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Medications and other Biological Treatments for Depression

The following treatment guidelines are meant as a reference tool only, and are not intended as treatment advice or to replace the clinical decision-making process of psychiatrists or other health professionals who administer these treatments. In clinical practice there are often good reasons why treatment approaches differ from what is described here.


There are various different biological treatments available today that are generally safe, well tolerated and effective in treating Depressive Disorders. The most common of these are antidepressant medications, which are among the most widely used of all medications, but there are various other kinds of treatments that are used or are in development, as described below.

To know more about when to consider using the different forms of treatments described below, see the guidelines for treating Depressive Disorders.

Antidepressant medications for Depression

Antidepressants, as the name would suggest, are the main category of medications used for treating Depressive Disorders. However, there has been some controversy in recent years over some of the specific uses of these medications.

Some studies have shown that these medications seem more effective for people suffering from moderate or severe episodes of Depression, while in cases of mild Depression using an antidepressant may not be much more effective than taking a placebo pill [ref]. Some studies have also claimed that antidepressants seem to be less effective for children and adolescents with Depression than for adults [ref].

However, one prominent study found that two very common antidepressants - Fluoxetine (Prozac) and Venlafaxine (Effexor) - are effective for all ranges of severity of depressive episodes [ref]. Furthermore, this study found that Fluoxetine (Prozac) is even more effective for treating depression in youth than in adults [ref].

While debate around these controversies continue, the fact remains that, overall, antidepressants are the first-line form of biological treatments for Major Depression.

Other medications for Depression

Other medications can be used in combination with antidepressants as a way to increase the efficacy of the treatment for Depression.  These include Lithium, Thyroid Hormone, the Atypical Antipsychotics, Buspirone, Lamotrigine, and Stimulants.

There is also evidence that Quetiapine XR (Seroquel XR), an Atypical Antipsychotic, is effective on its own for treating Depression [ref, ref].

Neurostimulation for Depression

Electroconvulsive therapy (ECT) for Depression

ECT works by stimulating the brain with an electrical current that causes a brief and controlled convulsion (seizure) while the person is under general anesthesia. A course of ECT for treating an episode of Depression usually involves a dozen or more of these sessions at a rate of two or three a week.

ECT remains the single most effective treatment that is known to exist for a Major Depressive Episode [ref], with success rates of 80-90% when used as a first-line treatment, and 50-60% when used by individuals who have not responded to trials of medications [ref]. It is considered a particularly good treatment choice in cases of Depression where individuals are having very strong suicidal impulses, psychosis, or where they have not responded to other forms of treatment [ref].

ECT tends not to be used as a first-line treatment for all cases because it requires the use of general anesthesia, and also because of the stigma and the negative perception in popular culture that has been attributed to it.  However, it is a very safe treatment, and overall its side-effect burden is no greater than with medications [ref].

Repetitive transcranial magnetic stimulation (rTMS) for Depression

rTMS is a technique of applying a strong magnetic field to specific areas of the brain, which stimulates these areas by producing electrical currents. This is a non-invasive procedure where anesthesia is not required and the individual can remain conscious. A course of rTMS for treating an episode of Depression usually involves daily sessions over a period of a few weeks.

rTMS is indicated mainly for individuals with Depression who have not responded adequately to a trial of at least one antidepressant. The available evidence to date suggests that this treatment can bring an improvement to a quarter of the people who undergo it, and can resolve the Depression completely in close to 20% of cases [ref]. These rates are not as robust as with ECT, but on the other hand, rTMS causes few if any side-effects and does not require general anesthesia, which are significant benefits over ECT. People who should not use rTMS are those who have metallic devices implanted in their bodies, who suffer from seizure disorders, or who have other serious medical conditions like increased intracranial pressure and severe heart disease [ref].

Because rTMS is a relatively new form of treatment that has only been approved for use in the USA in 2008, it is only available in highly specialized treatment centers.

Vagus nerve stimulation (VNS) for Depression

VNS is a technique where an electrode is implanted into an individual's body at the site of their left vagus nerve, which is a major nerve that communicates signals from the brain to the rest of the body. The electrode remains permanently implanted, and it delivers regular electrical pulses to the vagus nerve every few minutes.

This form of treatment remains somewhat experimental. Studies have found that in the short term, over the first several weeks of use, it does not provide very substantial benefits for Depression, but after several months or even a year or two anywhere from a quarter to a half of individuals will experience significant improvement in their symptoms [ref]. It is generally well-tolerated, but a significant proportion of patients will experience hoarseness, cough, shortness of breath, neck pain, headaches, and trouble swallowing.

Currently, this form of treatment is only offered in a few highly specialized treatment centers, and would be indicated mainly for individuals who have not responded to 4 or more trials of other standard treatments [ref].

Deep brain stimulation (DBS) for Depression

This experimental form of treatment involves implanting electrodes into frontal cortex areas of the brain, which are thought to mediate Depression. These electrodes remain permanently implanted and deliver a continuous electrical stimulation to these brain areas. Small studies have found that DBS can help over half of these individuals improve, and over a third recover fully, from Depressions that did not respond to other forms of treatment [ref]. DBS thus looks promising, but further studies are required before it can be more widely recommended.

Natural Treatments for Depression

Light therapy for Depression

Light therapy is a method of using a special type of bright light for about 30 minutes a day. It is a first-line treatment for Seasonal Affective Disorder and is as effective as antidepressants for this condition [ref, ref]. It is also useful for treating Major Depression when it is added to an antidepressant [ref].

Sleep deprivation for Depression

Sleep deprivation is a technique of keeping a person awake a full night (40 hours of wakefulness) or allowing sleep for only a few hours in the night. Usually, this is done in cycles of a period of sleep deprivation followed by sleep recovery, over the course of a few weeks. Depressed moods can brighten quickly with this technique, but the challenge is to have the moods remain improved once the sleep is restored. For this reason, this form of treatment is recommended mainly in conjunction with antidepressant use [ref]. It can be a difficult regimen to follow for many patients, which is a factor that limits its use.

Exercise and yoga for Depression

Following an exercise program, or doing yoga on a regular basis, can bring an added benefit to people who are already taking an antidepressant for an episode of Depression, but it is unlikely that these activities can, on their own, help most individuals recover from Depression [ref].

Natural supplements for Depression

St John's Wort (Hypericum) seems to be effective on its own for treating mild or moderate episodes of Depression, and in more severe cases it is also recommended as an add-on to antidepressant medications [ref].

Omega-3 fatty acids can be effective for treating Depression when added to antidepressants [ref] and also shows promise when used on its own for treating Depression in Children and Adolescents [ref].  

Creatine is a natural supplement that has been shown in one study to enhance the effects of antidepressant treatment for Major Depression in women [ref]. This study found that when creatine (at 3g per day for one week, and then at 5g per day) was added to Escitalopram (Lexapro, Cipralex), women's depression improved more quickly and to a greater extent as compared with the antidepressant alone [ref].

L-methylfolate is a natural supplement, similar to Folic Acid or Vitamin B9, but in a form that is easily absorbed into the brain. At 15 mg/day, it can help to increase the effectiveness of SSRI antidepressants [ref].

SAMe is a synthetic form of a dietary amino acid that has been shown in some studies to be effective on its own for treating mild or moderate episodes of Depression [ref]. It should be used with caution when combined with SSRIs or other novel antidepressants because of the risk of a serotonin syndrome.

Tryptophan is a dietary amino acid that the body uses to make serotonin, and it tends to be used by some doctors as a way to boost the effects of antidepressants. However, there is not enough research evidence available to know whether or not this is actually effective [ref].



Major Depressive Episode