Psychosis - Stahl's Flashcards
A 24-year-old male initially presents with acute auditory hallucinations and is treated with medication. Four days later he arrives at your office for evaluation. You observe that he is neatly dressed, avoids eye contact, and gives very short answers to your initial questions. Which of the following questions would be most beneficial for determining his degree of negative symptoms?
A. How often have you visited with friends in the past week?
B. Have the voices you’ve heard persisted or returned?
C. Have you ever thought about hurting yourself or someone else?
D. In the past week have you had difficulty concentrating?
A Correct. How often have you visited with friends in the past week: This is a useful question when assessing for negative symptoms, as an important component of negative symptoms is reduced social drive.
A 22-year-old man with a history of cognitive and social delay has just been diagnosed with schizophrenia. In early elementary school his language development was normal but he had difficulty reading and was diagnosed with a learning disability. He had increased academic difficulty beginning in high school but did graduate and began working at a supermarket. However, he began to exhibit difficulty functioning, including losing things, trouble following simple directions at work, disorganization, and deterioration in communication. These impairments led to his dismissal from his job; 6 months later he experienced a psychotic episode and was diagnosed with schizophrenia. What pattern of cognitive functioning would you expect for this patient over the long-term course of his illness?
A. Progressive decline in cognitive functioning beyond what is expected with normal aging, with severity of cognitive symptoms independent of psychotic symptom status
B. Progressive decline in cognitive functioning beyond what is expected with normal aging, with severity of cognitive symptoms fluctuating with psychotic symptom status
C. No further decline in cognitive functioning beyond what is expected with normal aging, with severity of cognitive symptoms independent of psychotic symptom status
D. No further decline in cognitive functioning beyond what is expected with normal aging, with severity of cognitive symptoms fluctuating with psychotic symptom status
C Correct. Like most individuals who ultimately develop schizophrenia, this man had cognitive impairment from an early age and showed substantial further decline in cognitive functioning during late adolescence (during the prodrome phase). However, a large body of research shows that after disorder onset cognitive deficits generally remain stable over the course of the disorder, and do not worsen beyond that expected with normal aging. Additionally, cognitive impairment in schizophrenia does not seem to be correlated with psychotic symptoms.
A 24-year-old woman is hospitalized after an altercation in which she screamed at and attacked her neighbor when he knocked on her door. Her mother reports that she has been increasingly erratic recently, with emotional outbursts and impulsive behavior. Which of the following brain regions is most likely associated with these symptoms?
A. Dorsolateral prefrontal cortex
B. Nucleus accumbens
C. Orbital frontal cortex
D. Substantia nigra
C Correct. Orbital frontal cortex: Aggressive symptoms such as those exhibited by this patient are hypothetically associated with impairment in impulse control, which is largely regulated by the orbital frontal cortex.
A Incorrect. Dorsolateral prefrontal cortex: This brain region is hypothetically associated with cognition and executive functioning, not with aggression.
B Incorrect. Nucleus accumbens: This brain region is hypothetically associated with positive symptoms such as delusions and hallucinations. Although aggressive symptoms, such as those exhibited by this patient, often occur in conjunction with positive symptoms, they may not be localized to the nucleus accumbens.
D Incorrect. Substantia nigra: This region in the brainstem houses dopaminergic cell bodies that project to the striatum. The substantia nigra is not particularly linked to aggression.
A 44-year-old male with schizophrenia has been taking an antipsychotic medication since initial diagnosis 12 years ago. He has recently begun experiencing difficulty with fluid movement of his arms as well as involuntary facial grimaces. Which of the following likely underlies these symptoms?
A. Upregulation of serotonin 2A receptors
B. Downregulation of serotonin 2A receptors
C. Upregulation of dopamine 2 receptors
D. Downregulation of dopamine 2 receptors
C Correct. Tardive dyskinesia is associated with upregulation of dopamine 2 receptors. This upregulation can occur following long-term blockade of dopamine 2 receptors such as may occur with long-term antipsychotic treatment, particularly conventional antipsychotic treatment.
Based on thorough evaluation of a patient and his history, his care provider intends to begin treatment with a conventional antipsychotic but has not selected a particular agent yet. Which of the following is most true about conventional antipsychotics?
A. They are very similar in therapeutic profile but differ in side-effect profile
B. They are very similar in both therapeutic and side-effect profile
C. They differ in therapeutic profile but are similar in side-effect profile
D. They differ in both therapeutic and side-effect profile
A Correct. Although individual effects may vary from patient to patient, in general conventional antipsychotics share the same primary mechanism of action and do not differ much in their therapeutic profiles. There are, however, differences in secondary properties, such as degree of muscarinic, histaminergic, and/or alpha adrenergic receptor antagonism, which can lead to different side-effect profiles.
A 34-year-old male recently began experiencing breast secretions while receiving perphenazine. After switching to quetiapine the secretions ceased. Which of the following is the most likely pharmacological explanation for the resolution of this side effect? A. Dopamine 2 antagonism B. Serotonin 2A antagonism C. Serotonin 2C antagonism D. Histamine 1 antagonism
B Correct. Stimulation of serotonin 2A receptors stimulates prolactin release. Since they have opposing effects on prolactin, adding serotonin 2A antagonism to dopamine 2 antagonism results in a neutral effect on prolactin and may relieve breast secretions caused by dopamine 2 antagonism alone.
A Incorrect. Stimulation of D2 receptors inhibits prolactin release; thus a dopamine 2 antagonist such as perphenazine could increase prolactin release and potentially lead to breast secretions.
A 37-year-old woman with schizophrenia has failed to respond to two sequential adequate trials of antipsychotic monotherapy (first olanzapine, then aripiprazole). Which of the following are evidence- based treatment strategies for a patient in this situation?
A. High dose of her current monotherapy (aripiprazole)
B. Augmentation of her current monotherapy with another atypical antipsychotic
C. Switch to clozapine
D. A and C
E. A, B, and C
C Correct. After failure of two sequential adequate trials of antipsychotic monotherapy, the recommended and evidence-based treatment strategy is to switch to clozapine.
A 24-year-old patient with schizophrenia who has prominent cognitive symptoms and social impairment is being evaluated for treatment. Her care provider is considering initiating ziprasidone, quetiapine, or aripiprazole, all of which share the property of serotonin 1A agonism. This receptor binding property is expected to have clinical effects in schizophrenia most similar to: A. Serotonin 2A antagonism B. Dopamine 2 antagonism C. Histamine 1 antagonism D. Serotonin transporter blockade
A Correct. Serotonin 2A antagonism: Serotonin 1A partial agonism has similar net effects to serotonin 2A antagonism. That is, it enhances dopamine release and thus may theoretically improve extrapyramidal side effects, hyperprolactinemia, and cognitive and negative symptoms.
A 24-year-old man has just been diagnosed with schizophrenia. His clinician elects to prescribe iloperidone and begins treatment according to the dosing schedule in the label. What is the rationale for the slow dosing schedule with iloperidone? A. Minimize agitation B. Minimize sedation C. Prevent orthostatic hypotension D. Prevent gastrointestinal upset
C Correct. Iloperidone has a very slow titration schedule in order to avoid orthostatic hypotension, which is theoretically due to its potent alpha 1 antagonism.
A patient who has been taking an atypical antipsychotic for 6 months has experienced a 22-pound weight gain since baseline. Which of the following pharmacologic properties most likely underlies this patient’s metabolic changes? A. Dopamine 2 antagonism B. Serotonin 2A antagonism C. Serotonin 2C antagonism D. Alpha 1 adrenergic antagonism
C Correct. Antagonism of serotonin 2C receptors is associated with increased risk for weight gain, perhaps in part due to stimulation of appetite regulated by the hypothalamus, and especially in combination with histamine 1 antagonism
A 38-year-old woman was diagnosed with schizophrenia approximately 2 years ago and after multiple trials of different medications she has been maintained on haloperidol for the last several months with good response. Two weeks ago she began exhibiting mild motor symptoms of parkinsonism. Which of the following would be the most appropriate adjunct medication for this patient? A. Cholinesterase inhibitor B. Muscarinic 1 antagonist C. Alpha 1 adrenergic agonist D. Histamine 1 antagonist
B Correct. Antagonism of the muscarinic 1 receptor for acetylcholine would prevent it from binding there and thus reduce its effects, potentially relieving EPS.
A 38-year-old man was diagnosed with schizophrenia 14 years ago, and over the course of his illness has taken several different antipsychotics, all with partial response and no severe side effects. He now presents with acute exacerbation of hallucinations and delusions. He recently had bowel resection due to a gastrointestinal disorder, and blood levels reveal that he is not absorbing his medications well. One option for this patient would be to prescribe heroic oral doses of his antipsychotic. Aside from this approach, which of the following antipsychotics have formulations that may be good long-term options for bypassing his problem with absorption?
A. Asenapine, paliperidone, risperidone
B. Paliperidone, risperidone, quetiapine
C. Risperidone, quetiapine, ziprasidone
D. Quetiapine, ziprasidone, asenapine
A Correct (asenapine, paliperidone, risperidone). For patients with difficulty absorbing medications, the best options in order to reach therapeutic blood levels would be to prescribe heroic oral doses or to use parenteral, sublingual, or suppository administration. Asenapine has a sublingual formulation, while paliperidone is available in a 4-week and a 3-month formulation and risperidone is available as an intramuscular depot administered every 2 weeks. A 4-week olanzapine depot is also available. Additional antipsychotics with depot formulations include flupenthixol, fluphenazine, haloperidol, pipothiazine, and zuclopenthixol. Clozapine, olanzapine, and risperidone have orally disintegrating tablets; however, these medications are not absorbed sublingually and must be swallowed in order to undergo absorption in the gut. Chlorpromazine has a suppository formulation, and other antipsychotics may also be able to be administered as suppositories. Aripiprazole has two long-acting injectable formulations: one that is administered every 4 weeks and another that can be administered every 4 or 6 weeks. Iloperidone is in early trials for a 4-week depot.
A 28-year-old man was recently diagnosed with schizophrenia. He has a body mass index of 30, fasting triglycerides of 220 mg/dL, and fasting glucose of 114 mg/dL. Which of the following is least likely to worsen his metabolic profile? A. Olanzapine B. Quetiapine C. Risperidone D. Ziprasidone
D Correct. Ziprasidone in general seems to be weight neutral and has been shown to lower triglyceride levels. It is therefore a recommended choice for individuals for whom metabolic issues are a primary concern.
A 27-year-old male who has been treated with risperidone for the last 8 weeks is now having his medication changed to quetiapine. What is the recommended switching method in this situation, assuming the need to do this expeditiously, but not urgently, as an outpatient?
A. Maintain therapeutic dose of risperidone while uptitrating quetiapine to effective dose, then discontinue risperidone
B. Down-titrate risperidone over several weeks while uptitrating quetiapine over the same time period
C. Down-titrate risperidone over at least 1 week while uptitrating quetiapine over at least 2 weeks
D. Down-titrate risperidone over at least 2 weeks while uptitrating quetiapine over 1 week
C Correct. Down-titrate risperidone over at least 1 week while uptitrating quetiapine over at least 2 weeks: Tolerability may be best if quetiapine can be titrated up over the course of 2 weeks, while keeping the estimated D2 receptor occupancy constant as the risperidone is stopped.
A 16-year-old female is brought to the hospital by her mother because she is complaining that her neighbors spy on her and submit their observations to the government. After evaluation, she is diagnosed with schizophrenia and prescribed risperidone. Which of the following is the appropriate target therapeutic dose for this patient? A. 0.5 mg/day B. 3 mg/day C. 6 mg/day D. 12 mg/day
B Correct. 3 mg/day: This is the recommended therapeutic dose for adolescents (ages 13 to 17) with schizophrenia.
