A 32-year-old man is brought to the office by his mother for a follow-up visit for depressive disorder. The mother is very concerned because the patient has become increasingly withdrawn and has behaved strangely for the past 2 weeks. She reports that he expresses fears that his body is decomposing and hears the voice of his long-deceased father telling him, "Come to me." Current medications include venlafaxine and lorazepam as needed for anxiety. Vital signs are normal and physical examination is unremarkable. On mental status examination, the patient appears depressed and makes poor eye contact. At times, he does not answer and mumbles to himself. The decision is made to add quetiapine to treat psychosis. Which of the following is the primary mechanism of action of this medication?

Question

A 32-year-old man is brought to the office by his mother for a follow-up visit for depressive disorder.  The mother is very concerned because the patient has become increasingly withdrawn and has behaved strangely for the past 2 weeks.  She reports that he expresses fears that his body is decomposing and hears the voice of his long-deceased father telling him, "Come to me."  Current medications include venlafaxine and lorazepam as needed for anxiety.  Vital signs are normal and physical examination is unremarkable.  On mental status examination, the patient appears depressed and makes poor eye contact.  At times, he does not answer and mumbles to himself.  The decision is made to add quetiapine to treat psychosis.  Which of the following is the primary mechanism of action of this medication?

Quizplus · Accepted Answer

This patient has developed psychotic symptoms (ie, delusions that his body is decomposing, auditory hallucinations) requiring the addition of an antipsychotic to his antidepressant, venlafaxine. Quetiapine is a commonly used second-generation antipsychotic (SGA) whose primary mechanism of action is mixed serotonin-dopamine antagonist activity with binding at both serotonin 2A and dopamine D2 receptors. The addition of serotonin antagonism, together with lower dopamine binding affinity when compared with first-generation antipsychotics, is believed to contribute to the decreased risk of extrapyramidal side effects seen with SGAs. SGAs also have affinities for other receptors (eg, alpha adrenergic, muscarinic, histaminic) to varying degrees, resulting in different adverse effect profiles. Alpha-1 adrenergic blockade may cause orthostatic hypotension, and muscarinic receptor antagonism may result in anticholinergic adverse effects. Histaminic antagonism contributes to weight gain and sedation. (Choice A) Although antipsychotics block alpha-1 adrenergic receptors and may block other dopamine receptors, including dopamine D1 receptors, it is dopamine D2 blockade that is thought to be responsible for their antipsychotic effect. (Choice B) Dopamine reuptake inhibition and stimulation of dopamine release are the mechanisms of action of stimulants commonly used in the treatment of attention deficit hyperactivity disorder. (Choice C) Norepinephrine and dopamine reuptake inhibition is the mechanism of action of the antidepressant bupropion. (Choice D) Serotonin and norepinephrine reuptake inhibition is the primary mechanism of action of venlafaxine, as well as other serotonin and norepinephrine reuptake inhibitors and tricyclic antidepressants. Educational objective: Second-generation antipsychotics (SGAs) are serotonin 2A and dopamine D2 antagonists. The added serotonin receptor binding and lower dopamine binding affinity of SGAs reduce the likelihood of extrapyramidal adverse effects. References: Second-generation antipsychotics and extrapyramidal adverse effects. (http://www.ncbi.nlm.nih.gov/pubmed/24995318) Dopamine targeting drugs for the treatment of schizophrenia: past, present and future. (http://www.ncbi.nlm.nih.gov/pubmed/27291902)

A 32-Year-Old Man Is Brought to the Office by His