A 2025 study from the University Clinic for Psychiatry in Skopje examined whether neurofeedback could improve outcomes when added to standard antidepressant treatment in adults with affective disorders. Because the paper is recent, it fits squarely within new emerging research with novel insights. That matters, especially in mood-disorder care, where many patients improve only partially, improve slowly, or remain symptomatic despite otherwise appropriate pharmacologic treatment.
This is exactly the kind of clinical space where interest in self-regulation approaches tends to grow. Biofeedback refers broadly to training people to modify physiological signals that are usually outside conscious awareness, such as heart rate, muscle tension, or skin conductance. Neurofeedback is the EEG-based branch of that family, in which individuals receive real-time information about aspects of their brain activity and learn, over repeated practice, to shift those patterns in a more adaptive direction. In depression and related affective presentations, the promise is not that neurofeedback replaces medication or psychotherapy, but that it may help stabilize arousal, improve emotional flexibility, and accelerate recovery in selected patients.
The present study asked a straightforward clinical question: if patients continue with antidepressants, can neurofeedback serve as a meaningful adjunctive intervention that helps them feel better sooner? In this sample, the answer leans toward yes. The combined-treatment group improved more quickly on clinician-rated depression and anxiety scales than the medication-only group. At the same time, the paper also illustrates the recurring tension in neurofeedback research: encouraging outcomes paired with incomplete protocol detail and design features that make interpretation more cautious than the headline result might suggest.
Methods
This was a prospective, randomized, controlled outpatient study conducted over a two-month period at a university psychiatric clinic in North Macedonia. The investigators enrolled 100 adults diagnosed with affective disorders under ICD-10 categories F32, F33, and F34, covering depressive episode, recurrent depressive disorder, and persistent affective disorder. Participants were randomized into two groups of 50.
The study group received standard antidepressant treatment plus neurofeedback, while the control group received antidepressant monotherapy. Medication choices reflected routine clinical practice rather than a single standardized regimen. The paper lists selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants, with examples including escitalopram 10 mg, duloxetine 60 mg, and mirtazapine 30 mg. That pragmatic approach is clinically recognizable, although it also introduces heterogeneity that complicates strict causal inference.
The neurofeedback intervention used the Encephalan-EEGR-19/26 device with Rehacor software and was described as alpha/theta training. Patients completed 10 sessions lasting 25 minutes each. That is helpful as a starting point, but several details that matter to clinicians and researchers are not reported: electrode placement, reward and inhibit bands, threshold-setting logic, whether training was eyes open or eyes closed, whether sessions were delivered daily or several times per week, and whether protocols were individualized. Those omissions do not negate the findings, but they do limit reproducibility.
Outcome assessment relied on structured psychiatric interview plus two familiar clinician-rated scales: the 17-item Hamilton Depression Rating Scale (HAM-D17) and the Hamilton Anxiety Rating Scale (HAM-A). Assessments were conducted at baseline, at two weeks, and at one month after treatment initiation. Statistical analysis used SPSS v23.0 with independent-samples t tests, dependent-samples t tests, chi-square tests, and Fisher’s exact tests as appropriate, with significance set at p < .05. Ethics approval and informed consent were reported.
One methodological caution appeared before treatment even began: although sex distribution was similar between groups, age distribution differed significantly, with the study group skewing younger and the control group skewing older. For a mood-outcome study, that imbalance matters.
Results
At baseline, the two groups were broadly similar in symptom burden. Depression severity was comparable on the HAM-D, with mean scores of 17.98 ± 5.7 in the study group and 18.42 ± 6.1 in the control group. Anxiety was also similar at baseline in the main results tables, with HAM-A means of 20.84 ± 7.0 and 22.20 ± 8.2, respectively, and no significant between-group difference. One small reporting issue is worth noting: the abstract lists different baseline HAM-A values than the body tables, suggesting a likely editorial inconsistency.
By the first follow-up at two weeks, the combined-treatment group had pulled ahead. On the HAM-A, the study group improved from 20.84 to 17.98, a reduction of 2.86 points or 13.72%, compared with a reduction of 0.84 points or 3.78% in the control group. The between-group difference at that time point was statistically significant (p = .028), and the within-group change in the study group was highly significant (p < .0001).
A similar pattern appeared for depression symptoms. At two weeks, HAM-D scores fell from 17.98 to 15.56 in the study group, a 2.42-point reduction or 13.46%, whereas the control group changed minimally from 18.42 to 18.30, a 0.12-point reduction or 0.65%. The between-group difference at first follow-up was significant (p = .022), and only the neurofeedback-plus-medication group showed a clearly robust within-group change (p < .0001).
The separation between groups persisted at one month. HAM-D scores were 14.50 ± 5.5 in the study group versus 17.56 ± 6.2 in the control group (p = .0064). HAM-A scores were 16.82 ± 6.7 versus 20.14 ± 8.3 (p = .029). Clinically, that pattern suggests both a faster onset and a somewhat more sustained early response in the combined-treatment arm.
The paper also describes shifts across symptom-severity categories, with more patients in the study group moving toward milder anxiety and depression ranges over time. Still, the follow-up window remained short, and the study did not report remission rates, response rates, relapse data, adverse events in detail, or functional outcomes such as return to work, sleep quality, or quality of life.
Discussion
The clinical appeal of this study is easy to understand. Many practitioners working with depression and related affective disorders are not asking whether medication can help; they are asking what else can help when medication is incomplete, slow, poorly tolerated, or insufficient on its own. This paper offers an encouraging answer by placing neurofeedback in the role it may be best suited for: an adjunctive intervention. In a real-world outpatient psychiatric sample, adding alpha/theta neurofeedback to antidepressants was associated with greater early improvement in both depressive and anxiety symptoms than medication alone.
That finding matters because speed is not a trivial outcome in affective disorders. A two-week advantage can translate into better adherence, greater hope, less distress, and perhaps lower risk in vulnerable patients. The one-month results are also relevant. They suggest that the improvement was not merely a transient enthusiasm effect visible only at the first check-in, but a pattern that continued over the early treatment phase.
Mechanistically, the study is plausible. Alpha/theta training has long been used in contexts involving stress reduction, emotional processing, and state regulation. In theory, patients with affective symptoms may benefit when repeated training nudges the nervous system toward more flexible regulation rather than persistent hyperarousal, cognitive rumination, or rigid negative bias. That said, this paper does not directly test mechanism. It shows symptom change, not how the change occurred. Any explanation involving neural regulation, emotional processing, or network-level plasticity remains a clinically reasonable interpretation rather than a demonstrated result from this dataset.
The strongest reason for caution is study design. There was no sham neurofeedback condition, no blinding, and no attempt to separate specific neurofeedback effects from non-specific influences such as expectancy, increased therapist contact, structured attention, or motivational enhancement. The study group also received something extra: more time, more novelty, more procedural engagement. In neurofeedback trials, those factors are never trivial.
The age imbalance between groups is another real limitation. Despite randomization, the study group was substantially younger overall, while the control group contained a much larger proportion of middle-aged participants. Age can influence treatment response, illness chronicity, neurocognitive flexibility, comorbidity burden, and the pace of improvement. That imbalance weakens confidence that the observed differences are attributable solely to neurofeedback.
Protocol reporting is the other major limitation. We know the training was alpha/theta, lasted 10 sessions, and used a named device and software package. But we do not know the electrode montage, session spacing, feedback contingencies, artifact handling, target thresholds, or whether training was standardized or individualized. For research translation into practice, those details are not cosmetic. They are the bridge between “interesting result” and “replicable clinical method.”
Even with these caveats, the study still adds something useful. It suggests that adjunctive neurofeedback may be especially worth considering in patients with mixed depressive and anxious symptom profiles, where early state regulation could create a better platform for psychotherapy, medication adherence, and day-to-day functioning. For referring clinicians, the paper supports neurofeedback as a possible adjunct rather than a replacement therapy. For clients, it offers a hopeful but measured message: some people may feel improvement earlier when self-regulation training is layered onto standard care, but the evidence is not yet strong enough to promise a uniform effect. For neurofeedback professionals, the practical lesson is equally clear: enthusiasm should travel with documentation. The field will move faster when protocol details, adverse events, response rates, and longer-term outcomes are reported with the same care as p-values.
Brendan’s perspective
What I find especially encouraging about this study is how clinically usable the message is: neurofeedback appears to work as an adjunctive intervention even when the client is already taking medication. That point matters. Too often, neurofeedback is discussed as though it belongs only in a separate lane, reserved for people who want a non-pharmacological option or who have already stepped away from medication. In reality, that is not how many people arrive in practice. They come in medicated, partially improved, still symptomatic, often frustrated, and still looking for something that helps them feel more like themselves. This study supports a very practical conclusion: neurofeedback does not need to wait for medication to be absent in order to be useful.
To me, that is one of the strongest arguments for being more routinely proactive about offering neurofeedback in affective-disorder care. Not as a replacement for every other intervention, and not as a simplistic one-size-fits-all answer, but as a regular part of comprehensive treatment planning. If a client is depressed, anxious, emotionally rigid, stress-reactive, or stuck in chronic dysregulation despite appropriate medication support, why would we not want to add a learning-based intervention that may improve self-regulation directly? Medication can change symptoms. Neurofeedback can help train the person’s capacity to regulate state. Those are not identical contributions, and that is precisely why they pair so well.
I also think this paper quietly pushes back against a misconception that medication somehow prevents meaningful neurofeedback learning. Clinically, I do not see a reason to assume that. In fact, some medicated clients may be more available for neurofeedback because their symptom intensity has come down enough for them to engage consistently, tolerate sessions better, sleep a little more reliably, or feel less overwhelmed by their own internal experience. The medication may reduce noise in the system; neurofeedback may then help the brain and nervous system build more stable regulation on top of that foundation. This study does not settle the mechanistic question, but it absolutely supports the idea that neurofeedback remains relevant and potentially beneficial in medicated populations.
From that perspective, I think the field should become much more comfortable saying something simple and positive: yes, neurofeedback can be worth doing while someone is taking medication. We do not need to frame it as second-best or as something postponed until later. For many clients, earlier integration may be preferable. If neurofeedback can help improve state regulation, emotional flexibility, attentional steadiness, and stress tolerance during the treatment course, that may increase the effectiveness of everything else the client is already doing. Better sleep makes psychotherapy work better. Better regulation improves adherence. Less reactivity can make medication management easier. Gains in one domain often create traction in another.
At the same time, being strongly in favor of neurofeedback does not mean being casual about how we apply it. Quite the opposite. The more seriously we take neurofeedback, the more seriously we should take personalization. “Depression” is not a protocol. “Anxiety” is not a protocol. Even “anxious depression” is not a protocol. These are broad clinical containers, not precise physiological maps. One person’s presentation is dominated by hyperarousal, insomnia, muscle tension, rumination, and frontal overcontrol. Another is slowed, flat, sleepy, foggy, and underactivated. Another oscillates between collapse and activation. Another carries a heavy trauma load and limited tolerance for deep internal shifts. If we want the field to mature, we need to get better at matching neurofeedback to the specific regulatory pattern in front of us.
That is where biomarkers and individualized assessment become so important. Whether we are using qEEG-informed planning, careful symptom phenotyping, sleep profiling, autonomic measures, attention patterns, or other clinically meaningful markers, the goal should be the same: move beyond diagnosis-level shorthand and toward person-level protocol selection. I would like to see more research asking not only “Does neurofeedback help affective disorders?” but “Which affective presentations respond best to which forms of neurofeedback, under which physiological conditions, and at what stage of treatment?” That is the next step the field needs.
I am equally convinced that we need more studies examining neurofeedback as support during medication reduction or withdrawal. Clinically, this is a very relevant frontier. Many clients eventually want to lower their medication burden, transition off a medication that is no longer serving them well, or move through withdrawal with better nervous-system support. That process can be destabilizing. Sleep can worsen. Anxiety can spike. Mood can wobble. Somatic symptoms can become louder. In that window, neurofeedback may be especially valuable—not because it magically erases withdrawal, but because it may help support regulation, reduce reactivity, and provide the client with an active training process while the system is recalibrating. We need much better evidence here, but the clinical question is excellent and overdue.
I would love to see future trials compare several real-world pathways: neurofeedback plus medication maintenance, neurofeedback during gradual tapering, and neurofeedback after discontinuation, ideally with individualized protocols and follow-up long enough to tell us something meaningful about durability. We also need studies that include sleep outcomes, functional outcomes, adverse events, and stratification by arousal pattern, trauma history, and cognitive style. That is how neurofeedback research becomes more clinically intelligent.
So yes, my reading of this paper is very favorable to neurofeedback. Not because it proves everything, but because it reinforces something many clinicians already suspect from practice: neurofeedback can add meaningful value even when a client is medicated, and it probably deserves a more routine place in treatment planning than it currently gets. The future is not neurofeedback versus medication. The future is smarter integration, earlier use, better personalization, and more research on how neurofeedback can support clients not only during treatment, but also during the delicate transitions that follow it.
Conclusion
This study offers a useful, clinically relevant signal: when neurofeedback was added to antidepressant treatment, adults with affective disorders improved more quickly on clinician-rated depression and anxiety scales than those treated with medication alone. The effect appeared within two weeks and remained visible at one month, which is exactly the sort of early momentum clinicians hope for in mood treatment.
The most helpful way to hold these findings is not as an argument for neurofeedback as a stand-alone answer, but as support for neurofeedback as an adjunctive intervention. Read that way, the paper becomes both more realistic and more clinically valuable. It suggests that self-regulation training may provide additional leverage when layered onto standard care, particularly during the early phase of treatment when symptom relief and engagement matter most.
At the same time, the paper should still be read as promising rather than definitive. The absence of sham control, the significant age imbalance between groups, the short follow-up window, and the limited description of the neurofeedback procedure all place boundaries around what can be concluded. Even so, it points in a constructive direction: carefully individualized neurofeedback may help some patients gain traction sooner when it is integrated thoughtfully with medication, psychotherapy, and other regulation-focused supports.
References
Risteski, A., Arsova, S., Miceva-Velichkoska, E., Filipce, A., & Mitrovska, S. (2025). Measuring the efficacy of treatment with neurofeedback method in patients with affective disorders. Archives of Public Health, 17(1), 51-62. https://doi.org/10.3889/aph.2025.6134
