Original articles

Issue 1 - March 2026

Pramipexole augmentation for treatment-resistant or anhedonic depression. The real-world evidence

Pramipexole augmentation for treatment-resistant or anhedonic depression.

Authors

Antonio Tundo , Sophia Betrò , Rocco De Filippis , Federica De Angelis , Roberto Felici , Chiara Lucangeli , Fulvia Marchetti , Daniele Nacca , Roberta Necci

Keywords: pramipexole, treatment resistant depression, anhedonia, bipolar depression, unipolar depression, dopamine agonists
DOI: 10.36180/2421-4469-2025-1563
Publication Date: 2026-05-13

Summary

Objective. The aim of the present study is to assess the real-world evidence on the effectiveness and safety of pramipexole augmentation of traditional antidepressants (ADs) in patients with unipolar and bipolar treatment resistant depression (TRD) or with anhedonic depression.

Methods. This systematic review included observational studies and case series on adults receiving pramipexole as an AD augmentation strategy for unipolar and bipolar TRD or for anhedonic depression.

Results. We identified 12 studies: eight tested the effectiveness and safety of pramipexole augmentation for TRD; one compared the effectiveness and safety of pramipexole and aripiprazole augmentation in patients with unipolar TRD; one evaluated the effectiveness and safety of pramipexole augmentation in patients with unipolar TRD who failed to respond to aripiprazole augmentation; and two evaluated the efficacy and tolerability of pramipexole in patients with anhedonic depression. Overall, there were 308 participants, 20%-69.5% were women, the mean age was 25-62.2 years, In patients with TRD, pramipexole augmentation showed to be effective (response rate ranged from 33% to 80%), to be significantly superior to aripiprazole augmentation (response rate 63.9% vs. 33.2%; p= 0.005), and to be comparably effective in patients previous failed the aripiprazole augmentation and previously not treated with aripiprazole augmentation (response rate 65.2% and 62.1%; p= 0.79). In patients with anhedonic depression significantly improved anhedonia and depressive symptoms.

Conclusion. The results of this systematic review show that off-label use of pramipexole as ADs augmentation could be a useful and safe strategy for unipolar and bipolar TRD and for anhedonic depression.

INTRODUCTION

A major depressive episode (MDE) is central to the diagnosis of major depressive disorder (MDD) and the most common clinical manifestation of bipolar disorder (BD) 1,2, two common psychiatric conditions that affect around 20% of the population in the lifetime 3. These conditions are also the leading cause of premature death and ongoing disability 4. The pharmacological treatment of MDE includes a large number of antidepressants (ADs), which mostly act on serotonin and/or norepinephrine neurotransmission. ADs are used as monotherapy for unipolar depression 5 and in combination with mood stabilizers or second-generation antipsychotics (SGA) for selected cases of bipolar depression 6, 7. Despite these different options, about 30% of patients do not achieve symptomatic remission, even after multiple AD trials 8,9. A depressive episode that does not respond to two or more antidepressants (ADs), taken in adequate doses for an adequate duration and with adequate adherence to treatment, is defined as treatment-resistant depression (TRD) 10. This shared definition has been a significant advance in reducing the heterogeneity of the studies and enhancing the comparability regarding the clinical characteristics of patients with treatment-resistant depression and their responses to treatment. However, there are a number of issues that still require resolution 11. For instance, a dimensional classification would be preferable to a categorical one, since the response to the treatment does not change markedly after the second failure but rather decreases progressively with each new therapeutic attempt 12. There is a lack of scientific evidence regarding management options following three or more treatment failures, and consequently, guidelines are mainly based on expert opinion. A Delphi panel has demonstrated significant heterogeneity in the management of patients with TRD in Italy, confirming the need for standardised strategies and treatments that are specifically approved for TRD 13 Finally, it has been observed that the term “treatment-resistant depression” could be stigmatising, and it has been proposed that it should be replaced with the terms “difficult-to-treat “ or “(multiple) treatment failure” depression 11.

TRD is a severe condition that is associated with an elevated risk of suicide, a poor prognosis, and physical health decline 14,15. A significant risk factor for treatment resistance is the presence of prominent anhedonic features, regardless of the severity of the episode 16. Anhedonia, which is defined as a lack of interest or pleasure in activities that would typically be considered enjoyable, has been associated with impaired function of the mesolimbic reward system. Specifically, there is reduced activation of the ventral striatum/nucleus accumbens during anticipation of reward 17. Neuroimaging studies also demonstrate altered connectivity between the ventral striatum and prefrontal regions that are involved in motivation and reward valuation. This is likely to reflect deficits in dopaminergic function within cortico-striatal circuits 18.

Although there is no universally accepted treatment algorithm, several pharmacological strategies have been proposed for TRD. These include switching from an ineffective AD to a new AD from a similar or different class, combining two ADs (usually from a different class), or augmenting the efficacy of the current AD regimen with a second agent not thought to be an antidepressant itself 19. The latest treatment approaches for TRD include ketamine and esketamine, which specifically target the hypothesised dysfunction of glutamatergic 20. Another approach, currently still experimental, is psychedelic compounds, mostly psilocybin 20.

Currently, the most employed treatment in clinical practice is the augmentation of the current AD with a second-generation antipsychotic (SGA) or with Esketamine nasal spray. Despite the demonstrated efficacy of this strategy 20-22, a significant proportion of patients fail to achieve remission. The estimated number needed to treat with Esketamine spray nasal versus placebo to achieve remission is 6, and 9 with SGA 23. In view of the severity of TRD and the incomplete efficacy of available augmentation strategies, new and more effective drugs for AD augmentation are needed.

A substantial body of research has suggested the possible role of dopamine (DA) dysfunctions in major depressive episode, extending beyond anhedonic depression 24-26. In summary: (a) levels of DA are decreased, D2 receptor binding in the striatum and striatal DA transporter are increased in depression; (b) mesolimbic DA neurons could be linked to some nuclear symptoms of depression, such as loss of motivation and motor retardation; (c) different DA receptors and their distribution in different brain regions could be involved in the aetiology of depression.

Pramipexole is a full dopamine agonist with higher affinity for the D3 than for the D1, D2, and D4 receptors. It is an FDA-approved treatment for Parkinson’s disease and restless legs syndrome 27, 28. Its selectivity for D3 receptors, which are implicated in mental processes related to emotion and mood 25, its neuroprotective, antioxidant and anti-inflammatory activity 29, 30, and its ability to facilitate reward learning by inhibiting value decay 31, provide a rationale for the treatment of depression, including depression with prominent anhedonia.

In recent years there has been a growing interest in the potential antidepressant effect of pramipexole both in patients with Parkinson’s disease and with TRD.

The ability of pramipexole to alleviate depressive symptoms and anhedonia in patients with Parkinson’s disease, partially independent of motor symptoms improvement, has been shown in a randomized controlled trial (RCT) 32 and confirmed in a subsequent meta-analysis, including 18 randomized controlled studies and 1789 patients 33.

The potential efficacy of pramipexole as AD augmentation for TRD is suggested by the results of four small, controlled trials 34-37 and by a number of observational studies.

The aim of this study is to evaluate real-world evidence of the effectiveness and safety of pramipexole AD augmentation for patients with unipolar or bipolar TRD or anhedonic depression. There are two reasons why we have chosen to include only observational studies. Firstly, these studies more accurately reflect real-world conditions than controlled studies because they do not impose limitations based on age, gender, the presence of suicidal ideation, and psychiatric or physical comorbidity. Secondly, the effective dosage and titration of pramipexole for use as an augmentation therapy for AD have not been yet clearly defined. The flexible prescriptions used in observational studies, which are based on the clinical judgement of prescribers, provide valuable information on drug use, maximising both tolerability and effectiveness.

MATERIALS AND METHODS

Literature search

The PRISMA method 38 was followed in the literature search.

Specifically, PubMed/MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase databases were searched to identify peer-reviewed articles on the effectiveness and safety of pramipexole for major depressive episodes in unipolar and bipolar depression. The search string used the following terms: mood disorders, major depressive disorder, bipolar disorder, depression, mania, hypomania, anhedonia, pramipexole. We searched for ongoing and unpublished studies via Internet searches on ClinicalTrials.gov (www.clinicaltrials.gov) and on the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/). The detailed search strategies for each database are reported in the Supplementary Materials (Tab. S I).

To ensure the inclusion of all available articles, we also examined the references cited in included reports as well as abstracts of recent psychiatric research conferences, and contacted investigators and relevant study authors, seeking information about unpublished or incomplete studies.

No beginning date and no language restrictions were applied, and the last publication date was 30 June 2025.

Study selection

The review included prospective or retrospective observational studies and case series on adult receiving pramipexole as an AD augmentation strategy for unipolar and bipolar TRD and for depression with prominent anhedonia. Studies including patients with other comorbid psychiatric disorders, with suicidal thoughts or with serious medical illness were not excluded.

Randomized clinical trials, observational studies using pramipexole as monotherapy and observational studies including patients without TRD were excluded.

Data extraction

Two researchers (S.B., R.d.F.) read each article and evaluated the completeness of the data extraction independently. A structured data retrieval form was designed to ensure consistency of appraisal for each study. The data included study characteristics (such as lead author, publication year, journal, and study design), participant characteristics (sex, age, age at onset, and diagnosis), episode characteristics (duration, number of AD failed trials), intervention details (pramipexole dose, treatment(s) associated, trial duration), outcome (response, remission), and safety (drop-out due to any adverse event, (hypo)mania onset, and suicide attempt). Disagreements were resolved in a consensus meeting with a third researcher (AT).

RESULTS

Selected studies

The literature search yielded 1204 records, 892 through database searching and 312 through other sources. After the removal of the 29 duplicates, a total of 1175 titles and abstracts were assessed. A total of 1142 articles were excluded from the title and abstract, and 33 articles were retrieved in full text. We did not include 21 of these trials in the study. This was because five of these were reviews, five trials on people with depression that was not resistant to treatment, five randomised controlled trials, three letters to the editor, two trials on people with bipolar disorder in the euthymic phase, and one trial on people with bipolar disorder that did not report the results. A total of 12 studies were included in this review 39-50 (Fig. 1).

Study characteristics

The characteristics of the included studies are presented in Table I.

Eight studies aimed to test the effectiveness and safety of pramipexole augmentation for TRD. One of these studies included only patients with unipolar TRD 40, one only patient with bipolar TRD 46, and six patients with unipolar and bipolar TRD (5 analysed the results of the two samples separately 39, 41, 43-45, and one did not distinguish between them 42.

One study compared the effectiveness and safety of pramipexole and aripiprazole augmentation in patients with unipolar TRD 49, and one tested the effectiveness and safety of pramipexole augmentation in patients with unipolar TRD who failed to respond to aripiprazole augmentation 50. Finally, two studies evaluated the efficacy and tolerability of pramipexole in patients with anhedonic depression 47, 48.

Two studies 49, 50, analysing a subset of participants from a previous study included in the present review 45, were not considered in the description of the sample characteristics, as well in the “Response and remission to pramipexole augmentation” and “Safety” sections.

The total number of participants was 308, 178 with MDD and 118 with BD. One study did not specify how many of the 12 patients included had unipolar or bipolar disorder 45.

The sample size ranged from 7 to 116, 20%-69.5% were women, the mean age was 25-62.2 years, and the mean age at onset was 22.3-44.4 years. Three studies did not report the age of patients at onset 40,43,44.

In the studies reporting this information, the duration of the current episode was 1.5-27.6 months, and the number of antidepressants previously failed for 31 patients was 1 trial, for 116 2 trials, and for 63 patients 3 or more trials. Fourteen patients failed to respond also to electroconvulsive therapy.

All patients were treated with pramipexole and one or more antidepressants; 15 also received electroconvulsive therapy, and 102 mood stabilizer(s). The pramipexole mean maximum dosage was 0.69-2.18 (Tab. II).

Outcome and safety

Outcomes and safety for each study are presented in Table II.

Response and remission to pramipexole augmentation

The response rate in the nine studies reporting this outcome ranged from 33% to 80%. The studies reporting data stratified by diagnosis 39-41, 43-48 showed that the response rate for unipolar and bipolar depression are quite similar (range from 40% to 80% and from 40% to 78%, respectively).

Six studies also reported remission as an outcome 39, 40, 42, 44, 45, 46. The remission rate ranged from 28% to 66%, with a higher percentage observed in unipolar than in bipolar depression (range from 46% to 71% and from 28% to 57%, respectively).

Pramipexole and aripiprazole augmentation

In the study comparing the effectiveness of pramipexole and aripiprazole augmentation for unipolar TRD, pramipexole proved to be significantly superior to aripiprazole augmentation regards to response (63.9% and 33.2%, respectively; p=0.005) and remission (47.8% and 22%, respectively; p=0.013) rates at 12 weeks, as well as maintenance strategy over a twelve-month period (percentage of time spent on illness 17% and 28%, respectively; p=0.001) [49]. An observational study showed that non-response to aripiprazole augmentation did not change the short- and long-term effectiveness of pramipexole augmentation for unipolar TRD. Compared with patients previously not treated with aripiprazole augmentation, those who failed to respond to aripiprazole augmentation did not significantly differ on response (62.1% and 65.2%, respectively; p=0.79) and remission (44.8% and 52.2%, respectively; p=0.55) rate at 12 weeks and on the rate of sustained response at 24 weeks (84.2% and 72.7%, respectively; p=0.64).

Pramipexole and depression with significant anhedonia symptoms

In an open-label pilot study, 12 participants with unipolar or bipolar depression and significant anhedonia symptoms were treated with a combination of one or more antidepressants and pramipexole (mean daily dose: 3.6 mg). After 10 weeks, depressive symptoms (as measured by the Montgomery-Åsberg Depression Rating Scale) and anhedonia symptoms (as measured by the Dimensional Anhedonia Rating Scale and by the Snaith-Hamilton Pleasure Scale) showed significant improvement (p < 0.01). The response rate was 33% for depression and 25% for anhedonia 48.

A second open-label pilot study, including seven participants with unipolar depression and prominent anhedonia, showed that eight weeks of pramipexole treatment (2 mg/day) significantly improved anhedonia (as measured by the Mood and Anxiety Symptoms Questionnaire anhedonia subscale) and depressive symptoms (as measured by the Quick Inventory of Depressive Symptoms) (p=0.02 and p=0.05, respectively), with an 80% response rate for depression 47.

Drop out for adverse events

Discontinuation of the study due to one or more adverse events ranged from 0 to 22%.

The side effects that led to treatment discontinuation were: nausea (n=9, 26%), hypomania (n=8, 22.8%), lethargy-somnolence and psychomotor agitation (n=5, 14% each), anxiety, ataxia, confusion, edema, visual hallucination (n=2, 5.7% each), and impulse discontrol, insomnia, painful clonus, vomiting (n=1, 2.8% each). The side effects causing treatment discontinuation were not reported in two studies 41,46.

Notably, in the study comparing pramipexole and aripiprazole augmentation no difference in the proportion of dropouts due to side effects (9.8 % and 7.8%, respectively) or in the number of side effects in patients who did not drop-out (16 and 15, respectively) was observed 49.

Side effects

Common side effects (incidence > 1/100, < 1/10) were nausea (n=29, 9%), somnolence (n=13, 4%), headache (n=12, 3.7%), agitation (n=11, 3.5%), tremors (n=6, 1.9%), dry mouth (n=5, 1.6%), dizziness upon standing (n=5, 1.6%), irritability (n= 5, 1.6%), fatigue (n=5 1.6%), increased sexual drive (n=5, 1.6%), and insomnia (n=4, 1.3%).

Uncommon side effects (incidence > 1/1000, < 1/100) were visual hallucination, hypersexuality, skin rashes, delirium, ataxia, anxiety, difficulty urinating, vivid dreams, tics, increase appetite, vertigo (n= 2, 0.64% each), itching, word findings difficulty and heart palpitation (n= 1, 0.32% each).

Suicide attempts

No patients attempted suicide.

DISCUSSION

To the best of our knowledge, this is the first systematic review of the observational studies evaluating the effectiveness and safety of pramipexole as AD augmentation for TRD and for anhedonic depression.

This review suggests that pramipexole could be one of the most effective treatment strategies for treatment-resistant depression and could be useful for patients with an anhedonic symptom profile. As regards TRD, the response and remission rate for pramipexole augmentation in our study (33%-80% and 28%-66%, respectively) are close the higher boundary of the range of response and remission rate for aripiprazole augmentation (18.5%-60% and 7.4%-54%, respectively) 51, 52, the SGA with the strongest evidence of efficacy for TRD 53-55. Pramipexole showed also to be more effective than aripiprazole augmentation in the direct comparison 49, and to be effective for patients with TRD who previously failed to respond to aripiprazole augmentation 50. Due to the observational nature of the studies, these data should be interpreted with caution.

When the results were analysed according to diagnosis, pramipexole appeared to be equally effective in terms of response rates (range from 40% to 80% and from 40% to 78% respectively). This evidence, consistent with the results of previous small RCTs 36,56, supports the use of pramipexole augmentation for bipolar TRD but must be interpreted with caution, as the use of antidepressants in patients with bipolar disorder is a highly controversial issue.

Regarding anhedonic depression, two pilot studies showed that pramipexole positively affected both depressive and anhedonia symptoms, suggesting it could be a useful treatment for patients with this difficult-to-treat subtype of depression. Notably, the clinical improvement in these patients was associated with decreased peripheral inflammatory markers (high-sensitivity C-reactive protein) and increased reward circuit activity (ventral striatum), which is weaker in depressed individuals 48,57.

Our findings suggest that pramipexole augmentation is a relatively safe treatment for treatment-resistant depression (TRD), with nausea and somnolence being the most common side effects. The drop-out rate from the trials due to side effects and the number of patients who developed (hypo)mania were very low. Moreover, no patients attempted suicide, and in patients who did not drop out the side effects were limited in number and severity and often resolved spontaneously or through dose reduction 44, 45. In the study directly comparing pramipexole and aripiprazole augmentation the two treatments did not significantly differ on safety at short and long term 49.

The side effects reported in the reviewed studies were similar to those usually listed for patients with Parkinson’s disease (see information leaflet, https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020667s036lbl.pdf) but their frequency was much lower. Regarding the potentially more dangerous side effects, only a very small proportion of patients included in the reviewed studies reported visual hallucinations, lethargy or hypersexuality and no one gambling or compulsive shopping, which are common in patients with Parkinson’s disease who are receiving pramipexole 58.

The different susceptibility to these side effects between patients with mood disorders and those with Parkinson’s disease might be due to different neurobiological dysfunctions underlying these two diseases 59,60, although we cannot exclude that the relatively small sample size of patients with TRD treated with pramipexole limited the possibility to detect these adverse events.

Notably, according to the information leaflet, pramipexole does not affect metabolism, cause QTc prolongation or interact with lithium, valproate or carbamazepine. Although the leaflet reports a possible additive sedative effect when taken with antidepressants, antipsychotics and benzodiazepines, no study included in the present review reports dropout or side effects due to this interaction.

The main limitation of the present review is the small number of studies and participants. Other study limitations were: a) the high variability of dosing and of the time points at which outcomes were collected; b) the range of definitions and instruments for response and remission applied in the included studies, which may influence the comparability of reported outcomes; c) the lack of a formal risk-of-bias assessment. Results should therefore be interpreted with caution.

CONCLUSIONS

In conclusion, this review supports the effectiveness and safety of adding pramipexole to traditional antidepressants for patients with treatment-resistant depression. If these results are confirmed by larger and high-quality studies, we believe pramipexole augmentation should be included in international guidelines for treatment of TRD. Consequently, clinicians will have an additional treatment option for this condition and will be able to choose the most suitable treatment for each patient according to their sensitivity to side effects, medical condition and preference. Although preliminary data suggests that pramipexole is safe for treating bipolar TRD, further studies are needed to confirm its long-term low risk of inducing mixed features, (hypo)manic switches or rapid cycling. Further studies are also needed to confirm the preliminary positive evidence regarding the effectiveness of pramipexole in treating anhedonic depression.

We should bear in mind that pramipexole use for AD augmentation is off-label and should be reserved for patients with severe TRD who do not exhibit psychotic symptoms in their previous or current episode, since pro-dopaminergic agents can trigger psychosis in susceptible individuals.

Appropriate precautions must be taken when using pramipexole. The dosage should be increased gradually to minimise the risk of side effects, primarily nausea, and decreased gradually to avoid the risk of dopamine withdrawal syndrome. Patients and their family members must be instructed to report any potentially dangerous side effects immediately, such as lethargy, hypersexuality, gambling, compulsive shopping, hallucinations, psychotic symptoms or delirium.

Conflicts of interest statement

The authors declare no conflicts of interest.

Funding

This study was funded by the Fondazione dell’Istituto di Psicopatologia Onlus, Rome, Italy (grant N° 01/2024). The funding source had no role in the study design, collection, analysis or interpretation of the data, preparation of the manuscript, or the decision to submit the paper for publication.

Author contributions

A.T.: conceptualization, methodology, writing - original draft preparation, supervision; S.B.: investigation, data curation, writing - original draft preparation; RdF: investigation, data curation; FDA, RF, CL, FM, DN, RN: writing - review & editing.

Ethical consideration

Ethics approval was not required because the study is based on previously published data and does not involve primary data collection.

Figures and tables

FIGURE 1. Flowchart of the selected studies.

Study Design Participants tot (n) Age mean, years (SD) Females Age at onset mean, years (SD) Duration episode (months) Failed AD (number of participants)
MDD BPI BPII 1AD 2AD ≥3AD ECT
[42] Cassano et al., 2004 Prospective 12 2 9 52.8 (12.5) 69.5% 35.1(16) 15.3 12 9 2 0
[39] Hori et al., 2012 Open label trial 12 0 5 36.2 (9.2) 58.8% 28.1 (7.6) Not reported 1 3 13 0
[40] Inoue et al., 2010 Open label trial 10 0 0 43.7 (11.4) 40% 39.6 (11.5) 27.6 0 5 5 0
[41] Lattanzi et al., 2002 Prospective 14 6 11 53.7 (13.5) 67.7% 32 (15.3) 1.5 18 12 1 0
[43] Sporn et al., 2000 Retrospective 20 0 12 41.5(14) 53.1% 22.3 (10.8) 5.6 25 0
[44] Fawcett et al. 2016 Case series 24 6 12 53.97(13) 50% Not reported Not reported 0 0 42 8
[45] Tundo et al., 2022 Prospective 79 5 32 62.2 (13.3) 56% 44.4 (17.9) 12.4 0 87 0 2
[46] Perugi et al., 2001 Retrospective 0 0 18 55 (15.9) 61% 34.2 (14.8) Not reported Not reported 0
[47] Hack et al, 2024 open-label pilot study 7 0 0 25-45 20% Not reported Not reported Not reported 0
[48] Ventorp et al, 2022 open-label pilot study 12 45.2 (15.7) 67% Not reported Not reported Not reported 4
Abbreviations: MDD= major depressive disorder; BPI= Bipolar I disorder; BPII= Bipolar II disorder; AD= antidepressant; ECT= Electroconvulsive therapy
TABLE I. Characteristics of the included studies
Study Pramipexole mean maximum dose (mg) Association ADs Trial duration (weeks) Outcome measure Response criteria Remission criteria Response (responders number /total number, %) Remission (responders number /total number, %) Drop-out due to any adverse event (responders number /total number, %) Hypomania (n)
1AD 2AD ECT mood stab
[42] Cassano et al., 2004 0.99 not reported 21 6 6 48 LIFE not reported depression score < 2 not reported 61% 22% 3
[39] Hori et al., 2012 1.6 10 5 0 10 12 HDRS >50% total score reduction Total score < 7 71% 59% 0% 0
[40] Inoue et al., 2010 1.3 not reported 8 MADRS >50% total score reduction Total score < 10 60% 60% 20% 0
[41]Lattanzi et al., 2002 0.95 17 14 9 15 16 MADRS >50% total score reduction not reported 68% not reported 16% 2
[43] Sporn et al., 2000 0.69 22 not reported 24.4 CGI Improvement score < 2 not reported 44% not reported 12% 1
[44] Fawcett et al. 2016 2.18 not reported 69 Clinical Clinical assessment Clinical assessment 76% 48% 19% 0
[45] Tundo et al., 2022 1.05 not reported 38 0 51 24 HDRS >50% total score reduction Total score < 7 74% 66% 7% 1
[46] Perugi et al., 2001 1.23 9 2 0 18 17.6 CGI Improvement score= 2 Improvement score =1 44% 28% 5% 1
[47] Hack et al, 2024 2 not reported 8 QIDS >50% total score reduction not reported 80% not reported 0% 0
[48] Ventorp et al, 2022 3.6 2 10 MADRS > 50% total score not reported 33% not reported 0% 0
Abbreviations: AD= antidepressant; ECT= Electroconvulsive therapy
TABLE II. Outcomes of the included studies

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Antonio Tundo - Clinical Section, Institute of Psychopathology, Rome, Italy

Sophia Betrò - Clinical Section, Institute of Psychopathology, Rome, Italy

Rocco De Filippis - Clinical Section, Institute of Psychopathology, Rome, Italy

Federica De Angelis - Clinical Section, Institute of Psychopathology, Rome, Italy

Roberto Felici - Clinical Section, Institute of Psychopathology, Rome, Italy

Chiara Lucangeli - Clinical Section, Institute of Psychopathology, Rome, Italy

Fulvia Marchetti - Clinical Section, Institute of Psychopathology, Rome, Italy

Daniele Nacca - Clinical Section, Institute of Psychopathology, Rome, Italy

Roberta Necci - Clinical Section, Institute of Psychopathology, Rome, Italy

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Tundo, A., Betrò, S., De Filippis, R., De Angelis, F., Felici, R., Lucangeli, C., Marchetti, F., Nacca, D., & Necci, R. (2026). Pramipexole augmentation for treatment-resistant or anhedonic depression. The real-world evidence: Pramipexole augmentation for treatment-resistant or anhedonic depression . Italian Journal of Psychiatry, 12(1). https://doi.org/10.36180/2421-4469-2025-1563
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