The pharmacological treatment of bipolar disorder: the question of modern advances.

Introduction: Lithium has been the mainstay of treatment for patients with bipolar disorder in the United States since 1970. Major treatment guidelines recommend lithium as a first-line treatment for mania and maintenance treatment of bipolar disorder, yet lithium has fallen out of favor while other agents have grown in popularity. The purpose of this review is to examine the evidence for treatments that were available in 1970 and to determine if the field has made any significant advance in the treatment of mania, bipolar depression, and maintenance.

A randomized, double-blind, and placebo-controlled trial of quetiapine augmentation of fluoxetine in major depressive disorder.

The objective of this study was to investigate whether quetiapine, when compared with placebo, can speed the onset of action and improve the quality of response to fluoxetine treatment in patients suffering from major depressive disorder. A total of 114 patients with major depressive disorder were enrolled in an 8-week treatment study. Patients were initiated on a course of fluoxetine treatment and randomized to quetiapine or placebo.

Coadministration of modafinil and a selective serotonin reuptake inhibitor from the initiation of treatment of major depressive disorder with fatigue and sleepiness: a double-blind, placebo-controlled study.

Background: Previous studies suggest that adjunctive modafinil treatment provides benefit for patients with depression with significant sleepiness and fatigue.

Methods: We conducted a multisite, double-blind, placebo-controlled study of the treatment of major depression characterized by excessive sleepiness and fatigue, adding adjunctive modafinil or placebo to a selective serotonin reuptake inhibitor from the beginning of treatment. Seventy-three of 90 consenting patients met all screening criteria to begin treatment with open-label selective serotonin reuptake inhibitor therapy and double-blind addition of either modafinil (100 mg/d for 1 week then 200 mg/d) or matching placebo for 6 weeks.

General disaster psychiatry.

This article attempts to make further sense of disasters and specifically terrorism as one particular form of disaster from the perspective of psychology and mental health.

Challenges for psychiatry in serving homeless people with psychiatric disorders.

The authors examine current challenges confronting psychiatry in caring for homeless people with psychiatric disorders. After reviewing how psychiatry has historically addressed homelessness and mental illness, the authors discuss the roles that the profession has developed in working with homeless populations. These roles, which encompass clinical, administrative, academic, and advocacy functions, have evolved as a result of trends both in homelessness services and within the profession of psychiatry.

Effect of haloperidol dose on iodine-123-IBZM brain SPECT imaging in schizophrenic patients.

Unlabelled: Studies have suggested that antipsychotic drug therapy with haloperidol in schizophrenic patients requires an optimal dose that blocks the brain dopamine D2 receptors. We evaluated the effect of different doses of haloperidol on D2 receptor occupancy in schizophrenia.

Methods: Three normal subjects and three patients with acute schizophrenia had serial brain SPECT imaging studies (every 5 min) for 3 hr following the injection of [123I]IBZM.

The Dose Reduction in Schizophrenia (DORIS) Study: a final report.

Twenty-one medication-free chronic schizophrenics were randomly assigned to three treatment groups: 50% blockade of the bromocriptine growth hormone (GH) response, 100% blockade or 10 ng/ml haloperidol. Only seven of the 21 patients showed a significant improvement after 6 weeks in positive psychotic symptoms; six of the seven responders came from the 50 and 100% blockade groups, suggesting greater efficacy at lower doses. Fifty percent blockade was associated with an average daily haloperidol dose of 3.

Empirical evaluation of the factorial structure of clinical symptoms in schizophrenia: effects of typical neuroleptics on the brief psychiatric rating scale.

There has been little investigation of the effect of neuroleptic medication on the structure of symptoms in schizophrenia. In this study, 135 male schizophrenic patients were rated with the Brief Psychiatric Rating Scale (BPRS) after 4 weeks of treatment with typical neuroleptic medication and after 2 weeks free of neuroleptics, with the order of assessment varying across patients. Confirmatory factor analyses (CFA) found that there were no differences in symptom structure across medication status and no differences in the structure of symptoms in treatment responders and nonresponders.

Clinical characteristics of Kraepelinian schizophrenia: replication and extension of previous findings.

Objective: Subtypologies of schizophrenia based on cross-sectional criteria, such as the nomenclature of the DSMs, have not been successful in identifying valid diagnostic subgroups among patients with schizophrenia. A subtypology that uses criteria to classify individuals on the basis of longitudinal deficits in self-care may identify a more valid subgroup of schizophrenic patients.

Method: This study describes the clinical characteristics of a group of schizophrenic patients identified on the basis of a longitudinal criterion: at least 5 years of continuous and complete dependence on others for obtaining and maintaining the basic necessities of life, including food, clothing, and shelter.

Predictors of response to lithium in patients with psychoses.

Objective: This study sought to characterize a subset of patients with DSM-III schizophrenia or schizophreniform disorder who respond to lithium.

Method: Sixty-six psychotic patients were given a systematic therapeutic trial of lithium alone. Differences in demographic characteristics, symptoms, and family history of psychotic disorders between the responders and nonresponders to lithium were explored.

Further evidence of a dose-response threshold for haloperidol in psychosis.

Objective: The authors' goal was to determine whether higher doses of haloperidol improve antipsychotic response.

Method: During a 2-week, double-blind, randomized fixed-dose study, 24 psychotic patients were given 4, 10, or 40 mg/day of haloperidol.

Results: No clinically relevant difference between groups in favor of the higher antipsychotic doses could be detected.

Early response to haloperidol treatment in chronic schizophrenia.

This study examined the time-course of treatment response to haloperidol in chronic schizophrenia. Furthermore the predictive value of baseline psychopathology and early therapeutic changes for the identification of the eventual treatment outcome was examined. After a two-week drug-free period forty-three chronic schizophrenic patients were treated with haloperidol for five weeks.

Treatment with clozapine and its effect on plasma homovanillic acid and norepinephrine concentrations in schizophrenia.

Measurement of plasma concentrations of the dopamine metabolite, homovanillic acid (pHVA), is an indirect tool to assess changes in dopamine turnover. Levels of pHVA have been reported to decrease during treatment with conventional antidopaminergic, neuroleptics, with the decrement correlating with symptomatic improvement in schizophrenic symptoms. Clozapine, an atypical neuroleptic, is the only drug proved to be effective in treatment-refractory patients.

Nocturnal growth hormone secretion in schizophrenic patients and healthy subjects.

Plasma growth hormone concentrations were measured at hourly intervals between 10 p.m. and 8 a.

A new approach to dose reduction in chronic schizophrenia.

The bromocriptine growth hormone test (BGHT) was used to monitor D2 receptor activity in a group of 16 chronic schizophrenics who during the baseline phase were receiving greater than or equal to 20 mg/day haloperidol. In all subjects at baseline, the rise in plasma GH in response to the oral administration of bromocriptine (50 micrograms/kg) was blocked. The dose of haloperidol was then gradually reduced; the BGHT was repeated as each new dose was established.

Single- vs multiple-dose pharmacokinetics of clozapine in psychiatric patients.

Clozapine plasma levels were monitored in 16 patients during a series of three consecutive treatments (single dose-multiple dose-single dose). Each patient received a single 75-mg dose (3 x 25 mg) with clozapine tablets, and serial plasma samples were collected over 48 hr after the dose. At 48 hr, a multiple-dose regimen was started, consisting of an initial dose escalation period followed by dosing at a constant regimen for at least 6 days.

Lithium antagonism of ethanol-induced intoxication: relationship to intracellular lithium levels.

Seventeen detoxified chronic alcoholics participated in a double-blind trial comparing placebo and lithium (Li+) effects on acute ethanol (1 g/kg) intoxication. In a repeated measures, split-half crossover design, subjects were maintained for 7 days on Li+ or placebo before the ethanol challenge. Plasma Li+ levels on day 7 averaged 1.

RBC lithium transport in the psychoses.

In vitro and in vivo red blood cell (RBC) lithium (Li+) intracellular/extracellular ratios were determined in 93 DSM-III schizophrenics (SCZ) in 47 DSM-III schizophreniform disorder patients (SF), in 22 DSM-III bipolar manics (M), in 15 affective disorders patients with mood-incongruent psychotic features (AD-MIP), and in 40 normal controls. There were no significant differences among groups in the in vitro Li+ ratio. Similarly, there was no significant difference among patient groups in the in vivo Li+ ratio.

Clonazepam treatment of five lithium-refractory patients with bipolar disorder.

The authors describe the first five patients enrolled in an open clinical trial of clonazepam as a maintenance treatment in lithium-refractory bipolar disorder. All patients relapsed quickly after taking clonazepam (one within 2 weeks and four within 10-15 weeks), and the study was prematurely terminated. The results cast doubt over the usefulness of clonazepam as a prophylaxis in lithium-resistant bipolar patients who have histories of psychotic mania or delusional depression.

Drug response patterns as a basis of nosology for the mood-incongruent psychoses (the schizophrenias).

Interaction of therapeutic drugs with a series of different biopathological substrates of psychosis might be expected to generate a series of different response patterns. Herein the authors suggest that multi-modal response patterns following lithium and neuroleptic treatment of psychotic patients may aid in resolving the heterogeneity of psychotic disorders and lead to a new nosology of the psychoses.

Lithium transport in human fibroblasts: relationship to RBC lithium transport and psychiatric diagnoses.

Cultured fibroblasts were prepared from six normal controls, five DSM-III manic patients, and six DSM-III schizophrenic patients. Lithium (Li+) uptake, 24-hour Li+ ratios, and steady-state membrane potential were measured in these cell lines. The uptake of 10 mM Li+ reached maximum at 2 hours, with an intracellular concentration of approximately 15 mM.

Growth hormone response to apomorphine and family patterns of illness.

Sixty-five psychotic probands were divided into three groups (low, intermediate, and high) on the basis of the GH response to the dopamine receptor agonist apomorphine. Two hundred and sixty-five first-degree relatives of the probands were diagnosed according to SADS-DSM-III methods, and the relatives of the three groups of probands were compared so as to detect familial differences in the incidence of DSM-III Axis I disorders, schizotypal personality disorder, and antisocial personality. Although the morbid risk of schizophrenic spectrum disorder was only 3.

Relation of clinical symptoms to apomorphine-stimulated growth hormone release in mood-incongruent psychotic patients.

The relationship between dopamine receptor agonist (apomorphine hydrochloride)-stimulated growth hormone (GH) release and psychotic symptoms was examined in 138 schizophrenic or schizoaffective inpatients (Research Diagnostic Criteria) and ten healthy normal volunteers. Patients were divided into three groups: those demonstrating an abnormally large GH response, an average GH response (mean GH response), or an abnormally low GH response. Abnormally large GH responses were associated with higher total psychosis scores.