Whether or not you’ve ever taken an antidepressant, you’re probably familiar with the names; medications like Prozac, Paxil, Zoloft, Wellbutrin, Effexor, Cymbalta, etc., are widely prescribed and often helpful treatments for depression.
For some people, though, these antidepressants are either ineffective, or have bothersome side effects. For patients who prefer alternatives, it’s good to have a few extra tools in the tool belt. Here are some of the more commonly used and better-studied alternatives for traditional pharmaceutical antidepressants.
1. S-Adenosylmethionine, or SAMe
SAMe has been shown to be an effective treatment for depression when used as a sole agent, and also when used with an SSRI as an augmentation strategy (some citations if you’re interested: 1, 2, 3, 4).
SAMe is a methyl donor, meaning that it acts as a substrate for dozens of chemical reactions in the body, including the synthesis of neurotransmitters that are important in maintaining mental health. It tends to be stimulating, so can be especially helpful if you have the type of depression where you feel slowed down and tired. Most people start at a low dose and work their way up to 800mg twice a day. It has to be taken on an empty stomach to be properly absorbed.
Side effects are generally mild and include stomach upset, nausea, sweating, anxiety, and headache. Similar to pharmaceutical antidepressants, it should be avoided in patients with Bipolar Disorder who are not on a mood stabilizer, as it can induce mania.
The primary downside is the cost. No matter how much you bargain hunt, you will probably be paying $80+ for your monthly supply. However, for people unable to tolerate traditional pharmaceutical antidepressants because of side effects (including the unfortunately common sexual side effects), SAMe can be a good alternative.
Inositol, a sugar alcohol that is vital in the 2nd messenger system for numerous neurotransmitter reactions, has evidence supporting its use for depression, OCD (obsessive-compulsive disorder), and panic disorder (citations: 1, 2, 3).
Inositol started being tested as a treatment for depression after it was noted in studies that people with depression tended to have lower concentrations of inositol in their cerebrospinal fluid. It can be used on its own, or in conjunction with traditional antidepressants and mood stabilizers (it is not known to have any drug-drug interactions).
Doses typically range from 2-6 grams twice a day or three times a day, aiming for a total daily dose of 12 grams a day. Similar to antidepressants, it can take up to 4-6 weeks for the benefits to kick in.
Side effects tend to be mild and include nausea, gas, sleepiness, dizziness, and headaches. Care should be taken in Bipolar Disorder given the potential for inositol to trigger mania. It should not be used in pregnancy as it can potentially stimulate uterine contractions.
3. 5-Hydroxytryptophan, or 5-HTP
5-HTP, which is extracted from the Griffonia simplicifolia plant, is a precursor in the synthesis of serotonin, and is thought to treat depression through increasing production of serotonin in the brain.
While 5-HTP is not as well-studied as some of the other supplements on this list, I’m including it because many patients report finding it helpful, and many integrative psychiatrists recommend it. The most recent study I came across was a double-blinded, controlled study done in India which found similar efficacy of 5-HTP and fluoxetine (Prozac). Here is the Cochrane review of 5-HTP for depression, which found the evidence positive but inconclusive.
5-HTP can be sedating, making it helpful for people who have an anxious type of depression, or who have trouble sleeping. Dosing is typically 200-400mg daily divided twice a day.
4. St John’s Wort
So you’ve probably already heard of St John’s Wort, but I wanted to include it on the list anyway to go over some of the pros and cons of this commonly used herbal antidepressant.
Over-the-counter St John’s Wort is cultivated from the Hypericum Perforatum plant. It is unclear exactly what the active part of the plant is, and different sources mention both hyperforin and hypericin as active ingredients. It is thought to work by altering brain neurotransmitter levels through inhibiting reuptake of seratonin, dopamine, norepinephrine, glutamate and GABA. A common starting dose is 300mg 3 times a day (of standardized 0.3% hypericin or 2-5% hyperforin extract) and a maintenance dose of 300-600mg daily.
There is a large literature indicating that St John’s Wort is as effective as traditional pharmaceutical antidepressants for mild and moderate depression (this Cochrane review summarizes it). It is unclear if it is as effective for severe depression. Common side effects include headache, nausea, and rash.
Despite its well-documented effectiveness, though, there is a significant downside to St John’s Wort. It interacts with a key enzyme system of the liver, which can significantly alter the blood levels of other medications, including digoxin, warfarin, antiretrovirals, and oral contraceptive pills. It also can be dangerous to use with pharmaceutical antidepressants. For that reason, St John’s Wort may not be appropriate for some people.
If you’re considering using any of these supplements, make sure to talk to your doctor about if they’re appropriate for you, especially if you’re taking other medications. Don’t take this article as medical advice and start dosing yourself up.
If you have any personal experience either recommending or using these supplements, I’d love to hear about it in the comments!
Photo by Audrey