Pharmacology and adverse effects including suicide

Fluoxetine, paroxetine, and citalopram are hepatically metabolized by the cytochrome P450 system. The half-life of fluoxetine is 84 hours and the principal metabolite is equipotent with an extended half-life of seven days. The half-life of paroxetine (21 hours) and citalopram (36

hours) are prolonged in geriatric patients and the dose of paroxetine should be reduced in patients with renal dysfunction. Fluoxetine and paroxetine are both substrates and inhibitors of the 2D6 enzyme. The inhibition of 2D6 by fluoxetine and paroxetine could elevate serum levels of other analgesic medications, including tricyclic anti-depressants and tramadol.107 The metabolism of citalo-pram is more balanced in that the drug is metabolized by three different cytochrome enzymes including 2D6, 2C19, and 3A4.

Side effects associated with use of these medications are related to enhanced serotonergic transmission. Frequently encountered side effects include nausea, vomiting, tremor, anxiety, agitation, sweating, sleep disturbance, diarrhea, and sexual dysfunction. Paroxetine has affinity for muscarinic receptors which account for mild anticholinergic effects, predominantly dry mouth, constipation, and blurred vision. Long-term use of paroxetine has been associated with weight gain.108

One of the most important controversies related to use of SSRIs is the potential increased risk of suicide, particularly among adolescents with depression.109,110,111 However, further research is needed to firmly establish the overall risks and benefits of antidepressant therapy on both attempted and completed suicide.112,113114 Knowledge of the potential association between SSRIs and suicide is particularly important for pain medicine specialists given the high incidence of depression among patients with chronic pain. In the context of this ongoing controversy, physicians who prescribe antidepressant medications should be vigilant in accounting for the potential risk of this uncommon, but devastating, adverse event.

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