Database Studies of Treatment-Resistant Depression Should Take Account of Adequate Dosing

The objective of this study was to estimate how commonly patients with pharmacologically treated depression (PTD) do not receive adequate doses of antidepressant (AD) medications. Such prescribing would have epidemiologic and clinical implications. Patients with PTD have treatment-resistant depression (TRD) if they do not benefit from ≥ 2 AD medications taken with reasonable compliance for adequate durations at adequate doses. Some database studies of TRD do not assess AD medication dose and would, therefore, overestimate TRD incidence unless physicians treating PTD patients routinely prescribe AD medications at adequate doses before changing medications.

Using data from 3 US health services databases from September 1, 2010, through December 31, 2014, we created PTD cohorts and defined an AD medication era as a sequence of dispensings with ≤ 30 days between the end of the days' supply of each dispensing and the start of the next. We classified AD medication eras according to whether they had ≥ 1 dispensing at or above the minimum therapeutic dose.

The proportion of AD medication eras with ≥ 1 dose at or above the minimum therapeutic dose varied from 59.6% in the Medicaid database to 66.0% in a database of privately insured patients.

In the population at risk for TRD, a substantial proportion of AD medication dispensing eras do not reach the minimum therapeutic dose. TRD incidence is likely to be overestimated in database studies that do not take account of dose. Clinicians should be aware that AD medication regimens are often stopped without reaching the minimum therapeutic dose, which may cause unnecessary switching.