The Relationship between Weight Gain and Medications for Depression and Seizures

by Gay Riley, MS, RD, CCN
NetNutritionist.com

Are Americans now fatter than any other nation on the planet? This topic has been discussed, debated, and researched for the past 35 years. Americans continue to gain weight despite the billions of dollars that they spend annually on diets and diet foods. It is common knowledge that sedentary lifestyles, excessive consumption, and obsessive dieting are major factors in this trend. 

What else could be contributing to the skyrocketing obesity epidemic in the United States? Could the medications that some Americans take be a contributing factor in the obesity problem?

In the past decade, there has been an increase in the development and use of prescription medication to treat depression, seizures, and sleep disorders. Recently, we have also seen a rise in television, newspaper, and magazine advertisements for prescription medications led by the marketing of antidepressants, such as Prozac.

In 1999 Prozac, Zoloft, and Paxil were among the top 15 prescription medications dispensed in the US. Of the 124 billion dollars generated by the US prescription sales market, these three antidepressants were listed in the top 10 revenue-producing medications. Selective Seretonin Reuptake Inhibitors (SSRIs), Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs), and antipsychotics were listed in the top 6 money makers of the 20 leading prescription products ranked by US pharmaceutical industry sales.

Current studies suggest that long-term use of SSRIs, Prozac, Zoloft, and Paxil is associated with weight gain. The purpose of this article is to list some of the popular psychotropic and seizure disorder medications on the market today and discuss the relationship, if any, these medications may have with body weight changes. A review of several studies regarding exercise and depression will also be reviewed.

The information presented in this article is not intended to discourage, endorse, or recommend either treatment for depression or any of the products reviewed. It is intended solely as a review of the available information regarding weight changes associated with the products listed. As always, consult your physician or medical professional regarding any questions or medical conditions.

Many people are not aware that weight gain is one of the most common side effects associated with many antidepressants prescribed today. In fact, medications such as Fluoxetine (Prozac®) and Buproprion HCL (Wellbutrin®) have actually been marketed for obesity treatment.

Antidepressants can affect weight in several ways:

• They may increase or decrease basal metabolic rate without changing caloric intake.
• They may affect hormonal changes and increase appetite.

Unexpected weight gain can increase the difficulties associated with psychiatric and seizure disorders by further aggravating mood instability and low self-esteem.

The following paragraphs contain brief descriptions of several classes of psychotropic and seizure disorder medications.

SSRIs comprise one of the major classes of antidepressants currently being prescribed by primary care physicians. At first, SSRIs were thought to be associated with weight loss and reduced appetite. For a while, they were even marketed as anti-obesity drugs. It is now known that long-term use of SSRIs is associated with weight gain.

The reason that SSRIs contribute to weight gain is not known. Although it was a widely held belief that drugs that increase serotonin output also decrease hunger, this does not seem to be the case. Patients using SSRIs often report symptoms of hypoglycemia (weakness, dizziness, frequent hunger, and headaches) when they do not eat. Symptoms of hypoglycemia may indicate hyperinsulinemia (elevation of insulin in the blood).

The five most common SSRIs currently prescribed in the United States today are as follows:

• Citalopram (Celexa®)
• Fluoxetine (Prozac®)
• Fluvoxamine (Luvox®)
• Paroxetine (Paxil®)
• Sertraline (Zoloft®)

Paroxetine (Paxil®) appears to have the most significant impact on weight gain of all of the SSRIs. Studies show that patients using Paxil experience an increase in breast size as well as weight gain and increased serum prolactin. One case report linked cravings for carbohydrates with Citalopram (Celexa®) while other studies showed an average weight gain over time of 15-20 pounds with Sertraline (Zoloft), Fluoxetine (Prozac®), and Citalopram (Celexa®).

However, SSRIs cause less weight gain, fewer anticholinergic symptoms, and less toxic adverse effects than tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). These findings have led to the increase in SSRI prescriptions by psychiatrists and primary care providers. Primary care providers are not likely to be familiar with the difference between the various SSRIs relative to their possible weight gain side effects.

TCAs were the most commonly prescribed antidepressants before SSRIs became widely available. Tricyclic antidepressants are often used to treat sleep disorders and to help patients manage pain. Most physicians are aware that TCAs can contribute significantly to weight gain.

Weight gain and other side effects vary from one TCA to another as well as from one patient to another. Many drugs in this class induce slowing of the metabolism and carbohydrate cravings. Factors more clearly understood involve histamine and alpha 1 receptor blocking actions. Appetite stimulation and weight gain make it extremely difficult for the diabetic using a TCA to control blood sugar.

TCAs include the following:

• Amitriptyline (Elavil®)
• Amoxapine (Asendin®)
• Clomipramine (Anafranil®)
• Desipramine (Norepramine®, Pertofrane®)
• Doxepin (Adapin®, Sinequan®)
• Imipramine (Janimine®, Tofranil®)
• Nortriptyline (Aventyl®, Pamelor®)
• Protriptyline (Vivactil®)
• Trimipramine (Rhotramine®, Surmontil®)

Weight gain with TCAs is dose dependent and relative to the length of therapy.

The greatest weight gain among TCA patients has been observed with those using either amitriptyline (Elavil®) or imipramine (Janimine®, Tofranil ®).

There are two categories of MAOIs: nonselective, irreversible MAOIs and reversible inhibitors of monoamine oxidase type A (RIMAs). The nonselective irreversible MAOIs cause weight gain similar to TCAs while the newer, selective MAOIs do not appear to have any effect on body weight.

There is not much information available on the current use of MAOIs in clinical practice because they have some dangerous side effects and are used less frequently than other antidepressants.

Nonselective, irreversible MAOIs include the following:

• Isocarboxazid (Marplan®)
• Phenelzine (Nardil®)
• Tranylcypromine (Parnate®)
• Selective reversible RIMAs include the following:
• Moclobemide (Manerix®)
• Toloxatone (Humoryl®)

Other antidepressants that do not fall strictly under the classifications of SSRIs, TCAs, or MAOIs include the following:

• Buproprion HCL (Wellbutrin®)
• Mitrazapine (Remeron®)
• Nefazadone (Serzone®)
• Trazadone (Desyrel®)
• Venlafaxine (Effexor®)

Venlafaxine (Effexor®) has been shown to cause weight gain but not as severe as has been reported with the SSRIs paroxetine (Paxil®), fuoxetine (Prozac®), and sertraline (Zoloft®).

Mitrazapine (Remeron®) has been associated with significant weight gain, possibly secondary to interactions with the histamine (H1) receptor. It is not associated with gastrointestinal symptoms, sexual dysfunction, or increased heart rate, as seen with the SSRIs.

Trazadone (Desyrel®) is an antidepressant with sedative properties that is frequently used as a sleep aid as well as treatment for depression. It appears to cause less weight gain than amitriptyline (Elavil®) but more than buproprion HCL (Wellbutrin®).

There is currently no information available relating Nefazadone (Serzone®) to increased appetite or weight gain.

Buproprion HCL (Wellbutrin®) has not been associated with weight gain and is commonly used with some success in smoking cessation.

These drugs were initially used only for seizure disorders. The following anticonvulsants are now prescribed frequently in the treatment of bipolar disorder and other selected forms of depression:

• Carbamazepine (Tegretol®)
• Divalproex (Depakote®)
• Gabapentin (Neurontin®)
• Lamotrigine (Lamictal®)
• Topiramate (Topamax®)

Anticonvulsants tend to cause hyperinsulinemia (elevated insulin in the blood) and increased appetite leading to weight gain. Hyperinsulinemia also results in increased testosterone, which causes a risk to women on these medications for development of Polycystic Ovary Syndrome (POS). Polycystic ovary syndrome can cause weight gain, male pattern baldness, increased facial hair, skin tags, acne, infertility, high blood pressure, abnormal lipid levels, and heart disease.

Seizure disorder studies showed that patients taking anticonvulsants who had either a normal or below normal body mass index had the most severe weight gain.

Mood stabilizers were commonly used before anticonvulsants were developed for the treatment of bipolar disorder. Mood stabilizers commonly prescribed consisted primarily of the following:

• Lithium (Cibalith-S®, Duralith®,
• Ekalith®, Eskalith CR®, Lithane®,
• Lithobid®, Lithonate®, Lithotabs®)

Typically, one-third to two-thirds of the patients treated with Lithium gain weight. Of those, 25 percent gain enough weight to be classified as obese. Weight gain is dose dependent, but low doses of lithium (less than .8 mm/L) are often not therapeutic: therefore, low-dose lithium is usually not an alternative.

One of the most common reasons for noncompliance and discontinued use of antipsychotic medication is weight gain. The agent believed to be responsible for the increased food intake of patients taking antipsychotics is the serotonin blocker.

Conventional anti-psychotics include the following:

• Haloperidol (Haldol®, Peridol®)
• Molindone (Moban®)
• Thioridazine (Apo-Thioridazine®, Mellaril®, Novo-Ridazine®, PMS-Thioridazine®)
• Newer antipsychotics, classified as atypical antipsychotics, include the following:
• Clozapine (Clozaril®)
• Olanzapine (Zyprexa®)
• Quetiapine (Seroquel®)
• Risperidone (Risperdal®)
• Sertindole (Serlect®)
• Ziprasidone (Seldox®)

Haloperidol (Haldol®, Peridol®) is a conventional antipsychotic with a lower incidence of weight gain than the newer agents clozapine (Clozaril®), olanzapine (Zyprexa®), and sertindole (Serlect®).

A retrospective study showed that clozapine (Clozaril®) and olanzapine (Zyprexa®) had the greatest associated weight gain, followed by intermediate weight gain with risperidone (Risperdal®).

Patients treated with sertindole (Serlect®) had less weight gain than those treated with haloperidol. Another study linked clozapine (Clozaril®) to significant weight gain and lipid abnormalities, suggesting increased risk for diabetes.

Among the conventional antipsychotics, thioridazine and chlorpromazine have greater potential for weight gain, while molindone (Moban®) is the only antipsychotic shown not to increase weight on a consistent basis.

Studies show that antipsychotic agents have an effect on the reproductive hormones. Women receiving antipsychotics tended to display hyperprlactinemia and tended to be hypoestrogenic. Women with primary obesity did not have hyperprolactinemia and tended to have normal or elevated estradiol serum levels. These differences have pathogenic and therapeutic implications besides the effects on gonadal and adrenal steroids. Prolactin alone promotes appetite and insulin resistance that may underlie the excessive body weight observed in hyperprolactinemic conditions detected in both animal and clinical studies.

Exercise has been shown to alleviate depression in some studies. Exercise does not cause weight gain and may compliment medication or serve as an alternative for depression management, in some cases.

Researchers at Duke University studied patients diagnosed with major depression. After 16 weeks, patients that exercised and did not take antidepressants showed statistically significant improvement relative to patients that took antidepressant medication and exercised.

A more recent study followed the same patients for an additional six months and found that the patients who continued to exercise after completing the initial trial were much less likely to see their depression return. Only 8 percent of patients in the exercise group relapsed into depression while 38 percent of the drug-only group and 31 percent of the exercise-plus-drug group relapsed.

James Blumenthal, lead researcher and Duke psychologist who published the results of his team's study in the October issue of the journal Psychosomatic Medicine, stated the following regarding the results of the follow-up study:

"The important conclusion is that the effectiveness of exercise seems to persist over time, and that patients who respond well to exercise and maintain their exercise have a much smaller risk of relapsing.

We found that there was an inverse relationship between exercise and the risk of relapsing the more one exercised, the less likely one would see their depressive symptoms return. For each 50-minute increment of exercise, there was an accompanying 50 percent reduction in relapse risk. Findings from these studies indicate that a modest exercise program is an effective and robust treatment for patients with major depression. And if these motivated patients continue with the exercise, they have a much better chance of not seeing their depression return."

Dr. Blumenthal cautioned that the study did not include patients who were acutely suicidal or had what is termed psychotic depression. Also, since patients were recruited by advertisements, these patients were motivated to get better and interested in exercise.

A recent study by Dr. Fernando Dimeo and his colleagues at the Department of Sports Medicine, Freie University of Berlin, Germany found that aerobic exercise improved the symptoms of major depression in 8 out of 12 patients within 10 days. They concluded that their program produced a substantial improvement in symptoms in a short time. Dr. Dimeo had this to say on the topic:

"Given the fact that antidepressive drugs have latency time of two to four weeks before any therapeutic effect, the observed outcomes indicate the clinical benefit not obtainable with currently available pharmacological treatments."

Dr. Dimeo and his colleagues suggest that depressed patients who do not show improvement despite an optimal dosage of antidepressants consider that aerobic training could offer a safe therapeutic option.

Partial Information regarding antidepressants and weight gain in this article was taken from an article recently published in SCAN'S PULSE, a publication for sports, cardiovascular, and wellness nutritionists, Winter 2001 entitled "Weight Gain Liabilities of Psychotropic and Seizure Disorder Medications", by Millicent Lasslo-Meeks, MS, RD.

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