How Does Age Affect Response to Ketamine Treatment for Depression?

What you need to know

• Older patients may respond more slowly to ketamine treatment for depression, but ultimately achieve similar benefits as younger patients.
• Age does not appear to affect how long ketamine’s antidepressant effects last after treatment ends.
• Different mechanisms may be responsible for ketamine’s initial effects versus its longer-term benefits.

Background on ketamine for depression

Depression that does not improve after trying multiple antidepressant medications is called treatment-resistant depression. This affects up to one-third of people with major depressive disorder and can significantly impact quality of life. In recent years, the anesthetic drug ketamine has shown promise as a rapid-acting treatment for severe, treatment-resistant depression.

Unlike traditional antidepressants that can take weeks to start working, ketamine can lift depression symptoms within hours in many patients. However, the effects of a single ketamine dose typically wear off within a week. To extend the benefits, doctors sometimes give a series of ketamine infusions over several weeks.

While ketamine can be very effective, not all patients respond equally well to the treatment. Researchers are working to understand what factors influence how people respond, in order to optimize and personalize ketamine therapy. One factor that may play a role is the age of the patient.

How age affects brain plasticity

As people get older, the brain becomes less flexible and adaptable - a property known as neuroplasticity. The mechanisms involved in neuroplasticity, such as the formation of new connections between neurons, are thought to be important for ketamine’s antidepressant effects.

Some studies have found that older adults may not respond as well to ketamine for depression. However, the research has been limited and results have been mixed. To explore this issue further, researchers at the University of California, San Francisco and the San Francisco VA Health Care System examined how age impacted response to ketamine in a group of veterans with treatment-resistant depression.

The ketamine treatment study

The study included 49 veterans with an average age of 52 (ranging from 22 to 77 years old) who received a series of six ketamine infusions over three weeks. The patients had severe depression that had not improved with multiple previous treatments. Many also had post-traumatic stress disorder (PTSD).

Before each ketamine infusion, the patients completed a questionnaire called the Beck Depression Inventory (BDI-II) to measure their depression symptoms. They also completed the questionnaire 3 weeks after the final infusion to assess how long the effects lasted.

The researchers analyzed how the BDI-II scores changed over the course of treatment and whether age was related to the pattern of improvement.

Key findings on age and ketamine response

The study found several important results:

1. Overall, depression symptoms improved significantly over the course of the six ketamine infusions. The biggest drop in symptoms occurred after the first infusion.

2. Older age was associated with a slower response to ketamine in the middle of the treatment course. Specifically, after the 4th infusion, each decade increase in age corresponded to about 9% less improvement in depression symptoms.

3. However, by the end of the six infusions, patients of all ages had similar total improvement in their depression.

4. Age did not affect how long the antidepressant effects lasted in the 3 weeks after treatment ended.

What this means for ketamine treatment

These findings suggest that while older patients may respond more slowly to ketamine initially, they can still achieve the same benefits as younger patients by the end of a multi-infusion treatment course. The researchers propose this could mean different mechanisms are responsible for ketamine’s effects at different stages of treatment.

The rapid initial improvement seen in patients of all ages may involve ketamine’s effects on opioid receptors in the brain. The slower improvement in older patients during mid-treatment could reflect age-related declines in neuroplasticity mechanisms.

Interestingly, age did not impact how long ketamine’s effects lasted after treatment ended. This implies the mechanisms involved in maintaining the antidepressant effects may be less affected by age-related brain changes.

Implications for personalizing treatment

Understanding how age impacts ketamine response could help doctors optimize treatment for individual patients. For example:

• Older patients may need to be prepared for a potentially slower initial response to ketamine.
• Treatment courses may need to be longer for older adults to achieve maximal benefit.
• Age likely does not need to be factored in when planning the frequency of maintenance treatments to sustain ketamine’s effects.

Limitations and future research

This study had some important limitations to keep in mind. As a retrospective analysis of clinical data, it lacked the rigorous controls of a prospective, randomized trial. The sample size was relatively small, and most patients were male veterans, which may limit how well the results apply to other populations.

Additionally, other factors that change with age, like overall health status or medication use, could have contributed to the age-related differences observed. Larger, more controlled studies are needed to confirm and expand on these findings.

Future research should also explore the biological mechanisms underlying ketamine’s antidepressant effects at different stages of treatment. This could potentially lead to ways to enhance ketamine’s benefits, particularly in older patients who may have a slower initial response.

Conclusions

• Older patients with depression may respond more slowly to ketamine treatment initially, but can ultimately achieve similar benefits as younger patients.
• Age does not appear to affect how long ketamine’s antidepressant effects last after a treatment course.
• These findings can help guide treatment expectations and plans for patients of different ages receiving ketamine for depression.
• More research is needed to understand the mechanisms behind ketamine’s effects and how to optimize treatment for patients of all ages.