Dyskinesia and neuroleptics

EPS include acute dystonic reactions, parkinsonian syndrome, akathisia, tardive dyskinesia, and neuroleptic mahgnant syndrome. Although high-potency conventional antipsychotics are more hkely than low-potency conventional antipsychotics to cause EPS, all first-generation antipsychotic drugs are equally hkely to cause tardive dyskinesia. The atypical antipsychotics cause suhstantially fewer EPS, which is one reason that they are recommended as first-line agents. 

Risperdal was first marketed in 1994 as an atypical neuroleptic. The clinical trials, most of which lasted a few weeks, were too short to determine the rate of tardive dyskinesia and many other adverse effects. Indeed, the brief controlled clinical trials used for the approval of both clozapine and risperidone do not provide sufficient information to determine either efficacy or safety since the drugs would be used for months and years in individual patients, rather than for a few weeks (see chapter 13). Patients taking the medications over the coming years will provide the experimental data. However, since Risperdal is a potent dopamine blocker, it should have been anticipated that it would cause similar adverse reactions as the older neuroleptics. In my own experience, I have evaluated many cases of tardive dyskinesia caused by Risperdal, Zyprexa, and Geodon. Meanwhile, the Food and Drug Administration (FDA) has required the same tardive dyskinesia and neuroleptic malignant syndrome warnings on the labels of clozapine and risperidone as on the labels of the older neuroleptics. 

Severe and Potentially Irreversible Neurological Syndromes (Tardive Dyskinesia and Neuroleptic Malignant Syndrome) Caused by Neuroleptics... 

Spohn, H., Coyne, L. (1993). The effect of attention/information processing impairment of tardive dyskinesia and neuroleptics in chronic schizophrenics. Brain and Cognition, 23, 28-39. 

Assess for tardive dyskinesia and neuroleptic malignant syndrome (NMS). 

Binder RL, Kazamatsuri H, Nishimura T, et al Tardive dyskinesia and neuroleptic-induced parkinsonism in Japan. Am J Psychiatry 144 1494-1496,1987... 

The principal manifestations of phenothiazine toxicity involve the CNS and cardiovascular system. Signs of CNS toxicity include sedation, coma, respiratory depression (uncommon), seizures, hypothermia or hyperthermia, and extrapyramidal movement disorders (acute dystonia, parkinsonism, akathisia, tardive dyskinesia, and neuroleptic malignant syndrome) the extrapyramidal symptoms result from an imbalance between inhibitory dopamine and... 

Loxapine (10 mg b.i.d.) is indicated for the treatment of psychotic disorders. It exerts its antipsychotic effects in part by blocking postsynaptic dopamine receptors. It causes moderate sedation, possesses anticholinergic properties, and produces extensive movement disorders such as akathi-sia, dystonia, parkinsonism, tardive dyskinesia, and neuroleptic malignant syndrome. 

Rare Hepatic toxicity tinnitus bone marrow depression, including agranulocytosis seizures peripheral neuropathy severe cardiovascular effects in patients with cardiac disease photosensitivity dysarthria smttering withdrawal symptoms nausea, tremor, anorgasmia, and seizures may be more common with clomipramine tardive dyskinesia and neuroleptic malignant syndrome with amoxapine renal failure with overdosage of amoxapine... 

The typical antipsychotic drugs (e.g., chlorpromazine, thioridazine, fluphenazine, and haloperidol) act primarily as DA antagonists, blocking Dj receptors. Side effects include the induction of pseudo-Parkinsonism, akathisia, and/or acute dystonic effects. Their use and symptom management are discussed, as are other adverse effects including toxicity, tardive dyskinesia, and neuroleptic malignant syndrome. 

Additionally, ECT is highly effective for mania, catatonic states, and certain cases of schizophrenia. Moreover, it has been reported to ameliorate the motor symptoms of Parkinson s disease and various other movement disorders, such as tardive dyskinesia and neuroleptic malignant syndrome (NMS). ... 

Tan EC, Chong SA, Mahendran R, Dong F, Tan CH. Susceptibility to neuroleptic-induced tardive dyskinesia and the T102C polymorphism in the serotonin type 2A receptor. Biol Psychiatry 2001 50(2) 144—147. 

Monitor the patient for extrapyramidal reactions and early signs of tardive dyskinesia and potentiallyfatal neuroleptic malignant syndrome (such as altered mental status, fever, irregular pulse or blood pressure, and muscle rigidity)... 

Opinions vary as to the incidence and causes of tardive dyskinesias and their precise connection with the use of neuroleptics. Estimates of their incidence extend from 0.5% to 56% of all chronically hospitalized psychiatric patients a discrepancy that is attributed primarily to the differences in criteria governing the selection of patients for various investigations and to heterogeneous... 

Extrapyramidal reactions include parkinsonism, acute muscular dystonias, akathisia, tardive dyskinesia and malignant neuroleptic syndrome. They can also cause hypersensitivity reaction including cholestatic jaundice, skin rash, urticaria, photosensitivity and contact dermatitis. There is also blue pigmentation of skin, lenticular opacities on prolonged use of drug. 

In CONCLUSION, the use of the "classical" neuroleptics, as exemplified by the phenothiazines, thioxanthines, butyrophenones and diphenylbutyl-piperidines, has been a landmark in the pharmacotherapy of schizophrenia and psychotic disorders. The efficacy of such drugs in the alleviation of the symptoms of schizophrenia is universally accepted. However, it is also evident that they have a spectrum of adverse effects that frequently renders their long-term use problematic. Side effects such as akathisia, Parkinsonism, tardive dyskinesia and the all too frequent changes in peripheral autonomic activity are largely predictable from the structure of the molecules and the basic animal pharmacology data. Such adverse effects, and the difficulties encountered when attempting to reduce their frequency and severity by concurrent medication, has stimulated the development of "atypical" neuroleptics such as clozapine and risperidone which, hopefully, will combine efficacy with a reduction in side effects. 

Breggin, P. R. 1993a, Parallels between neuroleptic effects and lethargic encephalitis the production of dyskinesias and cognitive disorders, Brain Cogn., vol. 23, no. 1, pp. 8-27. 

Risperdal causes all the extrapyramidal reactions found with other neuroleptics, including tardive dyskinesia (Addington et al., 1995) and neuroleptic malignant syndrome (Mahendra, 1995 Singer et al., 1995 see chapter 4). It is too early to tell if the rate of tardive dyskinesia will differ from that of other neuroleptics. 

I have evaluated several children and young adults who developed severe cases of tardive dyskinesia following neuroleptic treatment for Tourette s. One, a 20-year-old man who had been treated with Risperdal, eventually recovered from Tourette s. However, his drug-induced severe abnormal tongue movements and jaw spasms have required treatment with Botox, and he may never fully recover from them. He had been able to live a happy and largely unimpaired life with Tourette s but the TD has severely impaired his school, occupational, and social life. 

Gualtieri, C., Quade, D., Hicks, R., Mayo, J., Schroeder, S. (1984). Tardive dyskinesia and other clinical consequences of neuroleptic treatment in children and adolescents. American Journal of Psychiatry, 141, 20—23. 

Neuroleptic drugs can produce a variety of adverse effects in several organ systems. Extrapyramidal reactions and sedation are common less common are seizures, unwanted behavioral effects, and tardive dyskinesia. Most neuroleptic drugs have anticholinergic effects and commonly produce dry mouth, blurred vision, and constipation. Postural hypotension is common. These effects usually disappear when the drug is stopped or the dosage is reduced. 

Chronically hospitalized elderly inpatients with schizophrenia (n = 121 mean age 74 years) were rated for tardive dyskinesia and cognition (288). Subjects with tardive dyskinesia (60%) were older than those without. In subjects who were taking typical neuroleptic drugs (n = 119) there was no difference in dosage between those with and without tardive dyskinesia. Cognitive scores (Mini-Mental Status Examination) were significantly lower in the subjects with tardive dyskinesia... 

In a study that was claimed to be the first published placebo-controlled dose comparison of neuroleptic drugs used to treat psychoses and disruptive behavior in dementia, haloperidol 2-3 mg/day was compared with 0.50-0.75 mg/day in 71 outpatients with Alzheimer s disease (588). After 12 weeks, there was a favorable therapeutic effect of haloperidol 2-3 mg/day, although 25% of the patients developed moderate to severe extrapyramidal signs. No patient developed tardive dyskinesia, but neuroleptic drug exposure needs to be considerably longer for that to occur. 

Faheem AD, Brightwell DR, Burton GC, Struss A. Respiratory dyskinesia and dysarthria from prolonged neuroleptic use tardive dyskinesia Am J Psychiatry 1982 139(4) 517-8. 

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