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Review Question - QID 214948

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QID 214948 (Type "214948" in App Search)
A 44-year-old woman with a history of diabetes and hypothyroidism presents to her primary care physician for depressed mood. These symptoms have persisted for the past 10 years. Her symptoms of increased appetite and sleeping all day have been much worse. She feels as if her arms and legs are “made of lead” and incredibly heavy, making it difficult to engage in everyday tasks. Her mood is very depressed and she is very sensitive to rejection. She feels guilty that she cannot accomplish more in her life as a result. She has minimal interest in her hobbies or spending time with friends anymore. Her medical history is significant for hypothyroidism, major depressive disorder, obesity, and chronic kidney disease. Before the current visit, she was prescribed fluoxetine and paroxetine each for a 2-year period with escalating doses but has noticed no improvement in her symptoms. The patient also has a medical history of obesity, chronic kidney disease, and a seizure disorder. She has had several breakthrough seizures this past month despite consistently taking her prescribed antiepileptics. Her temperature is 98.1°F (36.7°C), blood pressure is 142/82 mmHg, pulse is 86/min, respirations are 16/min, and oxygen saturation is 98% on room air. Physical exam reveals a young woman with a depressed mood. Her neurological exam is unremarkable. Laboratory studies are ordered as seen below.

Hemoglobin: 12 g/dL
Hematocrit: 36%
Leukocyte count: 6,500/mm^3 with normal differential
Platelet count: 197,000/mm^3

Na+: 141 mEq/L
Cl-: 101 mEq/L
K+: 4.1 mEq/L
HCO3-: 24 mEq/L
BUN: 29 mg/dL
Glucose: 129 mg/dL
Creatinine: 2.1 mg/dL
Ca2+: 10.2 mg/dL
Thyroid stimulating hormone (TSH): 0.04 mIU/L (normal 0.04-5.0)

Which of the following is the most appropriate treatment for this patient?
















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This patient is presenting with depression with atypical features (heavy or lead limbs, mood lability, hyperphagia, and hypersomnolence) and has failed treatment of her depression with at least 2 different selective serotonin reuptake inhibitors (SSRIs) with escalating doses with no improvement in her symptoms. Given her refractory and atypical depression, a monoamine oxidase inhibitor (phenelzine) is the most appropriate next step in management for this patient.

Depression classically presents when a patient has 5 or more SIGE CAPS criteria: Sleep disturbance, Interest loss, Guilt, Energy changes, Concentration difficulty, Appetite changes, Psychomotor retardation, and Suicidal ideation. Atypical features in depression include heavy limbs or psychomotor retardation, a high degree of mood volatility and hypersensitivity to rejection, hyperphagia, and hypersomnolence. The management of depression should start with an SSRI as these medications are very safe and effective. If depression persists, changing the dose and changing the drug are both viable options. After a patient has failed multiple agents and doses, it is appropriate to explore other agents, in particular, monoamine oxidase inhibitors (phenelzine, isocarboxazid, and tranylcypromine). Monoamine oxidase inhibitors are highly effective medications in treating depression, including atypical depression. There is concern that using these agents can cause a hypertensive crisis with the consumption of tyramine-containing foods, interact with other serotonergic drugs, and this calss of medications are not readily reversible. Otherwise, they are an important adjunct in treating refractory cases of depression.

Thomas et al. discuss the use of monoamine oxidase inhibitors in treatment-resistant depression. The authors find that some patients with treatment-resistant depression improve after initiating therapy with monoamine oxidase inhibitors. The authors recommend cautious use of combination therapy with monoamine oxidase inhibitors in patients with treatment-resistant depression.

Incorrect Answers:
Answer 1: Bupropion is an appropriate antidepressant for patients who are also trying to quit smoking. It is also weight neutral and has no sexual side effects; however, it should be avoided in patients with a seizure disorder. This is particularly important in this patient with a poorly controlled seizure disorder.

Answer 2: Escitalopram is another SSRI that would be appropriate to try as a first- or second-line agent. This patient has already tried 2 different SSRIs for prolonged periods of time; thus, it is unlikely that this drug will be effective given her refractory and atypical symptoms.

Answer 3: Lithium is a mood stabilizer that would be appropriate for bipolar I disorder which presents with episodes of mania and depression. It is a mortality-lowering agent with a narrow therapeutic agent. Lithium has been tried as an augmenting agent for treatment-refractory depression; however, given this patient’s chronic kidney disease and atypical symptoms, a monoamine oxidase inhibitor would likely be a better agent.

Answer 5: Thyroxine should always be given to patients with symptoms of depression who suffer from hypothyroidism which would present with fatigue, depression, weight gain, scarce lanugo, cold intolerance, bradycardia, and hyponatremia. It can also be given as an augmenting agent and may help in some treatment refractory cases of depression; however, this patient’s TSH is at the low end of normal suggesting that she is receiving appropriate doses of thyroxine at baseline. In addition, her atypical symptoms make a monoamine oxidase inhibitor a better treatment.

Bullet Summary:
Monoamine oxidase inhibitors are effective treatments for treatment-refractory depression with atypical features (heavy or lead limbs, mood lability and reactivity, hyperphagia, and hypersomnolence).

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