A 32-year-old man with a history of bipolar disorder is brought to the emergency department by his wife. He has been unable to sleep for more than 3 hours a night for the past week. Over the past several weeks, the patient has been irritable at home and has argued constantly with his wife. He has racing thoughts and speaks rapidly. The patient has stopped going to his job as a plumber, having decided to stay home and "unravel the secrets of the universe." He has been drawing shapes and equations on the walls, and he has accused his wife of working for the police and trying to steal his secrets. Prior to examination, the patient becomes increasingly agitated and is hospitalized against his will. He has no other medical conditions. Vital signs, physical examination, and laboratory findings are normal. He is prescribed multiple medications to address his symptoms. Five days later, the patient is calm but has difficulty moving spontaneously or getting out of bed. He does not respond appropriately to questions and appears newly disoriented and confused. Temperature is 39.4 C (102.9 F), blood pressure is 162/98 mm Hg, pulse is 98/min, and respirations are 20/min. Dysregulation of which of the following neurotransmitters is most likely to be the primary cause of this patient's new symptoms?

Question

A 32-year-old man with a history of bipolar disorder is brought to the emergency department by his wife.  He has been unable to sleep for more than 3 hours a night for the past week.  Over the past several weeks, the patient has been irritable at home and has argued constantly with his wife.  He has racing thoughts and speaks rapidly.  The patient has stopped going to his job as a plumber, having decided to stay home and "unravel the secrets of the universe."  He has been drawing shapes and equations on the walls, and he has accused his wife of working for the police and trying to steal his secrets.  Prior to examination, the patient becomes increasingly agitated and is hospitalized against his will.  He has no other medical conditions.  Vital signs, physical examination, and laboratory findings are normal.  He is prescribed multiple medications to address his symptoms.  Five days later, the patient is calm but has difficulty moving spontaneously or getting out of bed.  He does not respond appropriately to questions and appears newly disoriented and confused.  Temperature is 39.4 C (102.9 F), blood pressure is 162/98 mm Hg, pulse is 98/min, and respirations are 20/min.  Dysregulation of which of the following neurotransmitters is most likely to be the primary cause of this patient's new symptoms?

Quizplus · Accepted Answer

11ec160b_3b26_9c48_9249_a30115dcb7a6_MD0001_00 This patient initially had multiple symptoms of an acute manic episode (increased activity, decreased need for sleep, racing thoughts, pressured speech, grandiose and paranoid delusions) and likely received antipsychotic medication to target his agitation and psychosis. His subsequent development of fever, confusion, abnormal vital signs, and difficulty moving 5 days later is consistent with neuroleptic malignant syndrome (NMS), an uncommon but life-threatening complication of dopamine antagonists. NMS is characterized by hyperthermia, severe muscular rigidity, altered mental status, and autonomic dysfunction (eg, labile blood pressure, tachycardia, diaphoresis). It most commonly occurs within the first 2 weeks of initiation of therapy but can occur anytime during treatment. NMS is thought to be primarily due to dysregulation of dopamine. D2 antagonism is the mechanism of action of all first-generation and most second-generation antipsychotics. Central dopamine receptor blockade in the hypothalamus is believed to be responsible for autonomic dysregulation and hyperthermia. Dopamine antagonism in the nigrostriatal pathway may lead to the diffuse "lead-pipe" rigidity. (Choices A and E) 5-hydroxytryptamine (serotonin) and norepinephrine reuptake inhibition is the mechanism of action of many antidepressants (eg, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors). However, antidepressants are not used in the treatment of acute mania. Serotonergic drugs can cause serotonin syndrome (SS), but not NMS. SS has overlapping features with NMS (eg, autonomic dysregulation, mental status changes) but is characterized by neuromuscular irritability and hyperreflexia (eg, clonus) rather than generalized muscle rigidity. (Choice C) Medications that enhance the inhibitory effects of gamma-aminobutyric acid (eg, benzodiazepines) are often used as adjunctive treatment in acute mania to target agitation and insomnia. However, benzodiazepines do not cause NMS. (Choice D) Glutamate (which is the major excitatory neurotransmitter in the brain) may be affected by some antipsychotic medications and mood stabilizers, but it is not known to have a primary role in the development of NMS. Educational objective: Neuroleptic malignant syndrome (NMS) is characterized by severe muscular rigidity, mental status changes, autonomic dysregulation, and hyperthermia. Dopamine antagonism, the mechanism of action of most antipsychotics, has been implicated as a primary cause of NMS. __________ References: Neuroleptic malignant syndrome: a review from a clinically oriented perspective. (http://www.ncbi.nlm.nih.gov/pubmed/26411967)

A 32-Year-Old Man with a History of Bipolar Disorder Is