Leslie Citrome

Antipsychotic-induced weight gain and therapeutic response: A differential association

This study investigated the association between antipsychotic-induced weight gain and therapeutic response to haloperidol and three commonly used atypical neuroleptic medications in schizophrenia and schizoaffective disorder. The subjects were 151 patients enrolled in a double-blind experiment with a duration of 14 weeks comparing the therapeutic efficacy of haloperidol (n = 36), clozapine (n = 38), olanzapine (n = 38), and risperidone (n = 39). Absolute and relative (%) gain in body weight and body mass index (BMI) was determined for the entire duration of the double-blind treatment period; therapeutic response was assessed by the total score and the individual subscales of the Positive and Negative Symptom Scale. Compared with the pretreatment baseline, results indicated that for olanzapine and clozapine, therapeutic response was closely related to an absolute and relative gain in weight and to a gain in BMI. No association between weight gain and therapeutic response was found for risperidone and haloperidol. These findings suggest that patients who are likely to have the maximal benefits of olanzapine or clozapine treatment for symptom alleviation are at the highest risk of a clinically significant increase in weight gain.

Overt Aggression and Psychotic Symptoms in Patients with Schizophrenia Treated with Clozapine, Olanzapine, Risperidone, or Haloperidol

Abstract: The subjects were 157 treatment-resistant inpatients diagnosed with chronic schizophrenia or schizoaffective disorder. They were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol in a 14-week, double-blind trial. Incidents of overt aggression were recorded and their severity was scored. The Positive and Negative Syndrome Scale was administered. Atypical antipsychotics showed an overall superiority over haloperidol, particularly after the first 24 days of the study when the dose escalation of clozapine was completed. Once an adequate therapeutic dose of clozapine was reached, it was superior to haloperidol in reducing the number and severity of aggressive incidents. Patients exhibiting persistent aggressive behavior showed less improvement of psychotic symptoms than the other patients. There was an interaction between aggressiveness, medication type, and antipsychotic response: risperidone and olanzapine showed better antipsychotic efficacy in patients exhibiting less aggressive behavior; the opposite was true for clozapine. Clozapine appears to have superior antiaggresive effects in treatment-resistant patients; this superiority develops after the patient has been exposed to an adequate dose regimen.

Medication nonadherence and treatment outcome in patients with schizophrenia or schizoaffective disorder with suboptimal prior response.

OBJECTIVE To examine the impact of medication nonadherence on treatment outcome in schizophrenia and potential risk factors for nonadherence. METHOD A post hoc analysis of a randomized, double-blind, 8-week, fixed-dose study comparing olanzapine 10, 20, and 40 mg/day for patients with schizophrenia or schizoaffective disorder (DSM-IV criteria) with suboptimal response to current treatment (N = 599) was conducted between September 12, 2003, and November 3, 2005, at 55 study centers in the United States. Nonadherence was defined as not taking medication as prescribed based on daily pill counts. Because there was no significant difference in nonadherence between dose groups, effects of nonadherence on efficacy and safety outcomes were examined using all 3 groups combined. Baseline demographics and symptom severity were investigated as potential risk factors for nonadherence. RESULTS During the 8-week study, 34.5% of patients were nonadherent at least once. Nonadherent patients had significantly less improvement compared to adherent patients as measured by change in Positive and Negative Syndrome Scale total score (-22.57 vs. -26.84, p = .002). Longer duration of nonadherence was associated with reduced likelihood of treatment response (odds ratio = 0.94, 95% CI = 0.90 to 0.99, p = .008). The early treatment discontinuation rate was higher in nonadherent compared to adherent patients (40.8% vs. 24.5%, p < .001). Adherent and nonadherent patients had comparable outcomes in most safety measures, except for weight change, for which adherent patients had greater weight gain than nonadherent patients (2.63 kg vs. 1.96 kg, p = .02). Greater depression severity at baseline (p = .01) and greater hostility level during the study were significant risk factors for nonadherence (p = .02). CONCLUSIONS Medication nonadherence had a significantly negative impact on treatment response, highlighting the importance of adherence to achieve satisfactory treatment outcome. Findings may also help clinicians identify patients at risk for nonadherence and utilize interventions to improve adherence. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00100776.

Compelling or irrelevant? Using number needed to treat can help decide

Objective:  The metric of number needed to treat (NNT), defined as the number of patients who need to be treated to achieve one additional favorable outcome, can help clinicians appraise claims that one intervention is meaningfully superior to the other.

Lamotrigine as add-on therapy in schizophrenia: results of 2 placebo-controlled trials.

Objective: Lamotrigine previously was found to attenuate ketamine-induced behavioral changes and, in 2 placebo-controlled trials, to improve psychosis when added to antipsychotic medication. We sought to evaluate the potential role of lamotrigine augmentation in schizophrenia patients resistant to atypical antipsychotic medication. Methods: Two multicenter, randomized, double-blind, 12-week, parallel-group trials were conducted to compare flexibly dosed lamotrigine (100-400 mg/d) with placebo as add-on treatment in schizophrenia patients with stable, residual psychotic symptoms. The primary end point was changed in Positive and Negative Syndrome Scale total score at week 12. Results: Two hundred seventeen patients were enrolled in study 1 and 212 in study 2; completion rates in the intent-to-treat samples were 71% and 74%, respectively, and did not differ between treatment groups. Overall, mean Positive and Negative Syndrome Scale total scores improved in both studies and did not differ between treatment groups. In study 1, the Scale for Assessment of Negative Symptoms total score and Clinical Global Impression improved more with placebo than with lamotrigine; in study 2, the cognitive composite score improved more with lamotrigine than with placebo. Conclusions: Results from these 2 studies do not support the use of lamotrigine as an adjunct to atypical antipsychotics in patients with refractory psychosis. It is unclear why positive results from previous lamotrigine trials were not replicated. The positive effect of lamotrigine on cognition in one trial, while of uncertain significance, may merit further study.

Vortioxetine for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant – what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?

To describe the efficacy and safety of vortioxetine for the treatment of major depressive disorder (MDD).

Heterogeneity of violence in schizophrenia and implications for long‐term treatment

Aims:  Most patients with schizophrenia are not violent. However, persistent violent behaviour in a minority of patients presents a therapeutic challenge. Published treatment guidelines and most pharmacological and epidemiological literature on violence in schizophrenia treat overt physical aggression as a homogeneous phenomenon. The aim of this review is to address the subtyping of violent behaviour in schizophrenia, and to relate the subtypes to treatment.

Lurasidone for schizophrenia: a review of the efficacy and safety profile for this newly approved second-generation antipsychotic

Objective:  To describe the efficacy and safety of lurasidone for the treatment of schizophrenia.

Diabetes and schizophrenia 2005: are we any closer to understanding the link?

The association between schizophrenia and diabetes has been recognized for well over a century, but the underlying reasons for this association are unclear. In October 2003, an international group of diabetologists and psychiatrists met to review the literature relating to the association, and to create pragmatic guidelines for the management of diabetic risk in patients with severe mental illness. Since that meeting, over 100 additional papers have been published on the association between glucose abnormalities and schizophrenia, and this is a clear reflection of the level of interest in this clinically important area. Diabetes is highly prevalent among the schizophrenia population, but most sufferers remain undiagnosed in the community. The reasons why individuals with schizophrenia are more prone to developing diabetes than the general population are poorly defined, but likely to be multifactorial. The role of antipsychotic medications in the development of diabetes and other pre-diabetic states remains controversial, but it appears that the attributable risk is low. Traditional risk factors most probably account for much of the diabetes seen in schizophrenia populations, suggesting that routine screening and aggressive risk factor management are especially important in this patient group.

Do guidelines for severe mental illness promote physical health and well-being?:

The effective management of individuals with severe mental illnesses (SMIs) requires an holistic approach that offers reliable symptom control, but also addresses other clinical, emotional and social needs. The physical health of individuals with an SMI is often poor, with many being overweight or obese, having hypertension, diabetes or dyslipidaemia, and at significant risk of developing cardiovascular disease or other comorbidities. We have recently reviewed current UK and US guidelines for the management of individuals with schizophrenia and bipolar disorder, and found very different approaches to the holistic care of people with SMIs, especially in relation to the management of physical health and cardiovascular risk. UK guidelines acknowledge the high risk of physical morbidity and mortality in individuals with an SMI, but fail to address in detail the specifics of physical health monitoring and lifestyle management. US guidelines are more descriptive in terms of the type and extent of monitoring recommended, but there are inconsistencies between the guidelines produced by different organizations, and studies in the field suggest that none of them is being adequately implemented. Clear and consistent recommendations on how and when to monitor weight, cardiovascular function, and metabolic parameters and, importantly, what to do with the results, would support clinicians wishing to integrate physical and mental healthcare. Publication of specific recommendations on evidence-based physical health interventions that can work for people with SMIs would also help primary care and mental health services improve general well-being in their patients with severe mental illnesses.