Study Highlights Increased Mortality Risks in Difficult-to-Treat Depression

A comprehensive new population-based cohort study has shed light on the increased mortality risks associated with treatment-resistant depression (TRD).

The study, which tracked more than 176,000 Finnish MDD patients, offers critical new intel into the cause-specific mortality risks in patients whose depression defies conventional treatment.

Overview of Difficult-to-treat Depression

While most people diagnosed with MDD respond well to first-line treatments, such as selective serotonin reuptake inhibitors (SSRIs) or psychotherapy, a persistent subset fails to find relief even after numerous treatment attempts. Clinicians often categorize these patients as having TRD.

Most typically define TRD as the failure to respond to at least two adequate treatment trials of antidepressant medications. And, based on the established research, this group faces a higher risk of mortality compared to those who respond to treatment.

But researchers have failed to trace the exact source of this increased mortality. Speculation so far has considered natural causes, such as cardiovascular issues, or external factors such as suicide.

Study Design and Findings

The study included nearly 177,000 MDD patients between the ages of 15 and 65. Among them, 11 percent – about 19,000 – met the criteria for TRD less than two years after the start of treatment. Patients in the study typically take about eight months to be diagnosed with TRD.

Throught the course of follow-up, 8,621 of the participants died – 959 of them were in the TRD group. The other 7,662 deaths were from the non-TRD group. While most deaths in both groups could be attributed to natural causes, deaths related to external causes, such as accidents and suicides, were significantly more common among the TRD patients. More precisely, external causes accounted for 41 percent of the TRD group participants, compared to 31 percent among the non-TRD group.

Significantly, the researchers found a 17 percent higher overall mortality rate among TRD patients, with external causes driving that elevated risk. Specifically:

• TRD patients committed suicide nearly twice as frequently, with a 51% increased risk.
• TRD patients were also 27 percent more likely to die accidentally.

Factors Tied to Higher Mortality

The study also uncovered multiple covariates linked to increased mortality among TRD patients. For example, the researchers pegged men, psychotic depression, and unemployment or disability status as significant factors contributing to the heightened death risk. Additionally, failing treatment quickly – and meeting the TRD criteria within eight months – linked patients to an especially high risk of suicide.

The researchers also found no significant difference in mortality between the TRD and non-TRD groups in the broader population when it came to deaths by natural causes. Cardiovascular disease, cancer, and other natural deaths from natural appeared to be comparable across both groups. Consequently, the researchers inferred that TRD’s increased mortality stems mostly from external factors rather than any intrinsic physical health conditions.

Real-World Implications

The study results underscore the importance of early identification and intervention in possible TRD patients. These individuals, especially those who meet the criteria within a short time frame, are at a significantly higher risk for fatal outcomes such as suicides and accidental drug overdoses. 

The study’s authors urged clinicians to closely monitor these patients and contemplate stronger preventive measures, including closer evaluation for suicidal ideation and substance use.

Finally, the study emphasized the growing need for better therapeutic strategies targeting TRD patients. Rapid failure in response to initial treatment options should motivate healthcare providers to consider different interventions. These could potentially include more aggressive pharmacological treatments or therapeutic modalities such as electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS).

Overall, these research results offer critical insight into the mortality risks linked to TRD, illustrating the need for accelerated care and prevention strategies for individuals who don’t benefit from standard treatments. And while this research project looked at external causes of death, the authors stress that future studies should consider investigating whether younger TRD patients have elevated risks for natural causes of death, as the study’s preliminary findings suggest.

Further Reading

New Research Uncovers Six Depression Subtypes

Esmethadone Shows Potential in Difficult-to-Treat Depression

Study Reveals Differences Between Psilocybin, Escitalopram in Depression Treatment