5. What should I tell pregnant patients about the risks of SSRIs?
Be upfront with them that depression in pregnancy presents a dilemma.
Tell them that on the one hand, untreated depression has been found to increase the risk of preterm labor, low birth weight, decreased fetal growth, preeclampsia, and a worsening psychiatric condition after childbirth.22,23 In a 2006 study of 201 pregnant women with a previous diagnosis of depression, 43% relapsed during pregnancy. Those who were not taking antidepressants were 2.6 times more likely to relapse than women being treated for depression.24
Patients also need to be informed that antidepressant therapy during pregnancy carries its own set of risks. Five SSRIs are pregnancy category C,25 indicating either animal studies have found the drug to be harmful to fetuses and there are no well-done studies in pregnant women or that no animal studies and no human studies have tested its safety during pregnancy (the data were gathered after pregnancy). The sole exception is paroxetine, which has a D rating.25 Studies have linked paroxetine to an increased risk of cardiovascular malformations in babies who were exposed to it during the first trimester.26 These ratings may change shortly, however, as they are under FDA review. In May 2008, a new classification system for medication use in pregnancy was proposed.27 While this system would have great clinical utility, no target date for its release has been identified.
Use of SSRIs during the second and third trimester increases the risk of neonatal pulmonary hypertension. One study found that exposed newborns were 6 times more likely to experience persistent pulmonary hypertension, compared with newborns who were not exposed to SSRIs in the second and third trimesters.28
In addition, a derivative of the discontinuation syndrome is associated with neonatal withdrawal after in utero exposure, especially during the third trimester. Up to 30% of infants exposed to an SSRI may experience withdrawal symptoms, including increased or decreased muscle tone, jitteriness, feeding problems, irritability, sleep disturbance, and respiratory distress.29
Under the circumstances, the best you can do is to provide the patient with as much information as possible about the benefits and risks of each strategy. In any case, pregnant women suffering from depression should receive frequent follow-up and a referral to a mental health professional. Emphasize the importance of discussing their current medications and symptoms of depression with their obstetrician and psychiatrist or psychotherapist.
6. What can I tell adolescents and their parents about SSRI safety?
Explain that 4 SSRIs—escitalopram, fluoxetine, fluvoxamine, and sertraline—are approved for use in this age group, for specific indications. Fluoxetine and escitalopram are approved for the treatment of depression in children ≥8 and ≥12 years of age, respectively. Fluvoxamine, fluoxetine, and sertraline are approved for obsessive-compulsive disorder in children ≥8, ≥7, and ≥6 years, respectively.
You can also tell patients and parents that adolescents typically fare better when they receive a combination of medication and psychotherapy, compared with medications or therapy alone.
The FDA issued an initial warning about antidepressant use in pediatric and adolescent patients in 2003, based on data from 23 randomized controlled trials submitted by 8 different drug manufacturers.30 Most of the studies reported roughly twice the risk for suicidal ideation in adolescents taking SSRIs, compared with placebo. It is noteworthy, however, that there were no reports of completed suicides in the submitted trials.30 In fact, data suggest that despite some increased suicidal ideation when SSRIs are initiated, these antidepressants result in improved symptom control. In 2007, after a data review, the FDA issued an advisory warning physicians about increased suicidality in young patients.31
The FDA has recommended increased monitoring of adolescents taking SSRIs, with office visits once a week for the first month of treatment and every 2 weeks for the second month, followed by 1 visit every 3 months. This stringent schedule has proven difficult to adhere to. One study showed that only 5% of adolescent patients received this level of attention.32 The American Academy of Child and Adolescent Psychiatry and the American Psychiatric Association advocate an individualized treatment plan instead.33
If you prescribe SSRIs for depressed adolescents, educate patients and parents about the atypical presentation of depression that is common in patients of this age group. Advise them to watch closely for, and promptly report, increases in agitation, anxiety, impulsiveness, and restlessness, and symptoms of mania or hypomania.33
7. When should I refer a patient to a mental health professional?
Refer patients to a mental health specialist when the optimal treatment calls for a combination of psychotherapy and medication, as is the case with depressed adolescents. Referral is recommended, too, for any complex patients. Examples include elderly individuals who are taking multiple medications or have comorbidities that can interfere with optimal treatment, and pregnant women who need additional help weighing the benefits and risks of antidepressant therapy vs nonpharmacologic treatments.