ORIGINAL RESEARCH

Antipsychotic Drugs and Obesity: Is Prolactin Involved?
Trino Baptista, MD, PhD1, Anny Lacruz, MSc2, Teraiza Meza, MD3, Quilianio Contreras, PhD4, Carlos Delgado, MD5, Maria A Mejias, MD6, Luis Hernàndez MD7

Objectives: To correlate the anthropometric indexes (Body Mass Index [BMI] and Waist–Hip ratio [WHR]) with the serum prolactin levels in a heterogeneous population of patients treated with typical antipsychotic (AP) drugs.
Methods:  We evaluated BMI, WHR , and fasting serum prolactin of inpatients (n = 105) and outpatients (n =122) treated with APs, in outpatients receiving other psychotropic drugs (OPDs) (n = 77), and in drug-free subjects (n = 33). Outpatients had free access to food, whereas the inpatient sample comprised people with a monotonous diet of approximately 2000 Kcal daily.
Results:  Prolactin correlated positively with the BMI in the whole group of AP-treated outpatient men (P = 0.03) and with the WHR in AP-treated inpatient men (P = 0.053). Regarding treatment duration, prolactin and BMI correlated positively in men consecutively treated for more than 1 year (P = 0.023). By contrast, a trend toward a negative correlation between prolactin and BMI was observed in AP-treated outpatient women (P = 0.08). No significant correlation, or even a trend, was observed in the other groups.
Conclusions:  Prolactin may be involved in AP-induced weight gain, particularly in men. Future studies should characterize the period of maximal prolactin impact on body weight during AP treatment. Specific populations particularly sensitive to hyperprolactinemia might be identified as well. The negative correlation between prolactin and BMI detected in AP-treated women resembles the dampened prolactin response observed in severe primary obesity.

(Can J Psychiatry 2001;46:829–834)

Key Words:  typical antipsychotic drugs, gonadal steroids, insulin sensitivity, obesity, prolactin


Excessive body weight gain (BWG) associated with antipsychotic (AP) drug administration has been recognized since the introduction of chlorpromazine in psychiatry (1,2). There is an increasing interest in the subject, however, mainly because numerous studies have reported high rates of excessive BWG and carbohydrate metabolism abnormalities during treatment with atypical APs (3–5).

Research on the mechanisms by which APs promote BWG has focused on the direct interaction of these drugs with brain monoamines (such as dopamine, serotonin, and histamine) involved in feeding regulation. Most authors appear to agree that blockade of the serotonin (5-HT1A–5-HT2C) and histamine (H1) receptors in the brain is involved in AP-induced BWG (2,5).

Manuscript received March 2001, revised, and accepted September 2001.
1Full Professor, Department of Physiology, Los Andes University Medical School, Mérida, Venezuela.
2Associate Professor, Department of Physiology, Los Andes University Medical School, Mérida, Venezuela.
3Resident in Psychiatry, Department of Psychiatry, Los Andes University Medical School, Mérida, Venezuela.
4Associate Professor, Department of Physiology, Los Andes University Medical School, Mérida, Venezuela.
5Resident in Psychiatry, Department of Psychiatry, Los Andes University Medical School, Mérida, Venezuela.
6Full Professor, Department of Family Medicine, Los Andes University Medical School, Mérida, Venezuela.
7Full Professor, Department of Physiology, Los Andes University Medical School, Mérida, Venezuela.
Address for correspondence: Dr T Baptista, Douglas Hospital Research Centre, 6875 LaSalle Blvd, Verdun, QC H4H 1R3
e-mail: baptri@douglas.mcgill.ca

A vast literature on human and animal research outside the psychiatric field shows that prolactin plays an important role in body weight (BW) regulation and that hyperprolactinemia increases appetite and promotes fat deposition (6–11). Interestingly, 3 different research groups proposed several years ago that hyperprolactinemia might be involved in AP-induced obesity. Correa and others administered amantadine and decreased serum prolactin levels and BW in AP-treated patients (12). Parada and others proposed that prolactin mediated the obesity observed in AP-treated rats (13), and Baptista and others prevented BWG and hyperprolactinemia in AP-treated female rats by simultaneous administration of bromocriptine or tamoxifen (14–16). The relation between prolactin and weight regulation in AP-treated patients has, however received little attention in the recent literature on this subject (17,18). While prolactin levels have been monitored during some studies of AP-induced weight gain (19), to our knowledge no published clinical study has attempted to correlate BW and serum prolactin levels in AP-treated psychiatric patients.

This study evaluates the serum prolactin levels and correlates them with the anthropometric indexes (Body Mass Index [BMI] and Waist–Hip ratio [WHR]) of outpatients and inpatients chronically treated with APs, as well as with those of 2 control groups—outpatients receiving other psychotropic drugs (OPDs) and drug-free subjects receiving psychotherapy.

Methods

Patient Population

The outpatient group comprised all subjects attending the psychiatric

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