Tardive syndromes

Antipsychotics are a chemically diverse group of drugs having in common the ability to ameliorate psychotic symptoms. Unfortunately, a significant percentage of patients fail to respond adequately or may develop adverse effects such as acute EPS, various tardive syndromes (e.g., TD, dystonia, etc.), and, less commonly, even more serious adverse events such as NMS and agranulocytosis. 

Because the tardive syndromes that develop in adults are often irreversible and have no satisfactory treatment, care must be taken to reduce the likelihood of their occurrence. Antipsychotic medication should be prescribed only when necessary and should be withheld periodically to assess the need for continued treatment and to unmask incipient dyskinesia. Thioridazine, a phenothiazine with a piperidine side chain, is an effective antipsychotic agent that seems less likely than most to cause extrapyramidal reactions, perhaps because it has little effect on dopamine receptors in the striatal system. Finally, antimuscarinic drugs should not be prescribed routinely in patients receiving neuroleptics, because the combination may increase the likelihood of dyskinesia. 

Fernandez HH, Friedman JH. Classification and treatment of tardive syndromes. Neurologist. 2003 9 16-27. 

The risk of causing EPS, another SSRI-induced neurologist disorder, was apparent from early on. The FDA s Kapit (1986) warned, It is possible that a tardive syndrome related to fluoxetine may exist. It will be necessary to be on the lookout for such events (p. 32). By January 1993, more than two dozen reports of Prozac-induced tardive dyskinesia had reached the FDA (1993), but the profession has not taken much notice. Numerous case reports confirm that the SSRIs can produce persistent extrapyramidal reactions, including tardive dystonia with painful and disabling spasms of the neck and shoulder musculature. 

Jeste, D., Wisniewski, A., 6c Wyatt, R. (1986). Neuroleptic-associated tardive syndromes. Psychiatric Clinics of North America, 9, 183—192. 

Jeste DV, Wisniewski AA, Wyatt RJ. Neuroleptic-associated tardive syndromes. Psychiatr Clin North Am... 

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. 

Similar associations have been reported between dopamine D receptor variants with Tourette s syndrome, obesity (87-89), and alcohol dependence (90-93), although these findings are still the subject of debate in the literature. From the point of view of pharmacogenetics, the TaqlA polymorphism of the dopamine D receptor is associated with the development of tardive dyskinesia (88,94,95). While the results of these association studies vary (3,12), these data clarify our under-... 

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. 

Tiapride has weak antipsychotic activity. It has been used as a adjunct in patients with tardive hyperkinetic syndrome caused by other antipsychotics. 

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. 

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. 

Neuroleptic malignant syndrome or tardive dyskinesia has been reported. 

Unlabeled Uses Cerebral vasospasm, migraines, Raynaud s syndrome, reflex sympathetic dystrophy, refractory depression, tardive dyskinesia, thyrotoxic crisis. 

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)... 

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... 

Golden, G.S. (1985) Tardive dyskinesia in Tourette syndrome. Pediatr Neurol 1 192—194. 

Tourette s syndrome is a well-studied condition, characterized by motor and phonic tics and by behavioral and psychological problems. While many neurotransmitters were implicated in the etiology of this disorder, it is now believed that the dopaminergic system and noradrenergic systems are involved. Two major clinical trials (Shapiro et ah, 1989 Sallee et al, 1997) indicated that haloperidol and pimozide reduced the severity of tics by 65%. However, these medications are associated with side effects (including possible cognitive impairment, sedation, dysphoria, and tardive dyskinesia) that may limit their effectiveness in children with MR. 

Klaiber EL, Broverman DM, Vogel W, et al Estrogen therapy for persistant depression in women. Arch Gen Psychiatry 36 550-554, 1979 Klawans HL, Weiner WJ, Nausieda PA The effect of lithium on an animal model of tardive dyskinesia. Prog Neuropsychopharmacol 1 53-60, 1976 Klein DP Delineation of two drug-responsive anxiety syndromes. Psychopharmaco-logia 5 397-408, 1964... 

Educate the patient and family about the risks of developing metabolic syndrome, diabetes, obesity, dyslipidemia, and tardive dyskinesia. Document this discussion in the patient s chart. 

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. 

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. 

Muscettola G, Barbate G, Pampallona S, et al. Extrapyramidal syndromes in neuroleptic-treated patients prevalence, risk factors, and association with tardive dyskinesia. J Clin... 

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