Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Click here to sign up for SAGE Journal Email Alerts today!
Journal of Parenteral and Enteral Nutrition
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Jensen, G. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jensen, G. L.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Medline Plus Health Information
*Antidepressants
Hazardous Substances DB
*LITHIUM COMPOUNDS
*LITHIUM, ELEMENTAL
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

2007 Clinical Nutrition Week Research Workshop Papers

Drug-Induced Hyperphagia: What Can We Learn From Psychiatric Medications?

Gordon L. Jensen, MD, PhD

From the Vanderbilt Center for Human Nutrition, Nashville, Tennesee.

Address correspondence to: Gordon L Jensen, Vanderbilt Center for Human Nutrition, 514 Medical Arts Building, Nashville, TN 37232.

This brief review examines hyperphagia and associated weight gain as undesirable side effects of psychiatric medications; exploring the scope of the problem, proposed mechanisms, and potential interventions. Mechanisms of action appear to include drug-mediated effects on hypothalamic appetite pathways that have been implicated in other etiologies of obesity. There is great individual variation in response to these medications as well as variation in the degree of weight gain within drug classes. Gene polymorphisms may be a key factor in determining individual variations in response. Better understanding of the underlying mechanisms can guide useful interventions. Medication selection and dosing appear to be important strategies to minimize adverse weight gain.

Key Words: psychiatric • medications • hyperphagia • appetite • weight gain • obesity

Clinically significant weight gain is associated with a host of commonly prescribed medications, the majority of which are used in the treatment of psychiatric disorders, neurological disorders, and diabetes. Because research advances in hypothalamic food intake hormones and in pharmacogenetics have promoted rapid advances in our understanding of hyperphagia and weight gain with psychiatric medications, they will be the focus of this brief review, including antipsychotics, antidepressants, and mood stabilizers.


   Antipsychotics
Top
Antipsychotics
Antidepressants
 Mood Stabilizers
 Approaches to Limit Undesirable...
 What Can We Learn...
 
There is a marked disposition toward weight gain with both older neuroleptics as well as some of the newer atypical agents (clozapine, olanzapine, risperidone).1-3 The degree of weight gain varies by drug and individual response. Clozapine and olanzapine are associated with hyperphagia and are among those with the greatest weight gain/adiposity. With clozapine the average weight gain often exceeds 10% of body weight or 1.7 kg/mo or 2.4–31.3 kg total over the course of treatment.3-6 With olanzapine the average weight gain often exceeds 7% of body weight or 2.3 kg/mo or 4.2–7.4 kg total over the course of treatment.3,7-9 Risperidone is typically associated with more moderate weight gain of 1.0 kg/mo or 0.03–2.6 kg total over the course of treatment,3,10-12 but may be associated with more substantial weight gain in children and adolescents.13 Ziprasidone is distinctive with a weight neutral or weight loss effect in the 0–3.6-kg range.3,14,15

It is noteworthy that significant weight gain related to antipsychotic use is often associated with medical comorbidities such as diabetes mellitus, dyslipidemia, and metabolic syndrome.16 The effects of clozapine and olanzapine on glucose and lipid metabolism appear more potent than other antipsychotics.17 Indeed Eli Lilly (Indianapolis, IN) recently agreed to pay up to $500 million to settle 18,000 lawsuits from people who claimed that they developed diabetes or other diseases after taking olanzapine.18

The mechanisms of weight gain (Table 1) likely involve interactions with receptors for which antipsychotic drugs have a high affinity, including dopamine D2, serotonin 5-HT2c, and histamine H1 receptors.1-3,19 The antipsychotics causing the greatest weight gain, clozapine and olanzapine, are also those with particularly high affinity for the 5-HT2c receptor. Knockout 5-HT2c receptor mice have obesity and increased feeding.20 Clozapine may also mediate direct effects on neuropeptide Y (NPY) neurons and was observed to increase NPY-immunoreactive cell density in the rat arcuate nucleus.21 These hypothalamic neurons mediate the effects of the circulating anorexigenic hormone leptin on the regulation of food intake. Altered leptin levels have been described in patients receiving clozapine.1,2,22,23 Elevated serum ghrelin levels have also been associated with elevated body mass index in patients treated with atypical antipsychotics.24


View this table:
[in this window]
[in a new window]

  		Table 1. Proposed Mechanisms of Weight Gain

 

Gene polymorphisms may be a key factor in determining individual variation in response to antipsychotic drugs. Several 5-HT2c receptor promoter polymorphisms have been associated with weight gain and diabetes.19,25 Similarly, genetic variants in the leptin gene promoter region are associated with obesity and leptin function.26 Leptin and 5-HT2c promoter polymorphisms along with age and body mass index account for almost 30% of variation in short-term drug-related weight gain.19 A recent study looking for candidate genes associated with weight gain among patients receiving risperidone identified five polymorphisms that significantly influenced body weight, along with baseline body weight, age, gender, schizophrenia subtype, and treatment duration and efficacy.27


   Antidepressants
Top
Antipsychotics
 Antidepressants
Mood Stabilizers
 Approaches to Limit Undesirable...
 What Can We Learn...
 
With tricyclic antidepressants, weight gain correlates with dosage and duration of use. Average weight gain over the course of treatment with imipramine is approximately 3–4 kg, and with amitriptyline average weight gain is approximately 2 kg.3 Weight gain can be significant with 13.3% of patients on imipramine exhibiting a weight gain exceeding 10% of body weight over 5 months of treatment.28 In distinction, nortriptyline was not associated with weight gain in depressed older adults.29 Among the monoamine oxidase inhibitors, moderate weight gain is common, with phenazine being the most prominent in causing weight gain.3 Among the atypical antidepressants, effects on weight gain are drug specific, with mirtazapine associated with particularly marked weight gain.30,31 Other atypicals include trazodone, which is associated with a 0.5–1.1-kg average weight gain over the course of treatment32; nefazodone, which is not associated with weight gain33; and bupropion, which is associated with 3.0–4.4-kg average weight loss.34 The latter is subject to ongoing investigation as a potential weight loss medication.35-37 The selective serotonin reuptake inhibitors (SSRIs) exhibit differences in affinities for 5-HT2c, histamine H1, and dopamine receptors and inhibition of nitric oxide synthase.2 Effects of SSRIs on appetite are dependent upon dose and duration of therapy. They are generally hyperphagic at higher doses. Fluoxetine, sertraline, and paroxetine result in an initial weight loss followed by weight gain over long-term use.2,38 For example, in one trial fluoxetine resulted in an initial 0.35-kg initial weight loss followed by 2-kg gain over 1 year.39


   Mood Stabilizers
Top
Antipsychotics
 Antidepressants
 Mood Stabilizers
Approaches to Limit Undesirable...
 What Can We Learn...
 
The mood stabilizers include anticonvulsant drugs and lithium, which are used in the treatment of bipolar and schizoaffective disorders. Average weight gains with valproate and carbamazepine have been variable, in the 0–15-kg range3,40-43; whereas for topiramate, weight loss of 16.0%–20.5% of pretreatment body weight has been observed.3,44,45 Weight gain with valproate has been related to potent carbohydrate craving and possible leptin resistance.46 Topiramate has been subject to testing as a weight loss medication but has had a limiting side effect profile with paresthesias and central nervous system effects.47 Weight gain with lithium is observed in up to 65% of patients; 20% of patients gain 10 kg or more with long-term therapy.2,3,48,49


   Approaches to Limit Undesirable Weight Gain With Psychiatric Medications
Top
Antipsychotics
 Antidepressants
 Mood Stabilizers
 Approaches to Limit Undesirable...
What Can We Learn...
 
As might be anticipated, weight gain correlates with patient noncompliance with psychiatric drug regimen, so interventions to obviate weight gain are clearly a priority.50 Medication selection is very important because there can be considerable variation even within drug class. It is also desirable to use the lowest possible dose. Close monitoring and follow-up is indicated when therapy with psychiatric medications is initiated. Early weight gain is a risk factor for further weight gain.51 Patients should be counseled regarding realistic expectations and plans. Reversibility of weight gain and possible roles for diet, exercise, and behavior modification should be discussed. Use of adjunctive weight loss agents such as sibutramine, orlistat, or topiramate has not been subject to adequate testing to be broadly recommended.52-55 A systematic review of 16 studies testing approaches to limit weight gain associated with antipsychotics found that 5 of 8 pharmacologic intervention studies reported small (<5%) reductions in body weight, whereas those with behavioral interventions also reported small reductions in body weight or weight maintenance.56


   What Can We Learn From Psychiatric Medications?
Top
Antipsychotics
 Antidepressants
 Mood Stabilizers
 Approaches to Limit Undesirable...
 What Can We Learn...
 
Hyperphagia and weight gain associated with psychiatric medications are common and challenging concerns. Drug-mediated effects on hypothalamic appetite pathways are similar to those implicated in other etiologies of obesity. Gene polymorphisms may be a key factor in determining individual variations in response. Better understanding of the underlying mechanisms can guide useful interventions in modulating food intake for therapeutic applications in both appetite stimulation and suppression.


  
Top
Antipsychotics
 Antidepressants
 Mood Stabilizers
 Approaches to Limit Undesirable...
 What Can We Learn...
 
Financial disclosure: none declared.

The 2007 Research Workshop: Regulation of Food Intake was supported by grant number U13DK064190 from the National Institute of Diabetes and Digestive and Kidney Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institute of Diabetes and Digestive and Kidney Diseases or the National Institutes of Health.

Received for publication April 4, 2008. Accepted for publication April 7, 2008.

  1. Goudie AJ, Cooper GD, Halford JCG. Antipsychotic-induced weight gain. Diabetes Obes Metab.2005; 7:478 -487.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  2. Malone M. Medications associated with weight gain. Ann Pharmacother. 2005;39:2046 -2055.[Abstract/Free Full Text]
  3. Schwartz TL, Nihalani N, Jindal S, Virk S, Jones N. Psychiatric medication-induced obesity: a review. Obes Rev.2004; 5:115 -121.[CrossRef][Medline] [Order article via Infotrieve]
  4. Hong CJ, Lin CH, Yu YW, Yang KH, Tsai SJ. Genetic variants of the serotonin system and weight change during clozapine treatment.Pharmacogenetics . 2001;11:265 -268.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  5. Masi G, Mucci M, Millepiedi S. Clozapine in adolescent inpatients with acute mania. J Child Adolesc Psychopharmacol.2002; 12:93 -99.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  6. Allison D, Mentore J, Heo M, et al. Antipsychotic induced weight gain: a comprehensive research synthesis. Am J Psychiatry.1999; 156:1686 -1696.[Abstract/Free Full Text]
  7. Ratzoni G, Gothelf D, Brand-Gothelf A, et al. Weight gain associated with olanzapine and risperdone in adolescent patients: comparative prospective study. J Am Acad Child Adolesc Psychiatry.2002; 41:337 -343.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  8. Gothelf D, Falk B, Singer P, et al. Weight gain associated with increased food intake and low habitual activity levels in male adolescent schizophrenic inpatients treated with olanzapine. Am J Psychiatry. 2002;159:1055 -1057.[Abstract/Free Full Text]
  9. Robinson DG, Woerner MG, Napolitano B, et al. Randomized comparison of olanzapine versus risperidone for the treatment of first episode schizophrenia: 4-month outcomes. Am J Psychiatry.2006; 163:2096 -2102.[Abstract/Free Full Text]
  10. Ganguli R, Brar JS, Ayrton Z. Weight gain over 4 months in schizophrenia patients: a comparison of olanzapine and risperidone.Schizophr Res . 2001;49:261 -267.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  11. Barak Y. No weight gain among elderly schizophrenia patients after 1 year of risperidone treatment. J Clin Psychiatry.2002; 63:117 -119.[Web of Science][Medline] [Order article via Infotrieve]
  12. Russell JM, Mackell JA. Body weight gain associated with atypical antipsychotics: epidemiology and therapeutic implications. CNS Drugs. 2001;15:537 -551.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  13. Martin A, Landau J, Leebens P, et al. Risperidone-associated weight gain in children and adolescents: a retrospective chart review. J Child Adolesc Psychopharmacol. 2000;10:259 -268.[Web of Science][Medline] [Order article via Infotrieve]
  14. Cohen S, Fitzgerald B, Okos A, et al. Weight, lipids, glucose, and behavioral measures with ziprasidone treatment in a population with mental retardation. J Clin Psychiatry.2003; 64:60 -62.[Web of Science][Medline] [Order article via Infotrieve]
  15. Keck P, Versiani M, Potkin S, West SA, Giller E, Ice K, Ziprasidone in Mania Study Group. Ziprasidone in the treatment of acute bipolar mania: a 3 week placebo controlled, double blind randomized trial. Am J Psychiatry. 2003;160:741 -748.[Abstract/Free Full Text]
  16. Yumru M, Savas HA, Kurt E, et al. Atypical antipsychotics related metabolic syndrome in bipolar patients. J Affect Disord.2007; 98:247 -252.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  17. Wu RR, Zhao JP, Liu ZN, et al. Effects of typical and atypical antipsychotics on glucose-insulin homeostasis and lipid metabolism in first-episode schizophrenia. Psychopharmacology.2006; 186:572 -578.[CrossRef][Medline] [Order article via Infotrieve]
  18. Berenson A. Lilly settles with 18,000 over Zyprexa. New York Times. January 5,2007 .
  19. Reynolds GP, Hill MJ, Kirk SL. The 5-HT2c receptor and antipsychotic-induced weight gain—mechanisms and genetics. J Psychopharmacol. 2006;20:15 -18.[Abstract/Free Full Text]
  20. Tecott LH, Sun LM, Akana SF, et al. Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature.1995; 374:542 -546.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  21. Kirk S, Cahir M, Reynolds GP. Clozapine, but not haloperidol increases neuropeptide Y neuronal expression in the rat hypothalamus. J Psychopharmacol. 2006;20:577 -579.[Abstract/Free Full Text]
  22. Monteleone P, Fabrazzo M, Tortorella A, La Pia S, Maj M. Pronounced early increase in circulating leptin predicts lower weight gain during clozapine treatment. J Clin Psychopharmacol.2002; 22:424 -426.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  23. Atmaca M, Kuloglu M, Tezcan E, et al. Weight gain, serum leptin and triglyceride levels in patients with schizophrenia on antipsychotic treatment with quetiapine, olanzapine and haloperidol. Schizophr Res.2003; 60:99 -100.[Web of Science][Medline] [Order article via Infotrieve]
  24. Palik E, Birkas KD, Faludi G, Karadi I, Cseh K. Correlation of serum ghrelin levels with body mass index and carbohydrate metabolism in patients treated with atypical antipsychotics. Diabetes Res Clin Pract.2005; 68(suppl):S60 -S64.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  25. Yuan X, Yamada K, Ishiyama-Shigemoto S, Koyama W, Nonaka K. Identification of polymorphic loci in the promoter region of the serotonin 5-HT2c receptor gene and their association with obesity and type II diabetes.Diabetologia . 2000;43:373 -376.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  26. Mammes O, Betoulle D, Aubert R, Herberth B, Siest G, Fumeron F. Association of the G-2548A polymorphism in the 5' region of the LEP gene with overweight. Ann Hum Genet.2000; 64:391 -394.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  27. Lane HY, Liu YC, Huang CL, et al. Risperidone-related weight gain: genetic and nongenetic predictors. J Clin Psychopharmacol.2006; 26:128 -134.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  28. Frank E, Kupfer DJ, Bulik CM, Levenson JA. Imipramine and weight gain during the treatment of recurrent depression. J Affect Disord. 1990;20:165 -172.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  29. Paradis CF, Stack JA, George CJ, et al. Nortriptyline and weight change in depressed patients over 60. J Clin Psychopharmacol.1992; 12:246 -250.[Web of Science][Medline] [Order article via Infotrieve]
  30. Benkert O, Szegedi A, Kohnen R. Mirtazapine compared with paroxetine in major depression. J Clin Psychiatry.2000; 61:656 -663.[Web of Science][Medline] [Order article via Infotrieve]
  31. Leinonen E, Skarstein J, Behnke K, Agren H, Helsdingen JT. Efficacy and tolerability of mirtazapine versus citalopram: a double blind, randomized study in patients with major depressive disorder. Nordic Antidepressant Study Group. Int Clin Psychopharmacol.1999; 14:329 -337.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  32. Weisler RH, Johnston JA, Lineberry CG, Samara B, Branconnier RJ, Billow AA. Comparison of bupropion and trazodone for the treatment of major depression. J Clin Psychopharmacol.1994; 14:170 -179.[Web of Science][Medline] [Order article via Infotrieve]
  33. Davis R, Whittington R, Bryson HM. Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression.Drugs . 1997;53:608 -636.[Web of Science][Medline] [Order article via Infotrieve]
  34. Chouinard G. Bupropion and amitriptyline in the treatment of depressed patients. J Clin Psychiatry.1983; 44:121 -129.[Web of Science][Medline] [Order article via Infotrieve]
  35. Jain AK, Kaplan RA, Gadde KM, et al. Bupropion SR versus placebo for weight loss in obese patients with depressive patients. Obes Res. 2002;10:1049 -1056.[Web of Science][Medline] [Order article via Infotrieve]
  36. Anderson JW, Greenway FL, Fujioka K, Gadde KM, McKenney J, O'Neil PM. Bupropion SR enhances weight loss: a 48 week double blind placebo controlled trial. Obes Res.2002; 10:633 -641.[Web of Science][Medline] [Order article via Infotrieve]
  37. Gadde KM, Xiong GL. Bupropion for weight reduction. Expert Rev Neurother. 2007;7:17 -24.[CrossRef][Medline] [Order article via Infotrieve]
  38. Harvey BH, Bouwer CD. Neuropharmacology of paradoxic weight gain with selective serotonin reuptake inhibitors. Clin Neuropharmacol. 2000;23:90 -97.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  39. Michelson D, Amsterdam J, Quitkin FM, et al. Changes in weight during a 1 year trial of fluoxetine. Am J Psychiatry.1999; 156:1170 -1176.[Abstract/Free Full Text]
  40. Tohen M, Baker RW, Altshuler LL, et al. Olanzapine versus dival-proex in the treatment of acute mania. Am J Psychiatry.2002; 159:1011 -1017.[Abstract/Free Full Text]
  41. Chengappa KN, Chalasani L, Brar JS, Parepally H, Houck P, Leuine J. Changes in body weight and body mass index among psychiatric patients receiving lithium, valproate, or topiramate: an open-label, non-randomized chart review. Clin Ther.2002; 24: 1 576-1584.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  42. Lampl Y, Eshel Y, Rapaport A, Sarova-Pinhas I. Weight gain, increased appetite, and excessive food intake induced by carbamazapine.Clin Neuropharmacol .1991; 14:251 -255.[Web of Science][Medline] [Order article via Infotrieve]
  43. Luef G, Abraham I, Haslinger M, et al. Polycystic ovaries, obesity and insulin resistence in women with epilepsy. A comparative study of carbamazepine and valproic acid in 105 women. J Neurol.2002; 249:835 -841.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  44. Carpenter LL, Leon Z, Yasmin S, Price LH. Do obese depressed patients respond to topiramate? A retrospective chart review. J Affect Disord. 2002;69:251 -255.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  45. Brown RO, Orr CD, Hanna DL, Williams JE, Dickerson RN. Topiramate and weight loss in patients with neurodevelopmental disabilities.Pharmacotherapy . 2002;22:831 -835.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  46. El-Khatib F, Rauchenzauner M, Lechleitner M, et al. Valproate, weight gain and carbohydrate craving: a gender difference.Seizure . 2007;16:226 -232.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  47. Eliasson B, Gudbjornsdottir S, Cederholm J, Liang Y, Vercruysse F, Smith U. Weight loss and metabolic effects of topiramate in overweight and obese type 2 diabetic patients: randomized double blind placebo-controlled trial. Int J Obes (Lond).2007; 31:1140 -1147.[CrossRef][Medline] [Order article via Infotrieve]
  48. Baptista T, Tenaud L, Contreras Q, et al. Lithium and body weight gain. Pharmacopsychiatry.1995; 28:35 -44.[Web of Science][Medline] [Order article via Infotrieve]
  49. Freeman MP, Freeman SA. Lithium: clinical considerations in internal medicine. Am J Med.2006; 119:478 -481.[CrossRef][Medline] [Order article via Infotrieve]
  50. Weiden PJ, Mackell JA, McDonnell DD. Obesity as a risk factor for antipsychotic noncompliance. Schizophr Res.2004; 66:51 -57.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  51. Himmerich H, Schuld A, Haack M, Kaufmann C, Pollmacher T. Early prediction of changes in weight during six weeks of treatment with antidepressants. J Psychiatr Res.2004; 38:485 -489.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  52. Werneke U, Taylor D, Sanders TAB. Options for pharmacological management of obesity in patients treated with atypical antipsychotics.Int Clin Psychopharmacol .2002; 17:145 -160.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  53. Schwartz TL, Nihalani N, Virk S, Jindal S, Chilton M. Psychiatric medication-induced obesity: treatment options. Obes Rev.2004 :5:233 -238.[CrossRef][Medline] [Order article via Infotrieve]
  54. Kirov G, Treget J. Add-on topiramate reduces weight in overweight patients with affective disorders: a clinical case series. BMC Psychiatry. 2005;5:19 .[CrossRef][Medline] [Order article via Infotrieve]
  55. Nickel MK, Nickel C, Muehlbacher M, et al. Influence of topiramate on olanzapine-related adiposity in women: a random, double blind, placebo-controlled study. J Clin Psychopharmacol.2005; 25:211 -217.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  56. Faulkner G, Soundy AA, Lloyd K. Schizophrenia and weight management: a systematic review of interventions to control weight.Acta Psychiatr Scand .2003; 108:324 -332.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

Journal of Parenteral and Enteral Nutrition, Vol. 32, No. 5, 578-581 (2008)
DOI: 10.1177/0148607108321708
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?



This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Jensen, G. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jensen, G. L.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Medline Plus Health Information
*Antidepressants
Hazardous Substances DB
*LITHIUM COMPOUNDS
*LITHIUM, ELEMENTAL
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?