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Nasal Spray Effects on Treatment-Resistant Depression


Clinical trial finds that nasal spray is effective in treatment-resistant depression

Treatment-resistant depression (TRD) is when individuals diagnosed with depression do not experience significant improvement in their symptoms despite receiving adequate treatment with conventional antidepressant medications. Approximately one-third of people with depression may develop TRD.

This condition can be challenging to manage and significantly impacts the individual's quality of life. Treatment options for TRD often involve alternative approaches such as psychotherapy, augmentation strategies, or novel interventions like ketamine or esketamine. Close collaboration between patients and healthcare professionals is crucial to develop personalized treatment plans that address the unique needs of individuals with TRD.

Clinical Study

A clinical study investigated how baseline irritability affects the clinical outcomes of adults with treatment-resistant depression (TRD) treated with fixed or flexible doses of esketamine nasal spray combined with a newly initiated oral antidepressant (ESK+AD).

Additionally, the study aimed to explore whether the treatment with ESK had any impact on irritability symptoms over time. The research involved the analysis of data pooled from two phase 3 studies called TRANSFORM-1 and TRANSFORM-2. A total of 560 adults with TRD were included in the study and were randomly assigned to either the ESK+AD group or the placebo nasal spray plus oral antidepressant (AD+PBO) group.

The level of irritability was assessed using Item 6 of the 7-item Generalized Anxiety Disorder scale at screening and baseline. Changes in depression severity were evaluated using the Montgomery-Åsberg Depression Rating Scale (MADRS) total score, and treatment response and remission rates were examined.

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Among the participants with TRD, 52.9% had high irritability, 23.2% had low irritability, and 23.9% had varying levels of irritability. The analysis revealed that baseline irritability did not significantly influence the change in MADRS total score, treatment response, or remission at day 28. However, regardless of the baseline irritability level, the ESK+AD group showed more significant improvement in all outcomes than the AD+PBO group on day 28. The percentages of patients reporting adverse events were similar across the three baseline irritability groups.

The TRANSFORM-1 and TRANSFORM-2 studies were not initially designed to evaluate irritability outcomes.


The findings of this study indicate that ESK+AD is effective in treating patients with TRD, irrespective of their baseline level of irritability. The study highlights the positive impact of ESK+AD on depressive symptoms and supports the efficacy of this treatment approach for individuals with TRD. Further research is warranted to explore irritability outcomes and validate these findings comprehensively.

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This content is for informational and educational purposes only. It is not intended to provide medical advice or to take the place of such advice or treatment from a personal physician. All readers/viewers of this content are advised to consult their doctors or qualified health professionals regarding specific health questions. CenTrial Data Ltd. does not take responsibility for possible health consequences of any person or persons reading or following the information in this educational content. Treatments and clinical trials mentioned may not be appropriate or available for all trial participants. Outcomes from treatments and clinical trials may vary from person to person. Consult with your doctor as to whether a clinical trial is a suitable option for your condition. Assistance from generative AI tools may have been used in writing this article.