Tardive dyskinesia (TD) is a slow-onset, hyperkinetic movement disorder involving repetitive involuntary movements. It is classified as a medication-induced movement disorder that occurs in association with the use of dopamine-blocking agents–most commonly, antipsychotics. It is classically understood as an unremitting process, with a few cases of reversible conditions and uncertain remission rates. Aripiprazole possesses a distinct and unique mechanism that decreases its risk compared to other antipsychotics. In this case series, we discuss three cases involving Saudi women who developed aripiprazole-induced TD; notably, all cases remitted upon aripiprazole discontinuation or dose reduction without utilizing other forms of treatment. The current literature remains limited in describing aripiprazole-induced TD, lacking a clear understanding of the development of TD following aripiprazole administration, the determined remission rate, and definite management.
Tardive dyskinesia (TD) is a slow-onset, hyperkinetic movement disorder that involves repetitive, involuntary movements ranging from slight tremors to uncontrollable choreatic movements of the whole body. It presents mainly with orofacial movements, namely oral–buccal–lingual involuntary movements. However, in approximately half of all patients, it also involves the peripheral extremities and may involve the neck or trunk in 25% of patients. In severe cases, it can affect swallowing, speech, and mastication. In rare cases, respiratory muscle involvement can present and be life-threatening (
The underlying pathophysiology of TD remains uncertain; however, the most accepted theory links TD to the dopamine receptor hypersensitivity hypothesis. Prolonged blockade of dopamine D2 receptors by antipsychotics or other blocking agents prompts a compensatory upregulation and an increase in receptor density. Consequently, this adaptation leads to an exaggerated postsynaptic reaction to dopamine (
Several risk factors have been recognized including female sex, advanced age, long-term exposure to dopamine-blocking agents, mood disorders, negative symptoms in schizophrenia, intellectual disability, diabetes mellitus, and prior extrapyramidal symptoms (
The annual incidence of TD is estimated to be 2–5%, and its prevalence is estimated to be 25.3% (
Aripiprazole, similar to SGAs, is associated with a lower risk of developing TD than FGAs. Furthermore, aripiprazole has the lowest risk of developing TD compared to SGAs when compared to all FGAs (
In this study, we investigated three cases of TD related to the use of aripiprazole. Notably, all patients achieved remission after discontinuation of aripiprazole.
This case series was conducted at the Department of Neurosciences, King Abdullah bin Abdulaziz University Hospital (KAAUH) in Riyadh, Saudi Arabia. Ethical approval was obtained from the Institutional Review Board (IRB), and written informed consent was obtained from all participants.
A literature search was conducted using PubMed/MEDLINE to identify published cases of aripiprazole-induced TD. The search was conducted using “Aripiprazole AND Tardive Dyskinesia” and “Aripiprazole AND Tardive syndrome” and included articles published up to October 2025. We included all cases with aripiprazole being associated with TD. We excluded cases describing tardive syndromes other than TD, such as tardive dystonia. We also excluded cases presenting with pre-existing movement conditions.
A 57-year-old female patient diagnosed with bipolar affective disorder (BAD) was maintained on aripiprazole (15 mg/day) and quetiapine (300 mg at bedtime). After approximately four and a half years of stability on these regimens, the patient exhibited involuntary movements of the tongue and lip, with no other extrapyramidal symptoms. Prior to this regimen, she took olanzapine that was stopped a few months later due to over-sedation. No other antipsychotics were utilized. Her family history was unremarkable for TD. Her medical history was positive for hypothyroidism controlled with thyroxine (50 mcg daily). She did not smoke or consume alcohol. Aside from in-and-out tongue protrusion and lip smacking that she could not control, no other focal neurological deficits were detected, physical examination was otherwise unremarkable, and vital signs were within normal limits. The Abnormal Involuntary Movement Scale (AIMS) score was calculated to be 15 for the involuntary movements. Accordingly, the dosage of aripiprazole was gradually decreased until cessation, whereas quetiapine was maintained on the same dose of 300 mg daily. Shortly after aripiprazole discontinuation, tongue movements became partially subject to voluntary control (she could shortly inhibit them while attempting to do so). In the subsequent 2 months, her dyskinetic movements progressively diminished and ultimately resolved upon cessation. At the 1-year follow-up, the patient remained asymptomatic.
A 62-year-old female patient, diagnosed with BAD and aerophobia (fear of flying), was treated with aripiprazole at a dose of 5 mg/day for obsessive ruminative thoughts concerning her daughter, which was then titrated to 15 mg/day. The concomitant drugs comprised quetiapine (200 mg) at bedtime, bupropion 300 mg daily, and lamotrigine 200 mg daily. Shortly after, she showed akathisia that was managed sufficiently with propranolol 10 mg three times per day. However, 6 months after starting aripiprazole, she exhibited involuntary facial and lip movements and hand tremors that did not respond to propranolol. While she had not been exposed to other antipsychotics while receiving care at our clinics that was initiated about 3 years before initiating aripiprazole, previous exposure to other antipsychotics could not be established and was limited by an inability to conduct her earlier medical records and by the patient’s inability to recall. Although her family history was positive for BAD and major depressive disorder, no family member had experienced symptoms suggesting TD. Her medical history was positive for hypertension managed with lercanidipine (10 mg daily) and dyslipidemia managed with rosuvastatin (20 mg daily). She did not smoke or consume alcohol. Aside from this involuntary movement, no focal neurological deficit was detected, the physical examination was normal, and vital signs were within normal limits. The AIMS score was 14 for the involuntary movement. Aripiprazole was promptly terminated, propranolol was discontinued, and the quetiapine dosage was elevated to 300 mg/day, while other medications were maintained at the same doses. The patient showed gradual improvement after discontinuation of aripiprazole, with total symptom resolution at the 1-month follow-up and no recurrence throughout the 1-year follow-up while being treated with the last regimen.
A 26-year-old female patient diagnosed with schizoaffective disorder was maintained on aripiprazole 10 mg/day for approximately 1 year, achieving clinical stability. Subsequently, she received a single intramuscular long-acting injection of aripiprazole (400 mg), after which she developed involuntary jaw clenching, neck twisting, and irregular, purposeless left arm movement. She did not have any previous exposure to other antipsychotics, and her medical history was unremarkable. There was no family history of such movement or other movement disorders. She did not smoke or consume alcohol. Her physical examination was otherwise unremarkable, and vital signs were within normal limits. Laboratory tests were unremarkable and within normal ranges. The AIMS score was calculated to be 18 for the involuntary movement. The patient discontinued aripiprazole treatment without any additional pharmacological intervention. Over the next 2 months, her dyskinetic symptoms gradually improved, with complete remission thereafter. Oral aripiprazole was resumed without symptom recurrence. The patient remained clinically stable and symptom-free during the 1-year follow-up period.
This case series presents three cases of aripiprazole-induced TD. All patients were administered aripiprazole, either orally or via depot injection, and the symptoms resolved completely with discontinuation without requiring any other intervention. Although TD has historically been considered an unremitting pathology, reports involving remitted (i.e., reversible) cases have been published (
Management of TD remains a challenge and the available strategies remain suboptimal. The general approach to TD is broadly similar among different antipsychotics and include a revision of the offending agent and evaluating the clinical feasibility of dose reduction and discontinuation. Switching to another antipsychotic with a relatively lower TD risk, such as quetiapine or clozapine, should be considered, especially if TD has developed following treatment with an FGA. For persistent, distressing symptoms, adding a VMAT2 inhibitor (valbenazine or deutetrabenazine) should also be considered. Other management strategies still require stronger evidence (
Regarding the reversibility of aripiprazole-induced TD, in addition to the lack of large-scale studies, published cases have shown mixed outcomes, adding further to the debate on the possible reversibility and remission of TD. Many published case reports have indicated an irreversible course (
Cases of aripiprazole-induced TD improved by stopping aripiprazole with utilizing another low TD–risk SGA.
| Case report/year | Age/ sex | Underlying disorder | Prior antipsychotics | Aripiprazole dose | Treatment duration | TD onset | Management | Outcome |
|---|---|---|---|---|---|---|---|---|
| Evcimen et al./2007 ( |
54/Female | Schizoaffective disorder | Prior use of olanzapine for 5 years | 20 mg/day | 10 months | After 10 months | Aripiprazole discontinued, maintained on quetiapine | Dyskinesia resolved completely within 1 month |
| Abbasian and Power/ |
24/Female | Paranoid schizophrenia | 2 weeks on risperidone | 15 mg/day | 9 months | After 9 months of treatment | Aripiprazole cross-tapered with quetiapine 200 mg BD | Symptoms remitted completely within 4 weeks |
| Tomruk et al./ |
56/Female | Schizoaffective disorder | Haloperidol, risperidone, amisulpride, chlorpromazine | 30 mg/day | 1 year | After 1 year on aripiprazole alone | Aripiprazole was discontinued and quetiapine was initiated | Rapid improvement |
| Ono et al./ |
22/Male | Schizophrenia | Prior use of olanzapine | 24 mg/day | 6 months | Started with olanzapine, improved with aripiprazole 12 mg and recurred with 24 mg | Aripiprazole was discontinued and started quetiapine (50 mg/day) | Dyskinesia improved completely within weeks |
| She et al./ |
29/Female | Schizophrenia | Neuroleptic-naive other than aripiprazole | 10 mg/day | 8 years | After 8 years of treatment | Aripiprazole stopped; quetiapine (200 mg/day) and Ginkgo biloba (240 mg/day) administered | Effectively relieved within 3 months |
| She et al./ |
29/Female | Schizophrenia | Neuroleptic-naive other than aripiprazole | 10 mg/day | 10 years | After 10 years of treatment | Aripiprazole stopped; quetiapine (200 mg/day) and Ginkgo biloba (240 mg/day) | Effectively relieved within 3 months |
| Godhania et al./ |
23/Male | BAD | Ongoing use of aripiprazole in the community with mild TD | 200 mg IM depot | Not specified | Marked increase in dyskinesia after starting depot injection | Aripiprazole switched to quetiapine 400 mg BD | AIMS reduced from 20 to 2 after several weeks |
TD, tardive dyskinesia; SGA, second-generation antipsychotic; BAD, bipolar affective disorder; IM, intramuscular injection; BD, twice per day; AIMS, Abnormal Involuntary Movement Scale.
Cases of aripiprazole-induced TD improved by stopping aripiprazole and utilizing other interventions.
| Case report/year | Age/ sex | Underlying disorder | Prior antipsychotics | Aripiprazole dose | Treatment duration | TD onset | Management | Outcome |
|---|---|---|---|---|---|---|---|---|
| Wang et al./ |
52/Female | Schizophrenia | Prior use of sulpiride for 6 years | 10 mg/day | 2 months | After 2 months of aripiprazole only | Diphenhydramine 150 mg/day | Gradually disappeared in 3–4 months |
| Lungu et al./ |
62/Male | PTSD | Neuroleptic-naive other than aripiprazole | 15 mg/day | 18 months | After 18 months of treatment | Aripiprazole stopped; symptoms persisted and was unresponsive to trihexyphenidyl, baclofen, clonazepam, and botulinum toxin. Bilateral GPi-DBS was done. | DBS led to considerable benefit within 3 months |
| Alexander & Bickerstaff/ |
46/Female | BAD, borderline traits | History of substance abuse; previous risperidone-induced TD, resolved over 2 weeks of stopping | 10 mg/day | 2 weeks | Reemergence of TD after 2 weeks on aripiprazole | Aripiprazole discontinued, clonazepam 0.5 mg | “Good effect” timeframe not mentioned |
| Aguilar et al./ |
23/Female | Psychosis | Prior use of olanzapine | Up to 25 mg/day | 6 years | After 6 years of treatment | Aripiprazole discontinued. combination of tetrabenazine (75 mg/day), botulinum toxin, and clozapine (100 mg/day) | Significant improvement, timeframe not mentioned |
TD, tardive dyskinesia; PTSD, post-traumatic stress disorder; BAD, bipolar affective disorder; GPi, globus pallidus internus; DBS, deep brain stimulation.
Cases of aripiprazole-induced TD improved with dose reduction or discontinuation only.
| Case report/year | Age/ sex | Underlying disorder | Prior antipsychotics | Aripiprazole dose | Treatment duration | TD onset | Management | Outcome |
|---|---|---|---|---|---|---|---|---|
| Maytal et al./ |
62/Female | MDD, GAD, agoraphobia | Ziprasidone and risperidone | 15 mg/day | 18 months | After 18 months of treatment | Aripiprazole discontinued | Symptoms resolved completely within 2 weeks |
| Caykoylu et al./ |
45/Female | Unspecified psychotic disorder | Prior use of quetiapine (200 mg/day) for 3 years | Up to 15 mg/day | 3 months | After 3 months of treatment | Dose reduced to 10 mg/day, added biperiden 3 mg/day and TD improved, but worsened after stopping biperiden. Aripiprazole was stopped and TD resolved. | Movements resolved within 1 week |
| Patra/ |
19/Male | Paranoid illness | Neuroleptic-naive other than aripiprazole | 20 mg/day | 6 months | After 6 months, upon dose increase of fluoxetine | Dose reduced to 15 mg/day | Movements were reduced after 2 weeks |
TD, tardive dyskinesia; MDD, major depressive disorder; GAD, generalized anxiety disorder; BAD, bipolar affective disorder; IM, intramuscular injection; LAI, long-acting injection.
In conclusion, TD is classically recognized as a chronic and unremitting disorder (
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
The studies involving humans were approved by Institutional Review Board - PNU. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
SA: Conceptualization, Supervision, Writing – original draft, Writing – review & editing. AA: Writing – original draft, Writing – review & editing. LA: Writing – original draft, Writing – review & editing. JS: Writing – original draft, Writing – review & editing. LA: Writing – original draft, Writing – review & editing. AA: Writing – original draft, Writing – review & editing.
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