New Studies Show Ketamine’s Promise for Comorbid Anxiety and Depression

Studies suggest that around 60% of people diagnosed with depression also suffer from some form of anxiety, blurring the clinical lines and complicating treatment. Ketamine, the fast-acting anesthetic-turned-antidepressant, is beginning to challenge that. While it’s often celebrated for its rapid relief of depressive symptoms, emerging evidence suggests that ketamine may also alleviate anxiety. And perhaps most remarkably, it appears to act on both simultaneously.

Anxious depression has been studied for decades, but it still occupies a grey zone in psychiatric diagnostics. With ICD-10 acknowledging it as a distinct condition called “Mixed anxiety and depressive disorder” (MADD) and DSM-5 excluding it altogether, this lack of consensus continues to complicate timely diagnosis, access to treatment, and the development of targeted therapies — despite the disorder’s high prevalence and significant impact on quality of life.

People with anxious depression don’t just feel down or fatigued, they also experience persistent worry, inner tension, and agitation. These overlapping symptoms create a kind of emotional quicksand, pulling patients deeper into dysfunction and often leading to poorer outcomes with traditional antidepressants.

But a new wave of research is beginning to shift that narrative. Two recent studies — one conducted in China, the other in Australia — show that ketamine’s therapeutic effect is not limited to rapid and sustained antidepressant relief. It also reduces even high levels of anxiety in people with treatment-resistant depression, and appears to help maintain improved well-being for several months after infusions have stopped.

New Research, New Perspectives

The first study, published in the Journal of Affective Disorders, followed 107 patients diagnosed with depression, 67% of whom met criteria for anxious depression, over a nine-month period. All participants received six intravenous ketamine infusions over two weeks and were assessed for both symptoms and quality of life on five separate occasions, from Day 0 to Month 9. 

What the researchers found was striking: both anxious and non-anxious participants experienced significant improvements in quality of life across multiple domains, including psychological health, social functioning, and environmental satisfaction. And these gains held steady over time.

Crucially, there was no significant difference in the long-term outcomes between the anxious and non-anxious groups. In other words, the presence of anxiety didn’t appear to limit the benefits of ketamine—challenging a long-standing assumption that comorbid anxiety reduces the efficacy of treatment for depression.

At the same time, a complementary study out of Australia, the Ketamine for Adult Depression Study, looked more specifically at ketamine’s impact on anxiety itself. This randomized, double-blind trial compared subcutaneous ketamine with an active placebo (midazolam) over four weeks in 174 patients with TRD. 

Here, the results were dose-dependent. While lower, fixed doses of ketamine didn’t significantly reduce anxiety symptoms, a flexible, response-guided dosing approach (0.5–0.9 mg/kg) led to a meaningful reduction in anxiety scores, including inner tension—one of the most distressing symptoms for anxious depressives.

The anti-anxiety effect, however, wasn’t permanent. Four weeks after the final dose, anxiety levels had begun to creep back up in most participants. Still, the temporary relief was notable, and for many with chronic, treatment-resistant anxiety, even short-term reprieve can be transformative.

A More Integrated Model of Mental Health

So what’s going on here? Why is ketamine, primarily known for its impact on mood, also helping with anxiety and quality of life?

Part of the answer may lie in ketamine’s unique pharmacology. Unlike traditional antidepressants, ketamine reduces glutamate release at certain connections in the brain, and helps calm overactive brain circuits linked to depression. Some researchers believe it may specifically target regions involved in fear processing, emotional regulation, and memory, all of which are deeply implicated in anxiety disorders.

Another explanation is more psychological than pharmacological: depression and anxiety are linked and can intensify one another. Conditions like generalized anxiety, panic disorder, or separation anxiety can trigger depression, while anxiety increases the risk of developing secondary depression. Ketamine helps disrupt that cycle, restoring energy, dampening rumination, and creating emotional breathing room. It might offer patients the opportunity to engage differently with their inner experience, even after the drug leaves their system.

Equally important is what these studies chose to measure: not just symptom reduction, but quality of life. 

This is a significant departure from much of the psychiatric research of the past two decades, which has largely focused on numerical drops in standardized depression scores. The Chinese study, by using the WHO Quality of Life-BREF scale, paints a more human picture of recovery: patients sleeping better, relating more easily, returning to work or creativity, finding satisfaction in daily life. For people whose suffering has long resisted conventional care, that shift is profound.

Of course, ketamine is not a miracle cure. The studies have limitations: one was open-label, meaning participants knew they were receiving ketamine, which could have influenced their perceptions. The other didn’t follow participants long enough to assess durability. And ketamine itself, while legal in many countries for clinical use, remains unknown or inaccessible to many.

Still, these findings offer optimism. They encourage us to look beyond short-term symptom scales and ask bigger, better questions: Are patients thriving? Are they reconnecting with their lives? Are they finding relief not just from despair, but from the constant hum of fear that so often accompanies it?

As research evolves, we are witnessing both new and promising treatment options, and a potential paradigm shift in how we approach mixed anxiety and depression. While more long-term data is still needed, ketamine, which continues to prove effective across both fronts, when administered mindfully and at the right dose, may open the door to a more integrated, holistic approach to mental health care.