Neuroleptics tardive dyskinesia

Dystonic reactions occur within hours or days of initiating treatment with (or increasing the dose of) a neuroleptic. Tardive dyskinesia (TD) presents with a more... 

A 45-year-old patient developed severe hyperthermia (rectal temperature above 41° C), with intense rhabdomyolysis and liver cytolysis during tetrabenazine therapy for neuroleptic tardive dyskinesia [75 ]. There was a good response to parenteral sodium dantrolene and oral bromocriptine. In addition to tetrabenazine, this patient took lorazepam and two antidepressant drugs clomipramine and mianserin. 

Morgenstern, H. Glazer, W. M (1993). Identifying risk factors for tardive dyskinesia among long-term outpatients maintained with neuroleptic medications results of the Yale Tardive Dyskinesia Study. Arch. Gen. Psychiatry, 50, 723-33. 

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. 

The answer is e. (Hardman, pp 415, 442—443.) Tardive dyskinesia is an adverse effect of neuroleptics, not tricyclic, antidepressants. 

Patients who have received neuroleptics for long periods of time may develop a hyperkinetic disorder of the extrapyramidal system characterized by involuntary, purposeless movements affecting many parts of the body. This is known as tardive dyskinesia. Most commonly, these are manifested in a syndrome involving abnormal movements of the tongue, mouth and masticatory muscles. There are also choreoathetoid movements of the extremities. The mechanism by which these symptoms develop remains unknown. 

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. 

Many DA receptor antagonists (neuroleptics) for treating psychoses (for example, schizophrenia) have become efficient medicines. However, most of them induce severe extrapyramidal side-effects (EPS) akin to parkinsonian symptoms and also, more seriously, they induce tardive dyskinesias (TD). There is a need for improvements in the neuroleptics in the clinic. The substituted benzamides are D2 antagonists, some of which display a high degree of limbic selectivity. Such a regional selectivity has been suggested to be beneficial from the side-effects point of view [11,12]. 

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. 

Acute dystonias occur immediately after neuroleptization and are manifested by motor impairments, particularly in the head, neck, and shoulder region. After several days to months, a parkinsonian syndrome (pseudoparkinsonism) or akathisia (motor restlessness) may develop. All these disturbances can be treated by administration of antiparkin-son drugs of the anticholinergic type, such as biperiden (i.e., in acute dystonia). As a rule, these disturbances disappear after withdrawal of neuroleptic medication. Tardive dyskinesia may become evident after chronic neuroleptization for several years, particularly when the drug is discontinued. It is due to hypersensitivity of the dopamine receptor system and can be exacerbated by administration of anticholinergics. 

Tardive dyskinesia Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with neuroleptics (eg, antipsychotics). Amoxapine is not an antipsychotic, but it has substantive neuroleptic activity. 

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... 

Which neuroleptic agent has the lowest likelihood of producing tardive dyskinesia ... 

Neuroleptic malignant syndrome or tardive dyskinesia has been reported. 

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)... 

Eichhammer, P., Albus, M., Borrmann-Hassenbach, M., Schoeler, A., Putzhammer, A., Frick, U., Klein, H.E., and Rohrmeier, T. (2000) Association of dopamine D3-receptor gene variants with neuroleptic induced akathisia in schizophrenic patients a generalization of Steen s study on DRD3 and tardive dyskinesia. Am J Med Genet 96 187-91. 

Tardive dyskinesia is a potentially irreversible movement disorder characterized by choreoathetoid movements. The possibility of a primary neurological disorder should be considered when a patient being treated with an antipsychotic develops involuntary movements. It should also be noted that patients might develop transient withdrawal dyskinesias as the dosage of neuroleptics is lowered or discontinued (Campbell et ah, 1999). It appears that withdrawal dyskinesias are more common in children than adults. 

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. 

Amoxapine, which has a mild neuroleptic effect, can cause extra-pyramidal side effects, akathisia, and even tardive dyskinesia. 

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. 

Tardive dyskinesias are motor disturbances that sometimes arise following long-term treatment with neuroleptics. The first symptoms to appear are... 

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