A 38-year-old man is evaluated for a 2-month history of depressed mood. He explains, "I'm just exhausted all the time. I can't sleep. I can't think. I just feel worn out." During further discussion, the patient tearfully admits to thoughts of suicide but has no plan or intent to act on these thoughts. He has no medical conditions. Family history is significant for type 2 diabetes mellitus and hypertension in his father and hyperthyroidism in his mother. After physical examination and laboratory workup, major depressive disorder is diagnosed and antidepressant therapy is initiated. The patient's symptoms do not respond to monotherapy, so an antipsychotic medication is added. Over the course of several months, the patient's antidepressant dose is increased to the maximal therapeutic dose. At his 6-month follow-up, the patient's mood is improved and his depression is in remission. Temperature is 36.7 C (98.1 F), blood pressure is 148/91 mm Hg, pulse is 72/min, and respirations are 14/min. Compared to his most recent visit, he has lost 0.5 kg (1.1 lb); he has also new-onset hypertension. Which of the following medications is the most likely cause of this adverse effect?

Question

A 38-year-old man is evaluated for a 2-month history of depressed mood.  He explains, "I'm just exhausted all the time.  I can't sleep.  I can't think.  I just feel worn out."  During further discussion, the patient tearfully admits to thoughts of suicide but has no plan or intent to act on these thoughts.  He has no medical conditions.  Family history is significant for type 2 diabetes mellitus and hypertension in his father and hyperthyroidism in his mother.  After physical examination and laboratory workup, major depressive disorder is diagnosed and antidepressant therapy is initiated.  The patient's symptoms do not respond to monotherapy, so an antipsychotic medication is added.  Over the course of several months, the patient's antidepressant dose is increased to the maximal therapeutic dose.  At his 6-month follow-up, the patient's mood is improved and his depression is in remission.  Temperature is 36.7 C (98.1 F), blood pressure is 148/91 mm Hg, pulse is 72/min, and respirations are 14/min.  Compared to his most recent visit, he has lost 0.5 kg (1.1 lb); he has also new-onset hypertension.  Which of the following medications is the most likely cause of this adverse effect?

Quizplus · Accepted Answer

Venlafaxine, an antidepressant in the serotonin-norepinephrine reuptake inhibitor class, has been associated with dose-dependent hypertension. At lower doses, venlafaxine primarily inhibits the reuptake of serotonin. As the dose increases, however, the drug also inhibits norepinephrine reuptake, potentially causing increased systolic and diastolic blood pressure. The hypertensive effect is especially significant at doses >300 mg daily, in which the incidence may be >10%. Although the blood pressure increase is generally modest for most patients taking venlafaxine, blood pressure should be monitored regularly. If sustained increases are noted, dose reduction or discontinuation should be considered. In patients with preexisting hypertension, blood pressure should be well controlled prior to starting venlafaxine, or an alternative antidepressant with a more favorable side effect profile should be considered. (Choices A and G) Although second-generation antipsychotics (SGAs) are associated with weight gain, which can subsequently contribute to hypertension, they do not cause hypertension directly. Aripiprazole and ziprasidone are the least likely SGAs to cause weight gain, and this patient has actually lost weight since the initiation of therapy. (Choices B, C, and E) The selective serotonin reuptake inhibitors paroxetine and sertraline do not inhibit norepinephrine reuptake and are not associated with hypertension. Mirtazapine antagonizes presynaptic alpha-2 adrenergic receptors and is associated with increased appetite and sedation but not hypertension. (Choice D) Phenelzine is a monoamine oxidase inhibitor (MAOI) that is not used as a first-line antidepressant due to its unfavorable side effect profile and dietary restrictions. At therapeutic doses, MAOIs commonly cause hypotension, not hypertension. MAOI hypertensive crisis refers to severe hypertension that can occur after patients on MAOIs ingest foods containing tyramine, a sympathomimetic. Educational objective: Venlafaxine is a serotonin-norepinephrine reuptake inhibitor that can cause dose-dependent hypertension. Blood pressure should be monitored regularly, especially at higher doses. References: Accelerated hypertension after venlafaxine usage. (http://www.ncbi.nlm.nih.gov/pubmed/25328745) Drug-induced hypertension: an unappreciated cause of secondary hypertension. (http://www.ncbi.nlm.nih.gov/pubmed/22195528)

A 38-Year-Old Man Is Evaluated for a 2-Month History of Depressed