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Premium member Presentation Transcript Metabolic Effects of Psychiatric Medications : Metabolic Effects of Psychiatric Medications Marshall Dahl BSc MD PhD FRCPC cert Endo Clinical Professor, Division of Endocrinology, University of BC June 2012 Disclosures : Disclosures No Financial Disclosures I will discuss some off-label uses of medications: metformin, topiramate Objectives : Objectives Review common psychiatric medications with endocrine and metabolic effects Identify patients who require surveillance and treatment Understand screening and treatment recommendations Outline : Outline Non- “metabolic” endocrine systems and drugs: Thyroid, parathyroid, vasopressin, growth, prolactin, polycystic ovary syndrome Metabolic effects of antipsychotics. Slide 6: Cooper D. N Engl J Med 2005;352:905-917 Release Thyroid Function : Thyroid Function Lithium Inhibits thyroid hormone release Increases TSH (~15% of patients) stimulation of growth- goitre and nodules Reverses with discontinuation At risk population: Pre-existing Hashimoto’s disease and/or antibodies Family History thyroid disease Concomitant valproate and quetiapine use (similar effects to lithium) Thyroid Recommendations : Thyroid Recommendations Hashimoto’s disease: Anti-thyroperoxidase antibodies Increases risk of hypothyroidism with lithium Valproate or quetiapine without lithium: TSH at 3 months and 12 months Treat with thyroxine if elevated Dr. Hakaru Hashimoto 1881–1934 Thyroid Recommendations: Lithium : Thyroid Recommendations: Lithium Obtain baseline TSH before lithium. Recheck 6-8 weeks after starting lithium. Monitor 3, 6 and 12 months Hypothyroid on lithium? Start thyroxine and titrate to normal TSH at 6 week intervals. Parathyroid: Lithium : Parathyroid: Lithium Lithium “re-sets” the parathyroid’s calcium-sensing mechanism. Result: mild increase in PTH and serum calcium. Reversible. Not associated with renal stones. Recommendation: Check serum calcium before lithium and at months 1, 6 and 12. Stop lithium if calcium > 2.9 mmol/L (11.5 mg/dL) Vasopressin and Serum Sodium : Vasopressin and Serum Sodium ADH Hyponatremia : Hyponatremia Some drugs that stimulate vasopressin (ADH) release Barbiturates Carbamazepine Haloperidol Phenothiazines MAOIs Tricyclic antidepressants Uncertain mechanism: Sodium valproate SSRIs Thiothixene Hyponatremia : Hyponatremia Reference range serum Na: 135-145. Below 125: concerning Symptoms relate to level and rapidity of onset Severe: anorexia, nausea, malaise, cramps, headache, confusion, weakness, coma Chronic: cognitive slowing, ataxia Large differential diagnosis list outside of drugs: adrenal, thyroid, CNS, volume status Vasopressin and Serum Sodium : Vasopressin and Serum Sodium Carbamazepine Stimulates ADH secretion (SIADH) 18% prevalence mild hyponatremia (Na<135) Rarely clinically important but can be additive with other hyponatremic factors. Na < 125 requires action SSRIs Hyponatremia reported in older people, especially with diuretic and carbamazepine use Growth : Growth Psychostimulants for ADHD Some children have slowing of growth School-age 2.0 cm and 2.7 kg over 3 years* Perhaps 10% may have permanent deficit in ultimate height Probably appetite related: Growth Hormone normal *Swanson, J Journal of the American Academy of Child & Adolescent Psychiatry. 46(8):1015-1027, August 2007 Growth Recommendations : Growth Recommendations Plot height and weight on growth chart before therapy Yearly measurements If Height-for-weight declines by > 1 SD: discontinue medication Prolactin : Prolactin Prolactin : Prolactin Normal secretion of prolactin inhibited by tonic dopamine secretion from nerves of hypothalamus “Typical” antipsychotics: CPZ, Haloperidol Block dopamine Short-lived rise in prolactin Often normalizes over time Prolactin : Prolactin “Atypical” antipsychotics differ in their D2 agonism/antagonism Potency for PRL elevation: Risperadone>Haloperidol>Olanzapine>Ziprasidone>Quetiapine>Clozapine>Aripiprazole Estrogen increases these effects Chief issue is effect of hypogonadism Prolactin Recommendations : Prolactin Recommendations Ask about menstrual disturbances, nipple discharge, sexual function. Normal? Don’t measure prolactin Elevated Prolactin: rule out pregnancy and hormonal contraception. Look also for elevated TSH and Cr Reference Range 5-26 pmol/L Modest elevations OK if asymptomatic Prolactin Recommendations : Prolactin Recommendations Prl 26-90 and symptoms: change dose or agent Prl > 90 pmol/L (>200µg/L), change dose or agent and: If Prl still >90, scan pituitary to rule out adenoma or mass Normal scan: no further imaging All patients: establish normal menses for women: OCPs or cyclic progesterone normal testosterone for men prevent/treat osteoporosis Polycystic Ovary Syndrome(Anovulatory Androgen Excess) : Polycystic Ovary Syndrome(Anovulatory Androgen Excess) Infertility, PCOS is the most common cause of female infertility. Infrequent, absent, and/or irregular menstrual periods Hirsuitism Ovarian cysts Acne, oily skin, or dandruff Weight gain or obesity, usually with extra weight around the waist Male-pattern baldness or thinning hair Acanthosis nigricans Skin tags Pelvic pain Sleep apnea Slide 24: Pathophysiological Characteristics of the Polycystic Ovary Syndrome (PCOS). Nestler JE. N Engl J Med 2008;358:47-54. PCOS Diagnosis : PCOS Diagnosis NIH: 1990 All of oligoovulation signs of androgen excess (clinical or biochemical) other entities are excluded that would cause polycystic ovaries Rotterdam:2003 Any 2 out of 3 oligoovulation and/or anovulation excess androgen activity polycystic ovaries (by gynecologic ultrasound) Other entities are excluded that would cause these Androgen Excess PCOS Society:2006 All of: excess androgen activity oligoovulation/anovulation and/or polycystic ovaries other entities are excluded that would cause excess androgen activity Valproic Acid and Polycystic Ovary Syndrome : Valproic Acid and Polycystic Ovary Syndrome PCOS: chronic anovulation and hyperandrogenism With or without polycystic ovaries Oligomenorrhea, hirsuitism, acne, insulin resistance, obesity Prevalence of oligomenorrhea and hyperandrogenism Valproate: 10.5% Other anticonvulsant or lithium: 1.4% Valproic Acid and Polycystic Ovary Syndrome : Valproic Acid and Polycystic Ovary Syndrome Possible effect on ovaries independent of weight gain (2nd generation anti-psychotics don’t cause PCOS) Keep track of symptoms Consider lithium or lamotrigine as alternatives PCOS Treatments : PCOS Treatments Regular menses: OCPs, cyclic progesterone, metformin Metabolic syndrome: diet, exercise, metformin Hirsuitism and acne: topical preparations and spironolactone Antipsychotic Medications : Antipsychotic Medications Chlorpromazine introduction 50 years ago Primary indications: schizophrenia and related disorders Other on-label indications: bipolar mania, resistant unipolar depression, Tourette’s, autism-related irritability Off-label use common Antipsychotic Medications : Antipsychotic Medications 1st generation: 7 agents Overall effectiveness similar to 2nd generation, but higher side-effect profile 2nd generation: 13 agents Improved treatment persistence, relapse prevention and reduced extra-pyramidal side effects Kane: J Clin Psychiatry 79 1115-1124 2010 Leucht et al: Mol Psychiatry 14; 429-447 2009 Leucht et al: Lancet 373; 31-41 2009 Health Canada-Approved Indications in Adults : Health Canada-Approved Indications in Adults Schizophrenia and related psychotic disorders: Aripiprazole (Abilify), Olanzapine (Zyprexa), Paliperidone (Invega), Quetiapine (Seroquel), Risperidone (Risperdal), Ziprasidone (Zaldox) Acute manic or mixed episodes: Bipolar 1 Aripiprazole, olanzapine, ziprasidone Acute manic with bipolar: Quetiapine, risperidone Treatment-resistant schizophrenia Clozapine Acute depressive episodes with Bipolar 1 or 2 or resistant major depression Quetiapine Severe dementia with inappropriate behaviour Risperidone Horn et al, BCMJ 54, 2 75-82 2012 Metabolic Risks Associated with Antipsychotic Drugs : Metabolic Risks Associated with Antipsychotic Drugs Weight gain and obesity Type 2 diabetes Metabolic syndrome: hyperlipidemia, hyperglycemia, hypertension, central obesity Cardiovascular disease Most at-risk: first episode schizophrenia, drug-naïve patients, children and adolescents Psychiatric Illness and Metabolic Syndrome : Psychiatric Illness and Metabolic Syndrome Longstanding Observation: An general increase in the prevalence of diabetes and obesity Schizophrenia and affective disorders have rates 1.5-2.0x > general population Studies not controlled for other risk factors: weight, activity, drugs and co-morbidities including smoking Weight Gain in Adults : Weight Gain in Adults Even before treatment, increased risk of overweight (BMI 25-30), obesity (BMI ≥ 30) and central obesity (>102 cm men, >88 cm women) Schizophrenia: ~3 fold Bipolar ~1.5 fold Weight gain occurs with treatment with virtually any antipsychotic but worse with some… De Hert, M, et al: World Psychiatry 10, 52-77 2011 Weight Gain Mechamisms : Weight Gain Mechamisms Histamine transmission involved in energy homeostasis H1 receptor antagonism best predictor of degree of weight gain Serotonin 5-HT2a and 5-HT2c control food intake Clozapine and olanzapine potent in this regard: correlates with weight effects Dopamine blockade (D2, D3) promotes feeding Hormonal effects also possible: leptin Kroeze, WK et al Neuropsychopharmacology 28, 519-526 2003 Weight Gain Mechanisms : Weight Gain Mechanisms Small increase in intake? 500 kcal/day would be enough Many patients report increased appetite, binge eating, carbohydrate eating and decreased satiety Pleotrophic receptor activity: H1 receptors, serotonin, norepinephrine, dopamine Dopamine/norepinephrine receptors at lateral hypothalamus affect satiety Blocking serotonin receptors increases food intake particularly 5-HT₂c Risk of Weight Gain by Antipsychotic Agent : Risk of Weight Gain by Antipsychotic Agent High 1st: Chlorpromazine 2nd: Clozapine, Olanzapine Intermediate 1st: Thioridazine 2nd: Lloperidone, paliperidone, quetiapine, risperidone, sertindole, zotepine Low 1st: Fluphenazine, haloperidol, perphenazine, pomozide 2nd: Amisulpride, aripiprazole, asenapine, lurasidone, ziprasidone De Hert, M et al, Nat Rev Endocrinol 8, 114-126 (2012) Mean Change in Weight with Antipsychotics Estimated Weight Change at 10 Weeks on “Standard” dose : Mean Change in Weight with Antipsychotics Estimated Weight Change at 10 Weeks on “Standard” dose *4-6 week pooled data (Marder, et al. Schizophr Res. 2003;61:123). † Extrapolated from 6-week data. Adapted from: Allison, et al. Am J Psychiatry. 1999;156:1686-1696. Haloperidol Polypharmacy Risperidone Chlorpromazine Olanzapine Clozapine 6 5 4 3 2 1 0 -1 -2 -3 Placebo Molindone Fluphenazine Ziprasidone 13.2 Weight Change (lb) 11.0 8.8 6.6 4.4 2.2 0 -2.2 -4.4 -6.6 Weight Change (kg) Antipsychotics and Weight Gain: Comments : Antipsychotics and Weight Gain: Comments No agent is weight neutral Clinically relevant weight gain (≥ 7% pretreatment weight) in all agents vs placebo Greatest weight gain with first episode: (12 month trial) even with “neutral” agents, ziprasadone (4.8kg), haloperidol (6.3kg) Most weight gain in first 12 weeks in drug-naïve patients (3.8kg) Citrome, L. Psychiatric Times 1. 27-30 2007 Khan RS et al, Lancet 371, 1085-1097 2008 Tarricone I et al. Psychol Med 40, 187-200 2010 Metabolic Syndrome : Metabolic Syndrome 1988: Gerald Reaven “Syndrome X”: dyslipidemia, hypertension and hyperglycemia cluster together “Insulin Resistance Syndrome” WHO: “Metabolic Syndrome” avoids implication that insulin resistance is the primary or only cause of associated risk factors Metabolic Syndrome: Definition : Metabolic Syndrome: Definition 3 out of 5: Abdominal Obesity, Men>102cm (>40in) Women>88cm (35in) Triglycerides >1.7mmol/L HDL Men<1.04mmol/L Women<1.29mmol/L Blood Pressure >130/85 Fasting Glucose >6.0mmol/L Metabolic Syndrome : Metabolic Syndrome ~5 fold increase in risk of diabetes ~4 fold increase in risk of death from coronary artery disease Antipsychotics increase risk of metabolic syndrome Studies confounded by indication (high risk patients probably get low-risk agents) Metabolic Syndrome (Lipids and or Glucose) Risk by Agent : Metabolic Syndrome (Lipids and or Glucose) Risk by Agent 1st generation: High: chlorpromazine, thioridizine Low: fluphenazine, haloperidol, molindone, perphenazine, pimozide 2nd generation: High: clozapine, olanzapine Intermediate: quetiapine Less: amisulpride, lloperidone, paliperidone, risperidone, sertindole Least: aripiprazole, asenapine, lurasidone, ziprasidone De Hert, M et al, Nat Rev Endocrinol 8, 114-126 (2012) Weight Gain/ Metabolic Syndrome : Weight Gain/ Metabolic Syndrome Psychiatric patients have higher prevalence of these problems Sedentary lifestyle, poor diet Medications can worsen the situation All antipsychotics- especially atypicals Lithium, divalproex Metabolic Syndrome: Epidemiology : Metabolic Syndrome: Epidemiology Framingham: Predicts ~25% of all new-onset CAD CAD risk is probably a sum of the constituent risks: age, blood pressure, total cholesterol, diabetes, HDL The metabolic syndrome is highly predictive of the development of diabetes (50% of population-attributable risk) Schizophrenia and Metabolic Syndrome : Schizophrenia and Metabolic Syndrome Meta-analysis (112 studies, 23,799 patients) Metabolic syndrome most prevalent with clozapine (49.7%) But 1st episode: 15.3%, Never had drugs: 12.6% 25% had elevated glucose 50% had dyslipidemia Hypertension not an association Mitchell et al, Schizophr Bull 2012, in press Antipsychotics and Lipids : Antipsychotics and Lipids Highest risk: olanzapine and clozapine Quetiapine somewhat less Independent of weight gain High triglycerides, increased total cholesterol and LDL Low risk: risperidone Neutral: aripiprazole, ziprasidone Antipsychotics and Type 2 Diabetes : Antipsychotics and Type 2 Diabetes Genetic predisposition Modified by other factors Central obesity increases relative risk 4.10-17.50 Physical inactivity increases relative risk 1.12-2.18 Variable findings among studies for effects of antipsychotics on diabetes risk Qim L et al Eur J Epidemiol 25, 5-12 2010 Do Antipsychotics Increase Diabetes Risk? : Do Antipsychotics Increase Diabetes Risk? Danish database: 345,937 patients Increases with clozapine (RR 1.45), olanzapine (RR 1.29) risperidone (RR 1.23) FDA database RRs: olanzapine 9.6, risperadone 3.8, quetiapine 3.5, clozapine 3.1% ziprasadone 2.4, aripiprazole 2.4,haloperidol 2.0 Database studies are not causal and may be confounded by indication Systematic review of 22 randomized, prospective trials: no association of diabetes with any agent vs placebo, but study lengths were short Kessing et al, Br J Psychiatry 197 266-271 2010 Baker et al, Psychopharmacol. Bull 42, 11-31 2009 Bushe CJ et al J Clin Psychiatry 68 1682-1690 2007 Diabetes Comments : Diabetes Comments Prospective trial, drug-naïve, 1st episode patients (7139 pts) Time to onset diabetes shorter during 1st year for olanzapine than control patients No drugs or aripiprazole: reduced risk Risk greatest in the young: ages 0-24, compared to healthy controls Nielsen J et al Neuropsychopharmacology 35 1997-2004 2010 Hammerman A et al Ann Pharmacother 42, 1316-1322 2008 Slide 53: The CATIE Schizophrenia Trial National Institute of Mental Health randomized controlled trial evaluate the effectiveness of atypical and conventional antipsychotic medications patients with chronic schizophrenia 24 month period Metabolic effects were tracked Slide 55: Outcome Measures of Effectiveness Lieberman, J. et al. N Engl J Med 2005;353:1209-1223 Slide 56: Outcome Measures of Effectiveness Lieberman, J. et al. N Engl J Med 2005;353:1209-1223 Conclusions : Conclusions Olanzapine most effective: rates of discontinuation, efficacy scores Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism Efficacy of perphenazine similar to that of quetiapine, risperidone, and ziprasidone Lower metabolic side-effects Schizophrenia and 10-year Cardiac Risk : Schizophrenia and 10-year Cardiac Risk Framingham Heart study formula predictor of risk (sensitivity: 81.4%) Age and gender specific algorithm Smoking, hypertension, total cholesterol, HDL and diabetes 689 CATIE subjects Matched to National Health and Nutrition Examination Survey (NHANES) Goff et all: Schizophrenia Research 80 (2005) 45-53 Slide 59: Goff et all: Schizophrenia Research 80 (2005) 45-53 Schizophrenia and Metabolic Syndrome : Schizophrenia and Metabolic Syndrome CATIE women 251% more likely than NHANES cohort CATIE men 85% more likely than NHANES cohort “The metabolic syndrome is highly prevalent among US schizophrenia patients and represents an enormous source of cardiovascular risk, especially for women” McEvoy et al Schizophrenia Research 80 (2005) 19-32 Risk of Sudden Cardiac Death : Risk of Sudden Cardiac Death Several epidemiologic studies raised this concern: Uncertainties: Is underlying cardiac disease under-recognized? Are higher doses given to sicker patients who have worse somatic health as well? Following slides: low dose= CPZ< 100, medium CPZ100-299 and high CPZ 300+ Slide 62: Adjusted Incidence-Rate Ratios for Sudden Cardiac Death among Current Users of Antipsychotic Drugs, According to Type of Drug and Dose Ray WA et al. N Engl J Med 2009;360:225-235 Slide 63: Adjusted Incidence-Rate Ratios for Sudden Cardiac Death among Current Users of Six Frequently Prescribed Antipsychotic Drugs, According to Dose Ray WA et al. N Engl J Med 2009;360:225-235 Antipsychotics and QT Prolongation : Antipsychotics and QT Prolongation QTc > 500 ms or relative increase in QTc of 60+ms from baseline Increased risk torsade de pointes, ventricular fibrillation and sudden cardiac death High risk QTc prolongation: Pimozide, thioridizine, mesoridazine, sertindole, ziprasadone However: randomized study showed no increase in sudden cardiac death risk in 18,154 patients for ziprasadone vs olanzapine Note that high-risk patients excluded. Strom et al, Am J Psychiatry 168, 193-201 (2011) Risk of Sudden Cardiac Death : Risk of Sudden Cardiac Death Probable at-risk History: family history of SCD < 50 men and <55 women Heart murmur, diabetes, hypertension, irregular heart rate, syncope Baseline ECG Probably avoid the higher risk agents in this group J Am Coll Cardiol 48 e247-e346, 2006 Monitoring Recommendations 2nd generation antipsychotics : Monitoring Recommendations 2nd generation antipsychotics Personal and Family History Weight, waist circumference Measure at baseline and follow weight Encourage patients to track own weight At commencement, if overweight: nutrition and activity counselling Extra caution with coexistant valproate, lithium, depo-provera. Follow-up Monitoring : Follow-up Monitoring 4,8,12 weeks If weight >5% switch SGA class by cross-titration 3 months Fasting glucose, lipids, blood pressure If increase in glucose or lipids switch SGA by cross titration Diabetes Education Centre referral Goal blood sugars 4-7 ac, <10 2hr pc Immediate action at any time if glucose >16 Waist Circumference Measurement : Courtesy J.P. Després 2006 Waist Circumference Measurement Lifestyle Recommendations for Hypertension: Physical Activity : Exercise should be prescribed as an adjunctive to pharmacological therapy Lifestyle Recommendations for Hypertension: Physical Activity Should be prescribed to reduce blood pressure Lifestyle Recommendations for Hypertension: Alcohol : Lifestyle Recommendations for Hypertension: Alcohol Low risk alcohol consumption • Women: maximum of 9 standard drinks/week • Men: maximum of 14 standard drinks/week • 0-2 standard drinks/day A standard drink is about 142 ml or 5 oz of wine (12% alcohol). 341 mL or 12 oz of beer (5% alcohol) 43 mL or 1.5 oz of spirits (40% alcohol). Impact of Lifestyle Therapies on Blood Pressure in Hypertensive Adults : Impact of Lifestyle Therapies on Blood Pressure in Hypertensive Adults Padwal R. et al. CMAJ ･ SEPT. 27, 2005; 173 (7) 749-751 Lifestyle Therapies in Adults with Hypertension: Summary : Lifestyle Therapies in Adults with Hypertension: Summary Slide 73: Usual blood pressure threshold values for initiation of pharmacological treatment of hypertension III. Summary: Treatment of Systolic-Diastolic Hypertension without Other Compelling Indications : III. Summary: Treatment of Systolic-Diastolic Hypertension without Other Compelling Indications CONSIDER Nonadherence Secondary HTN Interfering drugs or lifestyle White coat effect Dual Combination Triple or Quadruple Therapy Lifestyle modification TARGET <140/90 mmHg *Not indicated as first line therapy over 60 y Initial therapy A combination of 2 first line drugs may be considered as initial therapy if the blood pressure is >20 mmHg systolic or >10 mmHg diastolic above target Slide 75: UKPDS: BP Control Study in Type 2 Diabetes Effect of BP on Complications Risk 0 - 10 - 20 - 30 - 40 - 50 - 60 - 70 - 24 - 32 - 37 - 44 - 56 Benefits of 144/82 vs. 154/87 Risk Reduction (%) Any Diabetes Related Endpoint Diabetes - Related Death Microvascular Endpoints Stroke Heart Failure Adherence to anti-hypertensive management can be improved by a multi-pronged approach : Adherence to anti-hypertensive management can be improved by a multi-pronged approach Assess adherence to pharmacological and non-pharmacological therapy at every visit Teach patients to take their pills on a regular schedule associated with a routine daily activity e.g. brushing teeth. Simplify medication regimens using long-acting once-daily dosing Utilize fixed-dose combination pills Utilize unit-of-use packaging e.g. blister packaging Replacing multiple pill antihypertensive combinations with single pill combinations Slide 77: Risk assessment options Framingham Risk Score [FRS] Commonly preferred → measures CVD (validated in Canada*) May underestimate risk in some patients Reynolds Risk Score [RRS] Measures CVD → optional risk engine (includes family history and hsCRP) hsCRP=high-sensitivity C-reactive protein; CVD=cardiovascular disease *Validated with Cardiovascular Life Expectancy Model Slide 78: http://www.ccsguidelineprograms.ca/images/stories/Dyslipidemia_Program/Tools_Resources/FRSworksheets/frs_worksheet_en.pdf Slide 79: iPhone Screenshots Collaborative Atorvastatin Diabetes Study (CARDS). Lancet 2004:364; 685-96 : Collaborative Atorvastatin Diabetes Study (CARDS). Lancet 2004:364; 685-96 Metabolic Care and Second Generation Antipsychotics : Metabolic Care and Second Generation Antipsychotics Make psychiatric drug decisions based on optimal psychiatric care Monitor and intervene early for smoking, blood pressure, lipids and blood sugar Start with: Hypertension: thiazide diuretic Lipids: statin Diabetes: Education centre and metformin Drugs for Prevention and Treatment of SGA Weight Gain : Drugs for Prevention and Treatment of SGA Weight Gain “Data... are limited” A number of agents have been tried (18 listed) Best accumulated evidence for metformin and topiramate Systematic review of 11 randomized, placebo-controlled trials Elinger et al, Ann Pharmacother 2010; 44:669-79 Metformin : Metformin Indicated in Type 2 diabetes Increases insulin sensitivity through reduction of hepatic glucose production Used off-label for polycystic ovary syndrome, fatty liver 6 RCTs for treatment: 2 found metformin superior to placebo. (-3.3 kg vs + 3.1 kg) Most marked in a trial with behavioural supports. (-3.3 kg vs + 3.1 kg) Generally mildly positive results for metformin in open-label trials of 2nd generation agents Doses varied 500- 2500 mg daily Nausea and diarrhea ~ 10%. Elinger et al, Ann Pharmacother 2010; 44:669-79 Topiramate : Topiramate Indicated for epilepsy and headaches Off label: bipolar Paresthesiae, fatigue, dizziness, appetite loss, concentration problems, metabolic acidosis (rare due to increased renal HCO3 excretion) 3 RCTs found benefit vs placebo for weight loss or decreased BMI T plus clozapine: more psychomotor retardation, drooling, paresthesiae T plus olanzapine: 4.4 kg loss. T 100 mg or 200 mg plus SGAs: 200 mg group: 5.35 kg loss but notable worsening of schizophrenia Elinger et al, Ann Pharmacother 2010; 44:669-79 Topiramate and Metformin : Topiramate and Metformin Metformin: better safety profile, larger body of evidence for weight loss, peripherally acting Cochrane review: insufficient evidence Topiramate: 25% decrease in risperadone serum concentrations needs monitoring, FDA 2008 warning about increased suicidal ideation with antiepileptics Summary by Medication : Summary by Medication Lithium: hypothyroidism, hypercalcemia Valproate: hypothyroidism, PCOS, weight gain Quetiapine: hypothyroidism Carbamazepine: hyponatremia Psychostimulants: growth retardation Antipsychotics: hyperprolactinemia, metabolic syndrome Objectives : Objectives Review common psychiatric medications with endocrine and metabolic effects Identify patients who require surveillance and treatment Understand screening and treatment recommendations You do not have the permission to view this presentation. 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