ADT and the risk for depression


It will come as no great surprise to most readers of this blog that androgen deprivation therapy (ADT) used in the treatment of  men with progressive forms of prostate cancer comes with a significant risk for depression (as well as other effects on cognitive function).

However, a new article by Dinh et al., in the Journal of Clinical Oncology, has now tried to quantify this risk for depression, and commentary on the article has already appeared in the New York Times “Well” blog and on other web sites like HealthDay.

Dinh et al.  looked at data for the period 1992 to 2006 in the SEER-Medicare-linked database. They set out to identify all men in that database who were > 65 years of age, had been diagnosed with AJCC Stage I to AJCC Stage III prostate cancer, and who had not had a psychiatric diagnosis of depression within the preceding 12 months.

Here is what they found:

  • There were 78,552 men who met the eligibility criteria.
  • 33,882/78,552 men (43.1 percent) received ADT (and 44,460 or 56.9 percent did not).
  • The 3-year cumulative incidence of depression was
    • 7. 1 percent among the men receiving ADT
    • 2.8 percent among the men not receiving ADT
    • This difference was statistically significant (P < 0.001)
  • The 3-year cumulative incidence of inpatient psychiatric treatment was
    • 2.8 percent among the men receiving ADT
    • 1.9 percent among the men not receiving ADT
    • This difference was statistically significant (P < 0.001)
  • The 3-year cumulative incidence of outpatient psychiatric treatment was
    • 3.4 percent among the men receiving ADT
    • 2.5 percent among the men not receiving ADT
    • This difference was statistically significant (P < 0.001)
  • Compared to the men who were not receiving ADT, the patients receiving ADT had
    • A 23 percent increase in risk for depression (adjusted hazard ratio [aHR] = 1.23)
    • A 29 percent increase in risk for inpatient psychiatric treatment (aHR = 1.29
    • A 7 percent increase in risk for outpatient psychiatric treatment (aHR= 1.07), which was not statistically signifciant
  • The risk for depression increased with duration of ADT,
    • From 12 percent for men with ≤ 6 months of treatment to
    • 26 percent for men with 7 to 11 months of treatment to
    • 37 percent for men with ≥ 12 months of treatment
  • Similar effects associated with duration of therapy were observed for both inpatient and outpatient psychiatric treatment.

Dinh et al. conclude that the use of medical/pharmacological forms of ADT (as opposed to surgical orchiectomy)

increased the risk of depression and inpatient psychiatric treatment in this large study of elderly men with localized [prostate cancer]. This risk increased with longer duration of ADT. The possible psychiatric effects of ADT should be recognized by physicians and discussed with patients before initiating treatment.

We should point out that this type of epidemiological study can not be used to “prove” that it is the ADT that causes the depression, but there is a very clear association between treatment with ADT and depression among prostate cancer patients in this cohort of men > 65 years of age.

In the New York Times “Well” blog, Dr. Paul Nguyen, the senior author of the paper observes that we are becoming much more aware of the wide range of side effects (“almost an avalanche” to use his precise language) associated with ADT, but that

Still, for some patients, especially those with severe disease, it can be a life saver. “You have to know what the potential upside is. For some guys it will still be worth it, but for some not.”

For men with evident, metastatic prostate cancer, and for men who need some form of short-term ADT in combination with first-line or salvage radiation therapy, it is likley that the benefits will outweigh any of the risks of depression. However, for men with non-metastatic, slowly-rising PSA levels after first-line or second-line treatment for localized or locally advanced disease, treatment with long-term ADT until this really is necessary may not be the best idea in the world, and needs to be carefully discussed with one’s doctor(s).

We would note that the absolute incidence and the absolute increases in risk among men taking ADT compared to the men not taking ADT (as opposed to the relative increase in risk) were not as high as might have been expected:

    • 7.1 − 2.8 = 4.3 percent for the 3-year cumulative incidence of depression
    • 2.8 − 1.9 = 0.9 percent for the 3-year cumulative incidence of inpatient psychiatric treatment
    • 3.4 − 2.5 = 0.9 percent for the 3-year cumulative incidence of outpatient psychiatric treatment

On the other hand, we also suspect that there are an awful lot of men who have depression associated with the prostate cancer who simply “tough it out” because they are unwilling or unable to talk about what they are going through — even with their wives/partners and family members, let alone with a doctor or a psychiatrist.

One Response

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

w

Connecting to %s

%d bloggers like this: