A 29-year-old male comes to your office at the urging of his wife because of some disturbing issues she has noticed recently. For the past month, he has been talking of a massive stadium in which he would gather tens of thousands of citizens to announce his political run for the senate. He has barely slept lately because of the work he needs to do on "these big plans." He says that he has so many ideas that he just doesn’t want to waste time in bed before he sees them become a reality. He has maxed out their new $10,000 credit card in just one week as he was buying items he considers essential in the preparation for his campaign. He also slept with 7 different women in the past month, which was the most disturbing issue, according to his the wife. He denies hearing voices or seeing things invisible to other people around him. When asked about his mood he says that he currently feels “elated” though he felt depressed a couple of times in the last few weeks because he did not feel his friends and family were taking him seriously. You note that he talks rapidly. His past medical history is otherwise unremarkable.
What is the most likely diagnosis of this patient?
Correct Answer C:
This patient’s symptoms are suggestive of bipolar disorder (choice C). It is a mood disorder characterized by episodes of mania alternating with episodes of depression. Bipolar I is characterized by manic episodes lasting at least 1 week, whereas the milder bipolar II requires only a hypomanic episode at least 4 days for diagnosis. Symptoms of manic/hypomanic episodes are:
The major difference between hypomanic episodes and manic episodes is the lack of social or occupational dysfunction in hypomanic episodes.
Depression episodes are characterized by depressed moods, marked diminished interest in activities, loss of energy or fatigue, decreased concentration, preoccupation with death or suicide.
→ Cyclothymia (choice A) is a relatively mild mood disorder with mild episodes of depression alternating with hypomania lasting at least 2 years.
→ Schizophreniform disorder (choice B) is diagnosed in patients who fulfill the criteria for schizophrenia diagnosis in terms of presentation only with 1 month of symptoms or longer but less than the 6 months (which is required to diagnose schizophrenia). Those symptoms are delusions, hallucinations, disorganized speech, and catatonic behavior.
→ Major depressive disorder (choice D) is incorrect. The patient describes his current mood as “elated”, hypersexuality is reported and not anhedonia, excessive shopping, and many other classic characteristics of mania.
→ Borderline personality disorder (choice E) is a cluster B personality disorder. Essential features are a pattern of marked impulsivity and instability of affects, interpersonal relationships, and self image.
Key point:
Bipolar disorder is characterized by manic episodes/hypomanic alternating with major depression episodes.
A 26-year-old female comes to your office complaining of amenorrhea, noticeable hair loss, and significant weight gain the last 3 months. She used to have regular menstrual periods every 30 days and her menarche was at the age of 12. She has gained 8kg in a short period of time without any significant change in her diet. She also says that at work, she noticed that she feels cold when other people seem to be fine. Her past medical history is only significant for bipolar disorder diagnosed last year, which is being treated medically. She is divorced and has a 2-year-old daughter. She says she has been sexually active with 2 partners in the past 6 months “on and off”, but she uses condoms and OCPs. Pregnancy test is negative. TSH is elevated.
Which of the following is the most likely cause of the patient’s current symptoms?
Correct Answer A:
This patient is presenting with many symptoms suggesting thyroid disease, specifically hypothyroidism: amenorrhea, weight gain, cold intolerance, and alopecia. It is confirmed by elevated TSH. This is likely to be a result of her mood disorder treatment. Among the choices given, lithium (choice A) is the most likely to cause hypothyroidism. For this reason baseline thyroid function tests should be measured prior to starting lithium therapy and subsequently monitored 3 months after starting the treatment and 6-12 months thereafter.
→ Valproate (choice B) can also be used in the treatment of Bipolar disorder. It is associated with fetal abnormalities especially neural tube defects in pregnant women, but it is not known to cause thyroid disease.
→ Birth control pills (choice C) would not explain the patient’s cold intolerance or alopecia.
→ Olanzepine (choice D) is an atypical antipsychotic drug that can be used to treat both schizophrenia and bipolar disorder. Through different mechanisms, it is associated with weight gain, amenorrhea, and constipation-symptoms that may be seen in patients with hypothyroidism, but it is not known to cause thyroid disease.
→ Risperidone (choice E) may also be used to treat schizophrenia and bipolar disorder. It is associated with amenorrhea because it causes hyperprolactinemia and weight gain. It does not affect the thyroid in the same way Lithium does and routine monitoring of thyroid function in patients taking risperidone without previous thyroid disease is not recommended.
Lithium is a useful drug in the treatment of bipolar disorder but it is associated with hypothyroidism. Thyroid function should be monitored regularly in patients taking lithium.
A 39-year-old combative male is brought in because of agitation as he was punching walls in his home saying that he was fighting with aliens from Mars who invaded the Earth. He has been unable to hold normal conversation with his family the last 2 days because of delusions. According to his wife, yesterday he walked completely naked into the living room where other family members were watching TV. Six weeks ago he was treated for a similar condition for 1 month. His symptoms had resolved though he experienced sudden dynamic tilts of his neck during this treatment. He has not been taking any medications for the last 2 weeks. Family history is unremarkable. He does not smoke, drinks alcohol during special occasions, and has never used any recreational drugs. He lives with his wife, 3 children, and mother-in law. They have not had any stressful events in their family recently.
Which of the following is the best initial treatment on admission?
Correct Answer E:
This patient is agitated and combative and is most likely having a relapse of psychosis. DSM-V defines brief psychotic disorder (also known as brief reactive psychosis) as an illness lasting from 1 day to 1 month, with an eventual return to the premorbid level of functioning. It is recommended that when a patient is agitated and combative the initial course of action should be sedation with a benzodiazepine (choice E). While some antipsychotics can achieve sedation, It is safer to achieve sedation with benzodiazepines as required rather than antipsychotics. Choosing a highly sedating antipsychotic drug at this stage is associated with impediments at discharge later. The use of benzodiazepines also allows for observation of the presenting symptoms and their course over the initial few days as well as time to do further investigations. Moderate agitation may be treated with 1-2 mg lorazepam orally or sublingually while severe psychosis should be managed with 3-4 mg of lorazepam orally if possible or intramuscularly.
→ Risperidone (choice A) would be the best antipsychotic drug to use in treating this patient. It is an atypical antipsychotic that has been shown to be very effective in treating acute psychotic episodes. Risperidone is not a sufficiently sedating drug and would not be very effective in sedating this combative patient.
→ Haloperidol (choice B) should be avoided in this patient given the history of torticollis when he was treated with antipsychotics few weeks earlier. The torticollis history is suggested by the sudden dynamic tilts of his neck the patient had when he was treated with antpsychotics, this is an acute dystonia side effect of typical neuroleptics.
→ Trihexyphenidyl (choice C) is an antimuscarinic antiparkinsonian drug used to treat the side effects of typical antipsychotics.
→ Quetiapine (choice D) is an atypical antipsychotic that has not been proven to be effective in treating acute psychosis.
An agitated patient with brief psychosis should first be sedated with benzodiazepine as required, then treated with an appropriate antipsychotic.
A 31-year-old female presents to your department for a schizophrenia treatment follow-up. She has no complaints except milky discharge from her breasts. She has adhered to her risperidone treatment as prescribed. She has no children, has never been pregnant, and her pregnancy test is negative.
Her current complaints are most likely due to:
This patient, with a history of schizophrenia, has been treated with risperidone and is presenting with galactorrhea. Risperidone is an atypical antipsychotic that has an affinity to dopamine D2 and serotonin 5HT2A receptors and blocks these receptors (choice E). Dopamine has the dominant influence over prolactin secretion and dopamine receptor blockage results in hyperprolactinemia and galactorrhea.
→ Serotonin receptor inhibition (choice A) is incorrect. While risperidone has some serotonin receptor inhibition effects, galactorrhea is primarily caused by dopamine receptor blockade.
→ Ryanodine receptor antagonism (choice B) is not the mechanism of action of risperidone. It is the mechanism of action of dantrolene.
→ Dopamine receptor agonism (choice C) would be useful to treat parkinsonism and is seen in drugs such as bromocriptine and cabergoline; it is not the mechanism of action of risperidone.
→ Histamine receptor inhibition (choice D) has been associated with galactorrhea especially with cimetidine. Risperidone leads to hyperprolactinemia and galactorrhea largely due to its anti-dopaminergic effects.
Risperidone is an atypical antipsychotic well known to cause galactorrhea. This is a result of its dopamine receptor blockade.
A 35-year-old female is brought to your department because of confusion and slurred speech for the last 3 days. She is disoriented to time of the day and date. She also has trouble following instructions. Her speech is slow and difficult to understand. She has never had a similar problem before. She denies urinary changes, constipation, diarrhea, and sleep disturbance. Her past medical history is significant for type I diabetes well managed with insulin and bipolar disease treated with lithium. For the last six weeks she had been having joint pain with activity and had been taking over-the counter naproxen, which she said had helped much and she had been able to continue her daily attendance to the gym. Her medical check up 3 months ago was normal.
Vital signs are temperature 37.40C, blood pressure is 115/70 mmHg, pulse is 70/min, and respirations 18/min. On physical examination the patient is poorly cooperative. Neurological examination reveals increased reflexes in all extremities and an intention tremor. Laboratory tests show:
What is the most likely cause of this patient’s condition?
This patient’s clinical presentation is consistent with lithium toxicity due to chronic large body burden of lithium most likely associated with non-steroidal antiinflammatory drug use and its effects on kidney function (choice C). Although lithium is commonly used to treat bipolar disorder it has a narrow therapeutic index. Relatively minor increases in serum concentrations may induce serious adverse sequelae, and in fact concentrations within the therapeutic range may result in toxic reactions. The safety of combining lithium with other medications is a major concern, and lithium is known to interact with diuretics, ACE inhibitors, and NSAIDs with potential adverse effects. This patient’s BUN and creatinine are increased and the lithium concentration is very high (0.6 mEq-1.2 mEq concentration is desired for therapeutic purposes) most likely due to naproxen nephrotoxicity and decreased renal clearance.
→ Lithium-induced thyroid disorder (choice A) is incorrect. While lithium can certainly cause thyroid toxicity, this patient’s thyroid function is normal as suggested by thyroid function studies.
→ Lithium-induced nephrogenic diabetes insipidus (choice B) may also occur in patients treated with lithium. This patient doesn’t have electrolyte disturbance and urinary changes suggestive of diabetes insipidus.
→ Naproxen-associated neurological toxicity (choice D) is incorrect. Naproxen inhibits prostaglandin biosynthesis and thromboxane and is associated with nephrotoxicity and gastrointestinal bleeding. While there have been some reports of naproxen-associated neurotoxicity, these are very rare and this patient’s condition is most likely associated with decreased lithium clearance.
→ Diabetic ketoacidosis due to treatment non-compliance (choice E) is incorrect. This patient’s anion gap is normal and she is unlikely to have diabetic ketoacidosis.
Classes that have been identified as potential participants in lithium toxicity are thiazide diuretics (increased risk of lithium toxicity), ACE inhibitors, and NSAIDs (increased steady-state plasma lithium levels).
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