Major depression with mixed features is complex and challenging to diagnose and treat. Many individuals with treatment-resistant depression and anxiety may actually have significant depression with mixed features but are being treated with the wrong kind of medicines. Have you tried several antidepressants and not seen improvement or even gotten worse? Are you tired of trying medicine after medicine but not getting any better? Have you ever wondered why antidepressants work so well for others but for you, they seem doomed to fail? If so, it may be time to explore other options.
Major depression with mixed features is a type of depression that is characterised by the presence of both depressive symptoms and manic or hypomanic symptoms. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), major depression with mixed features is diagnosed when an individual experiences at least three manic or hypomanic symptoms during a major depressive episode. These symptoms can include feelings of agitation, restlessness, impulsivity, irritability, racing thoughts, decreased need for sleep, and an inflated sense of self-esteem or grandiosity.
Research has shown that major depression with mixed features is a common condition, with up to 20% of individuals with major depression experiencing mixed features. Unfortunately, many individuals with major depression with mixed features are misdiagnosed as having other types of depression or anxiety disorders, and may not receive the appropriate treatment. This can result in treatment-resistant depression and anxiety, as traditional SSRI medications may not be effective in managing the symptoms of major depression with mixed features.
Many individuals with significant depression with mixed features may need to be treated with non-SSRI medications, even if they don’t display many mixed features. Oftentimes, the best predictor of whether they need those medications is how they responded (or didn’t respond) to previous antidepressants. These non-SSRI medications may include atypical antipsychotics, mood stabilisers, and other antidepressants, such as tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). These medications work by targeting neurotransmitters in the brain, such as dopamine and norepinephrine, which can help manage the symptoms of major depression with mixed features.
Additionally, newer treatments such as ketamine and Spravato (esketamine) have shown promise in treating major depression with mixed features. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been found to rapidly reduce depressive symptoms in some individuals with treatment-resistant depression, including those with significant depression with mixed features. Spravato is a nasal spray form of ketamine approved by the FDA to treat treatment-resistant depression. These treatments can rapidly relieve symptoms, but their long-term effectiveness is still being studied.
The mechanism in the brain that causes major depression with mixed features is not fully understood, but research suggests that it may involve the dysregulation of various neurotransmitters, including serotonin, norepinephrine, and dopamine. This dysregulation may lead to both depressive symptoms and manic or hypomanic symptoms, creating a complex and challenging condition to manage.
It’s important to work with a mental health professional who is experienced in treating major depression with mixed features to determine the best treatment for your individual needs. Psychotherapy, including cognitive-behavioural therapy (CBT) and interpersonal therapy (IPT), can also help manage symptoms and improve quality of life.
In conclusion, it is essential to recognise the possibility of major depression with mixed features in individuals with treatment-resistant depression and anxiety. Misdiagnosis can lead to ineffective treatments and prolonged suffering for the individual. It is crucial to have a thorough evaluation by a mental health professional and to consider alternative treatments, such as non-SSRI medications and therapies, as well as newer options like ketamine and Spravato.
Research has shown that individuals with significant depression with mixed features may have a dysregulation of several neurotransmitters, including serotonin, dopamine, and norepinephrine. This dysregulation may be why traditional SSRI medications may not work as effectively for this population.
Therefore, it is essential to consider alternative medications such as bupropion, venlafaxine, and duloxetine, which target multiple neurotransmitters, in addition to traditional SSRI medications. A personalised treatment plan, based on the individual’s specific symptoms and response to previous treatments, can lead to better outcomes.
Ketamine and Spravato, while still relatively new treatments, have shown promising results in treating major depression with mixed features. Ketamine targets glutamate receptors in the brain, leading to a rapid antidepressant effect. Spravato, a nasal spray form of ketamine, has been approved by the FDA for treatment-resistant depression, including major depression with mixed features.
It is important to note that while these treatments may be effective, they should only be administered by trained medical professionals in a controlled environment.
Overall, major depression with mixed features is a complex condition that requires a personalised and comprehensive treatment plan. By recognising the potential for misdiagnosis and considering alternative treatments, individuals can find relief from their symptoms and improve their quality of life.
Author: Dr. Joshua Bentley, DNP, APRN, PMHNP-BC
- American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.).
This is the manual used by mental health professionals to diagnose mental disorders, including major depression with mixed features.
- Nemeroff, C. B., et al. (2016). Ketamine for treatment-resistant unipolar depression: current evidence. CNS Drugs, 30(5), 419-427.
This article reviews the current evidence for the use of ketamine in treating treatment-resistant unipolar depression, which may include major depression with mixed features.
- Daly, E. J., et al. (2019). Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: A randomized clinical trial. JAMA Psychiatry, 76(9), 893-903.
This is a clinical trial that tested the efficacy and safety of Spravato, an intranasal form of ketamine, in treating treatment-resistant depression.
- Fornaro, M., et al. (2016). Mixed features specifier in bipolar disorder: A systematic review, meta-analysis, and meta-regression of prevalence, diagnostic validity, and clinical correlates. Frontiers in Psychiatry, 7, 147.
This article reviews the prevalence, diagnostic validity, and clinical correlates of the mixed features specifier in bipolar disorder, which shares some characteristics with major depression with mixed features.
- Bauer, M., et al. (2015). World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders. The World Journal of Biological Psychiatry, 16(2), 76-95.
These are guidelines from the World Federation of Societies of Biological Psychiatry for the biological treatment of unipolar depressive disorders, which may include major depression with mixed features. The guidelines cover traditional SSRI medications as well as alternative medications.
