A 72-year-old woman is brought to a physician by her husband, who is concerned about her declining health. She no longer prepares meals or cleans the house. She takes no interest in her bridge club and has not gone out with any friends for over 2 months. She sleeps about 14 to 16 hours a day. Her husband states that when she does wake up in the morning, he wishes she would just go back to bed, because she is always in a very foul mood. She says she feels fatigued. She has trouble remembering things.

On physical examination her vital signs show temperature 37.1 C, pulse 70/min, respiratory rate 14/min, and blood pressure 138/88 mm Hg. There are no abnormal findings. The mental status examination shows that she can remember 2 of 3 objects after 3 minutes. She can do serial sevens, but it takes a while. She is oriented. The physician becomes impatient as the examination drags on, and the patient is not cooperative, often replying, "I don't care" or "It doesn't matter."

Questions:

5.1 What is the most likely diagnosis?

She has findings of a major depressive disorder. The length and severity of her illness are more than expected for a dysthymic disorder. Her mental status exam does not suggest a neurodegenerative disorder. Underlying metabolic diseases such as severe anemia, hypoglycemia, hypothyroidism, and collagen vascular diseases may be ruled out. Her serum TSH is 5 mU/mL. Her Hgb is 14.3 g/dL. Her blood glucose is 77 mg/dL. Her antinuclear antibody test is negative.

5.2 What pharmacologic therapy may be indicated for treatment?

The first choice drugs are the serotonin reuptake inhibitors (SSRIs) include fluoxetine (Prozac ®), paroxetine, and sertraline.

Tricyclic antidepressants (TCAs) such as amitriptyline (Elavil) are alternatives.

The monoamine oxidase (MAO) inhibitors such as phenelzine are the last choice.

A sufficient dose of either an SSRI or a TCA for 6 to 8 weeks will have a similar effect. The side effects may occur immediately, and patients may initially feel worse. Therefore, almost half of patients "give up" on a drug if no significant effect occurs within a month, so support during this period is important.

5.3 Explain the mechanism of action of the drug therapy.

SSRIs inhibit serotonin reuptake.

TCAs inhibit reuptake of both norepinephrine and serotonin.

MAO inhibitors inhibit metabolic breakdown of norepinephrine and 5-hydroxytryptamine.

All of the above seem to cause a desensitization (down-regulation) of some adrenergic receptors in the brain, and that may be the reason for the antidepressant effect.