Serum iron and ferritin in acute neuroleptic akathisia

Abstract

Acute akathisia is a common and disturbing side effect of classic antipsychotic medication. Some evidence suggests a role for iron deficiency in chronic and tardive akathisia. In acute akathisia, however, the data are contradictory. Serum iron and ferritin levels of 33 inpatients with acute akathisia during classic neuroleptic medication were compared with those of 23 patients on classic neuroleptics without this side effect. Akathisia was rated by means of the Hillside Akathisia Scale. The groups were balanced for age (mean 38.5±14.5), medication (butyrophenone- and phenothiazine-derived neuroleptics) and diagnosis (schizophrenia, schizoaffective disorder, psychotic affective disorder). Patients with acute akathisia had significantly lower serum ferritin levels than the patients in the control group. However, the ferritin (56.94±39.54 ng/ml) and iron (88.52±40.0 mg/dl) levels in these patients were within the normal range (ferritin 30–300 ng/dl, iron 80–180 mg/dl). No correlations between serum iron or ferritin and akathisia ratings could be found. Although some reduction in serum ferritin was found in patients with acute akathisia compared to patients without akathisia, the difference was small and the ferritin levels were within the range of the normal population. These findings suggest a minor role for iron deficiency in acute akathisia.

Introduction

Akathisia is considered one of the most troubling side effects of neuroleptics and is a predominant reason for non-compliance (Van Putten, 1974, Schmidt et al., 1984). Clinical subtypes include acute, withdrawal (Barclay and Lang, 1992), tardive and chronic akathisia (Sachdev and Lonergan, 1991b, Sachdev, 1994). The onset of acute akathisia is within hours or days (Sachdev, 1995a) of drug initiation or dose increase (Braude et al., 1983, Miller et al., 1997). In approximately 80%, acute akathisia develops within 2 weeks (Miller et al., 1997). Akathisia that develops after 3 months or more is termed tardive akathisia (Sachdev, 1995b).

The pathogenesis of akathisia has been poorly understood. In recent years the role of iron metabolism as a possible pathophysiological factor in the development of akathisia has received increasing attention. Clinical studies on the relationship between iron metabolism and akathisia have yielded contradictory results (for review, see Gold and Lenox, 1995). Of nine studies, five found iron deficiency associated with akathisia (Brown et al., 1987, Barton et al., 1990, Fornazzari et al., 1991, Horiguchi, 1991, Valles et al., 1992). In contrast, however, another study yielded inconclusive results (O’Loughlin et al., 1991) and three studies yielded negative results in terms of such an association (Sachdev and Lonergan, 1991a, Barnes et al., 1992, Nemes et al., 1992). Of the six studies that investigated chronic and tardive akathisia, four reported a correlation with iron deficiency (Brown et al., 1987, Barton et al., 1990, Horiguchi, 1991, Valles et al., 1992). Of the two studies on acute akathisia, one prospective study did not find an association (Sachdev and Lonergan, 1991a) and another study yielded ambiguous results (O’Loughlin et al., 1991).

Given the inconsistent data in case of acute akathisia, the aim of the present study was to examine serum iron and serum ferritin levels in patients with acute akathisia. In contrast to existing studies on acute akathisia (O’Loughlin et al., 1991, Sachdev and Lonergan, 1991a), we measured serum ferritin, in addition to serum iron, as it represents a more sensitive peripheral marker of the body’s iron stores.