Serum iron and ferritin in acute neuroleptic akathisia.

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.

Beta 2-receptor density on mononuclear blood cells in patients suffering from neuroleptic-induced akathisia (NIA).

The effectiveness of beta-blockers in the treatment of neuroleptic-induced akathisia (NIA) suggests that beta-adrenergic overactivity is involved in the manifestation of NIA. As an approach to understanding this postulated overactivity, we investigated the beta 2-receptor density on mononuclear blood cells in 21 patients suffering from NIA as well as in 12 patients without NIA. The beta 2-receptor density in NIA-positive patients was significantly higher than that in NIA-negative patients (t = 2.84; p = .008). The NIA-positive patients were treated with 20 mg propranolol t.i.d. for 5 days. The beta 2-receptor density in treatment responders did not differ significantly from that in non-responders. Our results indicate that beta 2-receptors on mononuclear cells in patients with NIA may be of a certain degree of importance. With the prerequisites of replicability as well as correlation of this parameter with therapeutic success of beta-blockers, it may be considered as a predictor for treatment response.

Clinical and biochemical effects of nicergoline in chronic schizophrenic patients.

To investigate the potential effect of Nicergoline, an alpha-adrenolytic drug, on negative symptoms in patients suffering from chronic schizophrenia, we administered this compound to 20 male chronic schizophrenics. Patients were previously maintained on long-term neuroleptic (NL) medication. Neuroleptic treatment was discontinued for 12 days, patients were then treated with 30 mg Nicergoline per day. Under NL (A), after 12 days NL-withdrawal (B), after 15 (C) and 30 (D) days Nicergoline treatment clinical ratings (BPRS and AMDP) and stimulation with clonidine (0.002 micrograms/kg body weight) were carried out. Norepinephrine (NE), epinephrine (E), and human growth hormone (HGH) were measured before and after application. Seventeen patients finished the study, 3 dropped out. Some ratings on the AMDP and BPRS scales showed an improvement. However, this improvement was only weak and accompanied by a worsening in other subscores. The withdrawal-induced decrease in NE serum levels continued after 15 days NIC, followed by an increase after 30 days. HGH response to clonidine stimulation was only attenuated after 30 days NIC. Epinephrine, blood pressure and heart rate showed no significant changes throughout the entire study. Our data suggest that NIC in the dosage applied shows no clear and pronounced alpha-2-adrenolytic effects and no specific clinical benefits for chronic schizophrenics. Further investigations are required to evaluate its effect on alpha-1-adrenoceptors.

Neuroendocrine effects of clonidine in chronic schizophrenic patients under long-term neuroleptic therapy and after drug withdrawal: relations to psychopathology.

The sensitivity of the alpha-adrenergic hypothalamic pituitary system, as indicated by growth hormone (GH) release after clonidine (0.15 mg i.v.), was studied in nine chronic schizophrenic in-patients (study 1) under long-term neuroleptic (NL) therapy and after 5 days' drug withdrawal and in 17 chronic schizophrenic in-patients (study 2) under long-term NL therapy and after 12 days' drug withdrawal. GH response after 5- and 12-day drug-free periods did not differ significantly from that under NL treatment; however, it was significantly lower after 12 days' drug withdrawal (AUC: 319.9 +/- 445.5 ng/ml X min) compared to age- and sex-matched normal controls (579 +/- 611 ng/ml X min). The basal norepinephrine (NE) plasma levels under long-term NL therapy were significantly elevated in both studies (study 1:894 +/- 553 pg/ml; study 2:432 +/- 268 pg/ml) compared to controls (study 1:253 +/- 55 pg/ml, study 2:234 +/- 126 pg/ml), and were decreased significantly after 5 days' drug withdrawal compared to NL treatment. There was no significant correlation between age, duration of NL therapy, last daily dosage, psychopathology, and NE plasma levels and GH response. The data presented suggest hyposensitivity of alpha-adrenergic receptor function in the hypothalamic-pituitary axis after 12 days' drug withdrawal in chronic schizophrenics. The significantly elevated NE plasma levels under NL therapy indicate that there is no adaption mechanism, even after long-term treatment.