Severe Akathisia during Olanzapine Treatment of Acute Schizophrenia

Abstract

Olanzapine is a newly developed atypical neuroleptic with a marked affinity to the 5-HT2, D2 and D4 dopamine receptors. Like other atypical neuroleptics olanzapine is considered to show a reduced prevalence of extrapyramidal side effects when compared to classical neuroleptic drugs. We report on three patients with acute schizophrenia, who developed severe akathisia during treatment with olanzapine (20-25 mg/d). In two of these cases akathisia resolved after withdrawal of olanzapine and substitution by a classical or an atypical neuroleptic agent, respectively. In one of these patients olanzapine was well tolerated when reintroduced in combination with lorazepam after complete remission of akathisia. In the third patient akathisia was sufficiently controlled by dose reduction. Akathisia is generally considered to result from D2 dopamine receptor antagonism. In the case of atypical neuroleptics such as olanzapine a low but still considerable D2 dopamine receptor occupancy may be compensated by the 5-HT2 antagonism. However, this mechanism may fail under certain circumstances, in particular if D2 dopamine antagonism exceeds a certain threshold. One should therefore be aware of possible extrapyramidal side effects with olanzapine that are reduced compared to classical neuroleptic drugs but not completely eliminated.

A critical review of akathisia, and its possible association with suicidal behaviour

“…In the treatment of psychotic disorders newer atypical neuroleptics cause fewer side effects especially EPS, than the traditional antipsychotics, due to their different receptor-occupancy pro®le (Chung and Chiu, 1996;Collaborative Working Group on Clinical Trial Evaluation, 1998;Jauss et al, 1998). Nevertheless EPS and, indeed, akathisia also occur with newer drugs such as olanzapine and risperidone (Avantis et al, 1997;King et al, 1995), and so doses of these drugs should also be kept as low as the symptoms allow (Jauss et al, 1998).…”

“…Nevertheless EPS and, indeed, akathisia also occur with newer drugs such as olanzapine and risperidone (Avantis et al, 1997;King et al, 1995), and so doses of these drugs should also be kept as low as the symptoms allow (Jauss et al, 1998). The incidence of EPS with traditional antipsychotics varies, but the better designed studies agree that EPS occur in 30±50% of patients who take conventional antipsychotics at therapeutic doses.…”

“…A double-blind study carried out on 336 schizophrenic patients showed that quetiapine was no different to placebo with regard to akathisia (Avantis et al, 1997). Other atypicals have slightly raised the risk of akathisia, compared with placebo (Jauss et al, 1998). Healey's review (1994) on the¯uoxetine suicide controversy suggests that giving information about akathisia to the patient before medication is started is bene®cial.…”

Olanzapine-induced akathisia in OCD

“…4 In clinical trials of olanzapine in patients with schizophrenia, akathisia has been reported. 1 There have been only two reports describing individual cases of olanzapine-induced akathisia, 5,6 and these also occurred in patients with schizophrenia.…”

Association of dopamine D3-receptor gene variants with neuroleptic induced akathisia in schizophrenic patients: A generalization of Steen's study onDRD3 and tardive dyskinesia

“…Acute akathisia is a common and extremely distressing side effect of antipsychotic treatment [Barnes and Braude, 1985;Blaisdell, 1994;Miller et al, 1997;Sachdev, 1995] and is not restricted to the use of classical neuroleptics [Barnes and McPhillips, 1998;Jauss et al, 1998;Rosebush and Mazurek, 1999]. Incidence rates are reported to vary between 25 and 75% [Braude et al, 1983;Kopala et al, 1997;Miller et al, 1998;van Putten et al, 1984].…”