Saffron hasn't been widely studied. One study of a specific saffron extract (from the Novin Zaferan Company in Iran) showed that when taken orally, saffron seemed to improve symptoms of major depression. However, one study isn't enough to prove safety or effectiveness.
SAM-e (short for S-adenosylmethionine) is a molecule that naturally occurs within cells and is believed to influence chemicals involved in depression. In several small clinical studies, the dietary supplement SAM-e was shown to be a helpful treatment for major depression when given intravenously or intramuscularly to patients. SAM-e seems to reduce the symptoms of major depression when taken orally as well. Large scale studies are still needed to clarify the true effects of SAM-e in treating depression. SAM-e can have many side effects including nausea, diarrhea, anxiety, headache, and intense mood swings.
The plant St. John’s Wort (Hypericum perforatum) has been used for centuries to treat depression. It is sold in the U.S. as a dietary supplement. Research indicates that St. John’s Wort improves mood, and decreases the anxiety, physical symptoms, and insomnia related to mild to severe depression. St. John’s Wort, however, has never been shown to be more effective or significantly better-tolerated than conventional antidepressant medications. St. John’s Wort may cause drug interactions. Side effects include: skin rash with sun exposure, insomnia, vivid dreams, agitation, upset stomach, diarrhea, fatigue, dry mouth, dizziness and headache.
When it comes to treating depression, there is insufficient evidence or limited research to support the following supplements: