Tardive dyskinesia treatment

The anainoacridines, tacrine (19) and its 1-hydroxy metaboUte, velnacrine (20), are reversible inhibitors of AChE. Tacrine was synthesi2ed in the 1940s and has been used clinically for the treatment of myasthenia gravis and tardive dyskinesia (115). Placebo-controUed studies have indicated modest efficacy of tacrine to treat AD dementia (122,123) and in 1993 the dmg was recommended for approval by the PDA under the trade name Cognex. Tacrine (19) has been shown to interact with sites other than AChE, such as potassium channels (124) and muscarinic receptors. However, these interactions are comparatively weak and are not thought to contribute to the biological activity of the dmg at therapeutic levels (115). 

Because there is no known treatment for tardive dyskinesia and because it is irreversible in some patients the nurse must immediately report symptoms These indude rhythmic, involuntary movements of the tongue, face, mouth, jaw, or the extremities... 

Tardive dyskinesia A chronic disorder of the nervous system characterized by involuntary jerky or writhing movements of the face, tongue, jaws, trunk, and limbs, usually developing as a late side effect of prolonged treatment with antipsychotic drugs. 

Jeste DV, Lacro JP, Palmer B et al. (1999) Incidence of tardive dyskinesia in early stages of low-dose treatment with typical antipsychotics in older patients. Am I Psychiatry 156(2) 309-311 Klotz U (1998) Effect of age on pharmacokinetics and pharmacodynamics in man. Int I Clin Pharmacol Ther 36(11) 581-585... 

Tardive dyskinesia is a condition that sometimes results from chronic neuroleptic treatment lasting from months to years (Baldessarini 1996 Stahl et al. 1982). It occurs in 15-25% of treated chronic psychotic patients and is characterized by repetitive, athetoid writhing and stereotyped choreiform movements of the face, eyes, mouth, extremities, and trunk. Discontinuation of neuroleptic medication allows the symptoms to gradually decline, but sometimes they can persist indefinitely. The pathophysiology of tardive dyskinesia is poorly understood, but it appears to involve supersensitive postsynaptic dopamine receptors in the basal ganglia. 

Atypical Antipsychotics. The so-called atypical antipsychotics have revolutionized the treatment of schizophrenia and other psychotic disorders since their introduction in the 1990s. Similarly, they are replacing the older antipsychotics in the treatment of BPAD as well. They offer a similar degree of antimanic efficacy without a lessened long-term risk of tardive dyskinesia. For more information regarding the atypical antipsychotics, please refer to Chapter 4 Schizophrenia. 

Clozapine (Clozaril). Clozapine was introduced over 30 years ago but has only been available in the United States since 1990. It remains the medication of choice for treatment-resistant schizophrenia. Since its introduction, it has been used to treat acute mania with excellent results. Furthermore, it avoids the potential for tardive dyskinesia posed by haloperidol and the other typical antipsychotics. 

The occurrence of tardive dyskinesia after treatment with conventional antipsychotics for a long term raises some interesting questions. Remember, dyskinesias are a symptom of HD and other neurological disorders in which there is too much dopamine flowing through the nigrostriatal pathway. How can a dopamine-blocking medication produce symptoms similar to HD ... 

Some researchers have investigated the notion of intermittent treatment. Patients are intensively monitored off medication, and a medication is started once prodromal signs of an impending acnte exacerbation are detected. One thought is that this minimizes the risk of side effects snch as tardive dyskinesia. Althongh in theory this may sound attractive, nnfortnnately, it rarely is successful in practice. Patients receiving intermittent treatment are at exceptionally high risk for relapse. 

In the residual phase, the patient is unlikely to have an acute exacerbation even if (s)he stops taking an antipsychotic. Nevertheless, (s)he may still require treatment for residual symptoms. If medications are continued during a residual phase of schizophrenia, an atypical antipsychotic is preferred. Because positive symptoms are no longer a prominent aspect of the illness, there is usually little justification for using a typical antipsychotic and thereby exposing a patient to the risk of tardive dyskinesia. Moreover, atypical antipsychotics likely better treat the remaining negative symptoms of residnal schizophrenia. 

Antipsychotics also have a troublesome side effect burden that includes an often-irreversible movement disorder known as tardive dyskinesia (TD). Other side effects include so-called parkinsonism, dystonic reactions (i.e., abrupt onset of muscle spasms), akathisia (an uncomfortable sense of motoric restlessness), sedation, weight gain, dizziness, dry mouth, and constipation among others. These side effects, in particular the risk for TD, limit the usefulness of antipsychotics in the treatment of ADHD, and at this time the typical antipsychotics cannot be considered a reasonable monotherapy in uncomplicated ADHD. 

There are, of course, risks with long-term use of conventional antipsychotics. The most concerning is an irreversible movement disorder known as tardive dyskinesia. Nevertheless, some particularly fragile patients with BPD may require long-term antipsychotic treatment. If so, atypical antipsychotics are recommended. 

Tardive Dyskinesia (TD). As mentioned previously, TD is a potential side effect of long-term treatment with typical antipsychotics it is believed to be very rare but possible after atypical antipsychotic treatment. Although we now know that TD is not irreversible in all patients, about half will recover after discontinuation of the antipsychotic and the passage of several months time, others will exhibit the symp-... 

Tardive dyskinesia can occur in manic patients on neuroleptics alone, the frequency may be greater than in schizophrenics who are more likely to be on continuous medication. One possible explanation for this lies in the fact that neuroleptics are often administered to manic patients for short periods only, sufficient to abort the active episode, and then abruptly stopped. Thus high doses of neuroleptics are separated by drug-free periods, leading to a situation most likely to precipitate tardive dyskinesia. The recent increase in prescribing high potency neuroleptics such as haloperidol instead of low potency drugs such as chlorpromazine or thioridazine has undoubtedly increased the frequency of tardive dyskinesia. Clearly, use of the atypical antipsychotics with the very low frequency of EPS makes them the treatments of choice. 

In CONCLUSION, lithium is universally accepted as a mood-stabilizing drug and an effective antimanic agent whose value is limited by its poor therapeutic index (i.e. its therapeutic to toxicity ratio). Neuroleptics are effective in attenuating the symptoms of acute mania but they too have serious adverse side effects. High potency typical neuroleptics appear to increase the likelihood of tardive dyskinesia. Of the less well-established treatments, carbamazepine would appear to have a role, particularly in the more advanced stages of the illness when lithium is less effective. 

Tardive dyskinesia (TD) TD, a syndrome consisting of potentially irreversible, involuntary dyskinetic movements, may develop in patients treated with antipsychotic drugs. Both the risk of developing TD and the likelihood that it will become irreversible are increased as duration of treatment and total cumulative dose administered increase. 

The more disagreeable and troubling side-effect of long-term neuroleptic treatment is tardive dyskinesia. This occurs after variable duration of treatment, and may be precipitated by changing doses, and repetitive stopping and starting drugs. Its mechanism is not well known, and it may improve when... 

Excluding tardive dyskinesia, which appears to be produced to the same degree and frequency by all agents except clozapine. Pimozide is used principally in the treatment of Tourette s syndrome. 

All antipsychotics except clozapine have a similar potential for producing tardive dyskinesia, the most serious adverse effect. Clozapine is reserved for patients who have failed to respond to therapy with at least two other antipsychotics and for those who have disabling tardive dyskinesia. Therapy with clozapine has been reported to salvage up to half of otherwise treatment-refractory pa-... 

Tardive dyskinesia is a late-occurring syndrome of abnormal movements of the face and tongue with widespread choreoathetosis. It is the most serious adverse effect of the antipsychotic drugs. It can be expected to occur in 20 to 40% of chronically treated patients there is no established treatment, and reversibility may be limited. These reactions are more frequent and severe in the elderly. 

Unlabeled Uses Prevention of migraine treatment of behavior disorders in Alzheimer s disease bipolar disorder chorea, myoclonic, simple partial, and tonic-clonic seizures organic brain syndrome schizophrenia status epilepticus tardive dyskinesia... 

It is recommended that neurological side effects be monitored carefully throughout the course of antipsychotic treatment. Rating scales can assist in monitoring for EPS and the involuntary movements seen in tardive dyskinesia. These include the Neurological Rating Scale (Simpson and Angus, 1970), the Barnes Akathisia Scale (Barnes, 1989), and the Abnormal Involuntary Movement Scale ([AIMS] National Institute of Mental Health, 1985). 

The main indications for atypical antipsychotics are the acute and maintenance treatment of schizophrenic disorders, with an emphasis on the treatment of refractory and chronic disorders. However, because of the lower risk of EPS and in particular of tardive dyskinesia, there is a tendency toward a wider range of indications for some of the atypical neuroleptics. Favorable effects in drug-induced psychoses have been demonstrated for olanzapine. Clozapine seems effective in the treatment and relapse prevention of manic episodes and bipolar disorders, and risperidone has been shown to have good efficacy in conduct disorders and in the pervasive developmental disorders. 

Atypical neuroleptics. Because of the limited effectiveness and safety of conventional neuroleptics in TS, clinicians have turned to a new generation of neuroleptics that have been introduced for the treatment of schizophrenia. Risperidone, a member of a class of antipsychotics that blocks both DA and serotonin receptors, has been established as superior to placebo and equal, or superior, to haloperidol in the treatment of schizophrenia (Chouinard et al. 1993 Marder and Meibach 1994]. Risperidone has a more favorable side-effect profile than that of conventional neuroleptics and may have less potential for producing tardive dyskinesia. Compared with haloperidol, fewer extrapyramidal side effects are observed with risperidone in doses of 6 mg/ day or less. As encouraging reports appear in the literature (Lombroso et al. 1995 Stamenkovic et al. 1994 van der Linden et al. 1994], risperidone is currently being widely used by clinicians to treat tic disorders. 

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