Neuroleptics akathisia

Term used to describe a patient s restlessness and inability to sit still. Shortly after the introduction of neuroleptics, akathisia was recognized as one of the most common and distressing side effects. Propranolol is often useful in treating such symptoms. Movement disorder characterized by reduction or loss of ability to initiate voluntary muscle movements. Often associated with side effects of neuroleptics mask-like facial expression, absent arm swing, low voice. 

Barnes, T. (1992). Neuromuscular effects of neuroleptics Akathisia. In J. Kane J. Lieber-man (Eds.), Adverse effects of psychotropic drugs. New York Guilford. 

Hofmann M, Seifritz E, Botschev C, Krauchi K, Muller-Spahn F. Serum iron and ferritin in acute neuroleptic akathisia. Psychiatry Res 2000 93(3) 201-7. 

IS THE ACUTE NEUROLEPTIC-INDUCED AKATHISIA A DISPLACEMENT ACTIVITY ... 

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. 

In addition to the somatic side-effects of neuroleptics, there are a number of important psychiatric side-effects, such as demotivation or indifference (a direct effect of most drugs, actually part of the definition of the neuroleptic effect). This may mimic the negative features of the illness and may lead to prescriptions of an antidepressant when a reduction in dose or change of antipsychotic may be more appropriate. A second key problem is anxious activation or akathisia. This dose-dependent dysphoric state may lead to an apparent worsening in the clinical picture and accordingly an increase in antipsychotic dose rather than decrease and may be so intolerable as to lead on to suicide. 

Unlabeled Uses Treatment of arrhythmias, hypertrophic cardiomyopathy. Ml, mitral valve prolapse syndrome, neuroleptic-induced akathisia, pheochromocytoma, tremors, thyrotoxicosis, vascular headaches... 

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. 

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. 

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 general, lower doses (e.g., risperidone 2 to 6 mg/day olanzapine 5 to 20 mg/day) are preferable, usually sufficient, and help avoid toxicity. At these doses, results suggest that olanzapine has a substantially lower propensity than neuroleptics to evoke EPS, and perhaps TD. Indeed, early clinical trials were unable to distinguish olanzapine from placebo for EPS or akathisia. Further, there is some indication that doses of risperidone 10 mg may produce less improvement and more side effects than doses in the 4-8 mg dose range. 

Late-onset or tardive dystonia, akathisia, and possibly other types of EPS have also been described as separate disorders from classic TD. Tardive dystonia is characterized by the late appearance of dystonias that persist even though neuroleptics are discontinued. It is rare, with a prevalence of about 1.5%. It is probably a separate diagnostic entity inasmuch as anticholinergics benefit tardive dystonia, whereas these drugs can worsen TD. The onset of tardive dystonia occurs after a shorter total drug exposure time than generally seen with TD. 

In the international, multicenter, double-blind trial of olanzapine, the Simpson-Angus Scale and the Barnes Akathisia Scale were used to monitor treatment-emergent EPS. The acute phase was followed by a 52-week, double-blind, maintenance phase, during which there were significantly lower rates of treatment-emergent Parkinsonism and akathisia (p > 0.001), as well as TD (p < 0.003) in comparison with haloperidol (117). These results suggest that olanzapine has a substantially lower propensity than neuroleptics to evoke EPS, and perhaps TD. 

Adler LA, Rieter S, Corwin J, et al. Differential effects of propranolol and benzotropine in patients with neuroleptic-induced akathisia. Psychopharmacol Bull 1987 23 519-521. 

Kramer MS, Gorkin RA, Johnson C, et al. Propranolol in the treatment of neuroleptic-induced akathisia(nia) in schizophrenics a double-blind, placebo-controlled study. Biopsychiatry 1988 24 823-827. 

Adler L, Angrist B, Peselow E, et al. A controlled assessment of propranolol in the treatment of neuroleptic-induced akathisia. Br J Psychiatry 1986 149 42-45. 

Gagrat D, Hamilton J, Belmaker RH. Intravenous diazepam in the treatment of neuroleptic-induced acute dystonia and akathisia. Am J Psychiatry 1978 135 1232-1233. 

Lima AR, Weiser KV, Bacaltchuk J, Barnes TR. Anticholinergics for neuroleptic-induced acute akathisia. Cochrane Database Syst Rev. 2004 CD003727. 

Involuntary movement disorders also respond well to this class of drugs. These include restless leg syndrome, akathisia associated with neuroleptic use, choreiform disorders, and myoclonus. 

Akathisia, considered to be one of the leading causes of non-compliance with typical neuroleptics, is not thought to be linked to dopamine receptor... 

Parkinsonism, dystonias, akathisia Dopamine blockade of basal ganglia All potent typical neuroleptics... 

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. 

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