Using Lipid Guidelines To Manage Metabolic Syndrome For .
Savvy PsychopharmacologyUsing lipid guidelines to managemetabolic syndrome for patients takingan antipsychoticJessa Koch, PharmD, and Christopher J. Thomas, PharmD, BCPS, BCPPYour patient who has schizophrenia, Mr. W, age 48, requests that youswitch him from olanzapine, 10 mg/d,to another antipsychotic because he gained25 lb over 1 month taking the drug. He nowweighs 275 lb. Mr. W reports smoking at least2 packs of cigarettes a day and takes lisinopril, 20 mg/d, for hypertension.You decide to start risperidone, 1 mg/d.First, however, your initial work-up includes: high-density lipoprotein (HDL), 24 mg/dL total cholesterol, 220 mg/dL blood pressure, 154/80 mm Hg waist circumference, 39 in body mass index (BMI), 29 hemoglobin A1c, of 5.6%.A prolactin level is pending.How do you interpret these values?The impact of statin medicationson risk of metabolic syndromeMetabolic syndrome is defined as the clusterof central obesity, insulin resistance, hypertension, and dyslipidemia. Metabolic syndrome increases a patient’s risk of diabetes5-fold and cardiovascular disease 3-fold.1Physical inactivity and eating high-fat foodsDr. Koch is a PGY-2 Pharmacy Practice Resident, Chillicothe VeteransAffairs Medical Center, Chillicothe, Ohio. Dr. Thomas is Director of PGY-1and PGY-2 Pharmacy Residency Programs, Clinical Associate Professorof Pharmacology at Ohio University Heritage College of OsteopathicMedicine, Chillicothe Veterans Affairs Medical Center, Chillicothe, Ohio.DisclosuresThe authors report no financial relationships with any companywhose products are mentioned in this article or with manufacturers ofcompeting products.The contents of this article do not represent the views of the U.S.Department of Veterans Affairs or the United States Government.This material is the result of work supported with resources and theuse of facilities at the Chillicothe Veterans Affairs Medical Center inChillicothe, Ohio.typically precede weight gain and obesitythat, in turn, develop into insulin resistance,hypertension, and dyslipidemia.1Patients with severe psychiatric illnesshave an increased rate of mortality fromcardiovascular disease, compared withthe general population.2-4 The cause of thisphenomenon is multifactorial: In general,patients with severe mental illness receiveinsufficient preventive health care, do noteat a balanced diet, and are more likely tosmoke cigarettes than other people.2-4Also, compared with the general population, the diet of men with schizophreniacontains less vegetables and grains andwomen with schizophrenia consume lessgrains. An estimated 70% of patients withschizophrenia smoke.4 As measured byBMI, 86% of women with schizophreniaand 70% of men with schizophrenia areoverweight or obese.4Vicki L. Ellingrod,PharmD, FCCPDepartment Editorcontinued on page 62Practice Points Many patients with severe mentalillness who are being treated with anantipsychotic (and even those whoare untreated), are at high risk ofcardiovascular disease. B y using the Pooled Cohort Equation andthe treatment algorithm from the lipidguidelines, you likely will identify manypatients who meet criteria for a regimen ofstatin medication. I nitiate statin therapy case by caseto provide secondary prevention foratherosclerotic cardiovascular disease riskin this already high-risk population.Savvy Psychopharmacologyis produced in partnershipwith the Collegeof Psychiatricand NeurologicPharmacistscpnp.orgmhc.cpnp.org (journal)Current PsychiatryVol. 15, No. 759
Savvy Psychopharmacologycontinued from page 59Antipsychotics used to treat severe mental illness also have been implicated inmetabolic syndrome, specifically secondgeneration antipsychotics (SGAs).5 Severaltheories aim to explain how antipsychoticslead to metabolic alterations.Oxidative stress. One theory centers on theproduction of oxidative stress and the consequent reactive oxygen species that formafter SGA treatment.6Clinical PointMitochondrial function. Another the-Antipsychoticsused to treatsevere mentalillness—specificallySGAs—have beenimplicated inmetabolic syndromeory assesses the impact of antipsychotictreatment on mitochondrial function.Mitochondrial dysfunction causes decreasedfatty acid oxidation, leading to lipidaccumulation.7The culminating affect of severe mentalillness alone as well as treatment-emergentside effects of antipsychotics raises thequestion of how to best treat the dyslipidemia component of metabolic syndrome.This article will: review which antipsychotics impactlipids the most provide an overview of the most recentlipid guidelines describe how to best manage patientsto prevent and treat dyslipidemia.Impact of antipsychotics on lipidsDiscuss this article atwww.facebook.com/CurrentPsychiatry62Current PsychiatryJuly 2016Antipsychotic treatment can lead to metabolic syndrome; SGAs are implicated in mostcases.8 A study by Liao et al9 investigated therisk of developing type 2 diabetes mellitus,hypertension, and hyperlipidemia in patientswith schizophrenia who received treatmentwith a first-generation antipsychotic (FGA)compared with patients who received aSGA. The significance-adjusted hazard ratiofor the development of hyperlipidemia inpatients treated with a SGA was statistically significant compared with the generalpopulation (1.41; 95% CI, 1.09–1.83). The riskof hyperlipidemia in patients treated with aFGA was not significant.Studies have aimed to describe whichSGAs carry the greatest risk of hyperlipid-emia.10,11 To summarize findings, in 2004 theAmerican Diabetes Association (ADA) andAmerican Psychiatric Association releaseda consensus statement on the impact ofantipsychotic medications on obesity anddiabetes.12 The statement listed the following antipsychotics in order of greatest toleast impact on hyperlipidemia: clozapine olanzapine quetiapine risperidone ziprasidone aripiprazole.To evaluate newer SGAs, a systematicreview and meta-analysis by De Hert etal13 aimed to assess the metabolic risksassociated with asenapine, iloperidone,lurasidone, and paliperidone. In general,the studies included in the meta-analysisshowed little or no clinically meaningfuldifferences among these newer agents interms of total cholesterol in short-term trials, except for asenapine and iloperidone.Asenapine was found to increase the totalcholesterol level in long-term trials ( 12weeks) by an average of 6.53 mg/dL. Thesetrials also demonstrated a decrease in HDLcholesterol ( 0.13 mg/dL) and a decrease inlow-density lipoprotein cholesterol (LDL-C)( 1.72 mg/dL to 0.86 mg/dL). The impactof asenapine on these lab results does notappear to be clinically significant.13,14Iloperidone. A study evaluating theimpact iloperidone on lipid values showeda statistically significant increase in totalcholesterol, HDL, and LDL-C levels after12 weeks.13,15Overview: Latest lipid guidelinesCurrent literature lacks information regarding statin use for overall prevention of metabolic syndrome. However, the most recentupdate to the American Heart Association’sguideline on treating blood cholesterol toreduce atherosclerotic cardiovascular riskin adults describes the role of statin therapy
Savvy PsychopharmacologyTable 1Statin benefit groupsGroupStatin-therapy optionsClinical ASCVD (history of myocardial infarction,acute coronary syndrome, transient ischemicattack, or peripheral artery disease)Age 75: High-intensity therapyLDL-C 190 mg/dLHigh-intensity therapyType 1 or 2 diabetes mellitus, age 40 to 75Moderate-intensity therapyAge 75 or unable to tolerate high-intensitytherapy: Moderate-intensity therapy10-year ASCVD risk is 7.5%: High-intensitytherapyEstimated 10-year ASCVD risk 7.5% using thePooled Cohort EquationModerate-intensity or high-intensity therapyASCVD: atherosclerotic cardiovascular disease; LDL-C: low-density lipoprotein cholesterolto address dyslipidemia, which is one component of metabolic syndrome.16,17Some of the greatest changes seen withthe latest blood cholesterol guidelinesinclude: focus on atherosclerotic cardiovasculardisease (ASCVD) risk reduction to identify 4 statin benefit groups transition away from treating to a targetLDL valueClinical PointCurrent literaturelacks informationregarding statinuse for overallprevention ofmetabolic syndrome
Savvy PsychopharmacologyTable 2Levels of intensity of statin therapyIntensityExpected LDL-C-lowering capacityStatinLowLDL-C expected to decrease 30% frombaselineFluvastatin, 20 to 40 mg/dLovastatin, 20 mg/dPitavastatin, 1 mg/dPravastatin, 10 to 20 mg/dSimvastatin, 10 mg/dModerateLDL-C expected to decrease 30% to 50%Atorvastatin, 10 to 20 mg/dFluvastatin, 80 mg/dFluvastatin XL, 80 mg/dLovastatin, 40 mg/dPitavastatin, 2 to 4 mg/dPravastatin, 40 to 80 mg/dRosuvastatin, 5 to 10 mg/dSimvastatin, 20 to 40 mg/dHighLDL-C expected to decrease 50%Atorvastatin, 40 to 80 mg/dRosuvastatin, 20 to 40 mg/dClinical PointWhenever a patientis started on statintherapy, ordera liver function testand lipid profileat baselineLDL-C: low-density lipoprotein cholesterol use of the Pooled Cohort Equation toestimate 10-year ASCVD risk, ratherthan the Framingham Risk Score.Placing patients in 1 of 4 statinbenefit groups64Current PsychiatryJuly 2016Unlike the 2002 National CholesterolEducation Program Adult Treatment PanelIII (ATP III) guidelines, the latest guidelineshave identified 4 statin treatment benefitgroups: patients with clinical ASCVD (including those who have had acute coronary syndrome, stroke, or myocardial infarction, orwho have stable or unstable angina, transientischemic attacks, or peripheral artery disease,or a combination of these findings) patients with LDL-C 190 mg/dL patients age 40 to 75 with type 1 or type2 diabetes mellitus patients with an estimated 10-yearASCVD risk of 7.5% that was estimatedusing the Pooled Cohort Equation.16,17Table 1 (page 63) represents each statinbenefit group and recommended treatmentoptions.Selected statin therapy for each statinbenefit group is further delineated intolow-, moderate-, and high-intensity therapy.Intensity of statin therapy represents theexpected LDL lowering capacity of selectedstatins. Low-intensity statin therapy, onaverage, is expected to lower LDL-C by 30%. Moderate-intensity statin therapy isexpected to lower LDL-C by 30% to 50%.High-intensity statin therapy is expected tolower LDL-C by 50%.When selecting treatment for patients,it is important to first determine the statinbenefit group that the patient falls under,and then select the appropriate statin intensity. The categorization of the differentstatins based on LDL-C lowering capacity isdescribed in Table 2.Whenever a patient is started on statintherapy, order a liver function test and lipidprofile at baseline. Repeat these tests 4 to12 weeks after statin initiation, then every 3to 12 months.Transition away from treating to atarget LDL-C goalATP III guidelines suggested that elevatedLDL was the leading cause of coronaryheart disease and recommended therapywith LDL-lowering medications.18 The
Savvy Psychopharmacologypanel that developed the 2013 lipid guideline concluded that there was no evidencethat showed benefit in treating to a designated LDL-C goal.16,17 Arguably, treating toa target may lead to overtreatment in somepatients and under-treatment in others.Treatment is now recommended based onstatin intensity.Using the Pooled Cohort EquationIn moving away from the FraminghamRisk Score, the latest lipid guidelinesestablished a new calculation to assesscardiovascular disease. The Pooled CohortEquation estimates the 10-year ASCVDrisk for patients based on selected risk factors: age, sex, race, lipids, diabetes, smoking status, and blood pressure. Althoughother potential cardiovascular disease riskfactors have been identified, the PooledCohort Equation focused on those riskfactors that have been correlated with cardiovascular disease since the 1960s.16,17,19The Pooled Cohort Equation is intendedto (1) more accurately identify higher-riskpatients and (2) assess who would bestbenefit from statin therapy.Recommended lab tests andsubsequent treatmentWith the new lipid guidelines in place todirect dyslipidemia treatment and a better understanding of how certain antipsychotics impact lipid values, the next step ismonitoring parameters for patients. Beforeinitiating antipsychotic treatment and inaccordance with the 2014 National Institutefor Health and Care Excellence (NICE) guidelines, baseline measurements should includeweight, waist circumference, pulse, bloodpressure, fasting blood glucose, hemoglobinA1c, blood lipid profile, and, if risperidoneor paliperidone is initiated, prolactin level.20Additionally, patients should be assessed atbaseline for any movement disorders as wellas current nutritional status, diet, and level ofphysical activity.Once treatment is selected on a patientspecific basis, weight should be measuredRelated Resource AHA/ACC 2013 Prevention Guidelines Tools CV RiskCalculator. inesStatements/PreventionGuidelines/UCM457698 Prevention-Guidelines.jsp.Drug Brand NamesAripiprazole AbilifyAsenapine SaphrisAtorvastatin LipitorClozapine ClozarilFluvastatin LescolIloperidone FanaptLovastatin MevacorLurasidone LatudaOlanzapine ZyprexaPaliperidone InvegaPitavastatin LivaloPravastatin PravacholQuetiapine SeroquelRisperidone RisperdalRosuvastatin CrestorSimvastatin ZocorZiprasidone Geodonweekly for the first 6 weeks, again at 12 weeksand 1 year, and then annually. Pulse andblood pressure should be obtained 12 weeksafter treatment initiation and at 1 year. Fastingblood glucose, hemoglobin A1c, and bloodlipid levels should be collected 12 weeks aftertreatment onset, then at the 1-year mark.20These laboratory parameters should be measured annually while the patient is receivingantipsychotic treatment.Alternately, you can follow the monitoring parameters in the more dated 2004 ADAconsensus statement: baseline assessment to include BMI,waist circumference, blood pressure, fasting plasma glucose, fasting lipid profile,and personal and family history BMI measured again at 4 weeks,8 weeks, 12 weeks, and then quarterly 12-week follow-up measurement offasting plasma glucose, fasting lipids, andblood pressure annual measurement of fastingblood glucose, blood pressure, and waistcircumference.12In addition to the NICE guidelines andthe ADA consensus statement, use of thecurrent lipid guidelines and the PooledCohort Equation to assess 10-year ASCVDrisk should be obtained at baseline andthroughout antipsychotic treatment. If youidentify an abnormality in the lipid profile,you have several options:Clinical PointThe Pooled CohortEquation is intendedto (1) more accuratelyidentify higher-riskpatients and (2) assesswho would bestbenefit from a statinCurrent PsychiatryVol. 15, No. 765
Savvy PsychopharmacologyClinical PointPatients identifiedas being in 1 of the 4statin benefit groupsshould be startedon appropriatepharmacotherapy Decrease the antipsychotic dosage Switch to an antipsychotic consideredto be less risky Discontinue therapy Implement diet and exercise Refer the patient to a dietitian or otherclinician skilled in managing overweight or obesity and hyperlipidemia.21Furthermore, patients identified as beingin 1 of the 4 statin benefit groups should bestarted on appropriate pharmacotherapy.Non-statin therapy as adjunct or in lieuof statin therapy is not considered to befirst-line.16CASE CONTINUEDAfter reviewing Mr. W’s lab results, you calculate that he has a 24% ten-year ASCVD risk,using the Pooled Cohort Equation. Followingthe treatment algorithm for statin benefitgroups, you see that Mr. W meets criteria forhigh-intensity statin therapy. You stop olanzapine, switch to risperidone, 1 mg/d, andinitiate atorvastatin, 40 mg/d. You plan toassess Mr. W’s weight weekly over the next 6weeks and order a liver profile and lipid profile in 6 weeks.References1. O’Neill S, O’Driscoll L. Metabolic syndrome: a closer look atthe growing epidemic and its associated pathologies. Obes Rev.2015;16(1):1-12.2. McCreadie RG; Scottish Schizophrenia Lifestyle Group. Diet,smoking and cardiovascular risk in people with schizophrenia:descriptive study. Br J Psychiatry. 2003;183:534-539.3. Correll CU, Robinson DG, Schooler NR, et al. Cardiometabolicrisk in patients with first-episode schizophrenia spectrumdisorders: baseline results from the RAISE-ETP Study. JAMAPsychiatry. 2014;7(12):1350-1363.4. Nordentoft M, Wahlbeck K, Hällgren J, et al. Excess mortality,causes of death and life expectancy in 270,770 patients withrecent onset of mental disorders in Denmark, Finland andSweden. PLoS ONE. 2013;8(1):e55176. doi: 10.1371/journal.pone.0055176.66Current PsychiatryJuly 2016induced metabolic alterations. J Psychiatr Pract. 2010;16(5):325-333.7. Schrauwen P, Schrauwen-Hinderling V, Hoeks J, et al.Mitochondrial dysfunction and lipotoxicity. Biochim BiophysActa. 2010;1801(3):266-271.8. Watanabe J, Suzuki Y, Someya T. Lipid effects of psychiatricmedications. Curr Atheroscler Rep. 2013;15(1):292.9. Liao HH, Chang CS, Wei WC, et al. Schizophrenia patients athigher risk of diabetes, hypertension and hyperlipidemia: apopulation-based study. Schizophr Res. 2011;126(1-3):110-116.10. Lidenmayer JP, Czobor P, Volavka J, et al. Changes in glucoseand cholesterol levels in patients with schizophrenia treatedwith typical or atypical antipsychotics. Am J Psychiatry.2003;160(2):290-296.11. Olfson M, Marcus SC, Corey-Lisle P, et al. Hyperlipidemiafollowing treatment with antipsychotic medications. Am JPsychiatry. 2006;163(10):1821-1825.12. American Diabetes Association; American PsychiatricAssociation; American Association of Clinical Endocrinologists,et al. Consensus development conference on antipsychotic drugsand obesity and diabetes. Diabetes Care. 2004;27(2):596-601.13. De Hert M, Yu W, Detraux J, et al. Body weight and metabolicadverse effects of asenapine, iloperidone, lurasidone, andpaliperidone in the treatment of schizophrenia and bipolardisorder: a systematic review and exploratory meta-analysis.CNS Drugs. 2012;26(9):733-759.14. Kemp DE, Zhao J, Cazorla P, et al. Weight change and metaboliceffects of asenapine in patients with schizophrenia and bipolardisorder. J Clin Psychiary. 2014;75(3):238-245.15. Cutler AJ, Kalali AH, Weiden PJ, et al. Four-week, doubleblind, placebo-and ziprasidone-controlled trial of iloperidonein patients with acute exacerbations of schizophrenia. J ClinPsychopharmacol. 2008;28(2 suppl 1):S20-S28.16. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHAGuideline on the Treatment of Blood Cholesterol to ReduceAtherosclerotic Cardiovascular Risk in Adults: a report of theAmerican College of Cardiology/American Heart AssociationTask Force on Practice Guidelines. Circulation. 2014;129(25suppl 2):S1-S45.17. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. AmericanCollege of Cardiology/American Heart Association TaskForce on Practice Guidelines. 2013 ACC/AHA guideline onthe treatment of blood cholesterol to reduce atheroscleroticcardiovascular risk in adults: a report of the American Collegeof Cardiology/American Heart Association Task Force onPractice Guidelines. Circulation. 2014;129(25 suppl 2):S49-S72.18. National Cholesterol Education Program (NCEP)Expert Panel on Detection, Evaluation, and Treatment ofHigh Blood Cholesterol in Adults (Adult TreatmentPanel III). Third report of the National CholesterolEducation Program (NCEP) Expert Panel on detection,evaluation, and treatment of high blood cholesterol inadults (Adult Treatment Panel III) final report. Circulation.2002;106(25):3143-3421.19. Ioannidis JP. More than a billion people taking statins? Potentialimplications of the new cardiovascular guidelines. JAMA.2014;311(5):463-464.5. Young SL, Taylor M, Lawrie SM. “First do no harm.” Asystematic review of the prevalence and management ofantipsychotic adverse effects. J Psychopharma
on risk of metabolic syndrome Metabolic syndrome is defined as the cluster of central obesity, insulin resistance, hyper-tension, and dyslipidemia. Metabolic syn-drome increases a patient’s risk of diabetes 5-fold and cardiovascular disease 3-fold.1 Physical inactivity and eating
Lipid nanoparticles (LNPs) are a safe vehicle for drug delivery, made of physiological or physiologically related lipids. Many different types of LNPs have been engineered, the most important being solid lipid nanoparticles (SLNs), nanostrucured lipid carriers (NLCs), lipid-- drug conjugates (LDCs) and lipid nanocapsules (LNCs).
3.2. Lipid drug delivery systems Lipid-based DDS are an accepted, proven, commercially viable strategy to formulate pharmaceuticals for topical, oral, pulmonary or parenteral delivery. Lipid formulations can be tailored to meet a wide range of product requirements. One of the earliest lipid DDS- liposomes have been used to improve drug solubility.
Toxicity from lipid peroxidation affect the liver lipid metabolism where cytochrome P-450s is an efficient catalyst in the oxidative transformation of lipid derived aldehydes to carboxylic acids adding a new facet to the biological activity of lipid oxidation metabolites. Cytochrome P-450-mediated
Aug 08, 2016 · one clinical study involving lipid nanoparticles as an mRNA vector that reported results and of one ongoing study.20,27 Our formulation consists of an ionizable lipid, a phospho-lipid, cholesterol, a polyethylene glycol (PEG) containing lipid, and an additive for the delivery of mRNA vaccines
of LNP in hydrophilic environment. LNP are particularly well suited for transdermal drug delivery. Indeed, lipid nanoparticles are known to create a mono-layer film on the skin, limiting water evaporation and improving skin hydration [16]. Figure 2. Structure of lipid nanoparticles, from lipid nano-emulsions to solid lipid nanoparticles. 2.1.
distribution of lipid-based medicine. during which lipoid will use as a carrier fir delivery of poorly water soluble medicine. during this review, we have a tendency to discuss the consequences and role of lipoids and lipid digestion on drug delivery.[1] Fig. 1: Solid lipid nanoparticle. Solid Lipid Base Nano Particles
prospects in the pharmaceutical field. This review discusses the recent developments in the fields of solid lipid nanoparticle (SLN), nanostructured lipid carriers (NLC) and lipid drug conjugates (LDC) nanoparticle pertinent to therapeutic agent delivery covering those systems tested and/or validated.
ian curve fitting will be inaccurate in differentiating between lipid and lactate proportions, because the best fit is driven by the method of least squares rather than taking 2 Schematic diagram of the peak pattern in the lipid lactate range. (3A) Broad lipid peak due to short T2 (blue), sharp lactate doublet due to J coupling and long T2
