Pharmacopsychiatry 2000; 33(3): 81-88
DOI: 10.1055/s-2000-8451
Original Paper
Georg Thieme Verlag Stuttgart ·New York

Body Weight Gain after Administration of Antipsychotic Drugs: Correlation with Leptin, Insulin and Reproductive hormones

T. Baptista1 , A. Lacruz1 , S. de Mendoza2 , J. M. MendozaGuillén2 , R. Silvera3 , F. Angeles3 , M. T. Mendoza4 , L. Hernández1
  • 1Laboratory of Behavioral Physiology, School of Medicine, University of Los Anden, Mérida, Venezuela
  • 2Metabolism Center, Mérida, Venezuela
  • 3Department of Psychiatry, University of Los Andes, Mérida, Venezuela
  • 4San Marcos de León Clinic, Carabobo, Venezuela
Further Information

Publication History

Publication Date:
31 December 2000 (online)

Excessive body weight gain, hyperprolactinemia and low gonadal steroid serum levels are often observed during chronic administration of antipsychotic drugs (AP). Clinical and experimental findings suggest that leptin, the peptidic hormone involved in long-term body weight regulation, and reproductive hormones are interrelated. Therefore, we assessed circulating leptin levels in healthy, lean women (n = 12) and men (n = 7) before and after short-term administration of the AP sulpiride (SUL, 200 mg/day). In addition, we studied psychotic obese (n = 9) and lean women (n = 13) under chronic treatment with diverse AP. No significant weight changes were observed after SUL administration in healthy women - initial weight: 54.9 ± 2.6 Kg; final weight: 55.04 ± 2.6, NS. Leptin levels did not change either: 11.9 ± 1.5 ng/ml. vs. 10.6 ± 1.3, NS. By contrast, a small, but significant weight gain was found in SUL-treated men - 60.6 ± 1.9 Kg. vs. 61.3 ± 2.1, p = 0.004. Leptin and insulin levels were significantly higher after SUL administration - leptin: 2.77 ± 0.22 ng/ml. vs. 13.9 ± 2.5, p = 0.035; insulin: 3.59 ± 0.17, mIU/ml vs. 8.81 ± 0.81, p = 0.0001. In these subjects, leptin levels positively correlated with body weight change (p = 0.006), and serum prolactin change (p = 0.001). Obese psychotic women (Body Mass Index, BMI, Kg/m2 = 31.5 ± 1.03) displayed higher leptin levels than non-obese psychotic women (BMI = 25.5 ± 0.52): 26.8 ± 4.8, vs. 12.8 ± 3.4 ng/ml, p = 0.006. In these women, a significant positive correlation was found between leptin levels and BMI (p = 0.0001), and between leptin and basal insulin levels (p = 0.001). These results show that the expected circulating leptin elevation which is observed when body weight raises, is preserved in people treated with AP drugs.

References

  • 1 Baptista T, Parada M A, Hernández. Long-term administration of some antipsychotic drugs increases body weight and feeding in rats. Are D2 dopamine receptors involved?.  Pharmacol. Biochem. Behav.. 1987;  27 399-405
  • 2 Baptista T, Uzcátegui E. Substance abuse among resident doctors in Venezuela.  Drug & Alcoh. Depend.. 1993;  32 127-132
  • 3 Baptista T, López M A, Teneud L, Contreras Q, Alastre T, Quijada M, Araujo de Baptista A, Altemus M, Weiss S RB, Musseo E, Páez X, Hernández L. Amantadine in the treatment of neuroleptic-induced obesity in rats: behavioral, endocrine and neurochemical correlates.  Pharmacopsychiat.. 1997 a;  30 35-43
  • 4 Baptista T, Alastre T, Contreras Q, Martinez J L, Araujo de Baptista E, Páez X, Hernández L. Effects of the antipsychotic drug sulpiride on reproductive hormones in healthy men: relationship with body weight regulation.  Pharmacopsychiat.. 1997 b;  30 250-255
  • 5 Baptista T, Molina M G, Martinez J L, Quijada M, Calanche I, Acosta A, Páez X, Martinez J M, Hernández L. Effects of the antipsychotic drug sulpiride on reproductive hormones in healthy premenopausal women: relationship with body weight regulation.  Pharmacopsychiat.. 1997 c;  30 256-262
  • 6 Baptista T, Contreras Q, Alastre T, Martinez J L, de Baptista E, Burguera J L, de Burguera M, Hernández L. Effects of lithium carbonate on reproductive hormones in healthy men: relationship with body weight regulation. A pilot study.  Prog. Neuro-Psychopharmacol. & Biol. Psychiat.. 1997 d;  21 937-950
  • 7 Baptista T, LaCruz A, Hernández L. Glucose tolerante and serum insulin levels in an animal model of obesity induced by the antipsychotic drug sulpiride.  Pharmacol & Toxicol.. 1998;  83 57-61
  • 8 Baptista T, Reyes D, Hernández L. Antipsychotic drugs and reproductive hormones: relationship with body weight regulation.  Pharmacol. Biochem. Behav.. 1999;  62 409-417
  • 9 Baptista T. Body weight gain induced by antipsychotic drugs: mechanisms and management.  Acta. psychiatr. Scand.. 1999;  100 3-16
  • 10 Barash I A, Cheung C C, Weigle D S, Ren H, Kabigting E B, Kuijper J L, Clifton D K, Steiner R A. Leptin is a metabolic signal to the reproductive system.  Endocrinol.. 1996;  137 3144-3147
  • 11 Bech P, Kastrup M, Rafaelson O J. Mini-compedium of rating scales of anxiety, depression, mania and schizophrenia, with corresponding DSM-III syndromes.  Acta Psychiatr. Scand.. 1986;  326 (Suppl.) 7-36
  • 12 Beumont P J, Gelder M G, Friesen H G, Harris G W, Mackinnon P CV, Mandelbrote B M, Wiles D H. The effects of phenothiazines on endocrine function: I : Patients with inappropiate lactation and amenorrhoea.  Brit. J. Psychiat.. 1974;  124 413-419
  • 13 Beumont P JV, Corker C S, Friesen H G, Kakowska T, Mandelbrote B M, Marshall J, Murray M AF, Wiles D H. Effects of phenothiazines on endocrine function: II: effects in men and post-menopausal women.  Brit. J. Psychiat.. 1974;  124 420-430
  • 14 Bhavnani S M, Levin G M. Antipsychotic agents: a survey of the prevalence, severity and burden of side effects.  Int. Clin. Psychopharmacol.. 1996;  11 1-12
  • 15 Björntorp P. Endocrine abnormalities of obesity.  Metabolism.. 1995;  44 (suppl) 21-23
  • 16 Bromel T, Blum W F, Zeigler A, Schulz W, Bender M, Fleischhaker C, Remsschmidth H, Krieg J C, Heberbrand J. Serum leptin levels increase rapidily after initiation of clozapine therapy.  Mol. Psychiat.. 1998;  3 76-80
  • 17 Cabrera R, Mayor P, Fernández-Ruiz J, Calle C. Insulin binding and action an adipocytes from female rats with experimentally induced chronic hyperprolactinemia.  Mol. Cell Endocrinol.. 1988;  58 167-173
  • 18 Campfield L A, Smith F J, Burn P. The OB protein (Leptin) pathway - A link between adipose tissue mass and central neural networks.  Horm. Metab. Res.. 1996;  28 619-632
  • 19 Chehab F F, Mounzih K, Lu R, Lim M E. Early onset of reproductive function in normal female mice treated with leptin.  Science.. 1997;  275 88-90
  • 21 Crawford A MK, Beasley C HM, Tollefson G D. The acute and long-term effect of olanzapine compared with placebo and haloperidol an serum prolactin concentrations.  Schiz. Res.. 1997;  26 41-54
  • 22 Correa N, Opler L A, Kay S R, Birmaher B. Amantadine in the treatment of neuroendocrine side effects of neuroleptics.  J. Clin. Psychopharmacol.. 1987;  7 91-95
  • 23 Dagogo-Jack S, Fanelli C, Paramore D, Brothers J, Landt M. Plasma leptin and Insulin relationships in obese and nonobese humans.  Diabetes.. 1996;  45 695-698
  • 24 Demura R, Ono M, Demura H, Shizume K, Oouchi H. Prolactin directly inhibits basal as well as gonadotropin-stimulated secretion of progesterone and 17β-estradiol in the human ovary.  L. Clin. Endocrino. Metab.. 1982;  54 1246-1250
  • 25 Dorrington J, Gore-Langton R E. Prolactin inhibits oestrogen synthesis in the ovary.  Nature.. 1981;  290 600-602
  • 26 Evans B A, Agar L, Summers R J. The role of the sympathetic nervous system in the regulation of leptin synthesis in C57BL/6 mice.  FEBS Lee. 1999;  44 149-154
  • 27 Ferreira M F, Sobrinho L G, Santos M A, Sousa M F, Uvnas-Moberg K. Rapid weight gain, at least in some women, is an expression of a neuroendocrine state characterized by reduced hypothalamic dopaminergic tone.  Psychoneuroendocrinol.. 1998;  23 1005-1013
  • 28 Figlewicz D P, Schwartz M W, Seeley R J, Chave M, Baskin D G, Woods S C, Porte D. Endocrine regulation of food intake and body weight. J. Lab. Clin. Med. 1996: 328-332
  • 29 Foss M C, Paula F J, Paccola G M, Piccinato C E. Peripheral glucose metabolism in human hyperprolactinemia.  Clin. Endocrinol.. 1995;  43 721-726
  • 30 Friedman J M, Halaas J L. Leptin and the regulation of body weight in mammals.  Nature. 1998;  22 763-770
  • 31 Goodall E, Oxtoby C, Richards R, Watkinson G, Brown D, Silverstone T. A clinical trial on the efficacy and acceptability of D-fenfluramine in the treatment of neuroleptic-induced obesity.  Brit. J. Psychiat.. 1988;  153 208-213
  • 32 Greenman Y, Tordjman K, Stern N. Increased body weight associated with prolactin secreting pituitary adenomas: weight loss with normalization of prolactin levels.  Clin. Endocrinol.. 1998;  48 547-553
  • 33 Halbreich U, Palter S. Accelerated osteoporosis in psychiatric patients possible pathophysiological processes.  Schizophr. Bull.. 1996;  22 447-454
  • 34 Kissebah A H, Krakover G R. Regional adiposity and morbidity.  Physiol. Rev.. 1994;  74 761-798
  • 35 Kraus T, Haack M, Schuld A, Hinze-Selch D, Kuhn M, Uhr M, Pollmacher T. Body weight and leptin plasma levels during treatment with antipsychotic drugs.  Am. J. Psychiatry.. 1999;  156 312-314
  • 36 Lacruz A, Baptista T, de Mendoza S, Mendoza M, Hernández L. Antipsychotic drug induced obesity in rats : correlation between leptin, insulin and body weight during sulpiride treatment. Mol. Psychiat. 2000 5: 70-76
  • 37 Larrson H, Elmstahl S, Ahren B. Plasma leptin levels correlate to islet function independently of body fat in postmenopausal women.  Diabetes.. 1996;  45 1580-1584
  • 38 Mantzoros C S, Flier J S, Rogol A D. A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. Rising leptin levels may signal the onset of puberty.  J. Clin. Endocrinol. Metab.. 1997;  82 1066-1070
  • 39 Matsuda M, Mori T. Effect of estrogen on hyperprolactinemia-induced glucose intolerance in SHN mice.  Proc. Soc. Exp. Biol. Med.. 1996;  212 243-247
  • 40 Meltzer H Y, Goode D, Schyve P M, Young M, Fang V. Effect of clozapine on human serum prolactin levels.  Am J. Psychiat.. 1979;  136 1550-1555
  • 41 Mueller W M, Gregoire F C, Stanhope K L, Mobbs C V, Mizuno T M, Warden C H, Stern J S, Havel P. Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes.  Endocrinology.. 1998;  139 551-558
  • 42 Oades R D, Schepker R. Serum gonadal steroid hormones in young schizophrenic patients.  Psychoneuroendocrinol.. 1994;  19 373-385
  • 43 Reiss F M, Ribeiro-de-Oliveira P, Guerra R M, Reiss A M, Coimbra C C. Blood glucose and prolactin in hyperprolactinemic rats exposed to restraint and surgical stress.  Life Sci.. 1996;  58 155-161
  • 44 Remesa R X, Rafecas I, Fernández-López J A, Alemany M. Leptin.  Medic. Res. Rev.. 1997;  17 225-234
  • 45 Rinieris P, Markianos M, Hatzimanolis J, Stefanis C. A psychoendocrine study in male paranoid schizophrenic patients with delusional ideas of homosexual content.  Acta Psychiatr. Scand.. 1985;  3 309-314
  • 46 Stanton J M. Weight gain associated with neuroleptic meditacion: a review.  Schiz. Bull.. 1995;  21 463-472
  • 47 Wade G N, Gray J M. Gonadal effects an food intake and adiposity: a metabolic hypothesis.  Physiol. Behav.. 1979;  22 583-594
  • 48 Wade G N, Schneider J E. Metabolic fuels and reproduction in female mammals.  Neurosci. Biobehav. Rev.. 1992;  16 235-272
  • 49 Wagsstaff A J, Fitton A, Benfield P. Sulpiride. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in schizophrenia.  CNS Drugs.. 1994;  2 313-333
  • 50 Wang D Y, de Stanela B I, Bulbrook R D, Allen D S, Chaundry M, Hayward J I, Gravelle I H. The relationship between blood prolactin levels and risk of breast cancer in premenopausal women.  Eur. J. Cancer Clin. Oncol.. 1987;  23 1541-1548
  • 51 Wang J, Liu R, Hawkins M, Barzilai N, Rossetti L. A nutrient-sensing pathway regulates leptin gene expressin in muscle and fat.  Nature.. 1998;  393 684-688
  • 52 Woods S C, Seeley R J, Porte D, Schwartz M. Signals that regulate food intake and energy homeostasis.  Science.. 1998;  280 1378-1382

Trino Baptista

Apartado 93

Mérida, 5101-A

Venezuela

Email: conru@ing.ula.ve