Poor response to treatment is an unfortunate reality for many people with major depression (MDD). By some estimates, as few as 30% of people with MDD achieve complete and lasting remission of symptoms. Primary care physicians deal with this lack of treatment response in one of three ways: They may increase the dosage of an antidepressant medication, add a secondary medication, or switch to an alternative medication.
Dosage increases are often the first choice, assuming higher doses remain within reasonable safety parameters. Because of its unique chemistry, the selective serotonin reuptake inhibitor Lexapro (escitalopram) is an ideal candidate for dose escalation. Whereas other antidepressants reach a sort of effectiveness plateau, Lexapro’s mechanism of action becomes stronger in proportion to dose.
Lexapro is approved for daily doses of not more than 20 mg. In practice, however, doctors have prescribed up to 50 mg for patients showing no response to lower dosages. That said, little evidence exists on whether successively higher doses represent a good balance between efficacy and safety.
A recent investigation in Scotland sought to answer this question. A starting group of 60 people diagnosed with MDD was switched from Celexa (citalopram) to Lexapro for a 32-week period. At regular intervals, Lexapro dosage was increased up to a maximum of 50 mg or until remission of symptoms. Researchers employed standard psychological measures to quantify severity of depression and occurrence of side effects.
Results from the study revealed few problems with safety or tolerability of high-dose Lexapro. However, overall effectiveness was somewhat less than desirable. Of the 60 participants, 18 dropped out because of adverse effects or lack of efficacy. Most of these withdrawals happened earlier in the study, before reaching the higher dose levels.
Half of study participants experienced remission of symptoms. Thirty-eight percent of those required a dosage of 50 mg. At doses higher than 40 mg, side effects became more pronounced although not necessarily more severe. Diarrhea was the most frequent complaint for those at doses of 40-50 mg. Other common side effects included headache, nausea, fatigue, and dizziness.
Larger, more controlled studies will be useful in ascertaining whether the benefits of high-dose Lexapro outweigh the risks. The Scotland study indicated only marginal effectiveness, although participants generally tolerated the high doses of medication. It should be noted, of course, that the population in question has a history of poor response to treatment. It’s unlikely that any one avenue will prove beneficial to all.
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