A 30-year-old woman presents to your office for the evaluation of fatigue. For the past 2 months she has felt run down. She says that she doesn’t feel like participating in activities that she previously enjoyed, such as her weekly softball games. She has not been sleeping well and has not had much of an appetite. On questioning, she admits to feeling “down in the dumps” most of the time and has found herself crying frequently. She has never gone through anything like this before. She denies any thoughts of wanting to hurt herself or anyone else. Other than becoming tearful during her interview, her physical examination is normal. Her blood tests, including a complete blood count and thyroid function, are normal. A serum pregnancy test is negative. You diagnose her as having a major depression and, along with referring her for counseling, start her on fluoxetine.
What is the mechanism of action of fluoxetine?
What are the common side effects of fluoxetine?
Answers to case: Antidepressant agents
Summary: A 30-year-old woman with major depression is prescribed fluoxetine.
Mechanism of action of fluoxetine: Inhibition of the reuptake of serotonin (5-hydroxytryptamine, or 5-HT) at the prejunctional nerve terminal.
Common side effects: Headache, nausea, agitation, insomnia, and sexual disturbances (loss of libido and erectile dysfunction).
Clinical correlation
Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressant medications. They act by inhibiting the reuptake of serotonin by the prejunctional nerve terminal, allowing more serotonin to interact with postjunctional neurons in the central nervous system (CNS).
This is thought to mediate their therapeutic effect. They have been highly effective in the treatment of major depressive disorders and have an excellent safety profile. Unlike tricyclic antidepressants (TCAs), which have multiple severe and potentially fatal effects in an overdose, SSRIs have relatively few severe toxicities and a very low potential for fatality in an overdose. SSRIs do have several side effects of clinical significance. They often cause headache and gastrointestinal (GI) side effects such as nausea. In some cases, agitation, anxiety, and insomnia can be exacerbated. Many of these SSRI side effects tend to be temporary and can often be improved with dose reduction. Another common side effect of SSRIs is sexual disturbance. Decreased libido and erectile dysfunction occur frequently and do not generally spontaneously resolve while continuing SSRI therapy, often leading to reduced patient compliance.
Approach to pharmacology of antidepressant drugs
Objectives
1. List the classes of antidepressant agents.
2. Contrast the mechanisms of action of the antidepressant agents.
3. Contrast the adverse effects and toxicities of the antidepressant agents.
4. Describe the indications and contraindications to antidepressant drug use.
Definitions
Major depressive disorder: Unexplained, long-term difficulty coping with life events characterized by an inability to experience pleasure, abnormal sleep, decreased libido and appetite, feelings of guilt, and suicidal ideation.
Continuation: Case: Antidepressant agents. Discussion