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Antagonism of dopamine D2, histamine H1, and 5-HT receptors
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Antagonism of dopamine D2 receptors only
Enhancement of gamma-aminobutyric acid concentrations
Inhibition of 5-HT and norepinephrine reuptake
Inhibition of 5-HT reuptake
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This patient presents with persecutory delusions, auditory hallucinations, and disorganized thought that have been present for at least 6 months, which is suggestive of schizophrenia. First-line treatment for schizophrenia is an atypical antipsychotic, which antagonizes dopamine D2, histamine H1, and 5-HT receptors. Schizophrenia presents with delusions, hallucinations, disorganized speech or behavior, and/or negative symptoms such as flattened affect. Symptoms must be present for at least 6 months for a diagnosis of schizophrenia to be made. There are four main dopaminergic pathways in the central nervous system: nigrostriatal, mesolimbic, mesocortical, and tuberoinfundibular. The dopamine hypothesis of schizophrenia states that this condition is the result of dysregulation/overactivation of dopaminergic pathways in the brain. The first-line treatment for schizophrenia is an atypical antipsychotic such as risperidone or olanzapine. In addition to antagonism of the dopamine D2 receptor, the atypical antipsychotics have additional activity against histamine H1 and 5-HT receptors. Horacek et al. review the neuropsychopharmacology of atypical antipsychotics in the treatment of schizophrenia. They discuss the balance between therapeutic dosing and side effects in dopamine blockade to achieve antipsychotic effect while avoiding extrapyramidal symptoms. Incorrect Answers: Answer 2: Antagonism of dopamine D2 receptors only is incorrect because the atypical antipsychotics have additional activity against histamine H1 and 5-HT receptors. Answer 3: Enhancement of gamma-aminobutyric acid (GABA) concentrations is the mechanism of valproate, which is used in the treatment of manic episodes in bipolar disorder. Manic episodes present with distractibility, impulsivity, grandiosity, flight of ideas, increased activity, decreased need for sleep, and talkativeness. Hallucinations and delusions are not present. Answer 4: Inhibition of 5-HT and norepinephrine reuptake is the mechanism of tricyclic antidepressants such as imipramine. These are used in the treatment of depression, not schizophrenia. Answer 5: Inhibition of 5-HT reuptake is the mechanism of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine. SSRIs are used in the treatment of depression, not schizophrenia. Bullet Summary: The first-line treatment for schizophrenia is an atypical antipsychotic, which antagonizes dopamine D2, histamine H1, and 5-HT receptors.
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