The effects of antipsychotic drug treatment on prolactin concentrations in elderly patients.
OBJECTIVE
To describe the change in serum prolactin concentrations in elderly agitated nursing home patients with dementia who were newly initiated on olanzapine or switched to olanzapine treatment from either conventional antipsychotics or risperidone.


METHODS
During an 8-week open-label olanzapine efficacy trial in elderly nursing home patients demonstrating clinically significant behavioral and psychological symptoms of dementia, serum prolactin concentrations were drawn on four occasions: at time of consent, following a washout period from previous therapy, midway through the study, and at endpoint. To assess post-hoc the effects of prolactin concentrations upon switching to olanzapine treatment, patients were divided into three different groups, based upon status at time of consent: those not taking antipsychotic medication, those taking any conventional antipsychotic, and those taking risperidone. Prolactin concentrations were assessed using a mixed-effect repeated-measures model. Symptom severity was measured using the Brief Psychiatric Rating Scale (BPRS), the Cohen-Mansfield Agitation Inventory (CMAI), the Clinical Global Impression (CGI)-Severity scale, and the Mini-Mental State Examination (MMSE), and the same repeated measures analysis was performed on these scales.


RESULTS
Patients not on antipsychotic medication at study entry (29 females, 7 males) experienced a significant increase in prolactin concentration baseline to endpoint (P < 0.05) but remained below upper limit of normal for prolactin for both males and females. There was a nonsignificant increase in prolactin concentrations when patients were switched from conventional antipsychotic medications (mean dose 152.41 +/- 192.48 mg/day chlorpromazine equivalents) to olanzapine (2.5 to 10 mg/day) (22 females, 9 males). Patients who entered the study on risperidone (mean dose 1.31 +/- 0.91 mg/day) (13 females, 4 males) experienced a significant decrease in prolactin concentration (P < 0.001). While 62.5% of risperidone-treated patients had above-normal prolactin concentrations at baseline, only 21.4% had above-normal concentrations at endpoint (P = 0.033). Clear correlations between prolactin concentrations and clinical outcomes could not be determined.


CONCLUSIONS
Consistent with previous findings in younger patients, olanzapine appeared to be a prolactin-sparing antipsychotic medication in the elderly with only modest prolactin increases observed. In addition, patients who were receiving risperidone and then switched to olanzapine experienced a significant reduction in prolactin concentrations that was sustained over the 8-week treatment course with olanzapine. One possible explanation for olanzapine's relatively modest increase in prolactin is that, unlike conventionals or risperidone, olanzapine binds less tightly with the dopamine D(2) receptor.
Kinon
Bruce J
BJ
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
Stauffer
Virginia L
VL
McGuire
Hillary C
HC
Kaiser
Christopher J
CJ
Dickson
Ruth A
RA
Kennedy
John S
JS
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D003704:Dementia / Q000145:classification / Q000188:drug therapy* / Q000378:metabolism*; D016903:Drug Monitoring; D005260:Female; D015577:Geriatric Assessment; D006707:Homes for the Aged; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008609:Mental Status Schedule; D009735:Nursing Homes; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood* / Q000187:drug effects*; D011569:Psychiatric Status Rating Scales; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D018967:Risperidone / Q000494:pharmacology*; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D001569:Benzodiazepines; D010890:Pirenzepine; D011388:Prolactin; D018967:Risperidone; D000077152:Olanzapine