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), fluvoxamine (Luvox), citalopram (Celexa) and escitalopram (Lexapro). In comparison 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 different side effects and different 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 be increased up to 80 mg a day. Each titration must occur after a few weeks on the medication. It is not indicated for those less than 8 years old. Fluoxetine has a long half-life and is the 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 the levels of warfarin, phenytoin, carbamazepine, TCAs and benzodiazepines. It may lower the therapeutic effect of codeine. It may cause the serotonin syndrome when combined with other SSRIs and other antidepressants. It is pregnancy category C. Pregnancy category C means that there are no adequate animal or human studies that there are adverse fetal effects in animal studies but no human study data available.
Sertraline (Zoloft) is started at 25-50 mg orally every day, and the dose can be increased gradually to a maximum 200 mg per day. It is not indicated for those less than 6 years old. Common side effects include dizziness, fatigue, headache, insomnia, somnolence, diarrhea, 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 doses are missed. It has the strongest anticholinergic effects of any of the SSRIs. For major depression, the standard form is dosed 10 mg per day to start to a maximum of 50 mg orally per day, and the extended-release form (Paxil CR) is dosed at 12.5 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 somnolence, insomnia, dizziness, headache, nausea, xerostomia, constipation, diarrhea, weakness, tremor and diaphoresis. Sexual dysfunction is most problematic with paroxetine among the SSRIs.11
Fluvoxamine (Luvox) is approved for obsessive-compulsive disorders but is frequently used off-label in the treatment of 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 antifungal, omeprazole and carbamazepine. Side effects include: sleep disturbance, xerostomia, nausea and diaphoresis.
Escitalopram (Lexapro) is dosed at 10 mg once a day and may be increased to 20 mg after one week. It has few interactions but may interact with other SSRIs, cimetidine and alcohol. It is pregnancy category C. The FDA warns that both citalopram (more than 40 mg/day) and escitalopram (more than 20 mg/day) have the potential to prolong the QT interval, and may be fatal. They should be used cautiously in those with underlying heart disease and those who are prone to becoming hypokalemic.