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Depression is commonly encountered in the general population, affecting over 15% of people at some point during their lives. Consequently, the prevalence of patients taking mood-altering pharmaceuticals is significant. These medications include selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA), norepinephrine-dopamine reuptake inhibitors (NDRI), monoamine oxidase inhibitors (MAOI), and atypical antidepressants (Table 28-1). Each of these classes of medications present unique implications for the anesthetic management of the patient and thus it is essential to understand the mechanism of action, side effect profile, and drug interactions of each.

TABLE 28-1Common Antidepressants

Major depressive disorder (MDD) is classified by the DSM-IV as depressed mood or loss of interest/pleasure in life activities for at least 2 weeks, including at least two of the following symptoms:

  • Depressed mood most of the day

  • Diminished interest or pleasure in all or most activities

  • Significant unintentional weight loss or weight gain

  • Insomnia or sleeping too much

  • Agitation or psychomotor retardation noticed by others

  • Fatigue or loss of energy

  • Feelings of worthlessness or excessive guilt

  • Diminished ability to think or concentrate, or indecisiveness

  • Recurrent thoughts of death

It is important, however, for the anesthesiologist to distinguish major depressive disorder from secondary causes of depressed mood, especially hypothyroidism, substance abuse, dementia, Parkinson’s disease, and inflammatory conditions.


Selective serotonin reuptake inhibitors (SSRIs) are thought to be the most effective antidepressants with the safest pharmacological profile and thus are the most frequently encountered antidepressant by anesthesiologists. SSRIs work by preventing the reuptake of serotonin from neuronal clefts, thus potentiating the propagation of serotonergic impulses. They selectively work on serotonin and thus avoid altering the norepinephrine or acetylcholine pathways. Yet, despite their ubiquitous use, SSRIs still have several potential adverse effects, such as nausea, headache, loss of libido, erectile dysfunction, suicidal ideation, and most notably for the anesthesiologist serotonin syndrome.

It is also important to recognize that, within this class, escitalopram can precipitate hyponatremia and fluoxetine is a potent inhibitor of cytochrome P-450 2D6. The inhibition of the hepatic cytochrome P-450 system causes an unpredictable increase in concentrations of certain hepatically metabolized drugs, including beta-blockers, TCAs, codeine, donepezil, haloperidol, risperidone, and tramadol. Also, notably SSRIs do not affect the seizure threshold.

Serotonin Syndrome

Serotonin syndrome is a potentially life-threatening event associated with an increased level of serotonin in the blood, usually secondary to concomitant administration ...

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