Implications of Antipsychotic Use

Antipsychotic-Induced Movement Disorders, with a Focus on Tardive Dyskinesia
Open AccessPublished:October 10, 2019DOI:https://doi.org/10.1016/j.cnur.2019.08.004

      Keywords

      Key points

      • Antipsychotics are necessary and life-changing and saving medications, but like all medications they carry the risk of unwanted effects. These effects may include drug-induced movement disorders such as tardive dyskinesia (TD).
      • All antipsychotic-treated patients should be screened and monitored for movement disorders. Screening protocols for other antipsychotic-related effects, such as orthostatic hypotension, weight gain, or metabolic changes, already exist.
      • Screening may involve a simple visual observation for abnormal movements; however, assessments with formal instruments (eg, Abnormal Involuntary Movement Scale) are recommended.
      • Diagnosis of antipsychotic-induced movement disorders are based on the patient’s clinical presentation in combination with a thorough psychiatric, medical, and medication history. Differentiating between movement disorders may be challenging, but simple frameworks (eg, acute vs tardive, hypokinetic vs hyperkinetic) can help improve recognition.
      • Nurses play a key role in educating patients and families about antipsychotic-induced movement disorders. Central to this education is the availability of FDA-approved medications for TD that allow the patient to remain on their current antipsychotic regimen.

      Antipsychotic use and development

      Advancements in the development of antipsychotic medications have led to life-saving outcomes in patients with various psychiatric and nonpsychiatric conditions. Before the introduction of chlorpromazine in psychiatric clinical practice in 1952, there were no effective medications for the treatment of schizophrenia, which is one of the leading causes of disability worldwide.
      • Haddad P.M.
      • Correll C.U.
      The acute efficacy of antipsychotics in schizophrenia: a review of recent meta-analyses.
      • Lopez-Munoz F.
      • Alamo C.
      • Cuenca E.
      • et al.
      History of the discovery and clinical introduction of chlorpromazine.
      The first-generation antipsychotics, also known as “neuroleptics” or “typical” antipsychotics, were primarily dopamine D2 receptor antagonists. These medications continue to be used in schizophrenia and other psychotic disorders because they are effective in managing symptoms such as delusions, hallucinations, and disorganized speech, thoughts, or behavior.
      The development of second- and third-generation antipsychotics, also called “atypical” antipsychotics, has resulted in a substantial increase in antipsychotic use.
      • Cloud L.J.
      • Zutshi D.
      • Factor S.A.
      Tardive dyskinesia: therapeutic options for an increasingly common disorder.
      Currently, antipsychotics are routinely prescribed (both on-label and off-label) in numerous psychiatric and neuropsychiatric conditions beyond schizophrenia, including mood and affective disorders, Tourette syndrome, hyperactivity, and challenging behaviors in patients with intellectual developmental disability or other neurodevelopmental disorders (Table 1). Furthermore, use has expanded beyond disorders with psychotic components to conditions such as major depressive disorder, which are often treated in the primary care setting. Newer-generation antipsychotics, including aripiprazole, brexpiprazole, and cariprazine, are partial D2 agonists that act as functional agonists or functional antagonists depending on the surrounding levels of endogenous dopamine (Box 1). When a full agonist is not available, partial agonists bind to the receptors and increase postsynaptic activity (partial agonist); when a full agonist is available, the partial agonist binds to receptors but results in decreased activity compared with full agonist binding (partial antagonist).
      • Lieberman J.A.
      Dopamine partial agonists: a new class of antipsychotic.
      Table 1Antipsychotics and indicated uses
      Data from Refs.
      • Seida J.
      • Schouten J.
      • Mousavi S.
      • et al.
      First- and second-generation antipsychotics for children and young adults. Comparative Effectiveness Reviews No. 39.
      • Scheer C.
      Differentiating antipsychotics: an overview of properties impacting drug selection.
      • Galen US
      Adasuve [prescribing information].
      • Teva Pharmaceuticals USA
      Orap [prescribing information].
      • Roerig
      Navane [prescribing information].
      OptumRx. Therapeutic class overview: atypical antipsychotics.
      • Otsuka America Pharmaceutical
      Abilify [prescribing information].
      • Allergan USA
      Saphris [prescribing information].
      • Otsuka America Pharmaceutical
      Rexulti [prescribing information].
      • Allergan USA
      Vraylar [prescribing information].
      • HLS Therapeutics
      Clozaril [prescribing information].
      • Vanda Pharmaceuticals
      Fanapt [prescribing information].
      • Sunovion Pharmaceuticals
      Latuda [prescribing information].
      • Lilly USA
      Olanzapine [prescribing information].
      • ALZA Corp
      Invega [prescribing information].
      • AstraZeneca
      Seroquel [prescribing information].
      • Janssen Pharmaceuticals
      Risperdal [prescribing information].
      • Roerig
      Geodon [prescribing information].
      Antipsychotic

      Generic (Brand) Name
      Indicated Use(s)
      Schizophrenia or Schizoaffective DisorderMood or Other Affective DisordersOther Psychiatric DisordersOther Medical Conditions
      First generation
      • Seida J.
      • Schouten J.
      • Mousavi S.
      • et al.
      First- and second-generation antipsychotics for children and young adults. Comparative Effectiveness Reviews No. 39.
      • Scheer C.
      Differentiating antipsychotics: an overview of properties impacting drug selection.
       Chlorpromazine (Thorazine)
      • Schizophrenia
      • Bipolar disorder (manic)
      • Hyperactivity (children)
      • Severe behavioral problems (children)
      • Nausea and vomiting
      • Restlessness and apprehension before surgery
      • Acute intermittent porphyria
      • Adjunctive treatment of tetanus
      • Intractable hiccups
       Fluphenazine (Prolixin)
      • Psychotic disorders
       Haloperidol (Haldol)
      • Schizophrenia
      • Tourette syndrome
      • Hyperactivity
      • Severe behavioral problems (children)
       Loxapine (Loxitane, Adasuve)
      • Galen US
      Adasuve [prescribing information].
      • Schizophrenia
       Perphenazine (Trilafon)
      • Schizophrenia
       Pimozide (Orap)
      • Teva Pharmaceuticals USA
      Orap [prescribing information].
      • Tourette syndrome
       Thioridazine (Mellaril)
      • Schizophrenia in patients who have failed other antischizophrenia therapy
       Thiothixene (Navane)
      • Roerig
      Navane [prescribing information].
      • Schizophrenia
       Trifluoperazine (Stelazine)
      • Schizophrenia
      • Nonpsychotic anxiety (short-term)
      Second and third generation
      • Seida J.
      • Schouten J.
      • Mousavi S.
      • et al.
      First- and second-generation antipsychotics for children and young adults. Comparative Effectiveness Reviews No. 39.
      • Scheer C.
      Differentiating antipsychotics: an overview of properties impacting drug selection.
      OptumRx. Therapeutic class overview: atypical antipsychotics.
       Aripiprazole (Abilify)
      • Otsuka America Pharmaceutical
      Abilify [prescribing information].
      • Schizophrenia
      • Bipolar disorder (manic, mixed)
      • Adjunctive treatment of major depressive disorder
      • Autism
      • Tourette syndrome
       Asenapine (Saphris)
      • Allergan USA
      Saphris [prescribing information].
      • Schizophrenia
      • Bipolar disorder (manic, mixed)
       Brexpiprazole (Rexulti)
      • Otsuka America Pharmaceutical
      Rexulti [prescribing information].
      • Schizophrenia
      • Adjunctive treatment of major depressive disorder
       Cariprazine (Vraylar)
      • Allergan USA
      Vraylar [prescribing information].
      • Schizophrenia
      • Bipolar disorder (manic, mixed)
       Clozapine (Clozaril, Verscloz, FazaClo)
      • HLS Therapeutics
      Clozaril [prescribing information].
      • Schizoaffective disorder
      • Treatment-resistant schizophrenia
       Iloperidone (Fanapt)
      • Vanda Pharmaceuticals
      Fanapt [prescribing information].
      • Schizophrenia
       Lurasidone (Latuda)
      • Sunovion Pharmaceuticals
      Latuda [prescribing information].
      • Schizophrenia
      • Bipolar disorder (depressive)
       Olanzapine (Zyprexa)
      • Lilly USA
      Olanzapine [prescribing information].
      • Schizophrenia
      • Bipolar disorder
      • Adjunctive treatment of major depressive disorder
       Paliperidone (Invega)
      • ALZA Corp
      Invega [prescribing information].
      • Schizoaffective disorder
      • Schizophrenia
       Quetiapine (Seroquel)
      • AstraZeneca
      Seroquel [prescribing information].
      • Schizophrenia
      • Bipolar disorder
      • Adjunctive treatment of major depressive disorder
       Risperidone (Risperdal)
      • Janssen Pharmaceuticals
      Risperdal [prescribing information].
      • Schizophrenia
      • Bipolar disorder (manic, mixed)
      • Autism
       Ziprasidone (Geodon)
      • Roerig
      Geodon [prescribing information].
      • Schizophrenia
      • Bipolar disorder (manic, mixed)
      Definitions
      • Agonist: An agonist binds to the receptor and activates it, similar to the endogenous chemical.
      • Partial agonist: A partial agonist binds to the receptor and activates it. It may functionally serve as an agonist or antagonist based on the level of endogenous chemical in the synapse.
      • Antagonist: An antagonist binds to the receptor but does not activate, reducing postsynaptic activity.
      • Direct motor pathway: The direct motor pathway includes synapses in the basal ganglia and cortex, and primarily serves to initiate purposeful movements.
      • Indirect motor pathway: The indirect motor pathway also includes synapses in the basal ganglia and cortex but primarily serves to inhibit unwanted motor contractions.
      Based on their pharmacology, it was believed that the newer antipsychotics would reduce the unwanted effects associated with older antipsychotics, including antipsychotic-induced movement disorders such as tardive dyskinesia (TD), akathisia, dystonia, and parkinsonism. However, the newer medications did not eliminate this risk, as shown in a recent meta-analysis of antipsychotic clinical trials, which estimated the prevalence of TD as 20.7% for second-generation antipsychotics and 30.0% for first-generation antipsychotics.
      • Carbon M.
      • Hsieh C.H.
      • Kane J.M.
      • et al.
      Tardive dyskinesia prevalence in the period of second-generation antipsychotic use: a meta-analysis.
      It is worth noting, however, that this meta-analysis also showed that in patients who received second-generation antipsychotics TD prevalence was 7.2%, despite never being exposed to a first-generation antipsychotic.
      In this era of increased antipsychotics use, along with the ongoing risk for unwanted movement disorders, all patients should be regularly screened for any sign of abnormal or uncontrollable movements. Drug-induced movement disorders can be highly disruptive, causing behavioral disturbances, exacerbation of psychosis, reduction in quality of life, impairment of working memory performance, and increased treatment nonadherence.
      • Fujimaki K.
      • Morinobu S.
      • Yamashita H.
      • et al.
      Predictors of quality of life in inpatients with schizophrenia.
      • Mathews M.
      • Gratz S.
      • Adetunji B.
      • et al.
      Antipsychotic-induced movement disorders: evaluation and treatment.
      • Mentzel T.Q.
      • Lieverse R.
      • Bloemen O.
      • et al.
      Genetic Risk and Outcome of Psychosis (GROUP) Investigators
      High incidence and prevalence of drug-related movement disorders in young patients with psychotic disorders.
      • Potvin S.
      • Aubin G.
      • Stip E.
      Antipsychotic-induced parkinsonism is associated with working memory deficits in schizophrenia-spectrum disorders.
      Furthermore, the failure to diagnose and treat such disorders can lead to significant morbidity or mortality.
      • Poston K.L.
      • Frucht S.J.
      Movement disorder emergencies.
      Therefore, increased awareness is needed about how these disorders present and how they can be treated.

      Antipsychotic-induced movement disorders

      Historically, antipsychotic-induced movement disorders were called extrapyramidal symptoms (EPS). Because these movement disorders are distinct in presentation and pathophysiology, EPS is obsolete as an umbrella term for all antipsychotic-induced movement disorders. Its use is also clinically problematic because these disorders are not treated in the same way.
      A differential diagnosis of antipsychotic-induced movement disorders can be challenging, but some basic descriptive categorizations (e.g., acute vs tardive, hypokinetic vs hyperkinetic) offer a working framework for recognizing—and appropriately managing—these disorders (Fig. 1). Acute syndromes generally present within hours to days of initiating antipsychotic treatment, whereas tardive syndromes are usually associated with more prolonged antipsychotic exposure (months to years). Hypokinetic movement disorders, such as parkinsonism, are characterized by slow or insufficient movements. They are associated with an amplification of the indirect motor pathway, which is mainly responsible for reducing the speed and magnitude of movements.
      • Loonen A.J.
      • Ivanova S.A.
      New insights into the mechanism of drug-induced dyskinesia.
      Hyperkinetic movement disorders, such as TD, are characterized by excessive movements. Although not fully understood, it is thought that the pathophysiology of these disorders is primarily associated with dopamine imbalance in the direct motor pathway, which is responsible for increasing the velocity and amplitude of movements. However, hyperkinetic movement disorders may also involve stimulation of D2 receptors in the indirect motor pathway, resulting in decreased activity in this pathway that normally inhibits movement speed and magnitude.
      Figure thumbnail gr1
      Fig. 1Differentiation of movement disorders. Examples are provided to show how movement disorders can be differentiated. Of note, however, most abnormal movement types can be “acute” or “tardive” based on when symptoms occur. For example, parkinsonism that appears within a few days or weeks of initiating or changing antipsychotic treatment may be considered “acute.”
      Four common types of antipsychotic-induced movement disorders are described here and summarized in Table 2. This list is intended to be illustrative rather than exhaustive. The purpose is to show that all movement disorders are not the same, describe some of the key differentiating features, and highlight the role that nursing can play in recognizing these disorders.
      Table 2Symptoms and treatment of select antipsychotic-induced movement disorders
      Data from Refs.
      • Caroff S.N.
      • Campbell E.C.
      Drug-induced extrapyramidal syndromes: implications for contemporary practice.
      • Sachdev P.S.
      Neuroleptic-induced movement disorders: an overview.
      • Pringsheim T.
      • Gardner D.
      • Addington D.
      • et al.
      The assessment and treatment of antipsychotic-induced akathisia.
      • Stroup T.S.
      • Gray N.
      Management of common adverse effects of antipsychotic medications.
      • van Harten P.N.
      • Hoek H.W.
      • Kahn R.S.
      Acute dystonia induced by drug treatment.
      • Ward K.M.
      • Citrome L.
      Antipsychotic-related movement disorders: drug-induced parkinsonism vs. tardive dyskinesia-key differences in pathophysiology and clinical management.
      American Psychiatric AssociationDSM-5 Task Force
      • Bhidayasiri R.
      • Jitkritsadakul O.
      • Friedman J.H.
      • et al.
      Updating the recommendations for treatment of tardive syndromes: a systematic review of new evidence and practical treatment algorithm.
      • Salgado A.
      Mental health and psychiatric nursing skills: extrapyramidal symptom assessment.
      Movement DisorderSymptomsManagement or Treatment
      Acute akathisia
      • Pringsheim T.
      • Gardner D.
      • Addington D.
      • et al.
      The assessment and treatment of antipsychotic-induced akathisia.
      • Complaints of restlessness
      • Excessive fidgety movements (eg, pacing, rocking, inability to sit/stand still)
      • Symptoms typically develop within a few weeks of starting antipsychotic or raising dose
      • Reduce dose or switch antipsychotic
      • β-Blocker (eg, propranolol) or antihistaminic agent if β-blocker contraindicated (eg, mirtazapine)
      • Benzodiazepines (eg, clonazepam)
      Acute dystonia
      • van Harten P.N.
      • Hoek H.W.
      • Kahn R.S.
      Acute dystonia induced by drug treatment.
      • Severe muscle spasms of the eyes (oculogyric crisis), head, neck (torticollis), limbs, or trunk
      • Severe arching of the back or laryngospasm may occur
      • Symptoms typically emerge within a few days of starting antipsychotic or raising dose
      • Reduce dose or switch antipsychotic
      • Anticholinergics (eg, benztropine)
      • Antihistaminergic agents (eg, diphenhydramine)
      • Benzodiazepines
      • Physical therapy
      Parkinsonism
      • Ward K.M.
      • Citrome L.
      Antipsychotic-related movement disorders: drug-induced parkinsonism vs. tardive dyskinesia-key differences in pathophysiology and clinical management.
      • Shin H.W.
      • Chung S.J.
      Drug-induced parkinsonism.
      • Tremor
      • Muscular rigidity
      • Akinesia (loss of movement or difficulty initiating movement)
      • Bradykinesia (slowness of movement)
      • Symptom onset typically occurs within a few weeks to months of starting antipsychotic or raising dose
      • Reduce dose or switch antipsychotic
      • Anticholinergics
      • Amantadine
      Tardive dyskinesia
      • Bhidayasiri R.
      • Jitkritsadakul O.
      • Friedman J.H.
      • et al.
      Updating the recommendations for treatment of tardive syndromes: a systematic review of new evidence and practical treatment algorithm.
      • Involuntary, hyperkinetic, repetitive choreoathetoid movements
      • Most commonly observed movements occur in the orofacial region (eg, tongue protruding, facial grimacing, chewing motions of the jaw, excessive blinking)
      • Movements in extremities/trunk may also occur
      • Vesicular monoamine transporter 2 (VMAT2) inhibitors (deutetrabenazine, valbenazine)
        Approved by the United States Food and Drug Administration (FDA).
      • Only FDA-approved treatments
      a Approved by the United States Food and Drug Administration (FDA).

       Akathisia

      Akathisia is a common antipsychotic-induced movement disorder
      • Kane J.M.
      • Fleischhacker W.W.
      • Hansen L.
      • et al.
      Akathisia: an updated review focusing on second-generation antipsychotics.
      • Caroff S.N.
      • Campbell E.C.
      Drug-induced extrapyramidal syndromes: implications for contemporary practice.
      characterized by feelings of inner restlessness or tension. Estimates of akathisia prevalence among neuroleptic-treated patients ranges from 18% to 40%, with higher prevalence associated with certain drugs such as haloperidol.
      • Crawford G.B.
      • Agar M.M.
      • Quinn S.J.
      • et al.
      Pharmacovigilance in hospice/palliative care: net effect of haloperidol for delirium.
      • Halstead S.M.
      • Barnes T.R.
      • Speller J.C.
      Akathisia: prevalence and associated dysphoria in an in-patient population with chronic schizophrenia.
      • Janno S.
      • Holi M.
      • Tuisku K.
      • et al.
      Prevalence of neuroleptic-induced movement disorders in chronic schizophrenia inpatients.
      • Sachdev P.
      The epidemiology of drug-induced akathisia: Part II. Chronic, tardive, and withdrawal akathisias.
      • Berna F.
      • Misdrahi D.
      • Boyer L.
      • et al.
      Akathisia: prevalence and risk factors in a community-dwelling sample of patients with schizophrenia. Results from the FACE-SZ dataset.
      Patients may indicate an urge to move, are unable to keep still, or exhibit fidgety movements, all of which can be distressing for patients. Most cases will present within 1 to 6 weeks of starting an antipsychotic or increasing an antipsychotic dose.
      • Sachdev P.S.
      Neuroleptic-induced movement disorders: an overview.
      There are no Food and Drug Administration (FDA)-approved treatments specifically for akathisia, although amantadine is approved more generally for drug-induced extrapyramidal reactions in adults. In patients whose psychiatric symptoms will not be exacerbated, the antipsychotic may be switched or the dosage reduced. Though commonly used, there is limited evidence that adjunctive treatment with β-blockers, antihistaminergic agents, or benzodiazepines may alleviate symptoms.
      • Pringsheim T.
      • Gardner D.
      • Addington D.
      • et al.
      The assessment and treatment of antipsychotic-induced akathisia.
      Trazodone and mirtazapine (tetracyclic antidepressants) are also used for akathisia.
      • Forcen F.
      Akathisia: is restlessness a primary condition or an adverse drug effect?.
      • Stroup T.S.
      • Gray N.
      Management of common adverse effects of antipsychotic medications.

       Acute Dystonia

      An estimated 3% to 10% of patients exposed to a neuroleptic agent experience acute dystonia,
      • Goga J.K.
      • Seidel L.
      • Walters J.K.
      • et al.
      Acute laryngeal dystonia associated with aripiprazole.
      which is characterized by sustained muscle contractions, abnormal postures, or spasms. Symptoms may present anywhere in the body, with head and neck movements being most common. Symptoms may include back arching, neck extension, or forced eye movements, including oculogyric crisis or the prolonged upward deviation of the eyes. These movements may be dramatic, and patients may be frightened by their appearance. Aside from dystonic laryngospasm, which requires emergency medical intervention, acute dystonia is typically not life threatening. Acute dystonia can occur after a single dose of antipsychotic medication, although most instances emerge over the course of a few days. Treatment may include anticholinergics (eg, benztropine ) or antihistamines (eg, diphenhydramine).
      • Caroff S.N.
      • Campbell E.C.
      Drug-induced extrapyramidal syndromes: implications for contemporary practice.
      • Sachdev P.S.
      Neuroleptic-induced movement disorders: an overview.
      • van Harten P.N.
      • Hoek H.W.
      • Kahn R.S.
      Acute dystonia induced by drug treatment.
      In patients whose psychiatric symptoms will not be exacerbated, the antipsychotic dose may be reduced or the antipsychotic switched.

       Parkinsonism

      Antipsychotic-induced parkinsonism (or Parkinson-like symptoms) shares clinical features with Parkinson disease but occurs during antipsychotic use. Recently, a 30-year population-based study found the annual incidence rate of drug-induced parkinsonism to be 3.3 per 100,000 person years, with typical antipsychotics being the most common cause.
      • Savica R.
      • Grossardt B.R.
      • Bower J.H.
      • et al.
      Incidence and time trends of drug-induced parkinsonism: A 30-year population-based study.
      Symptoms may include bradykinesia, bilateral and symmetric rigidity, postural instability, and tremor. Typical onset is within 1 to 3 months of starting or increasing an antipsychotic dosage. Parkinsonism is best managed by modifying the antipsychotic regimen (ie, tapering and stopping the antipsychotic or switching to another antipsychotic) in patients whose psychiatric disease will not be affected. If the antipsychotic regimen cannot be adjusted, anticholinergics or amantadine may be used instead.
      • Caroff S.N.
      • Campbell E.C.
      Drug-induced extrapyramidal syndromes: implications for contemporary practice.
      • Sachdev P.S.
      Neuroleptic-induced movement disorders: an overview.
      • Ward K.M.
      • Citrome L.
      Antipsychotic-related movement disorders: drug-induced parkinsonism vs. tardive dyskinesia-key differences in pathophysiology and clinical management.
      • Shin H.W.
      • Chung S.J.
      Drug-induced parkinsonism.

       Tardive Dyskinesia

      In a prospective cohort study of outpatients from a community mental health center who received antipsychotics for ≥3 months, 31.5% of evaluated patients had TD on study entry,
      • Woods S.W.
      • Morgenstern H.
      • Saksa J.R.
      • et al.
      Incidence of tardive dyskinesia with atypical versus conventional antipsychotic medications: a prospective cohort study.
      consistent with the prevalence of 30.0% for first-generation antipsychotics found in the meta-analysis of antipsychotic clinical trials.
      • Carbon M.
      • Hsieh C.H.
      • Kane J.M.
      • et al.
      Tardive dyskinesia prevalence in the period of second-generation antipsychotic use: a meta-analysis.
      Among the community outpatients who did not have TD at study entry, the average incidence rate of new TD was 0.066 per patient-year. TD is a persistent and potentially irreversible movement disorder associated with prolonged exposure to antipsychotics. TD is characterized by uncontrollable movements of the head, face, trunk, or limbs,
      • Rana A.Q.
      • Chaudry Z.M.
      • Blanchet P.J.
      New and emerging treatments for symptomatic tardive dyskinesia.
      • Waln O.
      • Jankovic J.
      An update on tardive dyskinesia: from phenomenology to treatment.
      • Caroff S.N.
      • Davis V.G.
      • Miller D.D.
      • et al.
      Treatment outcomes of patients with tardive dyskinesia and chronic schizophrenia.
      • Zutshi D.
      • Cloud L.J.
      • Factor S.A.
      Tardive syndromes are rarely reversible after discontinuing dopamine receptor blocking agents: experience from a university-based movement disorder clinic.
      and may present as irregular contractions, lip smacking, tongue protrusions, chewing movements of the jaw, facial grimacing, slow writhing in the trunk or extremities, twisting or dance-like movements, and/or tapping of the fingers and toes.
      • Caroff S.N.
      • Campbell E.C.
      Drug-induced extrapyramidal syndromes: implications for contemporary practice.
      • Jain R.
      • Correll C.U.
      Tardive dyskinesia: recognition, patient assessment, and differential diagnosis.
      According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria,
      American Psychiatric AssociationDSM-5 Task Force
      a TD diagnosis requires use of an antipsychotic for at least a few months (and possibly shorter in older patients). The DSM-5 also recommends that the movements, if they appear after antipsychotic discontinuation, or change or reduction in dosage, be present for at least 4 to 8 weeks to rule out withdrawal-emergent dyskinesia, which develops after discontinuation or a reduction in dosage of an antipsychotic and typically resolves within 4 to 8 weeks.
      The delayed onset of this disorder means that it is often overlooked and underdiagnosed. Furthermore, TD may coexist with other movement disorders, leading to potential misdiagnosis. Patients may also experience considerable physical, social, and functional impacts because of their abnormal movements.
      • Strassnig M.
      • Rosenfeld A.
      • Harvey P.D.
      Tardive dyskinesia: motor system impairments, cognition and everyday functioning.
      • Yassa R.
      • Jones B.D.
      Complications of tardive dyskinesia: a review.
      • Browne S.
      • Roe M.
      • Lane A.
      • et al.
      Quality of life in schizophrenia: relationship to sociodemographic factors, symptomatology and tardive dyskinesia.
      • Ascher-Svanum H.
      • Zhu B.
      • Faries D.
      • et al.
      Tardive dyskinesia and the 3-year course of schizophrenia: results from a large, prospective, naturalistic study.
      Until recently, treatment options for TD were limited to altering the offending antipsychotic, off-label uses of medications (e.g., anticholinergics which can exacerbate TD) and herbal supplements for which evidence was either weak or limited.
      Summary of evidence-based guideline for clinicians treatment of tardive syndromes—American Academy of Neurology.
      In 2017, however, a novel vesicular monoamine transporter 2 (VMAT2) inhibitor, valbenazine, was the first medication approved by the FDA for the treatment of adults with TD
      • Neurocrine Biosciences
      Valbenazine [prescribing information].
      ; deutetrabenazine, a molecular form of tetrabenazine, was approved later that year.
      • Teva Pharmaceutical Industries
      Deutetrabenazine [prescribing information].
      Having been evaluated in rigorous double-blind, placebo-controlled clinical trials that demonstrated their efficacy and safety,
      • Teva Pharmaceutical Industries USA
      Austedo [prescribing information].
      • Neurocrine Biosciences
      Ingrezza [prescribing information].
      • Bhidayasiri R.
      • Jitkritsadakul O.
      • Friedman J.H.
      • et al.
      Updating the recommendations for treatment of tardive syndromes: a systematic review of new evidence and practical treatment algorithm.
      both drugs have shown strong evidence as first-line therapies for TD.
      • Bhidayasiri R.
      • Jitkritsadakul O.
      • Friedman J.H.
      • et al.
      Updating the recommendations for treatment of tardive syndromes: a systematic review of new evidence and practical treatment algorithm.

      Clinical practice: a key role for nurses

      No 2 clinical practices are the same, and the constraints on nurses’ time and attention can be considerable. However, there are several specific areas in which nurses play a key role in optimizing care for patients with TD: screening and assessments, education and resources, and treatment support (Fig. 2).
      Figure thumbnail gr2
      Fig. 2Nurses’ roles in optimizing patient care. AIMS, Abnormal Involuntary Movement Scale; BARS, Barnes Akathisia Rating Scale; ESRS, Extrapyramidal Symptom Rating Scale; SAS, Simpson-Angus Scale.

       Screening and Assessments

      Nurses should be aware that all patients taking antipsychotics, especially long term, should be monitored for the development of antipsychotic-induced abnormal movements. Ideally, screening would occur before antipsychotic initiation and any change in therapy (antipsychotic switch or dose increase/decrease), with regular assessments throughout the course of treatment.
      • Jain R.
      • Correll C.U.
      Tardive dyskinesia: recognition, patient assessment, and differential diagnosis.
      In many practices, patients are regularly checked for other adverse events associated with antipsychotics (eg, orthostatic hypotension, hyperprolactinemia, weight gain
      • De Hert M.
      • Detraux J.
      • van Winkel R.
      • et al.
      Metabolic and cardiovascular adverse effects associated with antipsychotic drugs.
      ). An assessment of the patient’s movements could be incorporated into that protocol.
      Screening may be informal, including simple visual observations; regular assessments can be more formal, using validated scales (Table 3). These include the Barnes Akathisia Rating Scale
      • Barnes T.R.
      A rating scale for drug-induced akathisia.
      for akathisia, the Simpson-Angus Scale
      • Simpson G.M.
      • Angus J.W.
      A rating scale for extrapyramidal side effects.
      for parkinsonism, and the Abnormal Involuntary Movement Scale
      • Guy W.
      Abnormal Involuntary Movement Scale (117-AIMS).
      for TD. The Extrapyramidal Symptom Rating Scale
      • Chouinard G.
      • Ross-Chouinard A.
      • Annable L.
      • et al.
      Extrapyramidal Symptom Rating Scale.
      can be used to differentiate between parkinsonism, akathisia, dystonia, and dyskinesia. It should be noted, however, that the diagnostic application of these scales is limited; they are more suited for assessing the severity of abnormal movements and monitoring changes over time. Diagnoses of antipsychotic-induced movement disorders are based on clinical presentation and the patient’s psychiatric and medical history, including exposure to antipsychotics or other dopamine-receptor blocking agents such as antiemetics (eg, metoclopramide); a few cases of antidepressant-associated TD have also been reported.
      • Yilmaz R.
      • Ustun D.
      • Tuncer Uzun S.
      • et al.
      A probable case of movement disorder (tardive dyskinesia) due to duloxetine treatment.
      • Albayrak Y.
      • Ekinci O.
      Duloxetine-associated tardive dyskinesia resolved with fluvoxamine: a case report.
      For TD, the American Psychiatric Association recommends an assessment at antipsychotic initiation and every 3 to 12 months thereafter, with the frequency of assessment depending on the type of antipsychotic used and other risk factors (eg, older age, history of other drug-induced movements).
      • Lehman A.F.
      • Lieberman J.A.
      • Dixon L.B.
      • et al.
      Practice guideline for the treatment of patients with schizophrenia, second edition.
      Now that approved TD treatments are available,
      • Teva Pharmaceutical Industries USA
      Austedo [prescribing information].
      • Neurocrine Biosciences
      Ingrezza [prescribing information].
      early identification ensures that patients receive timely treatment, which may minimize the negative physical and psychosocial effects associated with TD when left untreated.
      • Strassnig M.
      • Rosenfeld A.
      • Harvey P.D.
      Tardive dyskinesia: motor system impairments, cognition and everyday functioning.
      • Yassa R.
      • Jones B.D.
      Complications of tardive dyskinesia: a review.
      • Browne S.
      • Roe M.
      • Lane A.
      • et al.
      Quality of life in schizophrenia: relationship to sociodemographic factors, symptomatology and tardive dyskinesia.
      • Ascher-Svanum H.
      • Zhu B.
      • Faries D.
      • et al.
      Tardive dyskinesia and the 3-year course of schizophrenia: results from a large, prospective, naturalistic study.
      Table 3Commonly used movement rating scales
      Data from Seida J, Schouten J, Mousavi S, et al. First- and second-generation antipsychotics for children and young adults. In: Comparative Effectiveness Reviews No. 39. Rockville, MD: Agency for Healthcare Research and Quality; 2012; and Gervin M, Barnes TRE. Assessment of drug-related movement disorders in schizophrenia. Advances in Psychiatric Treatment. 2000;6:332-341.
      Rating Scale (Hyperlinked)Domains or ItemsScoring
      Abnormal Involuntary Movement Scale
      • Orofacial movements (4 items)
      • Movements in trunk or extremities (3 items)
      • Global judgments (3 items)
      • Dental status (2 items)
      • Items scored on a 5-point scale (0 = none to 4 = severe), with the exception of dental status items, which are yes/no responses
      • Higher scores (total score is calculated by summing scores from body regions) indicate greater severity of abnormal movements
      Barnes Akathisia Rating Scale
      • Objective measures
      • Awareness of or distress from restlessness
      • Global assessment
      • First 2 domains scored on a 4-point scale (0 = normal/no distress/absent to 3 = severe/constant movement)
      • Third domain is rated on a 6-point scale (0 = absent to 5 = severe)
      • Higher scores indicate greater severity
      Extrapyramidal Symptom Rating Scale
      • Parkinsonism questionnaire
      • Clinician examination for parkinsonism and akathisia, dystonia, and dyskinesia
      • Global impression of movement severity
      • First domain scored on a 4-point scale (0 = absent to 3 = severe)
      • Second domain items scored on 7-point scales (0 = absent to 6 = extremely severe)
      • Third domain scored on a 9-point scale (0 = absent to 8 = extremely severe)
      • Higher scores indicate greater severity
      Simpson-Angus Scale
      • Assesses changes in the following: gait, arm dropping, shoulder shaking, elbow and wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia
      • Domains scored on a 5-point scale (0 = absence of condition to 4 = condition present in extreme form)
      • Total score calculated by summing domain scores and dividing by 10
      • Higher scores indicate greater severity
      Not all patients report having abnormal movements, possibly because of underlying diagnosis (eg, schizophrenia versus mood disorder), embarrassment, greater concern about other psychiatric or medical conditions, or lack of knowledge that the movements may be due to their antipsychotic treatment. Some patients with severe schizophrenia may not be aware that they are experiencing movements at all. By contrast, patients with well-controlled mood disorders are more likely to be aware of their movements and highly distressed by even so-called mild irregularities. Given the heterogeneity of the patient population, screening and assessments should be multifaceted and include all patients who receive antipsychotic treatments.
      • Daniel S.J.
      • Kannan P.P.
      • Malaiappan M.
      • et al.
      Relationship between awareness of tardive dyskinesia and awareness of illness in schizophrenia.
      Often, caregivers and/or family members are also able to provide information, especially in cases where patients are not aware of their abnormal movements.

       Education, Resources, and Treatment Support

      Nurses play a crucial role in building supportive and therapeutically effective relationships with patients and their caregivers. As such, they are uniquely positioned to educate patients regarding the risks for antipsychotic-induced movement disorders. More importantly, they can reassure patients that effective treatments may be available if the appropriate diagnosis is made. In addition, nurses and other health care professionals can point patients to resources such as Web sites that provide support and advocacy for patients and families (see Fig. 2; www.movementdisorders.org; www.dystonia-foundation.org; www.talkabouttd.com).
      Perhaps the greatest impediment to the discussion of unwanted antipsychotic effects is the fact that the offending medication cannot be eliminated. Patients often require the antipsychotic to maintain psychiatric stability; discontinuing the drug or changing the dose may not be ideal or even feasible. In the case of TD the movements can be irreversible, so changing or discontinuing the dose of the antipsychotic may not resolve the movements. Health care professionals, patients, and caregivers may erroneously believe that the choice is also between treating the psychiatric condition or alleviating the movement disorder. However, in the case of TD, approved medications are available, and these medications have been studied and proved safe to use in conjunction with the patient’s stable antipsychotic therapy. Nurses can optimize patient care by reinforcing the importance of taking medications as recommended and referring them to pharmacists or other professionals if specific questions about dosing or drug interactions arise.

      Summary

      For many patients, antipsychotics are necessary and potentially life-saving medications; however, they come with certain unavoidable risks, including antipsychotic-induced movement disorders. Nurses play an important role in the recognition, assessment, and management of these antipsychotic-induced movement disorders. In the case of TD, there are now FDA-approved medications that can be taken while continuing with current antipsychotic therapy.

      Acknowledgments

      Medical writing and editorial services were provided by Mary Clare Kane, PhD, and Mildred Bahn, MA, at Prescott Medical Communications Group (Chicago, IL), with support from Neurocrine Biosciences, Inc (San Diego, CA).

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