Adverse effects of atypical antipsychotics in the elderly: a review.

Use of antipsychotic medication is very common in the elderly and often an essential therapy. However, successful treatment in the elderly requires appropriate multidimensional assessment of the patient, knowledge of possible multiple co-morbidities, and awareness of the complexities of polypharmacy, age-dependent changes in pharmacokinetics and pharmacodynamics, and drug-drug interactions in this age group. Antipsychotics are known to have a number of adverse effects. New antipsychotics, such as amisulpride, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, zotepine and aripiprazole, may interact with both dopamine and serotonin receptors. However, compared with conventional antipsychotics, they are less likely to cause extrapyramidal symptoms and are better tolerated in the elderly. At the same time, consistent differences between atypical antipsychotics have been demonstrated. Use of clozapine, for example, is limited by the risk of agranulocytosis, whereas this is not a disadvantage of olanzapine, risperidone, quetiapine and, more recently, ziprasidone, which are being widely used with good results in schizophrenia. However, use of the latter agents to treat the behavioural and psychological symptoms of dementia has been restricted because of recent observations of increased cardiovascular events in patients taking risperidone and olanzapine treatment. Nonetheless, careful review of the literature suggests that the available evidence does not support any causal relationship between use of risperidone or olanzapine and cardiovascular events. This article focuses on some of the main adverse effects commonly reported during administration of atypical antipsychotics to elderly patients. Such effects may be partly explained by age-related changes in pharmacokinetics and pharmacodynamics, and partly by the characteristics of the drugs themselves and their different receptor binding profiles.

Increase in plasma homocysteine levels induced by drug treatments in neurologic patients.

Homocysteine (Hcy) is a thyol amino acid resulting from de-methylation of methionine, an essential amino acid derived from dietary proteins. It is metabolized through two pathways: re-methylation and transsulfuration, which use as cofactors folate, vitamin B6 and vitamin B12. Hyperhomocysteinemia has been identified as a risk factor for cerebrovascular disease, dementia, impaired cognitive function and depression. Several drugs may interfere with metabolic pathways of Hcy, leading to an alteration of plasma Hcy levels. Lipid-lowering agents, used to reduce the risk of cerebral venous thrombosis or occlusive vascular disease in patients with high levels of plasmatic lipids, can increase plasma Hcy levels. Hyperhomocysteinemia has been also documented in Parkinson disease patients treated with levodopa and in epileptic patients after chronic treatment with antiepileptic drugs. In contrast, vitamins supplementations may be warranted in patients treated with lipid-lowering agents, levodopa and antiepileptic drugs in order to maintain normal plasma Hcy values. In contrast, higher doses of vitamins can induce dysfunctions in central and peripheral nervous system; therefore excessive supplements should be avoided.

Anticonvulsant effects of carbenoxolone in genetically epilepsy prone rats (GEPRs).

Carbenoxolone (CBX), the succinyl ester of glycyrrhetinic acid, is an inhibitor of gap junctional intercellular communication. Systemic administration of CBX was able to decrease the seizure severity score and to increase the latency time of seizure onset in genetically epilepsy prone rats (GEPRs). In particular, intravenous or intraperitoneal administration of carbenoxolone (5-30 mg/kg) produced a dose-dependent and significant reduction in the clonic and tonic phases of the audiogenic seizures in GEPRs. The anticonvulsant doses were not associated with an impairment of motor coordination. The bilateral microinjection of CBX (0.001-0.50 microg/0.5 microl) into the inferior colliculi, the substantia nigra (pars reticulata or compacta) and the inferior olivary complex was able to reduce the seizure severity score in a dose-dependent manner. The anticonvulsant effects were longer lasting after focal microinjection than after systemic administration. No anticonvulsant effects were observed following focal bilateral microinjections of glycyrrhizin into the same brain areas where CBX was shown to be effective.