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.”