WBR0094

Author	[[PageAuthor::Gonzalo Romero (reviewed by Yazan Daaboul, M.D., Rim Halaby, M.D. [1])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Behavioral Science/Psychiatry, MainCategory::Pharmacology
Sub Category	SubCategory::Neurology
Prompt	[[Prompt::A 25-year-old woman complains of generalized fatigue for the past 8 months. The patient reports she is generally unhappy and lacks motivation at work. She believes her co-workers reject her and admits she does not have any friends. She spends most of her time at home sleeping. When she wakes up, she is either watching TV or eating fast food. The patient also mentions that she feels an unusual sensation of heaviness in her arms and legs that makes it difficult for her to get out of bed sometimes. Upon further questioning, she denies suicidal or homicidal thoughts or feelings of worthlessness. The physician prescribes a pharmacologic agent to relieve the patient's symptoms. Which of the following is the mechanism of action of the drug the patient is receiving?]]
Answer A	AnswerA::Serotonin reuptake inhibitor
Answer A Explanation	[[AnswerAExp::Selective serotonin reuptake inhibitors (SSRIs) include paroxetine, sertraline, citalopram, and fluoxetine. They are prescribed for patients with major depression, generalized anxiety disorder, bulimia nervosa, social phobia, OCD, and PTSD.]]
Answer B	AnswerB::Norepinephrine reuptake inhibitor
Answer B Explanation	[[AnswerBExp::Maprotiline is an atypical antidepressant which blocks norepinephrine reuptake. Because it is commonly associated with sedation with early doses, it may be helpful among depressed patients with agitation or suicidal risk.]]
Answer C	AnswerC::Serotonin receptor agonist
Answer C Explanation	[[AnswerCExp::Buspirone, which is prescribed for patients with generalized anxiety disorder, stimulates serotonin (5-HT1a) receptors. Nootably, it is not associated with sedation, addiction or tolerance.]]
Answer D	AnswerD::Alpha-2 receptor antagonist
Answer D Explanation	[[AnswerDExp::Mirtazapine is an atypical antidepressant. It blocks alpha-2 receptors in the presynaptic neurons and increases the release of norepinephrine and serotonin. It causes sedation and therefore can be prescribed for depressed patients with insomnia. It might also cause an increase in appetite with possible weight gain.]]
Answer E	AnswerE::Serotonin, norepinephrine, and dopamine metabolism inhibitor
Answer E Explanation	AnswerEExp::Monoamine oxidase inhibitors (MAOi) are prescribed for patients with atypical depression. MAOi act by inhibiting the ubiquitous enzyme monoamine oxidase, which usually deaminates serotonin, norepinephrine, dopamine, and tyramine.
Right Answer	RightAnswer::E
Explanation	[[Explanation::Atypical depression is a common subset of major depression that commonly affects young women. It is characterized by hypersomnia, weight gain, and emotional lability and rejection sensitivity. It is also associated with leaden paralysis or a heavy feeling in the arms and legs. Women are two to three times more likely to be affected with atypical depression than men. The course is often chronic and unrelenting, making treatment difficult. Unlike typical depression, which is characterized by anhedonia, weight gain, generally "down" mood, and feeling of guilt, symptoms of patients with atypical depression may improve with some activities and do not usually include guilt sensation or suicidal/homicidal ideations. The treatment of choice for atypical depression is a monoamine oxidase inhibitor (MAOi), which inhibits 5-HT, norepinephrine, and dopamine metabolism. MAO is a ubiquitous enzyme present in mitochondria. The enzyme exists in 2 forms: A and B. MAO inhibitors act by inhibiting the ubiquitous enzyme monoamine oxidase, which usually deaminates serotonin, norepinephrine, dopamine, and tyramine. Not only do MAO inhibitors provide a good therapeutic option for patients with atypical depression, but also they play a role in the diagnosis. The diagnosis of atypical depression is usually confirmed when good response to MAO inhibitors is observed. MAO inhibitors include phenelzine, tranylcypromine, isocarboxacid, and selegiline. Selegiline is considered a selective MAO-B inhibitor. The most important side effects of MAO inhibitors are hypertensive crises when combined with tyramine, a compound found in cheese and wine. MAO inhibitors are also associated with serotonin syndrome when administered in excess or in combination with other medications that increase the availability of serotonin, such as SSRI, TCA, meperidine, and dextromethorphan. Educational Objective: Atypical depression is characterized by mood reactivity, hypersomnia, and weight gain. It is also associated with leaden paralysis, defined as a heaviness in the arms and legs. The treatment of choice is a MAO inhibitor, which inhibits 5-HT, norepinephrine, and dopamine metabolism. References: Pae CU, Tharwani H, Marks DM, Masand PS, Patkar AA. Atypical depression: a comprehensive review. CNS Drugs. 2009;23(12):1023-37. First Aid 2014 page 507]]
Approved	Approved::Yes
Keyword	WBRKeyword::Atypical depression, WBRKeyword::depression, WBRKeyword::psychiatry, WBRKeyword::MOI, WBRKeyword::monoamine oxidase inhibitor
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