Psychotropic-induced Weight Gain Research Articles

Psychotropic-induced weight gain and telomere length: results from a one-year longitudinal study and a large population-based cohort

Weight-inducing psychotropic treatments are risk factors for age-related diseases such as cardiovascular disorders, which are associated with both inflammation and telomere length shortening. With a longitudinal design, the present study evaluates telomere length trajectories after 1 year of weight-inducing psychotropic medication, accounting for weight changes and the inflammatory biomarker high-sensitivity C-Reactive Protein (CRP). Among 200 patients, an overall median telomere shortening of -41.2 bp was observed (p = 0.014), which is comparable with the general population’s yearly telomere attrition. Linear regression showed on average -93.1 and -58.9 bp of further telomere shortening per five units of BMI for BMI values < or ≥30 kg/m2, respectively (p = 0.003 and p = 0.009, respectively). Importantly, the overall telomere shortening was predicted to be increased four-fold among patients with low baseline weight (i.e., 50 kg) and with clinically relevant weight gain (≥ 7%) after 1 year of treatment (interaction term between relevant weight gain and baseline weight: +6.3 bp, p = 0.016). Patients with relevant weight gain showed greater CRP levels (+ 49%; p = 0.016), and a telomere shortening of -36.2 bp (p = 0.010) was estimated whenever CRP level doubled. Mendelian randomization using UKBiobank data showed a causal effect of BMI on telomere shortening, notably stronger among patients receiving weight-inducing psychotropic treatments (n = 9798) than among psychiatric patients without such drugs (n = 16228) and non-psychiatric controls (n = 252932) (beta: -0.37, -0.12, -0.06, respectively; p = 0.004, p < 0.001, p < 0.001, respectively). Ultimately, telomere trajectories were associated with 1 year weight gain and increases in CRP levels, with telomere shortening strongly enhanced by BMI increments among patients receiving weight-inducing psychotropic treatments.

Enriched developmental biology molecular pathways impact on antipsychotics-induced weight gain.

Psychotropic-induced weight gain (PIWG) may lead to increased risk for cardiovasculardiseases, metabolic disorders and treatment discontinuation. PIWG may be genetically driven. The analysis of complete molecular pathways may grant suffcient power to tackle the biologic variance of PIWG. Such identifcation would help to move a step forward in the direction of personalized treatment in psychiatry. A genetic sample from the CATIE trial (n = 765; M = 556, mean age = 40.93 ± 11.03) treated with diverse antipsychotic drugs was investigated. A molecular pathway analysis was conducted for the identifcation of the molecular pathways enriched in variations associated with PIWG. The developmental biology molecular pathway was signifcantly (P.adj = 0.018) enriched in genetic variations signifcantly (P < 0.01) associated with PIWG. A total of 18 genes were identifed and discussed. The developmental biology molecular pathway is involved in the regulation of β-cell development, and the transcriptional regulation of white adipocyte differentiation. Results from the current contribution correlate with previous evidence and it is consistent with our earlier result on the STAR*D sample. Furthermore, the involvement of the β-cell development and the transcriptional regulation of white adipocyte differentiation pathways stress the relevance of the peripheral tissue rearrangement, rather than increased food intake, in the biologic modifcations that follow psychotropic treatment and may lead to PIWG. Further research is warranted.

Psychotropic drug-induced genetic-epigenetic modulation of CRTC1 gene is associated with early weight gain in a prospective study of psychiatric patients

BackgroundMetabolic side effects induced by psychotropic drugs represent a major health issue in psychiatry. CREB-regulated transcription coactivator 1 (CRTC1) gene plays a major role in the regulation of energy homeostasis and epigenetic mechanisms may explain its association with obesity features previously described in psychiatric patients. This prospective study included 78 patients receiving psychotropic drugs that induce metabolic disturbances, with weight and other metabolic parameters monitored regularly. Methylation levels in 76 CRTC1 probes were assessed before and after 1 month of psychotropic treatment in blood samples.ResultsSignificant methylation changes were observed in three CRTC1 CpG sites (i.e., cg07015183, cg12034943, and cg 17006757) in patients with early and important weight gain (i.e., equal or higher than 5% after 1 month; FDR p value = 0.02). Multivariable models showed that methylation decrease in cg12034943 was more important in patients with early weight gain (≥ 5%) than in those who did not gain weight (p = 0.01). Further analyses combining genetic and methylation data showed that cg12034943 was significantly associated with early weight gain in patients carrying the G allele of rs4808844A>G (p = 0.03), a SNP associated with this methylation site (p = 0.03).ConclusionsThese findings give new insights on psychotropic-induced weight gain and underline the need of future larger prospective epigenetic studies to better understand the complex pathways involved in psychotropic-induced metabolic side effects.

Genetics of second-generation antipsychotic and mood stabilizer-induced weight gain in bipolar disorder: common and specific effects of key regulators of fat-mass homoeostasis genes.

Second-generation antipsychotics (SGAP) and mood stabilizers (MS) are prescribed widely for the treatment of bipolar disorder, but they are associated with the risk of relevant side-effects, among which is weight gain. The identification of genes that predispose to weight gain would represent a useful tool to evaluate the risk-benefit ratio of treatment. This study investigated the genetic factors associated with weight gain in bipolar patients treated with SGAP, MS and their combinations (n=486). Single-nucleotide polymorphisms belonging to 16 candidate genes supported by the literature were investigated in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) genome-wide dataset. Linear regression models were constructed including age, sex, initial weight and prescription of SGAP at high risk for inducing weight gain (olanzapine or clozapine) as covariates. Genes harbouring single-nucleotide polymorphisms associated with phenotypes were investigated by a pathway analysis. No association was found between phenotypes and individual polymorphisms or pathways after multiple-test correction. HTR2C, LEP, FTO and TBC1D1 represented the top genes for weight gain during treatment with a SGAP and/or MS. A genome-wide signal (FTO rs9930506) associated previously with obesity was associated with psychotropic-induced weight gain. The genes that influenced both SGAP and MS weight gain were FTO, TBC1D1, MTHFR and HRH1. ADCY9, ADCY5 and PRKAG2 were interesting candidate genes that emerged from the pathway analysis. This study was the first to compare the genes involved in SGAP-induced and MS-induced weight gain. Individual genes probably play a limited role in psychotropic-induced weight gain; further studies should focus on the extension from known candidate genes to wider groups of molecular pathways.

Weight gain associated with taking psychotropic medication: An integrative review

People with serious mental illness have higher morbidity and mortality rates than general populations, and overweight/obesity-related conditions are prevalent. Psychotropic medications are a primary factor in significant weight gain. Adolescents and young adults, particularly those with first-episode psychoses taking atypical antipsychotics, are susceptible to weight gain. This paper reports findings from an integrative review of research investigating the impact and treatment of psychotropic-induced weight gain. Four databases were searched, yielding 522 papers. From these and hand-searched papers, 36 research reports were systematically classified and analysed. The review revealed people experiencing psychotropic-induced weight gain perceive it as distressing. It impacts on quality of life and contributes to treatment non-adherence. Weight management and prevention strategies have primarily targeted adults with existing/chronic illness rather than those with first-episode psychoses and/or drug naiveté. Single and multimodal interventions to prevent or manage weight gain produced comparable, modest results. This review highlights that the effectiveness of weight management interventions is not fully known, and there is a lack of information regarding weight gain prevention for young people taking psychotropics. Future research directions include exploring the needs of young people regarding psychotropic-related weight gain and long-term, follow-up studies of lifestyle interventions to prevent psychotropic-related weight gain.

An Epidemiologic Study of Psychotropic Medication and Obesity-Related Chronic Illnesses in Older Psychiatric Patients

Adverse effects from medication vary with age. Weight gain with several psychotropics is well known in adults but less information is available related to extent and complications of psychotropic-induced weight gain in older psychiatric patients. We determined the relative incidence of 2 obesity-related conditions (diabetes and hypertension) in older psychiatric patients receiving antipsychotics, antidepressants, and mood stabilizers. A population-based case-control study of all psychiatric patients aged 67 years or older in contact with either specialist services or primary care using administrative data from Nova Scotia. We identified incident cases of diabetes (n = 608) and of hypertension (n = 1056), as well as an equal number of control subjects for each condition. Amitryptiline, selective serotonin reuptake inhibitors (SSRIs), and olanzapine were associated with an increased risk of presenting with hypertension 6 months after initial prescription. By contrast, conventional antipsychotics were associated with a reduced incidence of hypertension. Olanzapine was also significantly associated with diabetes after 6 months (OR adj = 2.58, 95% CI 1.12 to 5.92). The findings for SSRIs and olanzapine remained significant after adjusting for potential confounders such as sociodemographic characteristics, schizophrenia, beta blockers, thiazide diuretics, and corticosteroids. Our results suggest that the association of psychotropics and 2 obesity-related conditions, hypertension and diabetes, applies to older psychiatric patients as well as younger populations. Within drug classes, there are drugs that have a greater association than others, and this may be a factor when choosing a specific agent.

Efficacy of Add-On Topiramate Therapy in Psychiatric Patients with Weight Gain

Weight gain is a common adverse effect of many psychotropic medications including antipsychotics, antidepressants, and mood stabilizers. There is a growing body of evidence that topiramate may be useful as an add-on therapy to induce weight loss in patients who have experienced psychotropic-induced weight gain. To determine the efficacy and tolerability of topiramate for treatment of weight gain in a naturalistic mental health clinic setting. A retrospective chart review was conducted at a community mental health clinic. Subjects were non-elderly adults who received topiramate therapy beginning in 2002-2005 for documented weight gain during treatment with psychotropic drugs. Primary outcome measures included response rate (based on weight loss of any magnitude) and mean changes in weight and body mass index (BMI). Forty-one patients were included in the study. There was a 58.5% (n = 24) response rate. Mean reductions in weight and BMI were approximately 2.2 kg and 0.5 points, respectively. Responders lost an average of 7.2 kg, whereas nonresponders gained an average of 5.0 kg. Patients with a baseline weight of at least 91 kg and those receiving a greater number of psychotropic medications were more likely to experience success with topiramate therapy. Of the 24 patients who responded to therapy, 22 experienced onset of weight reduction by the next clinic visit (1-4 mo) following either initiation of therapy or titration to the eventual therapeutic dose, and the usual rate of weight loss was 0.45-1.4 kg per month. Therapy was typically initiated at 50 mg/day. The mean maximum dose was 93.9 mg/day and the median maximum dose was 100 mg/day. Seven (17.1%) patients had documented adverse effects to topiramate therapy. Topiramate therapy resulted in overall modest (ie, <2%) decreases in weight and BMI, but many patients experienced more impressive weight loss. Therapy was generally well tolerated.

Psychiatric medication-induced obesity: a review.

A majority of psychiatric medications are known to generate weight gain and ultimately obesity in some patients. There is much speculation about the prevalence of weight gain and the degree of weight gain during acute and longitudinal treatment with these agents. There is newer literature looking at the aetiology of this weight gain and the potential treatments being used to alleviate this side-effect. We found solid evidence that weight gain is often associated with the mood stabilizers, and antipsychotics and antidepressants. Only few weight neutral or weight loss producing psychotropics are available, and weight gain, outside of an immediate side-effect, may generate secondary side-effects and medical comorbidity. Weight gain may cause hypertension, diabetes, osteoarthritis, sedentary lifestyle, coronary artery disease, etc. Given the likelihood of inducing weight gain with psychotropic medications and the longitudinal impact on physical health, a thorough literature review is warranted to determine the epidemiology, aetiology and treatment options of psychotropic-induced weight gain.