Tardive Dyskinesia Associated with Atypical Antipsychotics: Prevalence, Mechanisms and Management Strategies

Abstract

All antipsychotics, including the atypical antipsychotics (AAPs), may cause tardive dyskinesia (TD), a potentially irreversible movement disorder, the pathophysiology of which is currently unknown. The prevention and treatment of TD remain major challenges for clinicians. We conducted a PubMed search to review the prevalence and etiology of and management strategies for TD associated with AAPs. TD prevalence rates varied substantially between studies, with an estimated prevalence of around 20% in patients using AAPs. The risk of TD is lower with AAPs than with typical antipsychotics (TAPs) but remains a problem because AAPs are increasingly being prescribed. Important risk factors associated with TD include the duration of antipsychotic use, age, and ethnicity other than Caucasian. Theories about the etiology of TD include supersensitivity of the dopamine receptors and oxidative stress, but other neurotransmitters and factors are probably involved. Studies concerning the management of TD have considerable methodological limitations. Thus, recommendations for the management of TD are based on a few trials and clinical experience, and no general guidelines for the management of TD can be established. The best management strategy remains prevention. Caution is required when prescribing antipsychotics, and regular screening is needed for early detection of TD. Other strategies may include reducing the AAP dosage, switching to clozapine, or administering vesicular monoamine transporter (VMAT)-2 inhibitors. In severe cases, local injections of botulinum toxin or deep brain stimulation may be considered. More clinical trials in larger samples are needed to gather valid information on the effect of interventions targeting TD.

Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology

“…Direct interventionist treatments are increasingly suggested for functionally incapacitating, crippling or life-threatening TD, but trial-derived evidence remains weak. Focal orofacial disorder, especially lingual protrusion, may be improved with injection of botulinum toxin into especially the genioglossus muscle, with benefits potentially extending beyond the target disorder, though these are likely to require repeating regularly (Stegmayer et al, 2018). However, such treatments have not been subjected to adequate trial evaluation using standardised administration protocols.…”

Use of Valbenazine in a 54-Year-Old Female with Severe Tardive Dyskinesia

“…She is on permanent disability and lives in a personal care home. Throughout the years, the patient was treated with numerous antipsychotic medications including mesoridazine, trifluoperazine, haloperidol, risperidone, olanzapine, quetiapine, 1 1 1 ziprasidone, aripiprazole, and clozapine. She started exhibiting the first signs of TD in 2008.…”

“…Antipsychotic medication is the cornerstone in the treatment of psychosis in schizophrenia, schizoaffective disorder, bipolar disorder as well as adjunctive therapy in major depressive disorder. The incidence of tardive dyskinesia (TD) in typical or first generation antipsychotic is 20-30% [1], while it is lower with atypical or second-generation antipsychotic at 13-15% [2]. While TD is a serious and often irreversible side effect of antipsychotic medication, discontinuation of antipsychotic medication is at times not possible as it results in worsening of the underlying psychiatric condition.…”

No evidence so far of a major role of AKT1 and GSK3B in the pathogenesis of antipsychotic‐induced tardive dyskinesia

“…Iatrogenic tardive dyskinesia (TD) is a debilitating and potentially irreversible neurological side effect of chronic treatment with a number of different types of medication, primarily with antipsychotics (Cornett, Novitch, Kaye, Kata, & Kaye, ; Tenback & van Harten, ). Typical antipsychotics are associated with higher, 30% incidence of TD, but incidence with atypical antipsychotics is still significant, incapacitating 20% of patients (Cornett et al, ; Stegmayer, Walther, & van Harten, ). The involuntary movements affect the orofacial area and trunk and limbs, defining orofacial and limb‐truncal types of TD.…”

“…The involuntary movements affect the orofacial area and trunk and limbs, defining orofacial and limb‐truncal types of TD. There is no consensus on the pathogenic mechanisms behind these features, and different neurotransmitter systems may be involved, but one of the best known hypotheses postulates that the D2 dopamine receptor (DRD2; Beaulieu & Gainetdinov, ) plays an important role (Stegmayer et al, ; Zai et al, ). Furthermore, the two recently FDA‐approved drugs to treat TD, valbenazine and deutetrabenazine, decrease the availability of synaptic dopamine by inhibiting the vesicular monoamine transporter type 2 (Stahl, ; Zai et al, ), which might also support the hypothesis that DRD2 is implicated in the pathogenesis.…”