In more recent years, serotonin reuptake inhibitors (SSRIs) have come on the market and have become a drug of choice for first-line treatment of depression. Medications in this class include fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), fluvoxamine (Luvox®), citalopram (Celexa®), and escitalopram (Lexapro®). Compared to older antidepressants, SSRIs are easy to titrate, have fewer side effects, have fewer drug interactions, and are less toxic.
Different medications in the SSRI class have other side effects and interactions, but a few common adverse effects include nausea, agitation, weight changes, delayed ejaculation, fatigue, impotence, and restlessness. One major concern with SSRIs is that there are reports of increased suicidal thoughts and attempts in children on SSRIs with depression.
Fluoxetine (Prozac®) is dosed at 20 mg in the morning and may increase to 80 mg daily. Each titration must occur after a few weeks on the medication. It is not indicated for those less than eight years old. Fluoxetine has a long half-life and is less likely to lead to withdrawal symptoms if abruptly discontinued. A weekly formulation is available that is dosed 90 mg once a week.
Fluoxetine can increase levels of warfarin, phenytoin, carbamazepine, TCAs, and benzodiazepines, and it may lower the therapeutic effect of codeine. It may cause serotonin syndrome when combined with other SSRIs and other antidepressants. Fluoxetine crosses the placenta, and its impact on pregnancy is not fully known. As a class, SSRIs in the third trimester can lead to multiple adverse effects, including apnea, hypoglycemia, feeding difficulty, seizures, and respiratory distress.
Sertraline (Zoloft®) is started at 25-50 mg orally daily, and the dose can be increased gradually to a maximum of 200 mg per day. It is not indicated for those less than six years old. Common side effects include dizziness, fatigue, headache, insomnia, drowsiness, nausea, tremor, and diaphoresis. It may interact with warfarin, cimetidine, digoxin, and diazepam. It is indicated for major depressive disorder, premenstrual dysphoric disorder, panic disorder, posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and social anxiety disorder.
Paroxetine (Paxil®) has a short half-life and may lead to discontinuation syndrome when the medication is stopped or missed doses. It has the strongest anticholinergic effects of any of the SSRIs. For major depression, the standard form is dosed 20 mg per day to start to a maximum of 50 mg orally per day, and the extended-release form (Paxil CR) is dosed at 25 mg once a day to a maximum of 62.5 mg orally every day. Paroxetine is indicated for major depressive disorder, panic disorder, OCD, social anxiety disorder, generalized anxiety disorder, PTSD, and premenstrual dysphoric disorder. Side effects include drowsiness, insomnia, dizziness, headache, nausea, dry mouth, constipation, diarrhea, weakness, tremor, and diaphoresis.
Fluvoxamine (Luvox®) is approved for obsessive-compulsive disorders but is used off-label to treat depression and anxiety. The starting dose for adults is usually 50 mg once a day and has multiple drug interactions, including benzodiazepines.
Citalopram (Celexa®) is indicated for depression and is dosed at 20 mg once a day, and the dose can be increased to 40 mg once a day after one week. It interacts with macrolide antibiotics, cimetidine, azole antifungals, omeprazole, and carbamazepine. Side effects include sleep disturbance, dry mouth, nausea, and diaphoresis.
Escitalopram (Lexapro®) is dosed at 10 mg once a day and increased to 20 mg after one week. It has few interactions but may interact with other SSRIs, cimetidine, and alcohol. The FDA warns that both citalopram (more than 40 mg/day) and escitalopram (more than 20 mg/day) can prolong the QT interval and may be fatal. They should be used cautiously in those with underlying heart disease and those prone to becoming hypokalemic.