Treatment-Resistant Depression: Let Psychiatric Nurses Manage Complex Cases

What’s happening – Managing treatment-resistant depression (TRD) can be challenging but a new review published in Perspectives in Psychiatry Care explores recent advances in the understanding of TRD and looks at the role Advanced Practice Nurses (APN) can play in bringing promising interventions to patients who are struggling.

Specifically, the authors reviewed the effectiveness of less traditional pharmacological treatments for TRD, including neuromodulation techniques and esketamine, for those refractory to common depression treatments, such as antidepressants which are often prescribed by primary care providers. They concluded that recent neurobiological findings show that these alternative approaches may be helpful in achieving remission. The researchers also called attention to the importance of training psychiatric APNs on these second- and third-line treatment options as psychiatric nurses typically work closely with patients and are capable of managing more complex cases. (More conclusions from the lead author Brayden N. Kameg in our Psy-Q Challenge below.)

Why it’s complicated – As many as 20% of people with major depressive disorder (MDD) are resistant to treatment. These individuals are more likely to require hospitalization, including frequent readmissions, which leads to higher healthcare costs and reduced quality of life.

Reports & Perspectives

  • A study in Dove Press looks investigates deep brain stimulation to treat TRD and provides suggestions to improve recruitment and participation for further research.
  • Mount Sinai researchers found that the epilepsy treatment ezogabine (also known as retigabine), a drug targeting KCNQ2/3 channels in the brain, may be effective in relieving a range of hard-to-treat depression symptoms.
  • Research published in the Journal of Affective Disorders shows that people with TRD responded well to transcranial magnetic stimulation (TMS).
  • Last year, Stanford’s Brain Stimulation Lab shared data and protocols on intermittent theta-burst stimulation (iTBS) for TRD as part of the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) program.
  • @jessgilbert (a neuroscientist) tweets: “Can non-invasive measures of excitation/inhibition coupling be used to quantify ketamine effectiveness in treatment-resistant depression? Our new paper in Translational Psychiatry suggests yes….”
  • @JClinPsychiatry shares: “How prevalent is treatment resident #depression (TRD), and what proportion of the burden of medication-treated #MDD is accounted for by #TRD? This study explores those questions using the most commonly accepted definition of TRD.”
  • @ChampalimaudF (research foundation) says: “According to Dr. Albnio Oliveira-Maia, head of the Neuropsychiatry Unit @ChampalimaudF and @Neuro CF, Treatment Resistant Depression is ‘a much more common and pressing concern than many realise,’ as can be seen in recently published multi-centre studies.”
  • @CHWF (Center for Workforce Studies) tweets: “New #researchalert@ Coming from @BHWRC, this study focuses on the Distribution of Advanced Practice Nurses Within the Psychiatric Workforce…”

In Practice

Psy-Q Challenge

Why are Advance Practice Nurses (APNs) particularly well-positioned to address treatment-resistant depression? Brayden N. Kameg DNP, PMHNP‐BC, CARN, CNE, answers.

Get the Answer


Differentiating Schizophrenia and Bipolar Disorder: Opposite Brain Patterns May Aid Diagnosis

What’s happening – It has long been believed that people with schizophrenia spectrum disorders, as well as those with bipolar disorder, share some common traits, including how both conditions trigger extreme neuronal responses to rewards. These responses can occur at either extreme of the spectrum, from blunt to exaggerated. Yet until now, no research has confirmed the full extent of the relationship. A new study published in Neuropsychopharmacology by Smucny et al suggests that the patterns of brain activation triggered by reward anticipation are opposite in people with bipolar disorder (who had a heightened response) and those with schizophrenia (who had a blunted response).

Smucny’s team predicts that these differences, identified via brain patterns during reward anticipation, may be helpful in diagnosing bipolar disorder and schizophrenia in the future.

Why it’s complicated – The team found that brain response did not differ between people with bipolar disorder and those with schizophrenia when actually receiving the reward. The changes were only seen in the reward-anticipation state.

Reports & Perspectives

  • A related study in the American Journal of Psychiatry which looked at neural correlates in youth determined that those with anxiety experience a stronger striatal response to rewards that may lead to better responses during therapy. This finding could guide more effective treatment approaches.
  • To better understand the relationship between common antipsychotic drugs, weight gain, and increased risk of type 2 diabetes, an article in Translational Psychiatry finds that antipsychotics not only work on the CNS but also seem to affect the pancreas, providing new insights that could drive better treatment options.
  • Psychiatric illnesses such as schizophrenia and bipolar disorder have common genetic roots, yet the way they present in different people can vary a great deal. A paper in Neuropsychopharmacology reveals that differences in gene transcript may determine how the ailment ultimately impacts each individual.
  • @bengoldstein73 (researcher) shares: “PhD student @MikaelaDimick uses neuroimaging to understand self-harm and the reward circuitry regions of the brain among youth with bipolar disorder….”
  • @IntlBipolar (International Bipolar Foundation) tweets: “Blunted and exaggerated neuronal response to rewards are hypothesized to be core features of schizophrenia spectrum disorders (SZ) and bipolar disorder (BD), respectively.”
  • @GENbio (Genetic Engineering and Biotechnology News) says: “New Genetic Mutation Discovered in People with Schizophrenia findings will allow researchers to zero in on a novel aspect of brain development and function in the quest to develop new treatments…”

In Practice 

Psychedelics and MDD: Sensor Predicts Hallucinogenic Response

What’s happening – Interest in psychedelic drugs to treat a host of conditions, including major depressive disorder (MDD), continues to grow and, while some psychedelics promise clinical benefits, their hallucinogenic effects can be worrisome. Researchers have developed a fluorescent sensor called psychLight that they embedded in the brains of mice to accurately predict whether a drug will cause a hallucinogenic response. Researchers also used the sensor to identify a highly promising non-hallucinogenic psychedelic analog that appears to reduce depression symptoms without triggering a hallucinogenic response. The findings may change drug development for depression and other mental health conditions.

Why it’s Complicated – The psychLight sensor replicates how the brain responds to serotonin as this is the process targeted by psychedelic drugs. When the drug compound binds to the sensor, the sensor changes shape, resulting in changes to its light displays. The researchers believe this change corresponds to the effect that a hallucogenic compound would have on the serotonin receptor in the brain, thus making it possible to predict the reaction.

Reports & Perspectives—

  • NIH reports on the potential of psychLight to identify non-hallucinogenic drugs to treat psychiatric conditions as well as dangerous designer drugs that are at risk of being misused.
  • C&EN contains an article with insights from a range of scientists about the accuracy of psychLight in predicting the hallucinogenic properties of drugs.
  • Medium reports on the challenges with making psychedelic drugs available to mainstream audience. The authors suggest psychLight may help circumvent the problems and help move psychedelic drug development forward to meet the need that exists.
  • @JasonCDong1 (researcher involved in the above study) tweets: “Welcome a new member joining the xLight series here @LinTianLab, psychLight! A genetically encoded, 5-HT2A receptor-based, high-affinity serotonin biosensor. It’s a ‘Light’ for endogenous 5-HT imaging AND a ‘Light’ for a new way to practice drug discovery.”
  • @AcademicTimes (academic journal) shares: “Psychedelic drugs show promise for treating metal disorders like depression. But they can cause intense hallucinations for 8 – 12 hours. @DEOlsonLab and @LinTianLab set out to find a solution.”
  • @CellCellPress says: “Online now! PsychLight is an engineered #biosensor that enables the identification of designer drugs of abuse and non-hallucinogenic psychedelic #therapeutics.”

In Practice 

  • Psychedelic researcher Andrew Penn, MS, NP, PMHNP-BC, on how to respond when clients say they want to try psychedelics.
  • The psychedelics in development
  • How to administer psychedelics
  • Understanding MDD and the microbiome


Last Updated: Aug 26, 2021