*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.

Dose equivalents

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.