*Dose equivalents for antidepressants*
The term “dose equivalents” means: How many milligrams of one antidepressant are equivalent to how many milligrams of another? This information is useful to know when:
1. Switching from one antidepressant to another.
2. Reading a research article comparing two antidepressants
Before you read on, please answer this: If a patient on paroxetine 40 mg/day was to be switched to fluoxetine, bupropion, mirtazapine, or venlafaxine, how many milligrams of each of these antidepressants would you use? Write down your answers and then read on to see what the research found.
How the dose equivalents were determined
A systematic approach to defining dose equivalents was carried out as follows (Hayasaka et al., 2015):
They identified all randomized, double-blind, flexible-dose clinical trials in which either fluoxetine or paroxetine was compared to any other antidepressant for the acute treatment of unipolar depressive disorders. Fluoxetine and paroxetine were used as the standards to compare other antidepressants to.
The ratios of the mean doses of each antidepressant (adjusted for sample size) were used to define how many milligrams of each antidepressant were equivalent to fluoxetine 40 mg/day. An important limitation to keep in mind is that antidepressants probably don’t have a simple linear dose-response relationship. For example, half of a dose will not necessarily have exactly half the response. So, the dose equivalents are only a rough guide.
The reason I briefly described the methodology here is so that we can understand what dose equivalents in this study meant.
1. In a blinded, flexible-dose study, the investigator increases the medication to an optimal level without knowing what the pill contains. So, within the limits of the doses allowed, the final dose achieved reflects clinical reality.
2. Since titration of a drug in a flexible-dose study depends on both the efficacy and the side effects reported by the participants, the “equivalence” defined in this study implies a composite of efficacy and tolerability.
Based on these analyses, the following doses are clinically equivalent:
Fluoxetine 40 mg/day
Paroxetine 34 mg/day
Agomelatine 53 mg/day
Amitriptyline 122 mg/day
Bupropion 349 mg/day
Clomipramine 116 mg/day
Desipramine 196 mg/day
Dothiepin 155 mg/day
Doxepin 140 mg/day
Escitalopram 18 mg/day
Fluvoxamine 143 mg/day
Imipramine 137 mg/day
Mirtazapine 51 mg/day
Moclobemide 575 mg/day
Nefazodone 535 mg/day
Nortriptyline 101 mg/day
Reboxetine 11.5 mg/day
Sertraline 99 mg/day
Trazodone 401 mg/day
Venlafaxine 149 mg/day
These numbers can be referred to when needed. I immediately noted two things from this data:
– Mirtazapine 15 mg/day may be too low a dose for most people
– Fluvoxamine at the full FDA-approved dose of 300 mg/day may be too high for many people.