The role of SAMe in the treatment of depression

VICUS.COM (25 May 2000) -- Sharon is a 48-year-old woman being treated with digoxin for congestive heart failure (CHF). In the past two months, she has complained of "a heavy heart." A thorough evaluation had revealed no evidence for a cardiac cause, with no EKG or laboratory irregularities consistent with myocardial infarction or digoxin toxicity. She was referred by her doctor for psychological evaluation.

During our first meeting, Sharon complained of "heaviness" in her chest, an inability to eat and sleep (early morning awakenings), and difficulty in concentrating and making decisions. She also suffered from "heartache" and feelings that her "usefulness" in life was coming to an end.

The psychiatric history revealed that this was the third acute incident of clinical depression in her lifetime. Her last episode occurred more than five years ago, although it is uncertain that her depression was ever fully resolved. I was concerned over a suicidal ideation -- with a plan -- that had recently developed. Suicidal ideation had not been a clinical feature in prior depressive episodes.

Assessment and management

In addition to CHF, Sharon was suffering from a moderate, recurrent major depressive episode secondary to her daughter's impending wedding. What should have been a joyous event was marred by feelings of loss and the end of motherhood for this "stay-at-home" mom. I started behavioral intervention designed to help Sharon identify and deal with the underlying thoughts that were triggering her depression. 

Due to an underlying dependent personality disorder that evidenced itself over the next few sessions, Sharon was slow to master the cognitive techniques I was trying to teach her. As a result, she continued to suffer from depression if I wasn't available to coach her. In addition, her suicidal plan was becoming better defined -- a dangerous development.

Options for drug therapy

Chemical intervention was considered to control her symptoms, however several factors limited the available options (see table below). Sharon had taken several selective serotonin reuptake inhibitor (SSRI) medications in the past and experienced nausea, diarrhea and a rash. In addition, her health insurance did not cover the cost of drug therapy, and she stated that she could not afford the cost of these prescription drugs.

Table. Treatment options for management of depression in Sharon.

Source: Gaster B. Alternative Medicine Alert, 1999.

Clinical experience with SAMe

One striking differentiator of SAMe is its cost. SAMe is three times as expensive as the most expensive prescription drug, Prozac (fluoxetine), and greater than five times the cost of desipramine, the tricyclic antidepressant. For the price Sharon would pay for one month of SAMe, she could buy 16 months worth of St. John's wort. However, in Sharon's case, the risk of an interaction with digoxin, combined with the added cost of blood tests to monitor her digoxin therapy under her cardiologist's care, outweighed perceived benefit.

Cost is not the only reason to be cautious about SAMe. Criticism of SAMe clinical trials has come from the alternative medicine and the conservative mainstream medical press.

Barak Gaster, M.D., writing in the Alternative Medicine Alert, acknowledged that numerous clinical trials have shown parenteral dosing of SAMe to be as effective as tricyclic antidepressants. Unfortunately, this dosage form is not available in the United States, and oral SAMe has a very low bioavailability (estimated to be less than 1%), so its usefulness as an oral agent is open to question. 

Bioavailability is distinct from the strength or potency of a drug or substance and reflects the physiological availability of the given amount of drug or active substance to the body's tissues. 

Additionally, The Medical Letter has criticized the results of clinical trials of orally administered SAMe from a methodological perspective. It notes that antidepressant drugs should be tested for at least six to eight weeks, partly because it sometimes takes four weeks for the drugs to be effective and perhaps even longer to demonstrate a sustained effect. In seven trials of orally administered SAMe, treatment lasted only three to four weeks. 

In addition to its poor oral bioavailability, the chemical stability of oral SAMe has been a problem, and none of the many formulations marketed in the United States are approved or have had their manufacturing regulated by the Food and Drug Administration. This problem, combined with a disturbing history in which assays of some oral formulations of SAMe contained no active drug, makes its selection for the treatment of depression problematic. 

Some preparations are claimed to be more stable than other forms, although product consistency, even from pill to pill, is not assured in the dietary supplement 
market as in the pharmaceutical industry. Two products, Pharmavite and enteric-coated tablets from GNC, are manufactured by Knoll Pharmaceuticals, which makes the Italian prescription drug. 

Dosing and monitoring

For those willing to pay the price, the results reported in clinical trials of SAMe are based on 800 mg taken by mouth twice daily. The main adverse effect has been mania, manifested as pressured speech and the display of grandiose ideas. Discontinuation of SAMe generally reversed this reaction. SAMe should not be used in patients with a history of mania or bipolar disorder. 

Irene Matiatos, Ph.D., is a licensed psychologist in New Jersey and New York, where she practices as a cognitive behaviorist in addiction and recovery phenomena. She hosts and moderates a program targeting anger and the verbally abusive.