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

Abstract

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.

Effect of mirtazapine on metabolism and energy substrate partitioning in healthy men

“…Total cholesterol and LDL slightly decreased with mirtazapine in our study, which is in contrast to previous studies (21,36) reporting hyperlipidemia under mirtazapine. We only found a rise in the so-called atherogenic index, i.e., the triglyceride/HDL quotient, which might be related to the desensitized insulin release mentioned above (37).…”

Overweight and the use of psychiatric drugs in patients with mental disorders attended at psychosocial care center, Teresina, Piauí, Brazil

“…Referring to the typical (neuroleptics) and atypical (second generation antipsychotics-ASG) antipsychotics, this study shows similar findings to those found in studies examining medications belonging to these groups alone (18)(19)(20)(21). The two categories showed significant associations with overweight, possibly due to the gate locking receptor of the mix mechanism 5-HT2c beta3-adrenergic, histaminergic H1 and dopaminergic D2 (22,23).…”

Association between Serum Lipids and Antipsychotic Response in Schizophrenia

“…The supplementary search through the reference sections of the identified studies resulted in the inclusion of two additional articles. Thus, a total of 14 studies that reported on the relationship between serum lipids and symptoms of schizophrenia over the course of antipsychotic treatment were retained [8,9,[11][12][13][14][15][16][17][18][19][20][21]. One study was a case report, two were randomized controlled trials, and 11 were observational studies.…”

“…After controlling for changes in body weight, waist circumference, and serum clozapine levels, every increase of 1 mmol/L in serum TG levels significantly predicted a decrease of 9.33 points in PANSS total scores, 2.85 points in PANSS positive subscale scores, and 1.93 points in PANSS negative subscale scores [15]. Terevnikov et al (2013) examined the relationship in participants with schizophrenia treated with first-generation antipsychotics (FGAs) augmented with mirtazapine (n = 20) or FGAs with placebo (n = 16) over a period of 6 weeks of double-blind treatment [16]. After controlling for duration of illness, antipsychotic dose, body weight change, and fasting glucose level change, every increase of 1 mmol/L in serum TC levels significantly predicted a decrease of 7.0 points in PANSS total scores, 1.7 points in PANSS positive subscale scores, and 1.8 points in PANSS negative subscale scores in the FGA-mirtazapine group, but no significant associations were observed in the FGA-placebo group [16].…”

“…Terevnikov et al (2013) examined the relationship in participants with schizophrenia treated with first-generation antipsychotics (FGAs) augmented with mirtazapine (n = 20) or FGAs with placebo (n = 16) over a period of 6 weeks of double-blind treatment [16]. After controlling for duration of illness, antipsychotic dose, body weight change, and fasting glucose level change, every increase of 1 mmol/L in serum TC levels significantly predicted a decrease of 7.0 points in PANSS total scores, 1.7 points in PANSS positive subscale scores, and 1.8 points in PANSS negative subscale scores in the FGA-mirtazapine group, but no significant associations were observed in the FGA-placebo group [16]. Sharma et al (2014) examined the relationship in 71 participants with schizophrenia spectrum disorders treated with a mix of antipsychotics [18].…”