Greg Mattingly, MD

Experts discuss how clinicians can better evaluate it by effectively and candidly communicating with patients about anhedonia.

Clinical Management of Anhedonia and Communication with Patients

Anhedonia, defined as loss of interest or pleasure, is a highly disabling residual symptom affecting up to 70% of depression patients. It has strong links to treatment non-response, recurrence, suicide risk, and functional impairment. There are anticipatory (motivation), consummatory (experience of pleasure), and cognitive (reward-based decision making) components.

Standard antidepressants like SSRIs downregulate dopamine, worsening anhedonia over time. The clinicians are excited about novel glutamatergic agents like dextromethorphan-bupropion that may directly improve anhedonia based on effects seen in clinical trials.

Rather than formal rating scales, they suggest practical ways of assessing anhedonia: asking about life engagement, looking forward to or enjoying activities, feeling meaning/purpose, intimacy/relationships sparking joy or anticipation. Compare current interests and relationships to baseline pre-depression state. Specific recreational interests, social interactions, or responsibilities can also demonstrate improved motivation and reward experience.

Symptom scores may decrease with treatment, but anhedonia persists, so assessing hedonic capacity beyond mood scores is critical. Studies show patients can be in “remission” symptomatically but still have significant anhedonia and life impairment. Getting patients to optimal functioning and wellness requires targeting negative and positive affect. Improving anhedonia is key to enabling true remission and recovery.

This summary was AI-generated and edited for clarity and readability.

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Dr Andrew Cutler and Dr Greg Mattingly review current understanding of anhedonia. They discuss how clinicians can better evaluate it by effectively and candidly communicating with patients about anhedonia.

The expert psychiatrists discuss when to evaluate treatment efficacy and the impact of patients’ quality of life and function in such evaluations.

Improvement in Quality of Life and Function in Patients with Major Depressive Disorder

The clinicians emphasize that not seeing improvement in depression symptoms within 2 weeks of starting or changing treatment predicts very low likelihood of eventual response. Studies show that making a change at 2 weeks leads to better outcomes compared to waiting months.

They liken this to not letting glucose stay dangerously high for months in diabetes or letting cancer linger untreated. Particularly with students or working-age patients, 2 weeks versus 2 months can mean the difference between finishing a semester or losing a job.

Too often both patients and clinicians accept "good enough" results with lingering symptoms and impairment. We must apply the same urgency and standards to depression as other illnesses. With PHQ-9 scores now in EMRs, clinicians can easily monitor between visits rather than waiting months to evaluate.

Lack of efficacy or side effects are clear reasons to adjust treatment, but residual symptoms like anhedonia or concentration impairment are also important treatment targets as they predict recurrence and dysfunction. Symptoms may partially improve but quality of life and function often lag behind.

The clinicians are encouraged that novel mechanisms like dextromethorphan-bupropion not only demonstrate rapid symptom improvement in line with their glutamatergic effects, but also early signals of improved functioning. This elevates the agent in their treatment algorithms and offers more comprehensive relief enabling patients to thrive, not just survive.

This summary was AI-generated and edited for clarity and readability. 

Dr Andrew Cutler and Dr Greg Mattingly talk about patient profiles they consider for treatment with dextromethorphan-bupropion.

Candidate Patients for Dextromethorphan-bupropion

This agent is approved in adults only (18+ years) currently. The clinicians have used it successfully across genders, ages, and occupations. However, there are some relative cautions and warnings to consider:

- Active eating disorders (anorexia, bulimia): Bupropion can lower seizure threshold, so caution is warranted in active seizure disorders as well.

- Recent psychotic episodes: The glutamatergic mechanism could theoretically worsen psychosis.

- Pregnancy/fetal development: There are specific warnings about potential fetal harm, though not an absolute contraindication.

Outside of those considerations, the clinicians emphasize it can be used broadly, not just in treatment resistant depression. It is approved for MDD after only 1-2 prior failures. Based on positive patient experiences, their group now offers it as a second line treatment after initial antidepressant non-response.

They note that with efficacy rates exceeding current options and generally good tolerability, cost/coverage is the only barrier to using it as a potential first line agent in many patients. They see it as beneficial across the depression spectrum but especially helpful for residual symptoms like anhedonia and concentration difficulties not addressed by traditional antidepressants.

They see the agent as an important new tool with a wide range of appropriate candidates, moving up their treatment algorithms based on superior efficacy/tolerability, but exercise caution in the labeled populations like active psychosis or eating disorders.

Dr Andrew Cutler and Dr Greg Mattingly talk about patient profiles they consider for treatment with dextromethorphan-bupropion.			

The expert psychiatrists share their clinical experience with dextromethorphan-bupropion.

Clinical Experience with Dextromethorphan-bupropion

In their clinical practice, the combination of dextromethorphan and bupropion has exceeded their expectations and become one of their most utilized treatments. They attribute this to it being the first oral glutamatergic agent targeting novel mechanisms compared to traditional antidepressants.

Patients tend to notice benefits within 1-2 weeks, consistent with the rapid onset seen in clinical trials. The clinicians ask what patients notice, and common responses are renewed hope, motivation, and ability to enjoy things again—addressing emotional blunting and anhedonia. One patient described feeling lighter, clarifying this meant no longer feeling stuck in her head and looking forward to activities again.

The clinicians agree the agent has a distinct feel compared to other antidepressants and has been broadly effective and well-tolerated. Dizziness is the most common reason for discontinuation. Since bupropion boosts dextromethorphan levels already, caution is warranted if patients are on strong CYP2D6 inhibitor medications or genetically slow metabolizers, with dose lowering often needed.

An example is shared of a trauma psychologist patient doing well on the combo alongside duloxetine. When she tried increasing the dose without guidance, she experienced significant dizziness. This reinforces the importance of close monitoring and dose adjustments if patients are on interacting medications.

In summary, real-world experience reflects clinical trial findings of fast onset and ability to improve anhedonia/blunting. The clinicians emphasize careful dosing, especially around drug interactions, but find the agent to be highly useful for many depression patients.

Summary was AI-generated and edited for clarity. 

Greg Mattingly, MD

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