Neuroleptic drugs long-term treatment with

Gross, G. Schumann, H. J. 1982, Effect of long term treatment with atypical neuroleptic drugs on beta adrenoceptor binding in rat cerebral cortex and myocardium, Naunyn Schmiedebergs Arch.Pharmacol., vol. 321, no. 4, pp. 271-275. 

Nielsen, E. G., Lyon, M. (1978). Evidence for cell loss in corpus striatum after long-term treatment with a neuroleptic drug (flupenthtxol) in rats. Psychopharmacology, 59, 85-89. 

Tardive Dyskinesia and Dopamine Receptor Supersensitivity - Tardive dyskinesia is a major complication of long term treatment with neuroleptic drugs 24,25,26,27 it is characterized by abnormal movement of facial muscles and extremities which frequently worsen when the neuroleptic dose is lowered or terminated. Increasing the dose, however, may temporarily alleviate the symptoms. The chronic treatment of rats and mice with neuroleptics leads to an increased motor activity and enhanced sensitivity to the motor stimulant effects of apomorphine, a direct dopamine receptor agonist28 ... 

The long-term toxic effects of lithium, such as nephrogenic diabetes insipidus, which has been calculated to occur in up to 5% of patients, and the rare possibility of lithium combined with neuroleptics being neurotoxic, has stimulated the research for other drug treatments. However, apart from the neuroleptics, these drugs have not been studied as extensively in the treatment of acute mania, but are worthy of consideration because of their reduced side effects. 

Richelson E, Nelson A Antagonism by neuroleptics of neurotransmitter receptors of normal brain in vitro. Eur J Pharmacol 103 197-204, 1984 Rickels K, Schweizer E The treatment of generalized anxiety disorder in patients with depressive symptomatology. J Clin Psychiatry 54 [suppl) 20-23, 1993 Rickels K, Weisman K, Norstad N, et al Buspirone and diazepam in anxiety a controlled study. J Chn Psychiatry 43(12 pt 2) 81-86, 1982 Rickels K, Feighner JP, Smith WT Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression. Arch Gen Psychiatry 42 134-141, 1985 Rickels K, Schweizer E, Weiss S, et al Maintenance drug treatment for panic disorder, 11 short- and long-term outcome after drug taper. Arch Gen Psychiatry 50 61-68, 1993... 

In this context, Lilly (474) reported a meta-analysis of three controlled studies of patients with TD who were treated with olanzapine. These authors found an 11-fold decrease in TD on olanzapine versus haloperidol based on the AIMS scale. There were a few patients who developed TD in the first 6 weeks of olanzapine, but this could have been from previous drug exposure, now not suppressed by the neuroleptic. Interestingly, there were no new cases (0/375) of TD developing in patients on long-term olanzapine treatment, whereas there were three of 83 cases on haloperidol. It is very difficult to arrive at definitive evidence about TD because most patients have received previous neuroleptic therapy and because TD-like symptoms occur spontaneously, providing an alternative explanation. It is clear that it is difficult to prove that olanzapine causes TD but equally difficult to prove that it does not. The 11-fold decreased incidence, however, is strong evidence that at least it produces much less TD. 

Akathisia has been associated with iron deficiency (SEDA-17, 49). However, the rationale for iron supplementation in the treatment of akathisia is poor, and there are potential long-term adverse consequences (SEDA-20, 38). This issue has been addressed in patients with acute psychotic disorders who received neuroleptic drugs 33 patients who developed akathisia were compared with 23 who did not (230). Serum iron was similar in the two groups but ferritin concentrations were significantly lower in akathisia nevertheless, iron and ferritin concentrations were within the reference ranges. 

---