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Changes in weight and body mass index with amitriptyline, fluoxetine and escitalopram therapy.

Walke, YSC, Pereira YS

Authors: Dr Yogeeta S.C. Walke, MD Pharmacology, Assistant Professor, Department of Pharmacology, Goa Medical College, Bambolim Goa India.

Dr (Mrs.) Yvonne Silva Pereira, MD Psychiatry

Director Professor, Institute of Psychiatry and Human Behaviour (IPHB)

ABSTRACT

Amitriptyline has been associated with weight gain as a very common side effect while fluoxetine is held to cause weight loss during acute treatment but weight gain over longer term treatment. The newer selective serotonin reuptake inhibitor (SSRI) escitalopram is believed to be efficacious and well tolerated. The study was conducted to find out the weight and BMI (body mass index) changes in patients on amitriptyline, fluoxetine and escitalopram therapy.

Patients with depressive symptoms were randomly allotted amitriptyline 50 mg/day, fluoxetine 20 mg/day or escitalopram 10 mg/day and the relationship between weight and BMI changes were assessed over a period of 24 weeks. There was a statistically significant mean weight gain of 3.63 kg in amitriptyline group while in fluoxetine and escitalopram group there was a statistically significant mean weight loss of 0.43 kg and 0.92 kg respectively. Amitriptyline group showed statistically significant >7% weight gain in 43.3% patients and BMI >25kg/m². Escitalopram group showed statistically significant BMI <25kg/m².Amitriptyline therapy is associated with statistically significant increase in weight and BMI. In fluoxetine group there was a small but statistically significant weight loss and no change in BMI whereas escitalopram group shows statistical significant weight loss and decrease in BMI.

Key words: Amitriptyline, fluoxetine, escitalopram, weight changes, BMI changes.

INTRODUCTION

Weight gain is a common undesirable effect of many tricyclic antidepressants (TCAs).Weight gain is also a major cause of antidepressant non compliance (Garland 1998). Amitriptyline is a TCA causes weight gain as a common side effect and is a primary cause of discontinuation of treatment (Berken 1984). Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) which is associated with modest weight loss during acute therapy but weight gain during long term therapy (David 1999). Escitalopram is a (SSRI) which is being widely used as it is efficacious and well tolerated. The FDA issued the approval of escitalopram for major depression in August 2002 and for generalized anxiety disorder in December 2003. Escitalopram may be a cost-saving alternative to citalopram for the treatment of severe depression (Wade 2005). Escitalopram may have a faster onset and greater overall magnitude of effect than citalopram in improving symptoms of depression and anxiety in patients with major depressive disorder (Moore 2005). Escitalopram has better efficacy in the treatment of severe depression than citalopram (Azorin 2004). There are insufficient prospective studies conducted to evaluate the effect of escitalopram on weight. The present study was undertaken to determine the effect of escitalopram on weight and BMI in comparison with amitriptyline and fluoxetine in Indian out patients.

METHODS

The sample (n=90) was selected from the out patient department of the Institute Of Psychiatry and Human Behaviour (IPHB) Goa using the criteria described below.

Inclusion Criteria

1. The age of the subjects (males and females) was in range of 18 – 70 years.

2. Diagnosed as depression, obsessive compulsive disorder or anxiety disorder.

3. Informed consent was taken from the patient and or a family member.

Exclusion Criteria

1. Pregnancy and lactation.

2. Patients with medical illnesses like uncontrolled hypertension, uncontrolled diabetes

mellitus, seizure disorder or ischaemic heart disease (IHD).

3. Patients with history of substance abuse or dependence.

4. Patients concomitantly on other antidepressants or anticonvulsants.

Study was approved by the local ethical committee. Patients who met the inclusion criteria were enrolled and randomly grouped into 36, 30 and 24 in amitriptyline, fluoxetine and escitalopram group respectively. At baseline along with a complete psychiatry history and physical examination their height and weight were recorded. They received amitriptyline 50 mg/day, fluoxetine 20 mg/day and escitalopram 10 mg/day. Weight was checked at monthly interval for a period of 6 months. 6 patients from amitriptyline group did not come for follow up and hence had to be dropped out.

For analysis parametric statistical methods such as ANOVA and t test were applied. A non parametric statistical test in form of chi square tests was also applied.

RESULTS

The average age in the amitriptyline, fluoxetine and escitalopram group were 39, 42 and 45 respectively. 83%, 57% and 71% patients were females in the amitriptyline, fluoxetine and escitalopram respectively. 89% patients were normal weight and 10% patients were obese at the start of the study. Amitriptyline group showed statistically significant weight gain of 3.63 kg whereas fluoxetine and escitalopram group showed statistically significant weight loss of 0.43 kg and 0.92 kg respectively. Amitriptyline group showed statistically significant >7% weight gain in 43.3% patients and BMI > 25 kg/m² whereas escitalopram group showed statistically significant BMI <25 kg/m².

DISCUSSION

Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) are most commonly prescribed antidepressants. Side effect profile of TCAs is more as compared to SSRIs. Our study shows weight gain in patients who were administered amitriptyline and weight loss in patients who were administered fluoxetine and escitalopram .The results are consistent with the weight gain reported with amitriptyline in several prior clinical trials. For example in 3-6 weeks study in 1973 & Harto-Truax et al study in 1983 noted weight gain of 2.9-5.1 pounds/month during therapy with amitriptyline (Sedman & Harto-Traux 1983). In a 9 month trial with 15 patients Paykel in 1973 found an increase of 1.7 lbs/month with mean amitriptyline doses of 120 mg/day (Paykel 1973) Berken 1984 found an increase of 2.9 lbs/month with mean doses 56 mg/day.

Weight gain is a very common side effect with amitriptyline less common with selective serotonin reuptake inhibitors like fluoxetine and escitalopram. Fluoxetine has been tried with some success as a part of management of obesity. Serotonin is believed to be involved in the regulation of satiety (Anonymous 1994). Fluoxetine has also been shown to increase resting energy expenditure and raise basal body temperature (Bross1995). A common dose for fluoxetine in the management of obesity has been 60 mg/day.

Fluoxetine has a dose related effect on weight loss (Levine1989). Reviews agree that fluoxetine can aid weight reduction in short term but after 16-20 weeks some patients have started to regain weight and its long term efficacy remains to be established (Anonymous 1994, Bray 1993 & Mayer 1998).

Escitalopram is a selective serotonin reuptake inhibitor (SSRI) and S enantiomer of Citalopram. The R enantiomer of Citalopram is associated with side effects, drug interactions and reduced drug efficacy (Stephen 2002). Vaya Lalit (2004) has concluded that Escitalopram, the S enantiomer of the citalopram is a safe and effective antidepressant in the Indian population. It has potentially superior efficacy than citalopram and a comparable efficacy to sertraline with fewer side effects than both citalopram and sertraline. In this study escitalopram was well tolerated by most of the patients. There was a significant weight loss in escitalopram treated patients over a period of 24 weeks.

Limitations of our study include how the random sampling was done, small sample size and the fact thatit was not a double blind study. Further studies are essential to throw light on the long term effects of escitalopram on weight.

REFERENCES:

Azorin JM, Llorca PM, Despiegel N, Verpillat P. Escitalopram is more effective than citalopram for the treatment of severe major depressive disorder. Encephale. 2004 Mar-Apr; 30(2):158-66.
Anonymous. Fluoxetine and other drugs for treatment of obesity. Med Lett Drugs Ther 1994;36:107-8.
Berken GH, Weinstein DO, Stern WC. Weights gain a side effect of tricyclic antidepressants. J Affect Disorder 1984; 7:133-138.
Bray GA. Use and abuse of appetite suppressant drugs in the treatment of obesity. Ann Intern Med 1993; 119:707-13.
Bross R, Hoffer LJ. Fluoxetine increases resting energy expenditure and basal body temperature in human. Am J Clin Nutr 1995; 61: 1020-5
David Michelson, Amsterdam JD, Quitkin FM et al. Changes in weight during one year trial of fluoxetine. Am J Psychiatry1999; 156:1170-1176.
Garland EJ, Remick RA, Zis AP. Weight gain with antidepressants and lithium. J Clin Psychopharmacol 1988; 8: 323-330.
Harto- Truax N. Stern W.C. Miller L.L. Sato T.L et al. Effects of bupropion on body weight. J Clin Psychiatry 1983; 44:183-186.
Levine LR, et al. Use of fluoxetine a selective serotonin- uptake inhibitor, in the treatment of obesity: a dose response study. Int J Obes 1989; 13:635-45
Moore N, Verdoux H, Fantino B. Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder. Int Clin Psychopharmacol. 2005 May; 20 (3):131-7. PubMed
Mayer LE, Walsh BT. The use of selective serotonin reuptake inhibitors in eating disorders. J Clin Psychiatry 1998; 59 (suppl.15): 28-34.
Paykel ES, Mueller PS, De La Vergne PM. Amitriptyline, weight gain and carbohydrate craving : a side effect. Br J Psychiatry. 1973; 123:501-507.
Sedman G. Trial of a sustained release form of amitriptyline in the treatment of depressive illness. Br J Psychiatry 1973; 123: 69-71.
Stephen M. Stahl. Mirror, mirror on the wall which enantiomer is fairest of them all? Primary care comparison. J Clin Psychiatry 2002; 4 (1).
15. Vaya L, Appaya P M., Hegde R P. Escitalopram versus Citalopram and Sertraline: a Double–Blind Controlled, Multi-centric Trial in Indian Patients with Unipolar Major Depression. Indian J of Psychiatry, 2004, 46(4) 333-341.
Wade AG, Toumi I, Hemels ME. A pharmacoeconomic evaluation of escitalopram versus citalopram in the treatment of severe depression in the United Kingdom. Clin Ther. 2005 Apr; 27(4):486-96. PubMed

Table1

Body weight changes during antidepressant treatment

Weight in Kg	Amitriptyline n=30 mean + SD	Fluoxetine n=30 mean + SD	Escitalopram n = 24 mean + SD
Basal Weight	53.3 ±8.89	56.6 ±11.95	56.46 ±7.7
Final Weight 24 weeks	56.93 ±8.94	56.17 ±11.93	55.54 ±7.79
Weight change per month	0.933 ±0.172	- 0.166 ±0.03	-0.37 ±0.06
Final Weight Change	+3.63 + 1.21	-0.43 + 0.57	-0.92 + 0.50

P<0.001 df= 2, 81 F = 165.521

Change in weight statistically significant in all 3 groups

Table 2

>7% change in weight

Groups

Amitriptyline

Fluoxetine

Escitalopram

Weight

Gain >7%

43.3

P<0.001 df =2 X² = 27

Statistically significant in amitriptyline group

p>0.05 not statistically significant in fluoxetine and escitalopram group

Table 3

BMI changes during antidepressant therapy

Groups	BMI <25 kg/m²		BMI >25 kg/m²
	Before (%)	After (%)	Before (%)	After (%)
Amitriptyline	80	50	20	50
Fluoxetine	93.3	93.3	6.7	6.7
Escitalopram	91.7	95.8	8.3	4.2

Normal Weight: BMI—18.5-24.9 kg/m²

Over Weight : BMI -- >= 25.0 kg/m²

BMI >25 kg/m² statistically significant in amitriptyline group

BMI <25 kg/m² statistically significant in escitalopram group

P<0.001 df = 2 X² = 22.67

BMI not statistically significant in fluoxetine group p>0.05

Acknowledgement

The authors acknowledge Dr J. S.C. Pereira for his help and cooperation and Mr. M. S.

Kulkarni, Lecturer in Demography for providing statistical information.

Ethical approval

Ethical approval granted by Institutional Ethical Committee, Goa Medical College India.

First Published August 2011

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