A distinction with a difference

Apathy and depression are among the most disabling non-motor features of PSP, and they’re not the same thing.  To quote the opening lines of an excellent 1998 paper from Morgan L. Levy and colleagues from UCLA, University of Iowa and the NIH,

“Apathy is defined as diminished motivation not attributable to decreased level of consciousness, cognitive impairment, or emotional distress.  Depression involves considerable emotional distress, evidenced by tearfulness, sadness, anxiety, agitation, insomnia, anorexia, feelings of worthlessness and hopelessness, and recurrent thoughts of death.”

That article, entitled, “Apathy Is Not Depression,” focused on Alzheimer’s, frontotemporal dementia, Parkinson’s, Huntington’s and PSP. It pointed out that while apathy is traditionally considered to be one of the many possible features of depression, it can also be analyzed separately.  So that’s what they did.  

They found that among their 22 patients with PSP, 77% had apathy without depression, 5% had depression without apathy, 14% had both and 5% had neither.  In the 154 patients overall, there was no correlation between apathy and depression. (Among the 22 with PSP, there were too few with depression to calculate the correlation specifically for that disease.)  Apathy was more common and severe in AD, FTD and PSP, while depression was more common and severe in PD and HD.  In the overall group, apathy was associated with disinhibition, but depression was associated with anxiety, agitation, irritability and hallucinations.

The prevalence of depression and apathy in PSP vary wildly across studies, depending on definitions and sources of patients.  For example, fast-forward to a December 2021 study from Sarah M. Bower and colleagues at Mayo Clinic Rochester.  In their 97 patients with PSP, depression was present in 55% and apathy in only 12%.  This proportion was roughly the same for each of the nine PSP subtypes evaluated except for PSP-speech/language, where depression was much less frequent.

Why should we care about the distinction between apathy and depression?  Because they’re both treatable and the treatments differ. Here’s a compilation of recommendations from experts at UCSF and from the CurePSP Centers of Care.  Keep in mind that these recommendations are generally based on experience and record reviews rather than on randomized trials.

  • Depression in PSP is typically treated with selective serotonin reuptake inhibitors (SSRIs) (except for paroxetine because of its anticholinergic side effects), serotonin-norepinephrine reuptake inhibitors (SNRIs) or bupropion.  Non-drug treatments include cognitive-behavior therapy, mindfulness yoga, professionally guided meditation, and in very severe cases, electroconvulsive therapy.

  • Apathy in PSP, on the other hand, is treated with one of the amphetamine-like drugs methylphenidate or modafinil, or sometimes an SNRI.  Apathy can be worsened by SSRIs.  Regular conditioning exercise is also useful.

So, add this to the long list of reasons why it’s so wrong for a doctor to tell someone with PSP, “Sorry, but there’s nothing I can do for you.”

5 thoughts on “A distinction with a difference

  1. Thank you for this post, Dr. Golbe. This blog is very informative for those of us who have had PSP
    Impact our lives and want to stay up to date on the latest news and treatments. I have had two generations of PSP in my family (grand parent and parent) and am
    Looking forward to the post (fingers crossed) when a major break through treatment has been discovered.

    I have a question about this post. Out of curiosity, why is paroxetine not one of the SSRIs used for treatment for depression in PSP patients.

    • Thanks for the kind feedback, Joey.
      Paroxetine should be avoided in those with PSP because of its potential for anticholinergic side effects. The most important of these are confusion, hallucinations, dry mucous membranes, thickening of secretions, urinary retention and constipation. I’ll update the post to include this — thanks for raising the issue.

  2. Why is it that doctors do not regularly suggest medication for apathy? Especially if it is so prevalent in PSP? As a caregiver that is one of the most frustrating things to deal with as it affects my husbands willingness to do anything to maintain physical independence or share in our life together.

  3. Dr. Golbe: Given your comment about medication for apathy, is there a reason that movement neurologists don’t regularly suggest this? As a caregiver, apathy is one of the most frustrating things to deal with. I spend so much time trying to find ways to support and keep my husband physically strong and with us. I know his apathy is part of the illness but it feels like whatever I do he remains uninterested in keeping up with exercises for balance or strength or in being an active participant in our life together. He was always active in the past but now he spends hours bingeing TV programs. Is there a viable hope that medication could assist with this aspect? And how do we get his doctors to consider prescribing? Thank you for this ever-helpful blog.

    • I’m as guilty as any other neurologists in not having paid adequate attention to the treatment of apathy (as distinguished from depression) in my own patients until relatively recently. This is not generally taught to medical students or even to neurology residents, but psychiatrists understand it. The problem is that psychiatrists aren’t usually the ones managing patients with PSP. The other problem is that drug treatment for apathy (or depression) in PSP has not been examined in formal trials, but only as anecdotal experience or retrospective record reviews, and those things, deservedly, don’t receive as much attention. So don’t assume that these drugs for apathy in PSP have a high likelihood of working – we don’t have enough good evidence to support such an expectation. But they may be worth a try if the patient and doctor are willing to deal with potential side effects as well as the cost and inconvenience of adding another medication.

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