What is the role of doxepin in intravenous-to-oral switch therapy?

Updated: Jul 30, 2018
  • Author: Shirin A Mazumder, MD, FIDSA; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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In 1997, Adler et al conducted a randomized, double-blinded, placebo-controlled study on doxepin to evaluate the effect of a switch from parenteral to oral administration upon symptoms of endogenous depression. They tested the hypothesis that the treatment response significantly worsens during the switch and concluded that this hypothesis must be rejected based on objective and subjective psychometric test findings. In fact, they noted continuous improvement. Preconditions included selection of patients with typical endogenous depression and maintenance of at least constant plasma levels of the active antidepressants. [48]

In patients younger than 65 years, doxepin plasma levels can be kept constant by switching in a ratio of 125 mg intravenous to 250 mg oral. Individual case studies indicated that declining progress after switching was correlated with a decreasing plasma level of the active drug. An already-low plasma level during the infusion period, insufficient response, and questionable compliance with the oral medication were associated factors. Owing to large (by a factor of 10) interindividual differences of plasma levels, measurements before and after switching were required.

Doxepin (Adapin, Sinequan) increases the concentration of serotonin and norepinephrine in the CNS by inhibiting their reuptake by presynaptic neuronal membrane. Effects are associated with a decrease in symptoms of depression. Adult dosing is 30-150 mg/d PO hs or 2-3 divided doses, gradually increased to 300 mg/d prn. In children < 12 years, doxepin is not recommended. In those >12 years, dosing is 25-50 mg/d PO hs or bid/tid, gradually increased to 100 mg/d. Doxepin is a pregnancy category C drug.

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