A 26-year-old man is hospitalized after he was found in the park shouting and laughing to himself. He insists on wearing a cap lined with several layers of aluminum foil and explains that the hat prevents laser beams from reprogramming his mind. For the past 3 years, the patient has been hearing the voices of his deceased mother, the devil, and a world-famous singer. He has had one previous psychiatric hospitalization, during which he responded well to haloperidol. However, the patient stopped the medication shortly after discharge because he did not like the way it made him feel. A decision is made to administer a second-generation antipsychotic medication. Compared with first-generation antipsychotics, this class of medication is associated with which of the following?
Common antipsychotic side effects | |
First-generation antipsychotics (FGAs) | High-potency (eg, haloperidol)
Low-potency (eg, chlorpromazine)
|
Second-generation antipsychotics (SGAs) |
|
This patient is experiencing an acute psychotic episode (delusions, hallucinations, disorganized behavior) most likely due to schizophrenia, a chronic psychotic illness with typical onset in young adulthood. His treatment history indicates a good response to the first-generation antipsychotic (FGA) haloperidol but poor adherence, likely because of tolerability issues. As a class, FGAs are associated with a high risk of extrapyramidal symptoms (EPSs) due to their potent D2 antagonism. Types of EPS effects include acute dystonic reactions, drug-induced parkinsonism, akathisia (inner restlessness and inability to sit still), and tardive dyskinesia.
Second-generation antipsychotics (SGAs) are often used for first-line treatment in schizophrenia due to their lower risk of EPSs compared with FGAs. However, SGAs are associated with weight gain and metabolic effects, including the development of diabetes. Side effect profiles of individual SGAs vary; olanzapine and clozapine are associated with the greatest risk of metabolic effects.
(Choice A) FGAs and SGAs appear to be equally effective in the treatment of positive psychotic symptoms.
(Choice B) Both FGAs and SGAs block muscarinic receptors to varying degrees. Low-potency FGAs (eg, chlorpromazine) and the SGAs olanzapine, quetiapine, and clozapine have the greatest risk.
(Choice C) SGAs are less likely to cause tardive dyskinesia than FGAs.
(Choice E) Compared with FGAs, SGAs have a greater risk of metabolic adverse effects.
(Choice F) Both FGAs and SGAs have been associated with lowering the seizure threshold. The SGA clozapine, in particular, has been associated with a dose-dependent increase in seizure risk.
Educational objective:
Second-generation antipsychotics are associated with a lower risk of extrapyramidal side effects compared with first-generation antipsychotics but may cause adverse metabolic effects.