Knowing When to Switch or Augment Treatment in Patients With Major Depressive Disorder

Only 1 in 3 patients will achieve remission on their first antidepressant, and 67% of patients require 4 antidepressant trials before symptoms remit, said Thomas L. Schwartz, MD, professor and vice chair, Department of Psychiatry, SUNY Upstate Medical University.

In a session at the 2017 Neuroscience Education Institute Congress in Colorado Springs, Colorado, Schwartz gave an informational session on strategies for switching, combining, or augmenting treatments for patients with major depressive disorder (MDD).

First, Schwartz explained what to look for when choosing the initial antidepressant. It is important to look at the comparable efficiency between and within classes of medications, and the initial selection of antidepressant is largely based on: anticipated side effects, safety/tolerability for individual patients, patient preference, medication response in prior episodes, and cost.

Then, Schwartz outlined factors to consider when choosing between switching or augmenting treatment. A physician should consider switching to a different antidepressant when:

• It’s the first antidepressant trial.
• There are poorly tolerated side effects to the initial antidepressant.
• There is no response (<35% improvement) to the initial antidepressant.
• There is more time to wait for a response (less severe, less functional impairment).
• The patient prefers to switch to another antidepressant.

There are several techniques for switching treatments, Schwartz said:

• Direct switch: Stop the first antidepressant abruptly, and start the new antidepressant the next day.
• Taper and switch immediately: Gradually taper the first antidepressant, then start the new antidepressant immediately after discontinuation.
• Taper and switch after a washout: Gradually withdraw the first antidepressant, then start with the new antidepressant after a washout period.
• Cross-tapering: Taper with the first anti-depressant (usually after 1-2 weeks or longer), and build up the dose of the new antidepressant simultaneously.

There is no evidence to support preference for one agent or class over another, and switching within the same class or to another class are both options, said Schwartz. The most commonly used treatments when switching are other selective serotonin reuptake inhibitors (SSRIs)/serotonin and norepinephrine reuptake inhibitors (SNRIs), bupropion, and mirtazapine. Underused treatments include tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs).

“Withdrawal symptoms can generally begin within hours to days of dose reduction,” said Schwartz.

Withdrawing SSRIs and SNRIs typically cause flu-like symptoms such as nausea, lethargy, and irritability, said Schwartz. Venlafaxine is associated with the most severe withdrawal effects, meanwhile fluoxetine rarely causes withdrawal symptoms due to the long half-life of the parent drug and its active metabolite. Paroxetine withdrawal effects can be more common or more severe with paroxetine than with some other SSRIs.

Closing the session, Schwartz explained that a physician should consider an adjunctive medication when:

• There have been 2 or more antidepressant trials.
• The initial antidepressant is well tolerated.
• There is partial response (>25% improvement) to the initial antidepressant.
• There are specific residual symptoms or side effects to the initial antidepressant that can be targeted.
• There is less time to wait for a response.
• The patient prefers to add on another medication.