"A highly unusual case report highlights that even commonly prescribed antidepressants like bupropion XL can, in rare instances, trigger new-onset tic disorders, emphasizing the importance of vigilant monitoring and differential diagnosis in psychiatric care."
This striking case, documented by clinicians at the Atal Bihari Vajpayee Institute of Medical Sciences and Dr. RML Hospital in New Delhi, sheds light on an exceptionally rare adverse reaction to bupropion XL, a widely used antidepressant. The report details the experience of a 27-year-old man who developed a distressing constellation of involuntary motor and vocal tics, including clapping, whistling, and bursts of uncontrollable laughter, approximately two months after initiating treatment with bupropion XL. This situation underscores a critical, albeit infrequent, potential side effect that clinicians must consider when managing patients on this medication.
The patient presented with a six-month history of disruptive, involuntary actions that significantly impacted his social functioning. These episodes, occurring multiple times per hour, were characterized by abrupt, repetitive clapping with both hands, interspersed with whistling and spontaneous, unbidden laughter. While he possessed a limited ability to suppress these tics through conscious effort, this control was transient, and his symptoms were exacerbated by anxiety and social stress. Importantly, the tics did not cease with distraction, a characteristic that helped differentiate them from other neurological conditions. He also continued to exhibit symptoms of depression, including low mood, anhedonia, fatigue, poor concentration, and diminished self-esteem, suggesting that the bupropion XL had not effectively addressed his primary complaint and had instead introduced a new and significant problem.
A thorough review of the patient’s medical history revealed no prior history of tic disorders, either in himself or his family. His existing medical conditions included well-controlled HIV, managed for four years with a stable undetectable viral load and a healthy CD4 count of 580 cells/µL. Previous neurological imaging had identified a stable arachnoid cyst and non-specific white matter changes, conditions that had remained clinically silent for years and were therefore deemed unlikely to be the direct cause of his sudden onset of tics. Standard laboratory investigations, including blood counts, kidney and liver function tests, and electrolyte levels, all fell within normal parameters. Consultation with a neurologist, coupled with the clear temporal relationship between the initiation of bupropion XL and the onset of symptoms, the absence of focal neurological deficits, and stable imaging findings, led the clinical team to forgo more invasive diagnostic procedures such as spinal fluid analysis.
To quantify the likelihood that bupropion XL was responsible for the patient’s symptoms, the clinicians employed the Naranjo Adverse Drug Reaction Probability Scale. This standardized tool assesses various factors to determine the probability of a drug-induced adverse event. The patient’s score of 7 placed his reaction firmly in the "probable" range, indicating a strong likelihood that the bupropion XL was the causative agent.
Bupropion XL is a commonly prescribed medication in the United States, utilized for the treatment of major depressive disorder and as a smoking cessation aid. It is generally perceived as having a more favorable profile regarding movement-related side effects compared to many other antidepressant classes. The drug functions as a norepinephrine-dopamine reuptake inhibitor (NDRI). The prevailing understanding of tic disorders points to dysregulation within the cortico-striato-thalamo-cortical circuits, with an overactive dopaminergic system in the striatum playing a significant role. Consequently, a medication that increases dopaminergic activity in this region, such as bupropion, could theoretically predispose an individual to the development of tics. Supporting this hypothesis, animal studies have demonstrated that bupropion can induce stereotyped behaviors, which bear some resemblance to tic-like movements.
While stimulants like methylphenidate are well-established triggers for tics, and selective serotonin reuptake inhibitors (SSRIs) have been occasionally linked to tic development, the association with bupropion, particularly its extended-release formulation, is considered exceptionally uncommon. The current case report is only the second published instance detailing new-onset tics directly linked to bupropion XL. A prior report described a similar phenomenon with the extended-release formulation, while another documented the exacerbation of a pre-existing tic disorder in a patient taking bupropion. It is noteworthy that the official FDA prescribing information for Wellbutrin XL (the brand name for bupropion XL) does not explicitly list tics as an adverse reaction. However, it does mention muscle twitching in clinical trial data and includes postmarketing reports of other movement-related effects, such as dyskinesia, dystonia, and extrapyramidal syndrome, which suggest a broader spectrum of potential neurological impacts.
Following the diagnosis, the clinical team initiated a management strategy focused on addressing the adverse reaction. Bupropion XL was gradually tapered and discontinued. Given the persistent and distressing nature of the tics, the patient was started on risperidone, an atypical antipsychotic, at a dose of 2 mg once daily. To manage his ongoing depressive symptoms, escitalopram, an SSRI, was initiated at a dose of 10 mg.
The impact of discontinuing bupropion XL was remarkably swift and significant. Within three weeks of stopping the medication, the frequency and intensity of both the motor and vocal tics showed a noticeable decline. By the six-week follow-up, the tics had decreased by over 70 percent. At the two-month mark, the patient’s tics had completely resolved. Concurrently, his scores on the Hamilton Depression Rating Scale improved, indicating a positive response to the treatment for his depression.
It is crucial to acknowledge that a single case report, while informative, cannot definitively establish causality. However, this case strongly demonstrates a clear temporal relationship between bupropion XL use and the onset of tics, proposes a plausible neurobiological mechanism, and effectively rules out alternative explanations. The concurrent initiation of risperidone alongside the discontinuation of bupropion means that the observed recovery cannot be solely attributed to either intervention. The authors emphasize the need for further pharmacovigilance efforts to better understand the incidence and risk factors associated with bupropion-induced tics.
The practical implications of this case are primarily directed towards healthcare professionals. The authors recommend that clinicians inquire about a personal or family history of tic disorders prior to initiating bupropion therapy. Furthermore, they advise that if new involuntary movements or sounds emerge during bupropion treatment, consideration should be given to the medication as a potential cause, rather than immediately assuming a primary neurological disorder. Patients experiencing any new involuntary movements or sounds while taking prescription medication are strongly encouraged to discuss these changes with their prescribing clinician rather than discontinuing treatment independently. This approach ensures appropriate medical evaluation and management, safeguarding patient well-being and optimizing therapeutic outcomes.
Key Questions Answered:
What symptoms did the patient develop?
The patient developed involuntary clapping, whistling, and episodes of uncontrollable laughter, occurring multiple times per hour. He could temporarily suppress these tics with conscious effort, and his symptoms were worsened by stress.
How long after starting the drug did symptoms appear?
The involuntary movements and sounds began approximately two months after the patient started taking bupropion XL. By the time he sought medical attention at the clinic that published the report, he had been experiencing these tics for six months.
How confident are the authors that bupropion was responsible?
The authors assessed the case using the Naranjo Adverse Drug Reaction Probability Scale and achieved a score of 7, which signifies a "probable" drug reaction. While a single case report cannot definitively prove causation, the strong temporal association, plausible mechanism, and exclusion of other causes support this conclusion.
Did the tics go away?
Yes. The frequency and intensity of both motor and vocal tics decreased significantly within three weeks of stopping bupropion XL. By six weeks, they had reduced by over 70 percent, and by the two-month follow-up, they had completely resolved. The patient was also receiving low-dose risperidone during this period.
Is this a common side effect of bupropion?
No. The authors describe this side effect as "exceptionally uncommon." They cite only one prior published case reporting new-onset tics associated with the extended-release formulation of bupropion.
Should people on bupropion be worried?
This case report does not alter current prescribing guidelines or suggest that patients should stop taking bupropion. However, it serves as a reminder for both patients and prescribers. Anyone experiencing new involuntary movements or sounds while on bupropion, or any other prescription medication, should promptly discuss these changes with their healthcare provider for proper evaluation and management.
