A 44-year-old female presents to your department because of excessive eye movements, tongue movements, and lip smacking. The patient’s past medical history is only significant for schizophrenia, diagnosed 4 years ago for which she is currently being treated with chlorpromazine. Psychotic symptoms have been well controlled with this medication. The patient’s mother also had schizophrenia.
On physical examination asking the patient to repeatedly touch the thumb to each finger amplifies the movement of the tongue, lip smacking, and eye blinking.
Which of the following would be the most effective therapy?
Correct Answer D:
This patient is presenting with oro-bucco-lingual stereotypy after four years of treatment with a typical neuroleptic, chlorpromazine, is most likely to be an extrapyramidal side effect known as tardive dyskinesia. It is caused by the dopamine-receptor blocking action of this drug. A known feature of neuroleptic-induced tardive dyskinesia is that the symptoms worsen when the attention is drawn away from the movement like observed in this patient when asked to touch the thumb to each finger.
When tardive dyskinesia develops, the best next step in management is to discontinue the offending antipsychotic by slow taper. Since full recovery of schizophrenia is unusual, and the prognosis is even poorer in patients with family history of schizophrenia, this patient should receive a replacement drug when chlorpromazine is discontinued. Clozapine and quetiapine are the best alternatives for replacing typical antipsychotics in patients with schizophrenia who develop tardive dyskinesia. Since tardive dyskinesia is serious and it is irreversible in many patients, an attempt should be made to treat it. It is hard to manage, but a number of drugs have been studied in treating. Tetrabenazine is considered the drug of choice in the treatment of persistent and disabling tardive dyskinesia. Therefore the most effective therapy for this patient is to discontinue chlorpromazine, treat with tetrabenazine and quetiapine (choice D). Other drugs considered to be effective in the management of these movements are reserpine, clonazepam, valproic acid, and trihexyphenidyl.
→ Immediately discontinue chlorpromazine (choice A) is incorrect. While this patient needs to discontinue the offending drug, psychotic symptoms are likely to recur without treatment. This is even more likely in patients with a family history of schizophrenia, so the patient should receive a replacement when chlorpromazine is discontinued.
→ Reduce chlorpromazine dose, add trihexyphenidyl treatment (choice B) is incorrect. While reducing chlorpromazine might reduce the side effects, this is not the best option for this patient as there’s still risk as long as the patient is exposed. When alternative therapies such as clozapine or quetiapine are available, they should be chosen. Trihexyphenidyl is a second-line drug in the treatment of tardive dyskinesia movements and the patient would benefit more with tetrabenazine treatment.
→ Discontinue chlorpromazine, treat with benztropine and amoxapine (choice C) is incorrect. Benztropine is used to treat acute dystonia but is not helpful in the management of tardive dyskinesia. While amoxapine name sounds like it is in the same class as clozapine and quetiapine, it is actually a tetracyclic antidepressant that is used to treat major depressive disorder and any schizophrenia treatment use is off-label. It is known to cause tardive dyskinesia and might even worsen this patient’s condition.
→ Discontinue chlorpromazine, treat with propranolol and clozapine (choice E) would not be the best choice for this patient as propranolol is not known to be effective in the management of tardive dyskinesia. It is used to treat essential tremor.
Key point:
Oro-bucco-lingual stereotypy in a patient on long-term treatment with chlorpromazine is suggestive of tardive dyskinesia. The best management is to discontinue the drug by gradual taper, replace it with clozapine or quetiapine, and treat tardive dyskinesia movements with tetrabenazine.
A 30-year-old male is brought to your department because of altered mental status and diaphoresis. He is disoriented and claims of seeing an army of soldiers carrying swords. Last week he was started on fluphenazine for schizophrenia management. Vital signs are temperature 40°C, BP 165/95 mmHg, heart rate 110/min, and respirations 24/min. On physical examination bilateral hyporeflexia and muscular rigidity are noted. Laboratory tests reveal elevated creatinine kinase.
What is the most likely diagnosis?
Correct Answer C:
This patient is presenting with fever, muscular rigidity, altered mental status, and signs of autonomic dysfunction a week after starting fluphenazine, a high potency typical antipsychotic. This is suggestive of neuroleptic malignant syndrome (NMS) (choice C). It is a life-threatening idiosyncratic reaction that is strongly linked with the dopamine D2 receptor blocking action of these antipsychotics. The clinical syndrome is thought to be secondary to decreased dopamine activity in the central nervous system either from blockade of dopamine D2-receptors or from decreased availability of dopamine itself. NMS shares clinical similarities with malignant hyperthermia and the serotonin syndrome, although the etiologies differ.
→ Serotonin syndrome (choice A) may also present in a similar fashion but it is caused by serotonin excess rather than dopamine depletion. It is most often caused by simultaneous ingestion of 2 or more proserotonergic medications. It is also associated with recent increase in dosing of a chronic medication.
→ Malignant hyperthermia (choice B) is also a life-threatening clinical syndrome of hypermetabolism involving the skeletal muscle with many similarities to NMS. It has a different etiology however, and most patients have a genetic predisposition due to mutations in the ryanodine receptor gene on chromosome 19. Most common scenarios are reactions that occur after anesthetics are given to the patient.
→ Medication-induced dystonic reaction (choice D) is a reversible movement disorder with involuntary contractions of different muscles of in the body that develops within few days of starting treatment with typical antipsychotic drugs. This patient’s presentation is more consistent with NMS.
→ Delirium tremens (choice E) certainly presents with altered mental status, hallucination, elevated temperature, and diaphoresis, but patients have an alcohol abuse history, which is absent in this patient.
Neuroleptic malignant syndrome is characterized by fever, muscular rigidity, altered mental status, and autonomic dysfunction in a patient who was recently started on typical antipsychotic medications.
A 29-year-old social worker comes to the office because of the difficulty keeping up with her tasks and responsibilities. She states she is easily distracted and has trouble concentrating and staying focused. Her mind seems to wander off many times during the day and it is difficult for her to keep still when she is alone. Her friends tell her that she is inattentive, talkative and generally unorganized. She had been doing well with her job despite the fact that her symptoms had been present since her youth. Additionally, ever since she was promoted eight months ago, her job demands are starting to overwhelm her and she feels that her condition is getting worse. She has no other illnesses at this time and her vital signs are within normal limits.
In addition to psychotherapy, what is the best pharmacologic therapy for this patient based on her presentation?
Correct Answer B:
The patient presents with symptoms of adult attention deficit hyperactivity disorder (ADHD). It is characterized by symptoms of inattention, impulsivity, and hyperactivity that emerge in childhood. However, presentation of ADHD in adults is different than in that of children due to a greater decrease of hyperactivity than in symptoms of inattention. Also, symptoms of ADHD in adults may manifest as employment or financial difficulties. Criteria for diagnosis of ADHD include evidence of inattention, hyperactivity, and impulsivity that have persisted for at least six months. Treatment includes psychotherapy (cognitive behavioral therapy), psycho-stimulants (such as amphetamine and methylphenidate) and non-psychostimulant (such as atomoxetine - norepinephrine transporter blocker). Amphetamine is the only psychostimulant among the agents listed; therefore, amphetamine (choice B) is the correct answer.
→ Alprazolam (choice A) is a benzodiazepine commonly used for generalized anxiety or panic disorder.
→ Paroxetine (choice C) is a selective serotonin reuptake inhibitor (SSRI) used most often for major depression or obsessive compulsive disorder.
→ Risperidone (choice D) is an atypical psychotic commonly used for schizophrenia, Tourette's syndrome, and bipolar disorder.
→ Trazodone (choice E) is a serotonin uptake inhibitor commonly used for major depression and insomnia.
Adult attention deficit hyperactivity disorder is characterized by symptoms of inattention, impulsivity, and hyperactivity that often emerge as interpersonal and/or workplace problems. It can be managed through psychotherapy and pharmacologic agents such as amphetamine, methylphenidate, and atomoxetine.
A 7-year-old boy is brought to a psychiatrist because he is doing poorly in first grade. He doesn’t seem to pay attention to the teacher, and has not made any friends. He is fascinated with insects and has spent almost all of the last two months in class looking at a book with pictures of insects in it. He had no delay in his language skills and converses normally, but limits his discussions to details about insects. In the office, he makes no eye contact and twirls his hair around his finger. His parents state he has always been like this.
What is the likely diagnosis?
Correct Answer A:
The hallmark of Asperger syndrome (DSM-IV) (choice A) / Autism spectrum disorder (ASD) (DSM-V) is atypical social development and restrictive, repetitive behaviours and interests but normal language skills.
→ According to DSM-V, childhood autism (choice B) is not a diagnosis. ASD encompasses disorders previously known as autistic disorder (classic autism, sometimes called early infantile autism, childhood autism, or Kanner's autism), childhood disintegrative disorder, pervasive developmental disorder-not otherwise specified, and Asperger disorder (also known as Asperger syndrome) if the current diagnostic criteria are met.
→ In OCD (choice C), repetitive behaviours and interests may also be present, but these are intended to prevent or reduce distress in some way. Social skills are not primary affected.
→ This patient does not demonstrate psychotic features such as delusions, hallucinations, or disorganized thought processes, which are required for the diagnosis of schizophrenia (choice D).
→ Childhood disintegrative disorder (choice E) is a syndrome of loss of previously acquired skills in language, behaviour, bowel or bladder control, play, or motor skills.
A 71-year-old male presents to your department with complaints of lack of motivation to do anything and decreased sleep. He reports that in the morning he doesn’t feel like getting up to do anything though he owns a restaurant and he is the major decision maker for the business. He feels his energy is low and it is hard for him to concentrate and he easily forgets things. He has noticed that for the last 2 weeks he wakes up at 3 am and is not able to fall asleep again. He has lost 3 kg over the last 3 weeks because of poor appetite. He denies any suicidal ideation though he wishes he could be with his wife “up there”. His wife of 46 years passed away 6 months ago and he somehow blames himself that he could have done something to save her from congestive heart failure. Physical examination is only remarkable for remembering 2 things out of 3 in 5 minutes.
Which of the following drugs is most appropriate for the management of this patient’s condition?
This patient presents with decreased sleep, anhedonia, guilt, decreased energy, concentration difficulties, and loss of appetite. These symptoms are suggestive of a depressive disorder. The patient also has memory impairment, which is confirmed by physical examination. Depression and dementia have increased incidence in patients > 65 years old. The prevalence of major depression in older adults in primary care settings is estimated to be at least 10%. Stressors such as chronic pain, medical disability, or the death of one's spouse are more commonly seen in the elderly and can result in a reactive depression.
Currently selective serotonin reuptake inhibitors are regarded as first-line drugs of choice in treating depression in the geriatric population. Compared to other equally effective drugs of other class such as tricyclic antidepressants (TCAs) for example, SSRIs have better tolerability, safer side effect profile, as they are less likely to cause cardiotoxicity, anticholinergic side effects, dizziness, and falls. Paroxetine is the only SSRI with anticholinergic side effects and they are 5 times less reported in patients using this drug than in those on nortriptylline. Citalopram (choice B) not only avoids these side effects but it is the only SSRI so far proven to be also effective in patients with dementia comorbidity. It is contraindicated in patients with QT prolongation and electrolytes should be monitored in patients on citalopram. The dose of citalopram should not exceed 40 mg/day and higher doses have not been proven to be more effective. In patents > 60 years old, the maximum recommended dose of citalopram is 20 mg/day.
→ Nortriptylline (choice A) is one of the most effective antidepressive medications, but as a TCA, it is more likely to cause cardiotoxicity, anticholinergic side effects, dizziness, and falls.
→ Diazepam (choice C) is a benzodiazepine that is used to treat anxiety, panic attacks, insomnia, muscle spasms, restless leg syndrome, and alcohol withdrawal. Compared to citalopram it is more likely to cause dizziness and falls. Studies have reported 30% incidence of falls and 17% severe falls in patients on either TCA or benzodiazepines.
→ Tranylcypromine (choice D) is incorrect. Despite their well-established efficacy, indications for monoamine oxidase inhibitors are currently very limited, due to their significant potential for adverse effects, many interactions, and the availability of newer and safer.
→ Bupropion (choice E) has not undergone rigorous studies in geriatric patients similarly to TCAs and SSRI, it is considered a second-line therapy for patients who are unresponsive or intolerant to first-line therapy.
SSRIs are the best drugs to treat depression in elderly patients. Citalopram has added benefits in those with dementia.
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