Case Report,  Int J Ment Health Psychiatry Vol: 11 Issue: 2

Utilization of Bupropion-Dextromethorphan to treat Atypical Depression in patients with Borderline Personality Disorder

Parinda Parikh^1*, Parthiv Pansuriya², Arnesh Shukla³, Himani J Suthar⁴, Aatish Dutta Bhatta⁵, Shaurya Kumar Singh⁶, Alisha Arul Alphonse⁷, Jeremy Kays⁸, Arushi Kaushik Chandra⁹, Mahiya Buddhavarapu¹⁰, Zoe Gellert¹¹, Sahia Manepalli¹², Mina Oza¹³

¹Department of Psychiatry, Weill Cornell Medical School, White Plains, United States

²Department of Medicine, Government Medical College Surat, India

³Department of Psychiatry, St. Martinus University, Willemstad, Curacao

⁴Department of Medicine, GMERS Medical College and Civil Hospital, Gandhinagar, India

⁵Department of Medicine, KIST Medical College and Teaching Hospital, Lalitpur, Nepal

⁶Department of Psychiatry, Pravara Institute of Medical Sciences, Loni, Maharashtra, India

⁷Department of Medicine, St. George’s University, Grenada, West Indies

⁸Department of Psychiatry, Windsor University School of Medicine, St.Kitts, West Indies

⁹Department of Medicine, NYU Steinhardt School of Culture, Education and Human Development, New York, United States

¹⁰Department of Medicine, University of Pittsburgh, Pennsylvania, United States

¹¹Department of Psychiatry, Tulane University, New Orleans, United States

¹²Department of Medicine, University of South Florida, United States

¹³Department of Medicine, 2ND ARC Associates, White Plains, United States

*Corresponding Author: Parinda Parikh
Department of Psychiatry, Weill Cornell Medical School, White Plains, New York, United States
E-mail: drparikh@2ndarc.com

Received date: 17 Jul, 2025, Manuscript No. IJMHP-25-167947; Editor assigned date: 07 Feb, 2025, PreQC No. IJMHP-25-167947 (PQ); Reviewed date: 21 Feb, 2025, QC No. IJMHP-25-167947; Revised date: 27 Feb, 2025, Manuscript No. IJMHP-25-167947 (R); Published date: 10 Mare, 2025, DOI: 10.4172/2471-4372.1000292.

Citation: Parikh P, Pansuriya P, Shukla A, Suthar HJ, Dutta A, et al. (2025) Utilization of Bupropion-Dextromethorphan to Treat Atypical Depression in Patients with Borderline Personality Disorder.11:292.

Abstract

Keywords: Borderline personality disorder; Generalized anxiety disorders; Depression

Introduction

Borderline Personality Disorder (BPD) is a serious mental health condition marked by long-standing patterns of unstable relationships, a fragile sense of self, intense emotional swings, hypersensitivity to rejection, fear of abandonment, feelings of loneliness and emptiness, self-harming, and impulsive behavior [1]. People living with BPD often face major challenges in daily functioning and are at higher risk for other psychiatric conditions, substance use, self-injury, and suicidal thoughts or actions [2].

The estimated prevalence of Borderline Personality Disorder (BPD) in the general population of western countries ranges from approximately 0.4% to 3.9% [3]. In clinical psychiatric settings, BPD is relatively common, affecting about 10% of outpatients and between 15% to 25% of inpatients [4].

Individuals with BPD frequently experience comorbid mental illnesses such as depression, bipolar disorder, post-traumatic stress disorder (PTSD), substance use disorders, and psychosis, with nearly all affected individuals having at least one lifetime comorbidity [5]. Many BPD symptoms resemble those seen in other psychiatric disorders and are often targeted with pharmacotherapy [5]. The most common disorder associated with BPD is major depressive disorder. Typical depression includes features like low mood, loss of reactivity, weight loss, low appetite, lack of motivation, loss of energy, and psychomotor agitation. In contrast, atypical depression has features like hypersensitivity to rejection, the ability to still feel happy at times, weight gain, increased appetite, increased sleep, and leaden paralysis [6].

A study reported that 61% of individuals with BPD had been prescribed antidepressants, 35% anxiolytics, 27% mood stabilizers, and 10% antipsychotics [7]. Antidepressant use was found to be twice as common as in patients with major depression with BPD [7].

In this case report, we present a case of a 23-year-old female with BPD and the role of dextromethorphan-bupropion in the regulation of her mood symptoms. Bupropion is a dopamine norepinephrine reuptake inhibitor, whereas dextromethorphan is a non-competitive NMDA (N-methyl-D-aspartate) antagonist that acts on the glutamate receptor. This combination promotes neuroplasticity, acts rapidly and stabilizes mood, enhances emotional resilience, and prolongs the effect of dextromethorphan by inhibiting the cytochrome P450 2D6 (CYP2D6). We aim to apply these properties of bupropion-dextromethorphan in treating the treatment-resistant cases or those presenting with atypical symptoms in BPD [8].

Case Presentation

The patient is a 22-year-old, homosexual female who came to a psychiatric care facility in February 2024. She had been seeing a psychiatrist since the age of 12, but was not happy with her lack of improvement in symptoms, which is why she decided to change psychiatrists. She lives with both of her parents. She has a brother in college and a sister in the seventh grade. The patient presented to the facility with a depressed and low mood. The patient denies feeling anything emotionally. The patient has a lack of motivation, a lack of energy, and a lack of drive. The patient endorsed experiencing hopelessness, helplessness, and worthlessness at times. The patient has feelings of emptiness and loneliness, but the patient denies any self-harm behavior or suicidal ideation. The patient made good eye contact and appeared to be a reliable and forthcoming reporter. She was anxious but had a full affect. Her speech was normal in rate, rhythm, and volume. Her thought process was linear, logical, and goal-directed. The patient reported that she sometimes experiences happiness when a positive event occurs. Her thought content was negative for any delusions, obsessions, or phobias. There was no evidence of flights of ideas, disorganized thinking or speech, circumferential thinking, or loosening of association. The patient admitted she was being reckless and had a habit of engaging in risky behaviors. The patient states that she has a history of lying to people more than she would like. The patient never had manic episodes or hypomanic behavior. Rapid Mood Screener (RMS) was used to screen manic behavior. She has fair insight and judgement, however, she has poor impulse control. She reported symptoms of generalized anxiety, social anxiety, and performance anxiety. The patient is hypersensitive to criticism and rejection. She isolates a lot and stated that she sometimes feels heavy in her legs. To assess the severity of BPD, we did the Borderline Symptom List-23 (BSL-23), which showed a mean score of 2.87, suggesting a very high severity of BPD. Patient Health Questionnaire-9 (PHQ-9) showed a score of 19 out of 27, suggesting moderately severe depression.

The patient has a past psychiatric history of borderline personality disorder, Generalized Anxiety Disorder (GAD), and Attention-Deficit Hyperactivity Disorder (ADHD). The patient has tried a course of fluoxetine, as well as duloxetine, but she reported no improvement in her symptoms. The patient takes amphetamine for her ADHD. The patient was then diagnosed with treatment-resistant atypical depression, and her medications were switched to a combination of dextromethorphan hypobromide-bupropion hydrochloride 45- 105 mg 1 tablet a day for two weeks. After 2 weeks, her medication dosage was increased to 2 tablets in the morning.

The patient was then interviewed 3 months after initiation of treatment with the dextromethorphan-bupropion combination. The patient stated that she is now sleeping well and has an improved mood. She used to sleep for up to 18 hours a day, but now states that she sleeps for 7 to 8 hours a day. She also states that her emotions are less intense and less permanent. The patient used to have a lot of thought blocking whenever she would have negative thoughts in the past, but she states that her thoughts are a lot better now.

Discussion

Borderline Personality Disorder has a prevalence of 0.4% to 3.9% in the general population [3]. Some common symptoms of borderline personality disorder include feelings of emptiness and loneliness, impulsivity, engaging in risky behaviors, mood instability, attention-seeking behaviors, self-harming behaviors, and hypersensitivity to interpersonal rejection and criticism [9]. Most people with BPD have coexisting mental disorders such as mood disorders (ie, major depression or bipolar disorder) (83%), anxiety disorders (85%), or substance use disorders (78%) [9]. Depression is a type of mood disorder that is further classified into various types, such as typical depression, atypical depression, seasonal depression, and dysthymia [9]. Typical depression includes features like low mood, loss of reactivity, weight loss, low appetite, lack of motivation, loss of energy, and psychomotor agitation. In contrast, atypical depression has features like hypersensitivity to rejection, the ability to still feel happy at times, weight gain, increased appetite, increased sleep, and leaden paralysis [10].

Although the standard therapy for depression includes Selective Serotonin Reuptake Inhibitors (SSRIs) and Cognitive Behavioral Therapy (CBT), sometimes patients do not respond to this treatment. Multiple other classes of antidepressants can be tried, such as selective norepinephrine reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors. In rare cases, neither of these therapies works for patients who are classified as having treatment-resistant depression (TRD). According to the official definition stated by the American Association of Family Physicians, depression may be considered TRD when at least two trials with antidepressants from different pharmacologic classes (adequate in dose, duration, and compliance) fail to produce a significant clinical improvement [11].

Bupropion and mirtazapine are 2 atypical antidepressants that can be tried to treat TRD. Mirtazapine is an alpha 2 antagonist, and bupropion is a norepinephrine and dopamine reuptake inhibitor [12,13]. They both have their own sets of advantages and disadvantages depending on the desired treatment goal. Mirtazepine, for example, can cause somnolence and increased appetite along with its antidepressant properties, which may be desired or not depending on the patient’s profile [13]. Bupropion, on the other hand, has been shown to help with smoking cessation along with its antidepressant effect. Bupropion also has a much more favorable sexual side effect profile compared to SSRIs which can often cause sexual dysfunction. One of the feared side effects of bupropion is its tendency to lower the seizure threshold, especially in patients who have a history of seizures or have an eating disorder [12].

Recently, there has been a new drug formulation on the market that has been shown to be effective in patients with depression. Three large phase 3 trials on the use of Dextromethorphan-bupropion has shown promising results in the treatment of MDD. The GEMINI trial, which was a double-blinded trial comparing dextramethorphan-bupropion to placebo in 327 adults diagnosed with MDD, demonstrated that dextramethorphan-bupropion is not only safe to use, but that it was also able to improve clinical signs of depression in patients as early as 1 week into treatment [14]. Another trial, called the EVOLVE trial, was a randomized double blinded trial done on 146 patients, and it demonstrated that the antidepressant effects of dextramethorphan-bupropion could be seen as early as 1 week from initiation of treatment, and for up to 6 weeks after starting [15]. It also showed a significant reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) score for the patients being treated with dextramethorphan-bupropion [16]. Finally, there was a third trial done called the ASCEND trial, which showed rapid and significant symptom improvements in patients with MDD, in comparison to patients using bupropion sustained-release tablets [17]. There are currently multiple other trials of dextromethorphan-bupropion that are in progress, some of which include treating TRD, agitation in Alzheimer’s disease, smoking cessation, and more trials on its use in MDD [18].

This novel combination combines the effects of two different drugs in order to have a superior antidepressant effect compared to either of the individual drugs alone. Dextromethorphan works by antagonising the NMDA receptors and also acts as a sigma 1 receptor agonist [19]. Dextromethorphan has also been shown to be a potent glutamate modulator which has been linked to its antidepressant effects [19]. Dextromethorphan has also been shown to have serotonin and norepinephrine reuptake inhibition, which could further explain its antidepressant effects [19]. On top of this, bupropion is a cytochrome P2D6 inhibitor which helps boost and prolong the effects of dextromethorphan by inhibiting its metabolism [12]. These effects help explain their promising antidepressant effects when used concurrently (Figure 2).

Our case is therefore the first of its kind to document the symptomatic remission of atypical depressive features in BPD using dextromethorphan-bupropion formulation. Given the patient’s lack of response to prior medications, our clinical team opted for a trial of dextromethorphan-bupropion which showed remission of symptoms in the patient. The patient’s marked improvement in sleep, mood stabilization, emotional modulation and reduction in negative thoughts supports emerging evidence for the effectiveness of NMDA modulating agents to be used in TRD.

Moreover, her subjective report that her “emotions are less intense and less permanent” may indicate a positive shift in affect regulation, which is a core deficit in BPD. This is particularly significant, as affect instability is often refractory to standard antidepressant medications. While dextromethorphan-bupropion is not specifically indicated for BPD or atypical depression in BPD, this case adds to the growing clinical interest in exploring its off label use in complex affective syndromes where emotional dysregulation and affective lability are prominent. Despite the clinical improvements seen in our case, caution is warranted when generalizing these findings. BPD remains a diagnostically complex condition, involving many different psychiatric components. The response in this case may reflect a particular neurobiological subtype responsive to dopaminergic and glutaminergic modulation. Long-term monitoring and further studies on a larger scale are required to evaluate the sustainability and generalizability of our findings.

Conclusion

This case highlights the potential of the combination therapy of dextromethorphan-bupropion to treat atypical depression in patients with BPD, especially when the standard treatment plan fails to improve the patient’s symptoms. The patient was prescribed with SSRI and SNRI with adequate dosage for an appropriate period of time, but there was no improvement in the symptoms noted. However, significant improvement in mood stability, thought process, emotional lability, and sleep irregularities was seen with the combination therapy of dextromethorphan-bupropion. While the patient's response to the dextromethorphan-bupropion was positive and sustained over three months, further studies are required to look for the safety and long-term impact of the dextromethorphan-bupropion combination to treat mood instability in patients with personality disorders.

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