to placebo. Conversely, when based on the Clinical Global Impression scale, risperidone did not seem to show any improvement in symptoms. Unfortunately, there is inadequate data to compare risperidone to the other atypical antipsychotics. When selecting a treatment modality for someone with schizophrenia, the adverse effect profile should be a main item for consideration.

Llerena et al. discuss how risperidone's pharmacogenetic profile could be used to improve its clinical use. There are genetic polymorphisms that affect risperidone's efficacy and adverse reactions. Genes involved in the drug's metabolism (various CYPs) seem to show the greatest prediction capabilities in terms of plasma concentrations of the drug, as well as its interaction profile. However, more data is needed before routine genetic screening should take place in clinical practice.

Illustration A depicts the mechanism of action of atypical antipsychotics.

Incorrect Answers:
Answer 1: This is an anticonvulsant and mood stabilizing drug used in the treatment of bipolar, epilepsy, and trigeminal neuralgia. It works by stabilizing the inactivated state of voltage-gated sodium channels, leaving the cell less excitable.
Answer 3: This is a tricyclic antidepressant that works by blocking the reuptake of serotonin and norepinephrine. Although it may have some dopamine-receptor blocking activity, this would take place at the level of D3 or D4.
Answer 4: This is a selective serotonin reuptake inhibitor that is used to treat depression.
Answer 5: This is a short-acting nonbenzodiazepine hypnotic medication used for insomnia. It works to potentiate GABA by acting as a full agonist at the level of the GABA receptor.