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. CONCLUSION: 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.

Metabolic Issues With Atypical Antipsychotics in Primary Care: Dispelling the Myths.

BACKGROUND: Recently, much attention has been focused on the increased rate of metabolic syndrome componen ts among psychiatric patients, including glucose intolerance, hyperglycemia, diabetes mellitus, hyperlipidemia, hypertension, and weight gain. Various reports have identified cases of newly diagnosed diabetes during treatment with atypical antipsychotic agents. However, the question remains whether there is a relationship between atypical antipsychotic use and the metabolic syndrome or whether there is a higher risk in this population irrespective of medication use. METHOD: Many articles on antipsychotics and metabolic issues are reviews of case reports or small, cross-sectional laboratory studies highlighting the suspected potential for differing rates of new-onset diabetes cases. We conducted a retrospective review of the literature from 1998 through 2002, using the MEDLINE database, and recent studies presented at major psychiatric medical conferences to create a broader perspective on the metabolic issues. RESULTS: We identified over 70 abstracts and published manuscripts, including case reports; cross-sectional lab studies; retrospective analyses of head-to-head, controlled clinical studies; retrospective database studies; pharmacoepidemiology studies; and prospective head-to-head studies presented in the past 4 years. Studies assessed differences in fasting plasma glucose, oral glucose tolerance tests (OGTT), modified OGTT, frequently sampled intravenous glucose tolerance tests, homeostasis model assessment-insulin resistance, odds or hazard ratios, prevalence, and incidence, as well as other elements of the metabolic syndrome. CONCLUSION: Data from this large body of scientific evidence indicate that the psychiatric patient population may be at a higher risk for the development of obesity, glucose homeostasis dysregulation, and hyperlipidemia compared with the general population. The available data do not demonstrate a consistent or clinically significant difference in the risk of new-onset diabetes during treatment with the various atypical antipsychotic agents.

Mood Disorders in Family Practice: Beyond Unipolarity to Bipolarity.

Primary care physicians increasingly have treated depressive disorders over the last decade. Unrecognized bipolar disorder, sometimes misdiagnosed as unipolar depression, may lead to treatment resistance or nonresponse. We describe differences between unipolar and bipolar disorders, focusing on recognition, diagnosis, and treatment of bipolar spectrum disorders such as bipolar I, bipolar II, antidepressant-induced mania, and cyclothymia. Broadening the understanding of these different disorders and their presentation in primary care settings can enable earlier and more targeted treatment. Though 3 mood stabilizers are U.S. Food and Drug Administration-approved for treatment of acute mania, no medications are currently approved for treating bipolar depression.

A Perspective on the Primary Care of Patients With Behavior, Mood, and Thought Disturbances: Clinical Applications of Olanzapine.

Primary care practitioners are in an ideal position to initiate treatment for patients with behavior, mood, and thought disturbances. It is believed that early identification and treatment of these symptomatic features of primary or secondary central nervous system disorders may significantly reduce morbidity and benefit the patient, his/her family, and involved caregivers, including the primary care physician. A broad list of central nervous system-active medications are utilized by family physicians to treat patients who exhibit symptoms of agitation, altered mood, and disordered thought. Some medications have demonstrated superiority over placebo or active medicines in reported clinical trials. This article is a brief overview of the safety and efficacy from reported studies of the use of medications frequently used to treat symptoms related to behavior, mood, and thought disturbances, with a specific focus on the clinical applicability of olanzapine.