What treatments are available for depression?

Regardless of the medication that may be used to treat depression, practitioners have become more aware that different ethnic groups may have different responses and have different risks for side effects than others.

Antidepressant medications

Selective serotonin reuptake inhibitors (SSRIs) are medications that increase the amount of the neurochemical serotonin in the brain. (Remember that brain serotonin levels are often low in depression.) As their name implies, the SSRIs work by selectively inhibiting (blocking) serotonin reuptake in the brain. This block occurs at the synapse, the place where brain cells (neurons) are connected to each other. Serotonin is one of the chemicals in the brain that carries messages across these connections (synapses) from one neuron to another.

The SSRIs work by keeping serotonin present in high concentrations in the synapses. These drugs do this by preventing the reuptake of serotonin back into the sending nerve cell. The reuptake of serotonin is responsible for turning off the production of new serotonin. Therefore, the serotonin message keeps on coming through. It is thought that this, in turn, helps arouse (activate) cells that have been deactivated by depression, thereby relieving the depressed person's symptoms.

SSRIs have fewer side effects than the tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), which are discussed below. SSRIs do not interact with the chemical tyramine in foods, as do the MAOIs, and therefore do not require the dietary restrictions of the MAOIs. Also, SSRIs do not cause orthostatic hypotension (sudden drop in blood pressure when sitting up or standing) and heart-rhythm disturbances, like the TCAs do. Therefore, SSRIs are often the first-line treatment for depression. Examples of SSRIs include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), fluvoxamine (Luvox), and escitalopram (Lexapro).

SSRIs are generally well tolerated, and side effects are usually mild. The most common side effects are nausea, diarrhea, agitation, insomnia, and headache. However, these side effects generally go away within the first month of SSRI use. Some patients experience sexual side effects, such as decreased sexual desire (decreased libido), delayed orgasm, or an inability to have an orgasm. Some patients experience tremors with SSRIs. The so-called serotonergic (meaning caused by serotonin) syndrome is a serious neurologic condition associated with the use of SSRIs. It is characterized by high fevers, seizures, and heart-rhythm disturbances. This condition is very rare and has been reported only in very ill psychiatric patients taking multiple psychiatric medications.

All patients are unique biochemically. Therefore, the occurrence of side effects or the lack of a satisfactory result with one SSRI does not mean that another medication in this group will not be beneficial. However, if someone in the patient's family has had a positive response to a particular drug, that drug may be the preferable one to try first.

Dual-action antidepressants: The biochemical reality is that all classes of medications that treat depression (MAOIs, SSRIs, TCAs, and atypical antidepressants) have some effect on both norepinephrine and serotonin, as well as on other neurotransmitters. However, the various medications affect the different neurotransmitters in varying degrees.

Some of the newer antidepressant drugs, however, appear to have particularly robust effects on both the norepinephrine and serotonin systems. These medications seem to be very promising, especially for the more severe and chronic cases of depression. (Psychiatrists, rather than family practitioners, see such cases most frequently.) Venlafaxine (Effexor), duloxetine (Cymbalta) and desvenlafaxine (Pristiq) are three of these dual-action compounds. Effexor is a serotonin reuptake inhibitor that, at lower doses, shares many of the safety and low side-effect characteristics of the SSRIs. At higher doses, this drug appears to block the reuptake of norepinephrine. Thus, venlafaxine can be considered an SNRI, a serotonin and norepinephrine reuptake inhibitor. Cymbalta and Pristiq tend to act as equally powerful serotonin reuptake inhibitors and norepinephrine reuptake inhibitors regardless of the dose. They are, therefore, also considered SNRIs.

Mirtazapine (Remeron), another antidepressant, is a tetracyclic compound (four-ring chemical structure). It works at somewhat different biochemical sites and in different ways than the other drugs. It affects serotonin, but at a postsynaptic site (after the connection between nerve cells). It also increases histamine levels, which can cause drowsiness. For this reason, mirtazapine is given at bedtime and is often prescribed for people who have trouble falling asleep. Like the SNRIs, it also works by increasing levels in the norepinephrine system. Other than causing sedation, this medication has side effects that are similar to those of the SSRIs but to a lesser degree in many cases.

Atypical antidepressants are so named because they work in a variety of ways. Thus, atypical antidepressants are not TCAs, SSRIs, or SNRIs, but they are effective in treating depression for many people nonetheless. More specifically, they increase the level of certain neurochemicals in the brain synapses (where nerves communicate with each other). Examples of atypical antidepressants include nefazodone (Serzone), trazodone (Desyrel), and bupropion (Wellbutrin). The United States Food and Drug Administration (FDA) has also approved bupropion for use in weaning from addiction to cigarettes. This drug is also being studied for treating attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD). These problems affect many children and adults and restrict their ability to manage their impulses and activity level, focus, or concentrate on one thing at a time.

Lithium (Eskalith, Lithobid), valproate (Depakene, Depakote), carbamazepine (Epitol, Tegretol), and lamotrigine (Lamictal) are mood stabilizers and anticonvulsants. They have been used to treat bipolar depression. Certain antipsychotic medications, such as ziprasidone (Geodon), risperidone (Risperdal), quetiapine (Seroquel),  aripiprazole (Abilify), asenapine (Saphris), and paliperidone (Invega), may treat psychotic depression. They have also been found to be effective mood stabilizers and are therefore sometimes been used to treat bipolar depression, usually in combination with other antidepressants.

Monoamine oxidase inhibitors (MAOIs) are the earliest developed antidepressants. Examples of MAOIs include phenelzine (Nardil) and tranylcypromine (Parnate). MAOIs elevate the levels of neurochemicals in the brain synapses by inhibiting monoamine oxidase. Monoamine oxidase is the main enzyme that breaks down neurochemicals, such as norepinephrine. When monoamine oxidase is inhibited, the norepinephrine is not broken down and, therefore, the amount of norepinephrine in the brain is increased.

MAOIs also impair the ability to break down tyramine, a substance found in aged cheese, wines, most nuts, chocolate, and some other foods. Tyramine, like norepinephrine, can elevate blood pressure. Therefore, the consumption of tyramine-containing foods by a patient taking an MAOI drug can cause elevated blood levels of tyramine and dangerously high blood pressure. In addition, MAOIs can interact with over-the-counter cold and cough medications to cause dangerously high blood pressure. The reason for this is that these cold and cough medications often contain drugs that likewise can increase blood pressure. Because of these potentially serious drug and food interactions, MAOIs are usually only prescribed after other treatment options have failed.

Tricyclic antidepressants (TCAs) were developed in the 1950s and '60s to treat depression. They are called tricyclic antidepressants because their chemical structures consist of three chemical rings. TCAs work mainly by increasing the level of norepinephrine in the brain synapses, although they also may affect serotonin levels. Doctors often use TCAs to treat moderate to severe depression. Examples of tricyclic antidepressants are amitriptyline (Elavil), protriptyline (Vivactil), desipramine (Norpramin), nortriptyline (Aventyl, Pamelor), imipramine (Tofranil), trimipramine (Surmontil), and perphenazine (Triavil).

Tetracyclic antidepressants are similar in action to tricyclics, but their structure has four chemical rings. Examples of tetracyclics include maprotiline (Ludiomil) and mirtazapine (Remeron), a drug that was discussed above under dual-action antidepressants.

TCAs are safe and generally well tolerated when properly prescribed and administered. However, if taken in overdose, TCAs can cause life-threatening heart-rhythm disturbances. Some TCAs can also have anticholinergic side effects, which are due to the blocking of the activity of the nerves that are responsible for control of the heart rate, gut motion, visual focus, and saliva production. Thus, some TCAs can produce dry mouth, blurred vision, constipation, and dizziness upon standing. The dizziness results from low blood pressure that occurs upon standing (orthostatic hypotension). Anticholinergic side effects can also aggravate narrow-angle glaucoma, urinary obstruction due to benign prostate hypertrophy, and cause delirium in the elderly. TCAs should also be avoided in patients with seizure disorders or a history of strokes.

Stimulants such as methylphenidate (Ritalin) or dextroamphetamine (Dexedrine) are used primarily for the treatment of depression that is resistant to other medications. The stimulants are most commonly used along with other antidepressants or other medications, such as mood stabilizers, antipsychotics, or even thyroid hormone. They are sometimes used alone but rarely. The reason they are usually used sparingly and with other medications for depression is that unlike the other medications, they may induce an emotional rush and a high in both depressed and nondepressed people. Therefore, the stimulants are potentially addictive drugs.

Electroconvulsive therapy (ECT)

In the ECT procedure, an electric current is passed through the brain to produce controlled convulsions (seizures). ECT is useful for certain patients, particularly for those who cannot take or have not responded to a number of antidepressants, have severe depression, and/or are at a high risk for suicide. ECT often is effective in cases where trials of a number of antidepressant medications do not provide sufficient relief of symptoms. This procedure probably works, as previously mentioned, by a massive neurochemical release in the brain due to the controlled seizure. Often highly effective, ECT relieves depression within one to two weeks after beginning treatments in many people. After ECT, some patients will continue to have maintenance ECT, while others will return to antidepressant medications or have a combination of both treatments.

Over the years, the technique of ECT has been much improved. The treatment is given in the hospital under anesthesia so that people receiving ECT do not hurt themselves or feel pain. Most patients undergo six to 10 treatments. An electrical current is passed through the brain to cause a controlled seizure, which typically lasts for 20 to 90 seconds. The patient is awake in five to 10 minutes. The most common side effect is short-term memory loss, which resolves quickly. ECT can usually be safely done as an outpatient procedure.

Psychotherapies

Many forms of psychotherapy are effectively used to help depressed individuals, including some short-term (10 to 20 weeks) therapies. Talking therapies (psychotherapies) help patients gain insight into their problems and resolve them through verbal give-and-take with the therapist. Behavioral therapists help patients learn how to obtain more satisfaction and rewards through their own actions. These therapists also help patients to unlearn the behavioral patterns that may contribute to their depression.

Interpersonal and cognitive/behavioral therapies are two of the short-term psychotherapies that research has shown to be helpful for some forms of depression. Interpersonal therapists focus on the patient's disturbed personal relationships that both cause and exacerbate the depression. Cognitive/behavioral therapists help patients change the negative styles of thinking and behaving that are often associated with depression.

Psychodynamic therapies are sometimes used to treat depression. They focus on resolving the patient's internal psychological conflicts that are typically thought to be rooted in childhood. Long-term psychodynamic therapies are particularly important if there seems to be a lifelong history and pattern of inadequate ways of coping (maladaptive coping mechanisms) in negative or self-injurious behavior