Drug-induced Acute Dyskinesia–Risperidone and Tramadol Interaction: A Case Report

Highlights

• Tramadol can induce acute dyskinesia in patients on long-term antipsychotic therapy.

• CYP450-mediated interactions play a significant role in this adverse reaction.

• Prompt discontinuation of tramadol and therapeutic adjustments led to full recovery.

• Multidisciplinary collaboration is crucial for effective management.

• This case underscores the importance of vigilant monitoring in polypharmacy cases.

Dear Editor,

Acute dyskinesia is a complex neurological disorder characterized by involuntary, repetitive movements that typically arise from the use of antipsychotic medications due to multifactorial mechanisms such as neuroadaptive changes in dopaminergic pathways, oxidative stress, and neuroinflammation. ¹ Tramadol, an atypical analgesic with pharmacological effects including weak mu-opioid receptor agonism, serotonin-norepinephrine reuptake inhibition, and dopaminergic modulation, is known to exacerbate movement disorders in susceptible individuals. This is particularly concerning when combined with antipsychotics due to shared metabolism via cytochrome P450 enzymes, specifically CYP3A4 and CYP2D6, which can lead to pharmacokinetic and pharmacodynamic interactions.^2–3 Tramadol affects noradrenaline and serotonin uptake, which could interact with risperidone’s effects at 5-HT2 receptors.^2–3 We present a rare case of acute dyskinesia induced by tramadol in a patient with schizophrenia on long-term risperidone therapy, emphasizing the need for vigilance in identifying drug interactions in patients receiving antipsychotics.

Case Report

The patient, a 49-year-old male, had a 20-year history of schizophrenia, multiple episodes, currently in complete remission as per International Classification of Diseases 11th Revision (ICD 11), ⁴ without any medical comorbidities. He had been on regular antipsychotic medication, taking risperidone 4 mg/day orally. He presented with complaints of hand shakiness, involuntary movements of the mouth, difficulty in swallowing, and difficulty in speaking one week after taking tramadol 100mg/day orally for pain relief for two days. During the clinical evaluation, the Abnormal Involuntary Movement Scale ⁵ was administered to assess the severity of dyskinesia. We obtained a higher score of 17, indicating a greater degree of abnormal movements. Imaging and laboratory tests showed no abnormalities, and the Naranjo Adverse Drug Reaction Probability Scale score was 6 (indicating probable causality). ⁶ Upon admission, physical examination revealed tremors, dysarthria, and dysphagia, indicating significant motor dysfunction. The management strategy involved discontinuing tramadol, cross-tapering risperidone 4 mg/day orally with aripiprazole 15 mg/day, and introducing trihexyphenidyl 4 mg/day orally to address the symptoms. However, the resolution of dyskinesia by retaining risperidone would have confirmed the offending drug as tramadol-induced interaction. For the patient’s health benefit, we did not want to risk a trial retaining risperidone. Considering the patient’s age as a risk factor and the need for a favorable metabolic profile, we cross-tapered to aripiprazole 15 mg/day orally. This therapeutic approach led to significant improvement. Abnormal Involuntary Movement Scale scores decreased to 12 on Day 5, 7 on Day 10, and 0 on Day 14. The patient experienced a complete resolution of symptoms, confirmed at a one-month follow-up, with no recurrence of involuntary movements.

Discussion

This case highlights the potential for drug-induced movement disorders in patients undergoing long-term antipsychotic therapy, particularly when exposed to medications with neuromodulatory properties like tramadol. The overlapping metabolic pathways of tramadol and risperidone, primarily via CYP3A4 and CYP2D6,^2–3 can lead to pharmacokinetic interactions, increasing the likelihood of adverse neurological effects. Given tramadol’s impact on serotonergic and noradrenergic transmission, its interaction with risperidone’s 5HT2 receptor blockade may further exacerbate dyskinetic symptoms. Clinicians should be cautious when prescribing opioid analgesics to individuals on dopamine-modulating drugs, as even a short duration of exposure can result in severe extrapyramidal side effects. This case underscores the importance of careful medication review, early symptom recognition, and prompt discontinuation of the offending agent. Alternative pain management strategies, such as nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or nonpharmacologic interventions, should be prioritized in psychiatric patients to minimize the risk of drug-induced movement disorders.

Conclusions

The findings from this case reinforce the need for heightened awareness regarding the neurological risks associated with polypharmacy in psychiatric patients. Early identification and timely intervention are essential to prevent irreversible motor dysfunction. This case further supports the necessity of personalized medication management, considering factors such as age, metabolic enzyme activity, and preexisting movement disorders. Clinicians must implement a proactive approach by regularly assessing for drug interactions, adjusting medication regimens when necessary, and utilizing alternative therapies when safer options exist. Future research should focus on understanding the precise mechanisms of drug-induced movement disorders and integrating pharmacogenomic testing to enhance patient safety.

Supplemental Material

Supplemental material for this article available online.