<p class="frontmatter-fieldnotes disclaimernew" style="margin-bottom:15px;">This work may not be copied, distributed, displayed, published, reproduced, transmitted, modified, posted, sold, licensed, or used for commercial purposes. By downloading this file, you are agreeing to the publisher’s <a href="/pages/termsofuse.aspx" target="_blank">Terms & Conditions</a>.</p>
<div id="x14l01687">
<div class="story">
<p class="ltrs-br-ltr-br-title"><span class="bold">Outpatient Metformin Management of Obese Individuals With Schizophrenia</span></p>
<p class="ltrs-br-ltr-br-body-text"><span class="semibold">To the Editor:</span> Antipsychotic medications are indispensable for the treatment of schizophrenia, but side effects of weight gain and obesity,<span class="htm-cite"><a href="#ref1">1</a></span> often accompanied by type 2 diabetes, are significant contributors to diminished life expectancy for patients with the schizophrenia.<span class="htm-cite"><a href="#ref2">2</a></span> The type 2 diabetes drug metformin is effective for weight loss among schizophrenia patients receiving antipsychotics in controlled research studies.<span class="htm-cite"><a href="#ref2">2–4</a></span> Whether metformin can be similarly effective after discharge when treatment is provided by local mental health outpatient clinics remains undemonstrated.</p>
<p class="ltrs-br-ltr-br-body-text"> </p>
<p class="ltrs-br-ltr-br-body-text"><span class="semibold-ital">Method.</span> Recently admitted patients with <span class="italic">DSM-IV</span> chronic schizophrenia or schizoaffective disorder, with body mass index (BMI) ≥<span class="thinspace"> </span>30, serum creatinine ≤<span class="thinspace"> </span>1.5 μmol/L, and no history of type 2 diabetes (glycated hemoglobin [HbA<span class="subscript">1c</span>] ≤<span class="thinspace"> </span>6.4% and fasting blood sugar [FBS] ≤<span class="thinspace"> </span>110 mmol/L), participated in our program of metformin sustained release (1,500 mg/d), individualized exercise, and dietary counseling. All patients were receiving a multitude of psychotropic agents.<span class="htm-cite"><a href="#ref5">5</a></span> Metformin was prescribed therapeutically after a full and witnessed patient-clinician discussion (noted in the hospital chart) of the risks and benefits of the drug; Declaration of Helsinki guidelines were followed in the absence of an ethical review committee. Measures included weight, HbA<span class="subscript">1c</span>, FBS, and a metabolic panel with a lipid profile. Of 47 qualified patients, 35 with BMI ranging from 30.2 to 51.9 (mean<span class="thinspace"> </span>±<span class="thinspace"> </span>SD<span class="thinspace"> </span>=<span class="thinspace"> </span>38.9<span class="thinspace"> </span>±<span class="thinspace"> </span>5.5) and aged from 20 to 63 years (mean<span class="thinspace"> </span>±<span class="thinspace"> </span>SD<span class="thinspace"> </span>=<span class="thinspace"> </span>41.6<span class="thinspace"> </span>±<span class="thinspace"> </span>11.1) were still in hospital and evaluated at 8 weeks. The 16 patients still in hospital at 16 weeks were again evaluated. Metformin was well tolerated by all patients. At discharge, patients were assigned a state-certified peer wellness counselor to facilitate program compliance and were entered into an outpatient program for 3 months of follow-up. Outpatient physicians were asked to prescribe metformin.</p>
<p class="ltrs-br-ltr-br-body-text"><span class="semibold-ital">Results.</span> Nonparametric statistics were used. For the 35 patients who were still in hospital at 8 weeks, mean<span class="thinspace"> </span>±<span class="thinspace"> </span>SD baseline and 8-week weights were 108.6<span class="thinspace"> </span>±<span class="thinspace"> </span>17.1 and 105.4<span class="thinspace"> </span>±<span class="thinspace"> </span>15.7 kg, respectively, which represented a significant loss of 3.2 kg (<span class="italic">Z</span><span class="thinspace"> </span>=<span class="thinspace"> </span>−4.10, <span class="italic">P</span><span class="thinspace"> </span>=<span class="thinspace"> </span>.00, Wilcoxon matched-pairs signed rank test<span class="htm-cite"><a href="#ref6">6</a></span>). For the 16 patients still in hospital at 16 weeks, baseline, 8-week, and 16-week weights were 106.3<span class="thinspace"> </span>±<span class="thinspace"> </span>17.1, 103.6<span class="thinspace"> </span>±<span class="thinspace"> </span>17.7, and 103.5<span class="thinspace"> </span>±<span class="thinspace"> </span>19.7 kg, respectively. Friedman analysis of variance<span class="htm-cite"><a href="#ref6">6</a></span> for baseline, 8 weeks, and 16 weeks indicated an overall effect of metformin (χ<span class="superscript">2</span><span class="subscript">2</span><span class="thinspace"> </span>=<span class="thinspace"> </span>8.18, <span class="italic">P</span><span class="thinspace"> </span>=<span class="thinspace"> </span>.02), with a significant 2.7-kg loss from baseline to 8 weeks (<span class="italic">Z</span><span class="thinspace"> </span>=<span class="thinspace"> </span>−3.02, <span class="italic">P</span><span class="thinspace"> </span>=<span class="thinspace"> </span>.00, Wilcoxon test<span class="htm-cite"><a href="#ref6">6</a></span>) and a nonsignificant 2.8-kg loss from baseline to 16 weeks (<span class="italic">Z</span><span class="thinspace"> </span>=<span class="thinspace"> </span>−1.60, <span class="italic">P</span><span class="thinspace"> </span>=<span class="thinspace"> </span>.11, Wilcoxon test<span class="htm-cite"><a href="#ref6">6</a></span>). No other measure showed significant change. Of the 35 patients discharged into 3-month follow-up, 20 could no longer be located by 3 months; of the remaining 15, 10 were still taking metformin and 5 were not, with weights of 109.2<span class="thinspace"> </span>±<span class="thinspace"> </span>13.3 and 107.4<span class="thinspace"> </span>±<span class="thinspace"> </span>19.4, respectively. There was no significant difference in weight between these 2 groups at 3 months (<span class="italic">Z</span><span class="thinspace"> </span>=<span class="thinspace"> </span>−0.74, <span class="italic">P</span><span class="thinspace"> </span>=<span class="thinspace"> </span>.46, Mann-Whitney rank sum test<span class="htm-cite"><a href="#ref6">6</a></span>), or between baseline and 3-month postdischarge weights in either group.</p>
<p class="ltrs-br-ltr-br-body-text"> </p>
<p class="ltrs-br-ltr-br-body-text">Our findings corroborate inpatient weight reduction with metformin for obese patients receiving polypharmacy, but discharged patients did not sustain weight loss at 3 months after discharge, since baseline and 3-month weights did not differ. There was also no weight difference between patients who did and did not remain on metformin, although small sample size and high variability may have precluded observing any difference. Of utmost importance, however, is that our single peer wellness coach and limited resources were inadequate to ensure compliance or monitor patient activity. Also, physicians were reluctant to prescribe metformin for nondiabetic patients. If the long-term benefits of metformin for managing obesity and its long-term consequences in patients receiving psychoactive drugs in the community are to be realized, major commitments to community aftercare services and physician education will be required.</p>
<p class="ltrs-br-ltr-br-references-head"><span class="smallcaps">References</span></p>
<p class="references-references-text-1-9"><a name="ref1"></a>1. Allison DB, Mentore JL, Heo M, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. <span class="italic">Am J Psychiatry</span>. 1999;156(11):1686–1696.<span class="pubmed-crossref"><a href="
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10553730&dopt=Abstract"> PubMed</a></span></p>
<p class="references-references-text-1-9"><a name="ref2"></a>2. Correll CU, Sikich L, Reeves G, et al. Metformin for antipsychotic-related weight gain and metabolic abnormalities: when, for whom, and for how long? <span class="italic">Am J Psychiatry</span>. 2013;170(9):947–952. <span class="pubmed-crossref"><a href="
http://dx.doi.org/10.1176/appi.ajp.2013.13060771">doi:10.1176/appi.ajp.2013.13060771</a><a href="
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=24030606&dopt=Abstract"> PubMed</a></span></p>
<p class="references-references-text-1-9"><a name="ref3"></a>3. Jarskog LF, Hamer RM, Catellier DJ, et al; METS Investigators. Metformin for weight loss and metabolic control in overweight outpatients with schizophrenia and schizoaffective disorder. <span class="italic">Am J Psychiatry</span>. 2013;170(9):1032–1040. <span class="pubmed-crossref"><a href="
http://dx.doi.org/10.1176/appi.ajp.2013.12010127">doi:10.1176/appi.ajp.2013.12010127</a><a href="
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=23846733&dopt=Abstract"> PubMed</a></span></p>
<p class="references-references-text-1-9"><a name="ref4"></a>4. Chen CH, Huang MC, Kao CF, et al. Effects of adjunctive metformin on metabolic traits in nondiabetic clozapine-treated patients with schizophrenia and the effect of metformin discontinuation on body weight: a 24-week, randomized, double-blind, placebo-controlled study. <span class="italic">J Clin Psychiatry</span>. 2013;74(5):e424–e430. <span class="pubmed-crossref"><a href="
http://dx.doi.org/10.4088/JCP.12m08186">doi:10.4088/JCP.12m08186</a><a href="
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=23759461&dopt=Abstract"> PubMed</a></span></p>
<p class="references-references-text-1-9"><a name="ref5"></a>5. Winsberg B, Yeager C, Hobbs B, et al. Metformin provides weight reduction for hospitalized patients receiving polypharmacy. <span class="italic">J Clin Psychopharmacol</span>. 2010;30(3):345–346. <span class="pubmed-crossref"><a href="
http://dx.doi.org/10.1097/JCP.0b013e3181db36db">doi:10.1097/JCP.0b013e3181db36db</a><a href="
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=20473081&dopt=Abstract"> PubMed</a></span></p>
<p class="references-references-text-1-9"><a name="ref6"></a>6. SPSS Version 12.0.1 for Windows [computer program]. Chicago IL: SPSS, Inc; 2003.</p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Bertrand Winsberg, MD</span></p>
<p class="ltrs-br-ltr-br-author"><span class="hyperlink"><a href="
mailto:bgw436@aol.com">
bgw436@aol.com</a></span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Ronald Wei, MD</span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Natarajan Elangovan, MD</span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Janet Camp-Lifshitz, MPhil</span></p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="semibold-ital">Author affiliations: </span>Private Practice, Great Neck, New York, and Department of Psychiatry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick (Dr Winsberg); Essex County Hospital Center, Cedar Grove (Dr Wei), New Jersey; Private Practice, Staten Island (Dr Elangovan); and Psychiatric Research Consultant, Pomona (Ms Camp-Lifshitz), New York.</p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="semibold-ital">Potential conflicts of interest:</span> None reported.</p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="semibold-ital">Funding/support:</span> Supported in part by grant CDC1H75DP003079-01, Centers for Disease Control and Prevention, Atlanta, Georgia.</p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="semibold-ital">Published online:</span> November 6, 2014.</p>
<p class="ltrs-br-ltr-br-copyright-doi"><span class="italic">Prim Care Companion CNS Disord 2014;16(6):</span><span class="doi">doi:10.4088/PCC.14l01687</span></p>
<p class="ltrs-br-ltr-br-copyright-doi"><span class="italic">© Copyright 2014 Physicians Postgraduate Press, Inc.</span></p>
</div>
</div>