Olanzapine and haloperidol in first episode psychosis: two-year data.

Few studies have assessed the comparative efficacy and safety of atypical and typical antipsychotic medications in patients within their first episode of psychosis. This study examined the effectiveness of the atypical antipsychotic olanzapine and the typical antipsychotic haloperidol in patients experiencing their first episode of a schizophrenia-related psychotic disorder over a 2-year treatment period. Two hundred and sixty-three patients were randomized to olanzapine or haloperidol in a doubleblind, multisite, international 2-year study. Clinical symptoms and side effects were assessed at baseline and longitudinally following randomization for the duration of the study. Olanzapine and haloperidol treatment were both associated with substantial and comparable reductions in symptom severity (the primary outcome measure) over the course of the study. However, the treatment groups differed on two secondary efficacy measures. Patients were less likely to discontinue treatment with olanzapine than with haloperidol: mean time (in days) in the study was significantly greater for those treated with olanzapine compared to haloperidol (322.09 vs. 230.38, p<0.0085). Moreover, remission rates were greater in patients treated with olanzapine as compared to those treated with haloperidol (57.25% vs. 43.94%, p<0.036). While extrapyramidal side effects were greater in those treated with haloperidol, weight gain, cholesterol level and liver function values were greater in patients treated with olanzapine. The data from this study suggest some clinical benefits for olanzapine as compared to haloperidol in first episode patients, which must be weighed against those adverse effects that are more likely with olanzapine.

Time to study discontinuation, relapse, and compliance with atypical or conventional antipsychotics in schizophrenia and related disorders.

To more clearly clarify the efficacy of the atypical antipsychotics compared to conventional antipsychotics, we add data on the outcome of patients diagnosed with schizophrenia from two large, international clinical trials comparing olanzapine with haloperidol (n = 1996) and olanzapine with risperidone (n = 339). Both studies comprised double-blinded, placebo controlled, random assignment trials. Health outcomes reported include: (i) time to discontinuation in the trial; (ii) clinical relapse; and (iii) time to drug non-compliance. When outcome was measured as time to discontinuation due to adverse events or lack of efficacy, olanzapine showed superiority over haloperidol and no difference compared to risperidone. Of those patients who had an initial response, there was no significant difference between olanzapine and haloperidol when outcome was measured using either: (i) 52-week relapse rates or (ii) time to first non-compliance. Using the measures of study discontinuation, relapse and non-compliance, in one trial the atypical antipsychotic olanzapine was superior to haloperidol, while in a second trial there were no differences between olanzapine and risperidone.

Treatment of the symptoms of schizophrenia: a combined analysis of double-blind studies comparing risperidone with haloperidol and other antipsychotic agents.

Combined data on efficacy were available from 12 double-blind short-term (maximum 8 weeks) trials comparing risperidone and other antipsychotics in patients with chronic schizophrenia. Patients received risperidone (n = 1056) or other antipsychotics (n = 703). Haloperidol (n = 473) was the most frequently prescribed other antipsychotic. Efficacy assessments include the Positive and Negative Syndrome Scale (PANSS) total, subscale (positive symptoms, negative symptoms and general psychopathology), cluster (cognitive and affective symptoms) and item (anxiety and hostility) scores. At endpoint, the mean decrease from baseline in PANSS total scores was significantly greater for patients receiving risperidone (-20.9) than other antipsychotics (-16.2; P < 0.001), or the subset receiving haloperidol (-14.3; P < 0.001). Risperidone-treated patients showed a significantly greater decrease in the positive (P < 0.01), negative (P < 0.05) and general psychopathology (P < 0.001) scores than patients receiving other antipsychotics or haloperidol. Scores for cognition, affective symptoms, anxiety and hostility each improved significantly (P < 0.05) more for patients receiving risperidone than those receiving other antipsychotics or haloperidol. Efficacy data on patients with an acute exacerbation were available from seven trials (risperidone n = 372, other antipsychotics n = 285, including haloperidol n = 120). At endpoint, the mean decrease from baseline in PANSS total scores was significantly greater for patients receiving risperidone (-24.7) than other antipsychotics (-19.8, P < 0.01) including haloperidol (-19.8, P < 0.05). Risperidone-treated patients also showed a greater decrease in positive symptom scores (-7.8) than those receiving other antipsychotics (-6.3; P < 0.01) or haloperidol (-7.1). A > or = 20% reduction in PANSS total score with risperidone, haloperidol and other antipsychotics was achieved by 65.9%, 54.3% and 54.9%, respectively; a > or = 30% PANSS reduction by 54.0%, 46.6% and 46.5% of patients, respectively; and a > or = 40% reduction by 43.8%, 33.7% and 34.4% of patients, respectively. These findings are consistent with earlier findings that show risperidone is more efficacious than haloperidol for reducing the symptoms of schizophrenia.

Treatment with atypical antipsychotics: new indications and new populations.

Atypical antipsychotics have revolutionized the treatment of schizophrenia, becoming the treatment of choice for patients not only during their first episode, but also throughout their life course. Of note, as of 1999 more than 70% of prescriptions for these drugs are being prescribed for conditions other than schizophrenia, such as bipolar disorder and geriatric agitation. While there have been very few controlled trials that have established the efficacy of the atypical antipsychotics for these "off-label" uses, there have been a large number of open trials and case reports. The few controlled trials suggest that the atypical antipsychotics may be useful for affective disorders (both mania and depression), geriatric conditions such as senile dementia and aggression, as well as a variety of other disorders. Atypical agents may be particularly helpful for elderly, child, or adolescent patients who are especially susceptible to the side effects of medications and whose risk of tardive dyskinesia is high but further controlled studies are necessary.

Family treatment and medication dosage reduction in schizophrenia: effects on patient social functioning, family attitudes, and burden.

The effects of 2 family intervention programs (supportive family management [SFM], including monthly support groups for 2 years; or applied family management [AFM], including 1 year of behavioral family therapy plus support groups for 2 years), and 3 different neuroleptic dosage strategies (standard, low, targeted) on social functioning of patients with schizophrenia. their relatives' attitudes, and family burden were examined. AFM was associated with lower rejecting attitudes by relatives toward patients and less friction in the family perceived by patients. Patients in both AFM and SFM improved in social functioning but did not differ, whereas family burden was unchanged. Medication strategy had few effects, nor did it interact with family intervention. The addition of time-limited behavioral family therapy to monthly support groups improved family atmosphere, but did not influence patient social functioning or family burden.

Psychopharmacologic treatment strategies for depression, bipolar disorder, and schizophrenia.

Patients with serious psychiatric disorders are frequently treated by primary care physicians, who may have difficulty keeping up with recent advances in psychiatry. This paper presents an updated synopsis for three major psychiatric illnesses: major depression, bipolar disorder, and schizophrenia. Current definitions, updated diagnostic criteria, short- and long-term treatment strategies with algorithms, and special challenges for the clinician are discussed for each of these illnesses. On the basis of each illness's distinct characteristics, five treatment principles are emphasized: 1) Treatment strategies should be long-term and should emphasize adherence, 2) treatment choice should be empirical, 3) combinations of medications may be helpful, 4) a combination of psychosocial and pharmacologic treatments may be more useful than either alone, and 5) the family or "significant others" as well as a consumer organization need to be involved. Some of the new directions in dinical research to refine these strategies and meet these challenges are also described.

Psychiatric conditions in sports: diagnosis, treatment, and quality of life.

The social stigma surrounding psychiatric illness may prevent athletes from seeking counseling, psychotherapy, medication, or other treatment when needed. Few controlled studies on athletes exist to guide the team physician, clinician, or psychiatrist who must deal with diagnostic issues. Management involves setting realistic goals, educating as well as inducing the patient into treatment, soliciting support from family or significant others, and delivering appropriate treatment (the most difficult task). The objective is to improve performance and quality of life. Confidentiality issues are paramount during diagnosis and treatment. Physicians who understand sports and team dynamics may have more success in helping patients follow through with treatment.

Divalproex for the treatment of geriatric bipolar disorder.

Divalproex is now commonly used to treat bipolar disorder in older patients. However, it has yet to be systematically studied in this population. This report describes six older bipolar patients treated with divalproex. Of the six, five showed some improvement with divalproex alone or in combination with other agents. Clearly, a double-blind, placebo-controlled study is an important next step to assess this promising medication.

Lithium augmentation fails to reduce symptoms in poorly responsive schizophrenic outpatients.

BACKGROUND: Nearly one third of patients suffering from schizophrenia do not fully respond to antipsychotic medication. Safe, effective, and cost-efficient methods to reduce symptoms are clearly needed; therefore, lithium as an adjunct to fluphenazine decanoate was tested in a placebo-controlled trial in outpatients who were part of the Treatment Strategies of Schizophrenia (TSS) study. METHOD: Forty-one patients with DSM-III schizophrenia or schizoaffective disorder were assigned to either adjunctive lithium or placebo after at least 6 months of fluphenazine decanoate treatment to stabilize symptoms had failed. The trial was designed for 8 weeks of treatment, and patients assigned to placebo could afterward be administered lithium in an 8-week, open-label study. RESULTS: Assessment of the intent-to-treat analysis revealed no significant differences in demographic variables between the lithium and placebo groups. Although both groups showed significant (p = .00135) improvement as measured by total scores on the Brief Psychiatric Rating Scale (BPRS), there were no significant differences in response between the lithium and placebo groups. Patients originally treated with placebo added to neuroleptic did not have significantly greater improvement when receiving open-label adjunctive lithium. CONCLUSION: Although success with lithium augmentation therapy for persistent psychosis has been reported in the past, this study of well-characterized patients showed no benefit for this common strategy, thus indicating that care be used in utilizing lithium augmentation.

A new algorithm for treating schizophrenia.

This article presents two algorithms dealing with the management of schizophrenia. One provides a strategy for initiating pharmacologic treatment of schizophrenia and for ongoing medication management. The other covers suggestions for managing several common comorbid psychiatric conditions and some common side effects. The major change from previous algorithms is the suggestion that the newer atypical antipsychotic agents may now be the treatment of choice for initiating therapy in most clinical situations.

Relapse and rehospitalization during maintenance treatment of schizophrenia. The effects of dose reduction and family treatment.

BACKGROUND: Previous studies have examined dose reduction and family treatment in schizophrenia, but none has examined their interaction. This study assessed the impact of dose reduction of antipsychotic medication and family treatment on relapse and rehospitalization during maintenance treatment. METHODS: Subjects were 313 male and female outpatients at 5 centers with a DSM-III-R diagnosis of schizophrenia or schizoaffective disorder. In a 3 x 2 design, subjects were randomized to 1 of 3 medication strategies using fluphenazine decanoate under double-blind conditions: continuous moderate dose (standard) (12.5-50 mg every 2 weeks); continuous low dose (2.5-10 mg every 2 weeks); or targeted, early intervention (fluphenazine only when symptomatic). Subjects also were randomized to 1 of 2 family treatment strategies (supportive or applied). Supportive family management involved monthly group meetings. The more intensive applied family management involved monthly group meetings and home visits where communication and problem-solving skills were taught. Patients and families were treated and assessed for 2 years. RESULTS: Both continuous low-dose and targeted treatment increased use of rescue medication and relapse; only targeted treatment increased rehospitalization. This pattern was consistent across both family treatments; there were no differences between family treatments. CONCLUSIONS: These findings reaffirm the value of antipsychotic medication in preventing relapse and rehospitalization. The absence of family treatment differences may be because both conditions engaged families.

Transition from acute to maintenance treatment: prediction of stabilization.

The stabilization period that follows the exacerbation of a schizophrenic illness represents a critical point in the course of the illness. Successful stabilization is a prerequisite to long-term tenure in the community and the possibility of improvement in functional outcome. In this paper we present an operational definition of stabilization, developed in the context of a study of long-term maintenance treatment that incorporates time, symptomatic equilibrium and consistency of medication dosage. Patients were identified at the time of hospitalization and followed prospectively to determine whether or not they met stabilization criteria. Characteristics that predicted successful stabilization included measures drawn from the domains of patient personal characteristics and psychiatric history, symptoms of psychopathology and side effects in response to initial treatment and family judgments. These patients were treated primarily with fluphenazine decanoate, and five distinct dosing strategies with this agent were identified retrospectively. The dosing strategies distinguished the length of time to subsequent stabilization. The implications of these findings for clinical management of schizophrenia are discussed.

Personality pathology among married adults with bipolar disorder.

The comorbidity of DSM-III-R axis II personality disorders in patients with bipolar disorder has received less attention than for unipolar depression perhaps because of the potential confounding of state vs. trait qualities. The current study took steps to separate pathological traits of personality from behaviors evidenced during discrete affective episodes in a sample of married, outpatient bipolar patients. Data indicated that 22% of our patients met criteria for a categorical diagnosis of personality disorder. Axis II pathology as represented by both categorical and dimensional scores was associated with increased psychiatric symptoms during subsequent treatment and poorer social adjustment.

The family, family therapy, and borderline personality disorder.

The authors review recent controlled studies on the interrelationship of the family and its members with borderline disorder and propose a new model for understanding and managing this relationship. The focus of the model is on psychopathology, evaluation, and treatment of patient and family as they influence each other. In the authors' view this illness originates in cerebral dysfunction, in the patient in combination with impaired relationships among family members. When the family is available, we believe that the treatment of choice is a multimodal approach involving family psychoeducation and family systems or dynamic intervention where possible, in combination with medications, individual psychotherapy, or both.

Effectiveness in psychiatric care. III: Psychoeducation and outcome for patients with major affective disorder and their families.

This hypothesis-generating study had the objective of dissecting the process of psychiatric care in an attempt to understand outcomes for patients and their families. In all, 24 patients who carried a DSM-III diagnosis of major affective disorder were identified 12-18 months after hospital admission. The patients, their families, and their doctors were interviewed using instruments measuring delivery of treatment and achievement of treatment goals; findings were then correlated with resolution of the index episode and patient global outcome. Delivery of patient and family psychoeducation was associated with better resolution of the index episode and better global outcome.

Clinical significance of inpatient family intervention: conclusions from a clinical trial.

OBJECTIVE: To test whether the statistically significant results of a randomized clinical trial of an inpatient family intervention were clinically significant for hospital practice, the authors reanalyzed outcome data using a measure of clinical significance based on the extent to which patients had recovered during the course of the intervention. METHODS: A total of 169 hospitalized subjects and their families were randomly assigned to a psychoeducational inpatient family intervention or to a comparison group. Patient and family outcome measures were assessed at admission, discharge, and six and 18 months after admission. Analyses of statistically significant differences in outcome suggested that inpatient family intervention was effective for certain patient subgroups identified by gender and diagnosis. Global Assessment Scale scores two or more standard deviations above the pretreatment (admission) mean were used as indicators for clinically significant improvement. RESULTS: The reanalysis confirmed that inpatient family intervention was associated with clinically significant improvement at discharge, especially for female patients and patients with chronic schizophrenia and bipolar disorder. These effects were maintained six months after admission before attenuating at 18 months. CONCLUSIONS: Inpatient family intervention results in clinically meaningful outcomes for certain subgroups of patients and their families.

Inpatient treatment of schizophrenia in general hospitals.

OBJECTIVE: To improve treatment of schizophrenic patients in short-term inpatient units, the authors review studies of interventions that have been implemented with schizophrenic patients during brief hospitalizations and suggest areas for future research. METHODS: The review is organized around seven general treatment domains, including the therapeutic alliance, continuity of care, family involvement, procurement of community services, psychosocial rehabilitation, medication compliance, and substance abuse treatment. RESULTS AND CONCLUSIONS: Because schizophrenic patients have traditionally been treated in long-term settings, little literature exists to inform interventions on short-term units. The authors suggest that general hospital staff strengthen the treatment alliance between patients and outpatient clinicians, aggressively pursue community supports, work to ensure patients' follow-up with outpatient care, and consider depot medications and patient education to promote medication compliance.