Summary
Some bodyweight gain is common with many of the psychotropic drugs frequently used to treat psychiatric disorders. Although in most instances the gain is not clinically significant, that induced by some drugs, such as lithium and atypical antipsychotics, can be quite large and clinically significant. Individual patients may not wish to continue with medications that increase bodyweight, even by amounts that have no significant effect on health. The true prevalence of bodyweight gain is often difficult to discern because of confounding factors within studies that have assessed this effect, such as the simultaneous use of multiple drugs and the absence of data on starting bodyweight. Risk factors for weight increase have not yet been well characterised, although in general the potential for drug-induced bodyweight gain is greatest in individuals with a past and/or family history of obesity. Little is currently known about the mechanisms of bodyweight gain that is induced by any drug.
Similar content being viewed by others
References
Pi-Sunyer FX. Medical hazards of obesity. Ann Intern Med 1993; 119: 655–60
Gitlin MJ, Cochran SD, Jamieson KR. Maintenance lithium treatment: side effects and compliance. J Clin Psychiatry 1989; 50: 127–31
Garrow JS. Energy balance in man: an overview. Am J Clin Nutr 1987; 45: 1114–9
Kerry FJ, Liebling LI, Owen G. Weight changes in lithium responders. Acta Psychiatr Scand 1970; 46: 238–43
Chen Y, Silverstone T. Lithium and weight gain. Int Clin Psychopharmacol 1990; 5: 217–25
Vestergaard P, Poulstrup I, Schou M. Prospective studies on a lithium cohort. 3. Tremor, weight gain, psychological complaints. Acta Psychiatr Scand 1988; 78: 434–41
Vendsborg PB, Bech P, Rafaelson OJ. Lithium treatment and weight gain. Acta Psychiatr Scand 1976; 53: 139–47
Vestergaard P, Schou M. Prospective studies on a lithium cohort. 1. General features. Acta Psychiatr Scand 1988; 78: 421–6
Peselow ED, Dunner DL, Fieve RR, et al. Lithium carbonate and weight gain. J Affect Disord 1980; 2: 303–10
Vendsborg PB, Bach-Mortensen N, Rafaelson OJ. Fat cell number and weight gain in lithium-treated patients. Acta Psychiatr Scand 1976; 53: 355–9
Gelenberg AJ, Kane JM, Keller MB, et al. Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder. N Engl J Med 1989; 321: 1489–93
Mathew B, Murti Rao J, Sundari U. Lithium-induced changes in body mass index. Acta Psychiatr Scand 1989; 80: 538–40
Chen Y, Goodall E, Silverstone T. The effects of lithium on body weight and food intake in normal subjects: a pilot study. Int Clin Psychopharmacol 1992; 7: 51–4
Kazes M, Danion JM, Krieger-Finance F, et al. Eating behavior and long-term lithium treatment. Lithium 1993; 4: 125–33
Van der Velde CD, Gordon MW. Manic-depressive illness, diabetes mellitus and lithium carbonate. Arch Gen Psychiatry 1969; 21: 478–85
Vendsborg PB, Rafaelson OJ. Lithium in man: effects on glucose tolerance and serum electrolytes. Acta Psychiatr Scand 1973; 49: 601–10
Gordon MW, Van der Velde CD. Metabolic adaptation in the manic-depressive. Nature 1974; 247: 160-2
Vendsborg PB, Prytz S. Glucose tolerance and serum lipids in man after long-term lithium administration. Acta Psychiatr Scand 1976; 53: 64–9
Shopsin B, Stern S, Gershon S. Altered carbohydrate metabolism during treatment with lithium. Arch Gen Psychiatry 1972; 26: 566–71
Heninger GR, Mueller PS. Carbohydrate metabolism in mania. Arch Gen Psychiatry 1970; 23: 310–8
Mellerup ET, Plenge PK, Rafaelson OJ. Lithium and insulin effects on carbohydrate and electrolyte metabolism. Dan Med Bull 1974; 21: 88–91
Battacharya G. Influence of lithium on glucose metabolism in rats and rabbits. Biochem Biophys Acta 1964; 93: 644–6
Clausen T. The relationship between the transport of glucose and cations across cell membranes in isolated tissues. IV. The ‘insulin-like’ effect of lithium. Biochem Biophys Acta 1968; 150: 66–72
Krulic R, Janko L, Cerny M. Metabolism of lipids in lithium-administered rats. Acta Univ Carol Med 1971; 17: 533–40
Birnbaum L, Pohl SL, Rodbell M. Adenyl cyclase in fat cells. J Biol Chem 1969; 244: 3468–76
Berens SC, Wolff J. The endocrine effects of lithium. In: Johnson FN, editor. Lithium research and therapy. New York: Academic Press, 1975: 445–64
Lydiard RB, Gelenberg AJ. Hazards and adverse effects of lithium. Ann Rev Med 1982; 33: 327–44
Davis R, Peters DH, McTavish D. Valproic acid: a reappraisal of its pharmacological properties and clinical efficacy in epilepsy. Drugs 1994; 47: 332–72
Egger J, Brett EM. Effects of sodium valproate in 100 children with special reference to weight. BMJ 1981; 283: 577–81
Dinesen H, Gram L, Andersen T, et al. Weight gain during treatment with valproate. Acta Neurol Scand 1984; 69: 65–9
Sharpe C, Buchanan N. Juvenile myoclonic epilepsy: diagnosis, management and outcome. Med J Aust 1995; 162: 133–4
Mattson RH, Cramer JA, Collins JE. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. N Engl J Med 1992; 327: 765–71
Coxhead N, Silverstone T, Cookson J. Carbamazepine versus lithium in the prophylaxis of bipolar affective disorder. Acta Psychiatr Scand 1992; 85: 114–8
Tartara A, Manni R, Galimberti CA, et al. Six-year follow-up study on the efficacy and safety of vigabatrin in patients with epilepsy. Acta Neurol Scand 1992; 86: 247–51
Loeb C, Gandolfo C, Del Sette M, et al. Single-blind, placebo-controlled multicenter trial of vigabatrin in the treatment of epilepsy: the Italian study group on vigabatrin. Ital J Neurol Sci 1992; 13: 741–7
Breum L, Astrup A, Gram L, et al. Metabolic changes during treatment with valproate in humans: implication for untoward weight gain. Metabolism 1992; 41: 666–70
Gidal B A, Anderson GD, Spencer NW, et al. Valproic acid (VPA)-associated weight gain in monotherapy patients with epilepsy. Epilepsia 1994; 35Suppl. 8: 142–8
Hetherington M, Rolls BJ. Methods of investigating human eating behavior. In: Rowland NE, Toates FM, editors. Techniques in the behavioral and neural sciences: feeding and drinking. Vol. I. New York: Elsevier, 1987: 87–99
Verity CM, Hosking G, Easter DJ. A multicentre comparative of sodium valproate and carbamazepine in paediatric epilepsy: the paediatric EPITEG collaborative group. Devel Med Child Neurol 1995; 37: 97–108
Rudorfer MV, Manji HK, Potter WZ. Comparative tolerability profiles of the newer versus older antidepressants. Drug Saf 1994; 10: 18–46
Paykel ES, Mueller PS, de la Vergne PM. Amitriptyline, weight gain and carbohydrate craving: a side effect. Br J Psychiatry 1973; 3: 501–7
Sedman G. Trial of sustained release form of amitriptyline (Lentizol) in the treatment of depressive illness. Br J Psychiatry 1973; 23: 69–71
Kupfer DJ, Coble PA, Rubenstein DR. Changes in weight during treatment for depression. Psychosom Med 1979; 41: 535–44
Berken GH, Weinstein DO, Stern WC. Weight gain: a side effect of tricyclic antidepressants. J Affect Disord 1984; 7: 133–8
Fernstrom MH, Krowinski RL, Kupfer DJ. Chronic imipramine treatment and weight gain. Psychiatry Res 1986; 17: 269–73
Haskell DS, Gambill JD, Gardos G, et al. Doxepin or diazepam for anxious and anxious-depressed outpatients? J Clin Psychiatry; 39: 135–9
Fernstrom MH. Drugs that cause weight gain. Obes Res 1995; 3(4 Suppl.): 435S–9S
Frank E, Kupfer DJ, Bulik CM, et al. Imipramine and weight gain during the treatment of recurrent depression. J Affect Disord 1990; 20: 165–72
Frank E, Kupfer DJ, Perel JM, et al. Three-year outcomes for maintenance therapies in recurrent depression. Arch Gen Psychiatry 1990; 47: 1093–9
Frank E, Kupfer DJ, Buhari A, et al. Imipramine and weight gain during the long-term treatment of recurrent depression. J Affect Disord 1992; 26: 65–72
Caffey EM, Rosenblum MP, Klett CJ. Side effects and laboratory findings in a study of antidepressant drugs. Dis Nerv Syst 1962; 23: 444–9
Kato ST, Murashita J, Yamada N, et al. Changes in the frequency distribution pattern of bodyweight in patients with major depression. Acta Psychiatr Scand 1993; 88: 3356–60
Fernstrom MH, Kupfer DJ. Antidepressant-induced weight gain: a comparison study of four medications. Psychiatry Res 1988; 26; 265–71
Wurtman JJ. Depression and weight gain: the serotonin connection. J Affect Disord 1993; 29: 183–92
Leibowitz SF, Arcomano A, Hammer J. Potentiating of eating associated with tricyclic antidepressant drug activation of alpha-adrenergic neurons in the paraventricular hypothalamus. Prog Neuropsych Biol Psychiatry 1979; 2: 349–58
Leibowitz SF, Arcomano A, Hammer J. Tranylcypromine stimulation of eating through alpha-adrenergic neuronal system in the paraventricular nucleus. Life Sci 1978; 23: 749–58
Leibowitz SF, Brown O, Tretter JB, et al. Norepinephrine, clonidine and tricyclic antidepressants selectively stimulate carbohydrate ingestion through noradrenergic system of the paraventricular nucleus. Pharmacol Biochem Behav 1984; 23: 541–50
Leonard BE. Pharmacologic differences of serotonin uptake inhibitors and possible clinical relevance. Drugs 1992; 43Suppl. 2: 3S–10S
Kasper S, Fuger J, Moller HJ. Comparative efficacy of anti-depressants. Drugs 1992; 43 Suppl. 2: 11S–23S
Beasley Jr CM, Sayler ME, Potvin JH. Fluoxetine versus amitriptyline in the treatment of major depression: a multicenter trial. Int J Clin Psychopharmacol 1993; 8: 143–9
Wurtman RJ, Wurtman JJ. Brain serotonin, carbohydrate-craving, obesity and depression. Obes Res 1995; 3(4 Suppl.): 477S–80S
Potter WZ, Rudorfer MV, Manji HK. The pharmacologic treatment of depression: an update. N Engl J Med 1991; 523: 633–42
Baldessarini RJ. Treatment of depression by altering monoamine metabolism: precursors and metabolic inhibitors. Psychopharmacol Bull 1984; 20: 224–32
Lesch K–P, Bengel D, Heils A, et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996; 274: 1527–31
Caffey EM, Rosenblum MP, Klett CJ. Side effects and laboratory findings in a study of antidepressant drugs. Dis Nerv Syst 1962; 23: 444–9
Gander DR. Treatment of depressive illness with combined antidepressants. Lancet 1965; I: 107–9
Winston F. Combined antidepressant therapy. Br J Psychiatry 1971; 118: 301–4
Evans D, Davidson H, Raft D. Early and late side effects of phenelzine. J Clin Psychopharmacol 1982; 2: 208–10
Baumhackl U, Biziere K, Fischbach R, et al. Efficacy and tolerability of moclobemide compared with imipramine in depressive disorder (DSM-III): an Austrian, double-blind, multicenter study. Br J Psychiatry 1989; 155(6 Suppl.): 78S–83S
Bakish D, Bradwejn J, Nair N, et al. A comparison of moclobemide, amitriptyline and placebo in depression: a Canadian multicenter study. Psychopharmacology 1992; 106Suppl. 1: 98–101
Feighner JP, Hendrickson G, Miller I, et al. Double-blind comparison of doxepin versus bupropion in outpatients with a major depressive disorder. J Clin Psychopharmacol 1986; 6: 27–32
Weisler RJ, Johnston JA, Lineberry CG, et al. Comparison of bupropion and trazodone for the treatment of major depression. J Clin Psychpharmacol 1994; 14: 170–9
Stanton JM. Weight gain associated with neuroleptic medication: a review. Schizophr Bull 1995; 21: 463–72
Martinez JA, Velasco JJ, Urbistondo MD. Effects of pharmacological therapy on anthropometric and biochemical status of male and female institutionalized psychiatric patients. J Am Coll Nutr 1994; 13: 192–7
McCreadie RG, Todd N, Livingston M. A double-blind comparative study of remoxipride and thioridazine in the acute phase of schizophrenia. Acta Psychiatr Scand 1988; 78: 49–56
Teicher MH, Glod CA, Aaronson ST, et al. Open assessment of the safety and efficacy of thioridazine in the treatment of patients with borderline personality disorder. Psychopharmacol Bull 1989; 25: 535–49
Silverstone T, Smith G, Goodall E. Prevalence of obesity in patients receiving depot antipsychotics. Br JPsychiatry 1988; 153: 214–7
Shooka A, Al Haddad MK, Mathur V. Adverse effects of two long-acting depot antipsychotic drugs. Drug Invest 1993; 6: 110–3
Jokinen K, Koskinen T, Selonen R. Flupenthixol versus diazepam in the treatment of psychosomatic disorders: a double-blind, multi-centre trial in general practice. Pharmatherapeutica 1984; 3: 573–81
Johnson DAW, Breen B. Weight changes with depot neuroleptic maintenance therapy. Acta Psychiatr Scand 1979; 59: 525–8
Cookson JC, Kennedy NM, Gribbon D. Weight gain and prolactin levels in patients on long-term antipsychotic medication: a double-blind comparative trial of haloperidol decanoate and fluphenazine decanoate. Int Clin Psychopharmacol 1986; 3Suppl. 1: 41–51
Wistedt B, Persson T, Hellbom E. A clinical, double-blind comparison between haloperidol decanoate and fluphenazine decanoate. Curr Ther Res 1984; 35: 804–14
Lawson WB, Karson CN. Clinical correlates of bodyweight changes in schizophrenia. J Neuropsychiatry Clin Neurosci 1994; 6: 187–8
Dufresne RL, Valentino DA, Kass DJ. Thioridazine improves affective symptoms in schizophrenic patients. Psychopharmacol Bull 1993; 29: 249–55
Parent MM, Roy S, Sramek J, et al. Effect of molindone on weight change in hospitalized schizophrenic patients. Drug Intell Clin Pharm 1986; 20: 873–5
Doss FW. The effect of antipsychotic drugs on bodyweight: a retrospective review. J Clin Psychiatry 1979; 40: 528–30
Leppig M, Bosch B, Naber D, et al. Clozapine in the treatment of 121 outpatients. Psychopharmacology 1989; 99 Suppl. 1: S77–9
Lamberti JS, Bellnier T, Schwarzkopf SB. Weight gain among schizophrenic patients treated with clozapine. Am J Psychiatry 1992; 149: 689–90
Leadbetter R, Shutty M, Pavalonis D, et al. Clozapine-induced weight gain: prevalence and clinical relevance. Am J Psychiatry 1992; 149: 68–72
Umbricht DSG, Pollack S, Kane JM. Clozapine and weight gain. J Clin Psychiatry 1994; 55(9 Suppl. B): 157–60
Bustillo JR, Buchanan RW, Irish D, et al. Differential effects of clozapine on weight: a controlled study. Am J Psychiatry 1996; 153: 817–9
Weiden P, Aquila R, Standard J. Atypical antipsychotic drugs and long-term outcome in schizophrenia. J Clin Psychiatry 1996; 57(11 Suppl.): 53–60
Owens DGC. Extrapyramidal side effects and tolerability of risperidone: a review. J Clin Psychiatry 1994; 55(5 Suppl.): 29–35
Lombroso PJ, Scahill L, King RA, et al. Risperidone treatment of children and adolescents with chronic tic disorders: a preliminary report. J Am Acad Child Adolesc Psychiatry 1995; 34: 1147–52
Frisbie JH, Aguilera EJ. Diazepam and body weight in myelopathy patients. J Spinal Cord Med 1995; 18: 200–2
Bjertnaes A, Block JM, Hafstad PE, et al. A multicentre placebo-controlled trial comparing the efficacy of mianserin and chlordiazepoxide in general practice patients with primary anxiety. Acta Psychiatr Scand 1982; 66: 199–207
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ackerman, S., Nolan, L.J. Bodyweight Gain Induced by Psychotropic Drugs. Mol Diag Ther 9, 135–151 (1998). https://doi.org/10.2165/00023210-199809020-00005
Published:
Issue Date:
DOI: https://doi.org/10.2165/00023210-199809020-00005