Ira D. Glick

First episode schizophrenia-related psychosis and substance use disorders: acute response to olanzapine and haloperidol.

BACKGROUND Co-occurring substance use disorders, mostly involving alcohol, cannabis or cocaine, occur commonly in patients with schizophrenia and are associated with increased morbidity and mortality. Available but limited data suggest that substance use disorders (especially cannabis use disorders) may also be common in first-episode patients and appear linked to a poor outcome in these patients. Strategies to curtail substance use form an important dimension of the treatment program for both first-episode and chronic patients. We report on rates of co-occurring substance use disorders in patients within their first episode of schizophrenia-related psychosis from a multicenter, international treatment trial of olanzapine vs. haloperidol. METHODS The study involved 262 patients (of 263 who were randomized and who returned for a post-randomization evaluation) within their first episode of psychosis (schizophrenia, schizoaffective disorder or schizophreniform disorder) recruited from 14 academic medical centers in North America and Western Europe. Patients with a history of substance dependence within 1 month prior to entry were excluded. RESULTS Of this sample, 97 (37%) had a lifetime diagnosis of substance use disorder (SUD); of these 74 (28% of the total) had a lifetime cannabis use disorder (CUD) and 54 (21%) had a lifetime diagnosis of alcohol use disorder (AUD). Patients with SUD were more likely to be men. Those with CUD had a lower age of onset than those without. Patients with SUD had more positive symptoms and fewer negative symptoms than those without SUD, and they had a longer duration of untreated psychosis. The 12-week response data indicated that 27% of patients with SUD were responders compared to 35% of those without SUD. Patients with AUD were less likely to respond to olanzapine than those without AUD. DISCUSSION These data suggest that first-episode patients are quite likely to have comorbid substance use disorders, and that the presence of these disorders may negatively influence response to antipsychotic medications, both typical and atypical antipsychotics, over the first 12 weeks of treatment.

A randomized clinical trial of inpatient family intervention. V. Results for affective disorders.

This paper reports the results at follow-up of a randomized clinical trial of combining family intervention with drug treatment during hospitalization for patients with affective disorder. The results suggest that female bipolar patients and their families benefited from family intervention, whereas unipolar patients and families did not. Patient outcome was positively correlated with the achievement of the goals of family intervention.

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.

Bipolar affective disorder and creativity: Implications and clinical management

Research on the relationship between creativity and mental illness is summarized, and studies documenting a relationship in writers between creativity and affective illness (particularly bipolar illness) are described. Writers have a high prevalence of affective illness, and both affective illness and creativity have increased frequency in their first-degree relatives. The clinical management of the creative individual is challenging. In general, creative individuals are most productive when their affective symptoms are under good control.

Insight in first-episode psychosis.

BACKGROUND We report here a study examining the relationships between insight and psychopathology, cognitive performance, brain volume and co-morbid depression in 251 patients experiencing a first episode of psychosis, who were then randomly assigned to 2 years of double-blind treatment with either olanzapine or haloperidol. METHOD Repeated measures of insight were obtained at baseline and 12, 24, 52 and 104 weeks by the Insight and Treatment Attitudes Questionnaire (ITAQ). RESULTS Older age, female gender and white ethnicity were associated with more insight. Higher total, positive, negative and general psychopathology scores on the Positive and Negative Syndromes Scale (PANSS) were associated with less insight. Higher depression scores were associated with more insight. Better neurocognitive function and large brain volumes were associated with more insight. More insight throughout the study was associated with longer time to medication non-adherence. However, baseline insight was not significantly related to the probability of discontinuing the study before 2 years. Insight improved significantly over the course of the study, but the improvement in insight was not significantly different between the two antipsychotic treatment groups. CONCLUSIONS Multiple factors contribute to insight. Patients experiencing a first episode of psychosis who have little insight are at increased risk of discontinuing their medication.

Multicenter open-label sertraline study in adolescent outpatients with major Depression

OBJECTIVE The aim of this multicenter outpatient study was to assess the therapeutic benefits, response patterns, and safety of sertraline in adolescent major depressive disorder (MDD). METHOD Fifty-three adolescent outpatients with MDD were treated in an open-label, 10-week, acute-phase trial with sertraline and, if responders, for an additional 12-week continuation phase. Diagnostic and response assessments included the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), 17-item K-SADS-derived depression severity score, Hamilton Depression Rating Scale, Beck Depression Inventory, and Clinical Global Impression Scale. RESULTS By 2 weeks, when analyzed as continuous variables, all severity scores showed significant differences from baseline. This pattern persisted through 10 weeks, with a significantly greater response occurring when treatment was extended from 6 to 10 weeks. Both clinician- and patient-rated improvement was maintained during continuation treatment. Response rates varied considerably when depression rating scales were analyzed categorically. Sertraline was generally well tolerated and did not induce manic symptoms. CONCLUSIONS In open treatment of adolescent MDD with sertraline, significant improvement occurred early on and was maintained for 22 weeks. Absolute response rates varied depending on the rating scales used, definition of response, and length of treatment. Maximal response rates were obtained by clinician-defined ratings after 10 weeks of treatment.

Predicting suicidal risk in schizophrenic and schizoaffective patients in a prospective two-year trial

BACKGROUND Enhanced ability to reliably identify risk factors for suicidal behavior permits more focused decisions concerning treatment interventions and support services, with potential reduction in lives lost to suicide. METHODS This study followed 980 patients at high risk for suicide in a multicenter prospective study for 2 years after randomization to clozapine or olanzapine. A priori predictors related to diagnosis, treatment resistance, and clinical constructs of disease symptoms were evaluated as possible predictors of subsequent suicide-related events. RESULTS Ten baseline univariate predictors were identified. Historical predictors were diagnosis of schizoaffective disorder, history or current use at baseline of alcohol or substance abuse, cigarette smoking, number of lifetime suicide attempts, and the number of hospitalizations in the previous 36 months to prevent suicide. Predictive clinical features included greater baseline scores on the InterSePT scale for suicidal thinking, the Covi Anxiety Scale, the Calgary Depression Scale (CDS), and severity of Parkinsonism. Subsequent multivariate analysis revealed the number of hospitalizations in the previous 36 months, baseline CDS, severity of Parkinsons, history of substance abuse, and lifetime suicide attempts. Clozapine, in general, was more effective than olanzapine in decreasing the risk of suicidality, regardless of risk factors present. CONCLUSIONS This is the first prospective analysis of predictors of suicide risk in a large schizophrenic and schizoaffective population judged to be at high risk for suicide. Assessment of these risk factors may aid clinicians in evaluating risk for suicidal behaviors so that appropriate interventions can be made.

The Effects of Social Class on Parental Values and Practices

My thesis is straightforward and relatively simple: that there are substantial differences in how parents of differing social-class position raise their children; that these differences in parental practices result chiefly from class differences in parents’ values for their children; and that such class differences in parental values result in large measure from differences in the conditions of life experienced by parents at different social-class levels. This essay attempts to spell out this thesis more concretely and explicitly.1 Without getting into technical aspects of methodology, it also attempts to give some idea of the type of empirical evidence on which the generalizations are based.

Metformin for Weight Loss and Metabolic Control in Overweight Outpatients With Schizophrenia and Schizoaffective Disorder

OBJECTIVE The purpose of this study was to determine whether metformin promotes weight loss in overweight outpatients with chronic schizophrenia or schizoaffective disorder. METHOD In a double-blind study, 148 clinically stable, overweight (body mass index [BMI] ≥27) outpatients with chronic schizophrenia or schizoaffective disorder were randomly assigned to receive 16 weeks of metformin or placebo. Metformin was titrated up to 1,000 mg twice daily, as tolerated. All patients continued to receive their prestudy medications, and all received weekly diet and exercise counseling. The primary outcome measure was change in body weight from baseline to week 16. RESULTS Fifty-eight (77.3%) patients who received metformin and 58 (81.7%) who received placebo completed 16 weeks of treatment. Mean change in body weight was -3.0 kg (95% CI=-4.0 to -2.0) for the metformin group and -1.0 kg (95% CI=-2.0 to 0.0) for the placebo group, with a between-group difference of -2.0 kg (95% CI=-3.4 to -0.6). Metformin also demonstrated a significant between-group advantage for BMI (-0.7; 95% CI=-1.1 to -0.2), triglyceride level (-20.2 mg/dL; 95% CI=-39.2 to -1.3), and hemoglobin A1c level (-0.07%; 95% CI=-0.14 to -0.004). Metformin-associated side effects were mostly gastrointestinal and generally transient, and they rarely led to treatment discontinuation. CONCLUSIONS Metformin was modestly effective in reducing weight and other risk factors for cardiovascular disease in clinically stable, overweight outpatients with chronic schizophrenia or schizoaffective disorder over 16 weeks. A significant time-by-treatment interaction suggests that benefits of metformin may continue to accrue with longer treatment. Metformin may have an important role in diminishing the adverse consequences of obesity and metabolic impairments in patients with schizophrenia.

Lamotrigine augmentation in schizophrenia and schizoaffective patients with obsessive-compulsive symptoms.

Obsessive-compulsive symptoms (OCS) are clinically important phenomena in schizophrenia patients. Lamotrigine has a modulating effect on glutamatergic neurotransmission relevant to pathophysiology of both schizophrenia and OCD. Efficacy and tolerability of lamotrigine in schizophrenia and schizoaffective patients with comorbid OCS were evaluated. In an 8-week, open-label trial, lamotrigine (25 mg/day for 1 week, 50 mg for 2 weeks, 100 mg for 2 weeks, 200 mg for 3 weeks) was added to ongoing psychotropic drug regimens in schizophrenia (N = 5) and schizoaffective disorder (N = 6) patients with clinically significant OCS [Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score > 16]. The Y-BOCS score for nine completers decreased significantly from baseline to week 8 (22.9 ± 6.1 vs 17.4 ± 3.6; t = 2.33, df = 1, P = 0.033). Five patients, all with schizoaffective disorder, were responders (≥35% decrease in Y-BOCS score). No significant changes were detected in schizophrenia symptom severity. Depressive symptoms, assessed with the Calgary Depression Rating Scale, improved significantly (6.4 ± 1.5 vs 4.0 ± 2.5; t = 3.19, df = 1, P = 0.013); this change positively correlated with OCS improvement (r = 0.69, P = 0.04). Lamotrigine was safe and well tolerated. Explicit evaluation of therapeutic efficacy of adjunctive lamotrigine in schizoaffective disorder patients with comorbid OCS merits further investigation.