- Approximately 30% of people with major depression, have treatment-resistant depression, meaning it doesn’t respond to first and second-line antidepressants prescribed.
- While older people aren’t more likely to have treatment-resistant depression, clinical depression is linked to cognitive decline in this group.
- It is unclear what the reasons for this are, but it poses a further threat to health and quality of life.
- A recent study has looked at the possibility that using antipsychotics alongside antidepressants in people with major depression over the age of 60 could improve outcomes in this group.
While many people who experience depression can be treated with antidepressants and talking therapies, a minority of patients don’t respond to first or second-line antidepressants.
These patients are deemed to have treatment-resistant depression. While not more prevalent in older people, depression is linked to cognitive decline, though reasons for the link are unclear.
One avenue for treatment researchers have recently been interested in is to see if combining existing antidepressants with other drugs, including other antidepressants, antipsychotics, and thyroid hormone medication could help hard-to-treat forms of depression, especially in older adults.
A recent study published in the New England Journal of Medicine looked at the effect of combining existing antidepressants with an antipsychotic or the mood-stabilizing drug lithium, compared to antidepressants often used to treat severe and intractable depression.
Prof. David Feifel, Emeritus professor of psychiatry at UC San Diego and founder of Kadima Neuropsychiatry Institute which specializes in treating patients with treatment-resistant depression, told Medical News Today that depression could be a symptom of cognitive decline in older adults, “but it is more likely that that the cognitive decline is a symptom of the depression.”
“Clinical depression is associated with something called ‘pseudo-dementia,’ a decline in cognition that is similar to the cognitive decline seen in dementia but it is not due to the progressive brain degeneration that is responsible for dementia and is reversible if the depression is effectively treated,” he explained.
This means that it is particularly important to tackle treatment-resistant depression in older people. There are currently a number of lines of research into what could help.
For example, researchers have investigated the effect of deep brain stimulation, as well as other forms of
The current study, instead, looks into augmenting the effects of existing medication.
As part of this study, 619 participants over the age of 60 with treatment-resistant depression were divided into three different groups in the OPTIMUM trial.
One group of 211 participants received their normal antidepressants alongside the antipsychotic drug aripiprazole, one group of 206 participants received their normal antidepressant medication alongside the antidepressant
Participants took the drugs for 10 weeks and had biweekly phone calls or in-person visits with clinicians, who adjusted the levels of medications as necessary. Researchers then measured the change in psychological well-being that occurred over the period of treatment.
Results show that while participants who received just bupropion had an overall improvement in their well-being of 2.04 points, indicating some improvement, participants on the other arms of the study saw more benefit.
Participants who remained on their normal antidepressant medication alongside the antidepressant bupropion saw an improvement of 4.33 points, and those on their usual antidepressant medication alongside the antipsychotic medication aripiprazole saw an improvement of 4.83 points.
About 28.9% of participants who took aripiprazole alongside their usual antidepressants, and 28.2% of participants who took bupropion alongside their usual antidepressants saw a remission in their depression. This was only 19.3% in the bupropion-only group.
The authors also looked at the effects of lithium, a mood-stabilizing drug when given alongside a participant’s usual antidepressants, compared to swapping usual antidepressants for nortriptyline, an antidepressant drug.
In a separate study, 127 participants who took lithium in addition to their existing medication saw their well-being scores improve by 3.17 points, and participants who had their antidepressant drug swapped to nortriptyline saw an improvement of 2.18 points.
About 18.9% of participants who took lithium and 21.5% of those who took nortriptyline entered into remission with their depression.
Drugs and fall risk
The study also collected data on the safety of the different drug regimes.
“Surprisingly [rate of falls was] not worse [with augmentation]. However, there is a higher rate of falls when the second, or augmentation, medication is bupropion vs. [when] it is aripiprazole. Thus, aripiprazole is safer as augmentation with respect to fall risk,” lead author Prof. Eric Lenze told MNT.
Prof. Feifel, who was not involved in the research, said antipsychotics have been tested for their effectiveness in people with treatment-resistant depression before.
“Yes, several newer or ‘second generation’ antipsychotics have been shown to be helpful in augmenting or ‘boosting’ the effectiveness of antidepressants, although they generally do not have potent antidepressant effects by themselves,” he said.
Apart from oral medication, there are many other potential treatments for treatment-resistant depression. Prof. Lenze listed a few:
“In short, there are many options, and nearly all people with depression will eventually benefit if they can persist in treatment. These include many medications, psychotherapies (there are many types of that as well), and neuromodulation which includes TMS and ECT.”
Prof. Jordan Karp, professor and chair at the Department of Psychiatry at the University of Arizona College of Medicine, and one of the authors of the paper, told MNT that the study results are encouraging yet more work needs to be done for more effective treatment.
“These results should make prescribers feel more confident when selecting an antidepressant for their older adults with difficult-to-treat depression. However, the fact that the best treatment only led to a 29% rate of remission means there is still a lot of work to be done to improve depression care in late life,” he said.