Here’s an all too common circumstance shared with me via e-mails or by patients of mine: They’ve used three or maybe four antidepressants over the years, all produced noticeable effectiveness at least initially, but eventually effectiveness went bye-bye.
What to do? I realize that many of you aren’t prescribers, but this doesn’t preclude patients of yours from discussing this issue with you. In fact, you (and me) for that matter, are often the first point of contact, not the prescriber. And maybe you’re an antidepressant user and have experienced this yourself. So here are the 3 best-studied augmenters for treatment-resistant depression – all of which I fully endorse, results-wise – that can be shared with patients, or used to your personal benefit.
Abilify (aripiprazole)
Abilify is in the second-generation family of antipsychotics and I favor it because it has more positive trials than any other agents within this category. In addition to its antipsychotic properties, Abilify enhances the actions of the neurochemical serotonin, rendering it compatible with the traditional SSRI antidepressants. For TRD, it should be started slowly at a dosage of 1-2mg daily for a week with a target daily dose of 5mg thereafter, if tolerated. It can be taken in the morning – or if fatigue sets in, evening dosing is just fine. The most commonly occurring and reported side effect is akathisia – manifesting as motor restlessness, agitation and an inability to stay still – thus the importance of “starting low and going slow.”
Lithium
Lithium is a favorite of mine for many reasons, and after the second-generation antipsychotics, is the next best-studied option for TRD. It has excellent antidepressant properties and I would consider it the agent of choice in patients with suicidal risk factors. Multiple respected studies indicate that lithium reduced the risk of suicide as much as fivefold in recurring unipolar depression and sixfold in bipolar disorder, where suicide can be quite the problem. These are stellar results. Lithium, as you likely know, requires careful blood level monitoring particularly upon initiation. The drug’s Achilles heel is possible renal failure – which can be ameliorated by taking the entire daily dose in the evening. Also, hypothyroidism may develop in 10-20 percent of lithium users. Baseline renal and thyroid chemistries should be obtained upon initiation, with follow-up labs, including lithium levels every 6-12 months. Given these potentially threatening adverse effects, it’s again imperative to start low (150-300mg daily) with slow titration upward every 5-7 days toward 900mg daily for TRD augmentation.
Thyroid
Hypothyroidism has long been associated with depressive symptoms and it’s one of the first things I inquire about when working with a new patient with depressive symptoms. Unfortunately, thyroid augmentation is often overlooked, although well supported by data. It’s more effective in cases of clinical or subclinical hypothyroidism, but people with normal TSH (thyroid-stimulating hormone) levels are also candidates for thyroid supplementation. Thyroid T4 (Synthroid) is routinely prescribed, but T3 (Cytomel) – the most active form of thyroid hormone, is better studied and more superior to T4 in a double-blind comparison. After assessing a baseline thyroid panel, Cytomel can be started at 12.5-25mcg daily with a weekly increase toward a target dose of 50mcg daily. TSH levels should be checked about a month after reaching the target dose, and then every 6 months thereafter.
All But Worthless Augmentation Strategies
Switching antidepressants is the least effective strategy overall so I won’t recommend this strategy at all to TRD patients. The contemporary antidepressants all affect essentially the same neurotransmitter systems so there’s nothing to be gained by switching to another agent targeting the very same chemicals.
Increasing dosage levels is, of course, a viable strategy toward reaching therapeutic thresholds, but improvement beyond daily recommended maximums is rare indeed.
Treatment-resistant depression can be quite the conundrum, but the 3 drug strategies discussed above provide amply studied and well-documented possibilities for success.
Attribution Statement:
Joe Wegmann is a licensed pharmacist & clinical social worker has presented psychopharmacology seminars to over 10,000 healthcare professionals in 46 states, and maintains an active psychotherapy practice specializing in the treatment of depression and anxiety. He is the author of Psychopharmacology: Straight Talk on Mental Health Medications, published by PESI, Inc.
To learn more about Joe’s programs, visit the Programs section of this website or contribute a question for Joe to answer in a future article: joe@thepharmatherapist.com.