Viacheslav Terevnikov

Orlistat in Clozapine- or Olanzapine-Treated Patients With Overweight or Obesity: A 16-Week Open-Label Extension Phase and Both Phases of a Randomized Controlled Trial

OBJECTIVE To explore long-term effects of orlistat in adult clozapine- or olanzapine-treated patients with DSM-IV-diagnosed schizophrenia and overweight or obesity who tolerate orlistat. METHOD Orlistat or placebo was added to clozapine or olanzapine in stable doses in a 16-week randomized controlled trial. Open-label orlistat was added to the antipsychotics during a 16-week extension phase for those completing the double-blind phase. No low-calorie diet or participation in behavioral programs was required. Body weight (primary outcome) and some metabolic parameters were measured prospectively. Analyses were performed for those completing both phases (ie, population differing from that reported earlier). The study was conducted from 2004 through 2005. RESULTS During the open-label phase, the 44 patients experienced mean ± SD body weight loss of -1.29 ± 3.04 kg, P = .007. During both phases, men (but not women) showed a weight loss of -2.39 ± 5.45 kg, P = .023. Some subgroups showed desirable changes in several metabolic parameters. Prolonged (32 weeks) orlistat treatment yielded no additional benefits as compared to short (16 weeks) treatment. CONCLUSIONS In clozapine- or olanzapine-treated overweight or obese patients able to take orlistat on a long-term basis, the drug, with no concomitant hypocaloric diet or behavioral interventions, caused moderate weight loss only in men. However, some metabolic benefits may be achieved independently of weight changes. In patients who do not respond to orlistat within the first 16 weeks, continuation treatment may provide no additional benefits. TRIAL REGISTRATION controlled-trials.com Identifier: ISRCTN65731856.

More evidence on additive antipsychotic effect of adjunctive mirtazapine in schizophrenia: an extension phase of a randomized controlled trial†‡

Adjunctive mirtazapine improved negative symptoms of schizophrenia in several studies. Recently, we found an improvement also in positive symptoms when mirtazapine was added to first generation antipsychotics (FGAs) in a 6 week randomized controlled trial (RCT). The short duration of that trial was its limitation. This study aimed to explore whether longer treatment is worthwhile.

In a randomized placebo-controlled add-on study orlistat significantly reduced clozapine-induced constipation.

Constipation is a common and potentially fatal side effect of clozapine treatment. Another important side effect of clozapine may also be significant weight gain. Orlistat is a weight-control medication that is known to induce loose stools as a common side effect. This study aimed to explore whether orlistat used to control clozapine-induced weight gain can simultaneously tackle clozapine-related constipation. In this 16-week randomized-controlled study, clozapine-treated patients received add-on orlistat (n=30) or add-on placebo (n=24). Colonic function was measured using the Bristol Stool Form Scale. There was a significant (P=0.039) difference in the prevalence of constipation in favor of orlistat over placebo in completers (n=40) at the endpoint. A decrease in the prevalence of constipation within the orlistat group (P=0.035) was observed (vs. no statistically significant changes in the placebo group). In clozapine-treated patients, orlistat may be beneficial not only for weight control but also as a laxative. As no established treatments for clozapine-induced constipation exist, orlistat can be considered for this population, although more studies are required.

Development of self-image and its components during a one-year follow-up in non-referred adolescents with excess and normal weight

BackgroundThe proportion of overweight and obese youths is high. The present study aimed to investigate the development of self-image and its components during a one-year follow-up among non-referred adolescents with excess and normal weight. Furthermore, we separately analyzed the data for girls and boys.MethodsAltogether 86 8th grades (41 girls and 45 boys) with a relative weight of 26% or more above the median and 91 controls (43 girls and 48 boys) with normal weight participated the follow-up. The Offer Self-Image Questionnaire, Revised (OSIQ-R) was used to assess self-image at baseline and on follow-up. In the OSIQ-R, a low total raw score implies positive adjustment, while a high raw score implies poor adjustment and a negative self-image. The study design was doubly correlated (pairs and time), and a linear mixed model was used in the statistical analysis.ResultsIn OSIQ-R total scores, a comparative improvement was observed in girls with normal weight. Among these girls, significant change scores compared to zero were seen in impulse control, social functioning, vocational attitudes, self-confidence, self-reliance, body image, sexuality, and ethical values. In girls with excess weight, none of the change scores compared to zero were statistically significant. When the girls with normal and excess weight were compared, the difference in change scores was largest in sexuality and vocational attitudes. Change scores compared to zero were significant in sexuality and idealism for boys with excess weight, and in impulse control, mental health, self-reliance, and sexuality for normal weight boys. When the boys with excess and normal weight were compared, no statistically significant differences emerged in change scores.ConclusionIn mid-adolescent girls, the influence of overweight and obesity on the development of self-image is substantial. Weight management programs directed at overweight adolescent girls should include psychological interventions aiming to diminish self-image distress, especially that associated with feelings, attitudes, and behavior towards the opposite sex, as well as future career plans.

Add-on mirtazapine improves orgasmic functioning in patients with schizophrenia treated with first-generation antipsychotics.

Abstract Aim: Sexual dysfunction, common in schizophrenia, may be further exaggerated by antipsychotics, especially those of First Generation (FGAs), and antidepressants, such as Selective Serotonin Reuptake Inhibitors (SSRs). Mirtazapine, an antidepressant characterized by its different action mechanism compared with that of the majority of other antidepressants, may improve SSRI-induced sexual dysfunction in patients with depression. It is unknown, however, whether mirtazapine improves sexual functioning in schizophrenia. Methods: This study randomly assigned FGA-treated patients with schizophrenia to receive either an add-on mirtazapine (n = 20) or a placebo (n = 19) for 6 weeks. Sexual functioning was prospectively measured using five relevant items from the Udvalg for Kliniske Undersogelser side-effect rating scale (UKU-SERS). Results: Orgasmic function improved with statistical significance in the mirtazapine group (p = .03), with no changes in any other sexual functions in either group. Conclusion: Add-on mirtazapine appears to relieve orgasmic dysfunction in FGA-treated patients with schizophrenia.

Relationships between pharmacotherapy-induced metabolic changes and improved psychopathology in schizophrenia: data from a mirtazapine and first-generation antipsychotics combination trial

Clinical efficacy and metabolic side-effects of antipsychotics seem to correlate with each other. In this study, interrelationship of similar metabolic effects of mirtazapine and its earlier reported desirable effects on psychopathology in first-generation antipsychotics (FGAs)-treated schizophrenia were explored. Symptomatic FGAs-treated patients with schizophrenia received a 6-wk double-blind treatment with add-on mirtazapine (n = 20) or placebo (n = 16), followed by a 6-wk open-label mirtazapine treatment. Mirtazapine (but not placebo) induced an increase in body weight and cholesterol levels. The latter was associated with a clinical improvement in all (sub)scales of the Positive and Negative Syndrome Scale [PANSS; an increase of cholesterol by 1 mmol/l predicted 7 points reduction on the PANSS total score (r = 0.85, p = 0.001)]. In schizophrenia, mirtazapine-induced weight gain and increase of total cholesterol are associated with the improved efficacy of mirtazapine-FGAs combination--a novel observation with possible clinical and theoretical implications.

Antidepressants in Schizophrenia: A Place for Them?

Antipsychotic monotherapy is often insufficient to achieve optimal outcome in schizophrenia. One of the numerous adjunctive psychopharmacological strategies proposed to overcome this drawback is a combination of an antipsychotic with an antidepressant. Existing evidence on the efficacy of such combination is ambiguous and varies by syndrome domains and antidepressant classes and—within a class—by individual compounds. The most dependable data favor—as a group—receptor-blocking antidepressants. Of these, mirtazapine demonstrates probably the most consistent beneficial effects, in particular for negative symptoms and cognitive deficits. While current guidelines warn about possible antidepressant-provoked psychotic exacerbation, no data today support these reservations, at least in chronic schizophrenia and when a contemporaneous antipsychotic therapy continues. Moreover, one randomized controlled trial (RCT) revealed an additive antipsychotic effect of an adjunctive antidepressant (mirtazapine) and, according to a recently published large cohort study concomitant antidepressants can reduce suicide rates and overall mortality of patients with schizophrenia. It appears hence that caution regarding the add-on antidepressant use recommended by current guidelines can be soon softened. Due to scarcity of data, conservative use of antidepressants may, however, be still justifiable in acute schizophrenia. If an antipsychotic-antidepressant combination is to be prescribed, a thorough knowledge of pharmacodynamic and pharmacokinetic (especially, regarding several CYP450 liver enzymes) interactions is essential to avoid adverse effects and complications.

Is there an interrelationship between the effects of antipsychotics on psychopathology and on metabolism

Abstract Background: Increased body weight and hyperlipidemia caused by antipsychotics may be associated with improved antipsychotic efficacy in schizophrenia. If this association has a causal interrelationship via a genuine pathophysiological mechanism, then body weight loss in antipsychotic-treated patients would be accompanied by worsened psychopathology. This could have clinical implications. Aim: To explore whether the decreased body weight in these patients is associated with a worsened psychopathology. Methods: In our previously published study, a 16 week treatment period with add-on orlistat (but not placebo) resulted in body weight loss in male (but not female) clozapine- or olanzapine-treated overweight or obese patients. In the current study, we investigated whether body weight loss in those male patients could worsen psychosis. Changes in the Positive and Negative Syndrome Scale (PANSS) scores within groups and body weight changes and lipid profiles over the treatment period were analysed by the paired samples t-test. Between-group comparisons were analysed by the independent samples t-test. Results: Over the treatment period body weight decreased by 2.56 ± 3.25 kg from initial 106.02 ± 12.61 kg (p = 0.04) for the orlistat group, with no statistically significant changes for the placebo group. Lipid levels did not change in either group. The orlistat-induced weight decrease was not associated with worsening in the PANSS scores. Conclusions: Weight loss was not associated with a worsening of psychosis. The interrelationship between the antipsychotic-induced weigh gain and improved schizophrenia psychopathology observed in earlier studies appears to be indirect. Orlistat treatment in our study did not worsen psychopathology in this population.

Add-on mirtazapine improves depressive symptoms in schizophrenia: a double-blind randomized placebo-controlled study with an open-label extension phase

Depression is common in schizophrenia and worsens its course. The role of antidepressants for schizophrenic depression remains unclear. In this study, the efficacy of add‐on mirtazapine on depression in schizophrenia was explored in a subsidiary arm of a recent randomized controlled trial.

Add-on mirtazapine improves depressive symptoms in schizophrenia: a double-blind randomized placebo-controlled study with an open-label extension phase: Add-on mirtazapine in schizophrenia

Depression is common in schizophrenia and worsens its course. The role of antidepressants for schizophrenic depression remains unclear. In this study, the efficacy of add‐on mirtazapine on depression in schizophrenia was explored in a subsidiary arm of a recent randomized controlled trial.