Diagnosis and Management of Medication-Induced Movement Disorders (MIMDs)
The prevalence of antipsychotic-associated movement disorders ranges from 19-44% (Martino 2023). It is important for clinicians to monitor for medication-induced movement disorders at every visit in the routine review of systems and physical exam. Clinicians should inquire about stiff joints or muscles, intermittent or constant muscle spasms, shuffling gait, decrease in normal movement, inability to sit still, an inner sense of restlessness, or tremors at baseline, weekly for the first 2 weeks after initiation until stable, and weekly for 2 weeks following dose increases. On the physical exam, clinicians can look for the following:
- Vital signs: fever or other signs of autonomic instability
- General Appearance/Behavior: pacing, restlessness, fidgetiness, involuntary movements (chorea, tremor), shuffling gait, abnormal gait, diminished or absent normal movements (bradykinesia or akinesia), abnormal posture
- HEENT: decreased facial expressions, repetitive facial movements
- Musculoskeletal: muscle spasms
- Neurological: difficulty maintaining balance; muscle tone with increased resistance to passive movement that is constant ("lead pipe" rigidity) and/or intermittent with small rhythmic jerks ("cog wheel" rigidity)
Screening
There are several screening tools that can be used to assess for specific movement disorders. Clinicians should complete a structured screening for tardive MIMDs every 6 months for patients on first generation (typical) antipsychotics or who have other high-risk factors (see below) and at minimum every 12 months for all others. Table 2 provides examples of screening and assessment tools to evaluate for medication-induced movement disorders.
Table 2. Screening or Assessment Tools
| Abnormal Involuntary Movement Scale (AIMS) | 12-item clinician-rated anchored scale developed by the National Institute of Mental Health to assess the severity of tardive dyskinesia and tardive dystonia. |
|---|---|
| Barnes Akathisia-Rating Scale (BARS) | 4-item validated instrument used to screen and assess severity of akathisia. |
| Extrapyramidal Symptom Rating Scale (ESRS) | 7-item validated questionnaire, a clinician-rated physical exam, and severity rating instrument used to assess the severity of tardive dyskinesia, tardive dystonia, akathisia, and parkinsonism. |
| Simpson-Angus Scale (SAS) | 10-item validated clinician-rated instrument to assess parkinsonism. |
When a patient on antipsychotic treatment develops extrapyramidal symptoms, clinicians must first develop a differential diagnosis. While the risk for movement-related adverse reactions can be high with certain medications, the clinician must also consider primary movement disorders and other conditions such as stroke, traumatic brain injury, or infection that can mimic extrapyramidal symptoms (Rissardo 2023). A careful history of present illness, neurological exam, laboratory and other testing, and consultation with other specialists may be needed to reach a diagnosis. Empiric treatment of possible extrapyramidal symptoms is appropriate even while completing the workup.
Similarly, it is important to rule out neuroleptic malignant syndrome (NMS). NMS is a life-threatening complication of antipsychotic treatment characterized by fever, severe muscle rigidity, and autonomic and mental status changes (Strawn 2007). If a patient develops severe muscle rigidity, it is important to assess for a change in mental status and check vital signs. If they have a fever or other abnormal vital signs, such as elevated heart rate or blood pressure, or if there has been a deterioration in mental status, they must be referred to an emergency department for urgent laboratory testing, including a comprehensive metabolic panel, complete blood count with differential, and creatine kinase. NMS is a medical emergency and may require treatment in a medical intensive care unit.
Pediatric Differential Diagnosis
Children and adolescents have distinct vulnerabilities regarding medication-induced movement disorders. They are particularly sensitive to extrapyramidal side effects (EPS) such as dystonia and akathisia, which can significantly disrupt their developmental trajectory. The stigma associated with visible abnormal movements may contribute to bullying, social isolation, school refusal, and reduced self-esteem. Providers must prioritize age-specific considerations in evaluating, diagnosing, and managing EPS in youth, understanding that pediatric presentations can differ markedly from adults.
Parkinsonism and Dystonia
Diagnosis and Clinical Features:
Parkinsonism is characterized by rigidity, lack or slowing of movement (akinesia/bradykinesia), and tremor, resembling Parkinson's Disease. It is caused by antipsychotic medications blocking D2 dopamine receptors in the nigrostriatal pathway of the basal ganglia. D2 receptors, when activated, inhibit another movement inhibitory circuit mediated by gamma-aminobutyric acid (GABA). When a medication blocks the D2 receptor, it inadvertently allows unchecked inhibition of movement, resulting in symptoms of decreased or loss of fluidity in movement (Stahl 2021).
Acute dystonia is an intermittent spasmodic or sustained involuntary contraction of the muscles in the face, neck, trunk, pelvis, or extremities (Stahl 2021). It often causes twisting, repetitive movements, or abnormal sustained postures. The neck, face, and limbs are the most affected areas. More severe dystonias can cause difficulty speaking or swallowing, an oculogyric crisis where the eyeballs deviate (typically up) and "get stuck," and dystonic opisthotonus where the extensor muscles of the neck, trunk, and lower limbs contract leading to a backward arch from neck to heels. Symptoms appear within hours or days of starting a medication or increasing the dose. Adolescents (particularly boys) have higher incident rates of dystonic reactions and young adults and Asians may also be at higher risk. High-potency D2 receptor blockers such as haloperidol or fluphenazine are more associated with acute dystonia than lower potency agents (Rissardo 2023).
Management:
As with any medication side effect, it is important to re-assess the risk-benefit ratio of continuing the antipsychotic medication. Development of acute movement disorders increases the risk for future tardive movement disorders (APA 2022). Whenever possible, clinicians should decrease the dose of the antipsychotic medication or switch to an alternate agent, especially if the reaction was severe.
Anticholinergic medications such as benztropine or diphenhydramine can be used to reduce extrapyramidal reactions. Since excessive nigrostriatal D2 receptor blockade leads to a chain reaction involving cholinergic and GABAergic neurons that inhibit movement, administration of anticholinergic medication helps restore downstream feedback loops and reduces symptoms (Stahl 2021).
Clinicians should avoid starting anticholinergic medications as prophylaxis for possible future extrapyramidal reactions on patients starting antipsychotic treatment, unless there is a clear history of prior extrapyramidal symptoms with this medication. Excessive anticholinergic burden is a contributor of cognitive symptoms in schizophrenia and can lead to other side effects such as dry mouth, drowsiness, urinary retention, constipation, blurred vision, falls, and other autonomic dysfunction (Stahl 2021 and Mancini 2025). Clinicians who begin working with individuals already on anticholinergic medications should determine if there was a prior history of extrapyramidal symptoms and reduce/discontinue the anticholinergic agent whenever possible.
Children and adolescents, especially males and younger age groups, have a significantly increased risk for acute dystonic reactions, particularly when initiated on high-potency D2 receptor blockers. Prompt recognition and intervention are essential due to potential airway compromise or intense discomfort. Providers should explicitly counsel families on recognizing early signs and symptoms of dystonia and establish clear emergency response plans.
Akathisia
Diagnosis and Clinical Features:
Akathisia is a sense of inner restlessness and difficulty sitting or standing still due to an urge for continuous movement. It has been associated with insomnia, decreased concentration, cognitive problems, significant distress, reduced quality of life, depressed mood, agitation, and suicidal ideation (Rissardo 2023). Young adults and adolescents experiencing a first episode of psychosis and men are at higher risk for akathisia (Bjarke 2022).
Unlike with acute dystonia that is primarily caused by dopaminergic blockade in the nigrostriatal pathway, akathisia's underlying biology is less clear. It is associated with dopaminergic hypoactivity in the ventral striatum and serotonergic dysfunction (Rissardo 2023).
Akathisia usually occurs within a few days or weeks of starting or increasing the dose of an antipsychotic medication. It generally has a short duration, but akathisia can also be chronic. The term tardive akathisia describes akathisia that persists after discontinuation of medications. Similarly to all extra-pyramidal symptoms, akathisia is associated with typical, first-generation antipsychotics, such as haloperidol, but it can also be caused by second-generation antipsychotics, with aripiprazole having the highest risk (Bjarke 2022).
Clinicians can generally identify akathisia by specifically asking the individual if they are experiencing inner restlessness or difficulty sitting or standing still, and it often can be identified in the mental status exam. Additionally, the Barnes Akathisia-Rating Scale (BARS) is a 4-item validated screening tool that may be useful (Barnes 1989).
Management:
It is important to re-assess the risk-benefit ratio of continuing treatment with the antipsychotic causing the symptoms, as akathisia can in itself lead to agitation and suicidality that was not present prior to initiating treatment. If possible, the clinician should reduce the dose or switch to a different medication with less risk for akathisia, such as clozapine or quetiapine. An additional or alternate option is to add a medication to reduce akathisia, such as a benzodiazepine, propranolol, or mirtazapine (Bjarke 2022). Serotonin 2A receptor antagonists such as trazodone or nefazodone may also be helpful (Stahl 2021). Anticholinergic medications are not generally used to treat akathisia unless other extra-pyramidal symptoms are also present.
In children and adolescents, akathisia may not present as explicit subjective restlessness but rather as behavioral agitation, irritability, impulsivity, or worsening hyperactivity. Such presentations may be misinterpreted as attention deficit hyperactivity disorder (ADHD), anxiety disorders, oppositional behaviors, or increased psychotic agitation. Clinicians must carefully differentiate akathisia from primary psychiatric or behavioral conditions through targeted history and behavioral observation.
Tardive Dyskinesia and Tardive Dystonia
Diagnosis and Clinical Features:
Tardive dyskinesia (TD) is a late-developing and/or slow-evolving movement disorder associated with use of antipsychotic medications characterized by a wide variety of involuntary repetitive movements, including abnormal choreoathetoid movements generally in the tongue, lower face and jaw, and extremities. Myoclonus and tremors may also be present (APA 2022 and Rissardo 2023). It usually persists after discontinuation of the medication. Orofacial dyskinesias may be more common in older individuals whereas limb or truncal dyskinesias without orofacial involvement may be more common in younger individuals. Paradoxically, symptoms of TD may worsen on discontinuation of the medication (APA 2022).
Tardive dystonia (and tardive akathisia) clinically resembles its acute counterpart and may also persist or worsen after discontinuation of the medication (APA 2022).
About 4-8% of individuals treated with typical antipsychotics will develop TD every year. In the elderly, the risk of developing TD may be as high as 25% in the first year of treatment. For individuals who have only taken the newer second-generation antipsychotics, the risk is significantly lower (APA 2022 and Stahl 2021). Individuals at greater risk of developing tardive dyskinesia include those older than 55 years; Black individuals; women; those with a history of mood disorder, substance use disorder, intellectual or developmental disabilities, central nervous system injury (e.g., traumatic brain injury, prior CNS infection, prior stroke), diabetes mellitus, prior extrapyramidal reactions (e.g., acute dystonia, parkinsonism, akathisia); and greater cumulative exposure to high-potency D2-receptor antagonists (Rissardo 2023 and APA 2022). Children and adolescents are at risk of withdrawal dyskinesias which are lower for second generation antipsychotic medications than first generation antipsychotic medications, frequently reversible, and reduced by slow and overlapping cross-titration (Correll 2008).
TD is caused by persistent D2 receptor blockade that leads to synthesis of more D2 receptors resulting in increased sensitivity to dopamine. Instead of parkinsonism from excessive D2 blockade, the increased sensitivity for dopamine leads to the opposite reaction – involuntary hyperkinetic movements (Stahl 2021). It is possible to have acute extrapyramidal symptoms superimposed on a background of TD.
In addition to regularly assessing for acute extrapyramidal symptoms at every visit, all clinicians should use the Abnormal Involuntary Movement Scale (AIMS) at minimum every six months for patients at elevated risk for TD and yearly for anyone else on antipsychotic treatment. Additionally, the patient, family members, and friends should receive education about TD and be asked to report any concerning observations. It is possible to complete most of the AIMS in a video visit if the camera and the patient are carefully positioned. Using the AIMS helps clinicians track the longitudinal course of TD and its response to treatment. There is no specific TD diagnostic threshold score on the AIMS, but it can help distinguish between mild, moderate, and severe presentations (APA 2022).
Management:
If the D2 antagonist is discontinued immediately after onset of TD symptoms, symptoms may resolve. However, discontinuing the antipsychotic is not an option for many people because of the risk of worsening mental health (Stahl 2021).
Clozapine is the antipsychotic of choice for individuals with refractory schizophrenia and has a very low propensity for causing TD. In fact, unlike with other antipsychotics, there is some evidence that it could reduce TD symptoms. Switching treatment to clozapine is an option for management of psychosis in patients who have developed TD, particularly if they are not sufficiently stabilized on their current treatment regimen (Wong 2022).
Vesicular monoamine transporter 2 (VMAT2) inhibitors are a treatment option for TD and should be started for individuals who have moderate or severe TD and considered in individuals with mild TD if accompanied by disability or impaired social function. Due to their longer half-life, deutetrabenazine or valbenazine are preferred over tetrabenazine. Tetrabenazine and deutetrabenazine are contraindicated in individuals with hepatic impairment. Sedation is the primary side effect of VMAT2 inhibitors. Tetrabenazine can also result in other extrapyramidal effects, insomnia, anxiety, nausea, and falls (APA 2022). Clinicians should review the package insert of VMAT2 inhibitors prior to prescribing them.
Many medications used for EPS, including VMAT2 inhibitors (deutetrabenazine, valbenazine), have limited pediatric data and may lack FDA approval for use in children. Clinicians should clearly communicate these limitations to caregivers, utilize cautious dosing approaches, and involve pediatric psychiatric specialists or pediatric neurologists for treatment initiation and monitoring.
