
First Antidepressant Not Effective? 7 Options and a Reminder
When the treatment doesn’t work, consider the options. Or, question your diagnosis.
You treated Mr. Baker’s depression with sertraline 50 mg. After 2 weeks, he showed no improvement, so you increased the dose to 100 mg. At 6 weeks from his first dose, with still no symptom improvement, you are considering the next step. Here are 7 options:
1. Watch for another 4 to 6 weeks
2. Increase the dose up to 150 mg
3. Augment with an agent that might take over treatment of depression entirely, then taper the sertraline if symptoms improve; or keep the sertraline in case improvement was due to synergy
5. Switch to a different antidepressant
6. Get genetic testing and use it to determine what to do next
7. Switch to a different antidepressant modality (eg, psychotherapy, rTMS)
Since Mr. Baker has shown no response at all to sertraline, many psychiatrists would now switch to a different antidepressant (Option 5). If he can access good psychotherapy (and will go get it), he could do that now (Option 7). Other providers would increase sertraline to 150 mg for a “full trial” (Option 2). Which is the most common strategy? At minimum we can say that switching is common, based on the sheer number of antidepressant prescriptions patients receive (a recent primary care study found a mean of
Ironically, according to a 2018 update2 of a
On the other hand, as one of our colleagues explained, “An increase in dose not only gives them more medication it gives them the most important ingredient in fighting the depression battle-
Though many users of genetic testing (Option 6) might have done so before Mr. Baker’s first antidepressant, is there any point in doing it now? Not with sertraline, it appears. The Clinical Pharmacogenetics Implementation Consortium (CPIC)
Option 4: augment – usually we reserve this for patients who’ve had at least a partial response to their antidepressant, and are tolerating it well. Mr. Baker has had no response at all. The only reason for further consideration of augmentation would be suicidal ideation that preceded sertraline but did not improve on it. (If SI followed sertraline, consider induction of a mixed state and rapid tapering). SI should bring to mind augmentation with low-dose lithium. It may only
All this leads back to a reminder about a step that precedes 1 through 6 above. It’s the old maxim: “When your treatment doesn’t work, question your diagnosis.” Be sure, before going on, that Mr. Baker has a purely unipolar depression. Rule out bipolarity again, perhaps this time delving more deeply into the non-manic markers: family history, age of onset, course of illness (how episodic are these depressions?), and response to treatment (was there an obvious positive response that rapidly faded, when sertraline was begun?). Then consider giving Option 1 greater consideration, based on the meta-analyses by Bschor and colleagues2-if you and Mr. Baker can find sufficient hope in that approach.
Disclosures:
Dr. Phelps is Director of the Mood Disorders Program at Samaritan Mental Health in Corvallis, Ore. He is the Bipolar Disorder Section Editor for Psychiatric Times. Dr. Phelps stopped accepting honoraria from pharmaceutical companies in 2008 but receives honoraria from McGraw-Hill and W.W. Norton & Co. for his books on bipolar disorders, including
References:
1. Phelps JR, James J 3rd. Psychiatric consultation in the collaborative care model: The "bipolar sieve" effect. Med Hypotheses. 2017;105:10-16.
2. Bschor T, Kern H, Henssler J, Baethge C.
3. Bschor T, Baethge C.
4. Solvason HB, DeBattista C. Antidepressant Dosing for the Acute Treatment of Unipolar Depression. Prim Psychiatry. October 1, 2009.
5. Blanchfield CA. Increase the Dose or Give it a Few More Weeks. Psychiatry (Edgmont). 2007; 4: 15.
6. Hicks JK, Bishop JR, Sangkuhl K, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors (see Table 3b, page 132).
7. Abou-Saleh MT, Müller-Oerlinghausen B, Coppen AJ. Lithium in the episode and suicide prophylaxis and in augmenting strategies in patients with unipolar depression. Int J Bipolar Disord. 2017;5:11.
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