Medications For Depression - Treating Depression: Depression

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Medications for depression

More medications are available to treat depression than ever before. Some antidepressant classes have fallen out of favor, while others have risen in popularity. Currently, the most commonly prescribed antidepressants are drugs that have been developed since the mid-1980s. SSRIs lead the list in popularity. Some medications don't fall into one class. They include bupropion (Wellbutrin), mirtazapine (Remeron), venlafaxine (Effexor), and duloxetine (Cymbalta). Two older classes of antidepressants, tricyclic antidepressants (TCAs) and MAOIs, are still very useful — some people take them without being bothered by side effects — but on average their side effects have made them less appealing as a first-line treatment.

Selective serotonin reuptake inhibitors (SSRIs)

SSRIs stepped into the spotlight in the late 1980s. The serotonin system involves many regions of the brain and affects mood, arousal, anxiety, impulses, and aggression. SSRIs slow the reuptake of serotonin — that is, they keep it from being quickly reabsorbed by the neurons that released it. By blocking reuptake, they permit serotonin to work for a longer time at receptor sites (see Figure 3). SSRIs also appear to change the number and sensitivity of receptors and to indirectly influence other neurotransmitters, including norepinephrine and dopamine.

Figure 3: How SSRIs work When neurotransmitters such as serotonin bind with receptors on a neighboring neuron, they carry the impulse to the next cell. But in someone with symptoms of depression, the cell that released the serotonin may reabsorb it too quickly. As a result, there may not be enough serotonin available to bind to the next cell and allow the signal to pass. SSRIs slow the reuptake of serotonin, leaving more of this neurotransmitter in the synapse. This permits it to work for a longer time, improving the transmission of nerve impulses.

Prozac, the first SSRI introduced, quickly became a celebrity. Not only did it relieve depressive symptoms in many people, but it also appeared to help with a wide variety of problems, including anxiety, shyness (social phobia), obsessions (obsessive-compulsive disorder), and eating disorders (anorexia or bulimia). Other SSRIs have since been introduced to the market (see Table 1).

SSRIs have several advantages over the TCAs and MAOIs that came before them. Unlike TCAs, they rarely cause side effects like dry mouth, constipation, or dizziness. Nor do they disrupt heart rhythms, a potentially fatal side effect of an overdose of TCAs. And with SSRIs, you don't have to worry about dietary restrictions, as you would if you took MAOIs.

On the other hand, SSRIs do have their own problems. The best known of these are sexual side effects. It's fairly common for men taking these medications to have problems sustaining an erection. Both sexes may find that the drugs dampen desire or make it difficult to reach orgasm (see "Sexuality and SSRIs").

Other side effects include nausea, insomnia, and a slight increased risk of excessive bleeding, particularly if taken with aspirin or the blood thinner warfarin (Coumadin). Ironically and tragically, SSRIs can also increase the risk of suicidal tendencies in a small percentage of adults and children taking them (see "Can antidepressants trigger suicide?" and "Treating depression in teens and children").

In addition, SSRIs can interact with certain antihistamines, anticonvulsants, other antidepressants, and drugs used to quell mood disorders. One such problem, called the serotonin syndrome, can occur when MAOIs overlap with SSRIs. This condition is marked by a racing heart, fever, sweating, high blood pressure, trembling, and confusion. Potentially, at least, it can also occur when an SSRI is combined with lithium or the herb St. John's wort. Fortunately, this happens rarely.

Although these side effects may seem daunting, keep in mind that some of the older antidepressants also can be dangerous. The main advantage of SSRIs and other newer antidepressants isn't necessarily that they cause fewer side effects or less discomfort, but that the most dangerous side effects tend to occur less frequently.

Newer types of antidepressants

Since the early 1990s, many newer antidepressants have supplanted MAOIs and TCAs as treatment options. The change reflects a number of factors — for example, the newer antidepressants have less severe side effects, are easier to prescribe, and have been promoted with intense marketing campaigns. In any case, having more treatment options available increases the likelihood that people who are depressed will find one that works for them.

These newer medications, which don't fall neatly into a single class, often work through mechanisms that differ from those of the older classes of antidepressants. For example, bupropion (Wellbutrin) affects the neurotransmitters norepinephrine and dopamine, and mirtazapine (Remeron) affects norepinephrine and serotonin. On the other hand, venlafaxine (Effexor) and duloxetine (Cymbalta) work in part by slowing the reuptake of serotonin, like SSRIs do, but they also slow the reuptake of norepinephrine. Because of their twofold action, they are designated as dual serotonin and norepinephrine reuptake inhibitors.

Side effects vary from medication to medication (see "Medications used for depression and bipolar disorder"). Because these medications are fairly new, much isn't known yet about long-term side effects, but none are apparent at this time.

In general, studies haven't found that the newer medications are more or less effective than older ones like SSRIs. But, as mentioned previously, individuals respond differently to different antidepressants. So while a newer medication may not work better for all — or even most — people, some individuals may find it more helpful or may tolerate it better than another drug.

Doctors are still inclined to prescribe an SSRI first because they have more experience with SSRIs (since these drugs have been available longer and more research has been done using them) and people have tolerated them well. However, these newer drugs can be good second choices and may become more common first choices in time.

Tricyclic antidepressants (TCAs)

TCAs, named for their three-ring molecular structure, have been used since the 1960s. Doctors believe TCAs lift depression mainly by increasing the availability of both norepinephrine (which affects mood, anxiety, and drive) and serotonin (which affects mood, arousal, anxiety, impulses, and aggression). TCAs do this by slowing the reabsorption of these neurotransmitters into the neurons that released them.

At the same time, though, TCAs influence another neurotransmitter, acetylcholine, which can lead to dizziness, constipation, blurred vision when reading, and trouble urinating. These drugs can also cause weight gain. But their most serious side effect is a dangerously abnormal heart rhythm, so they aren't the first choice of antidepressants for people with heart disease. While TCAs are generally safe for people with healthy hearts, a two-week supply of pills could fatally disrupt heart rhythms if a person were to attempt suicide by taking them all at once.

Monoamine oxidase inhibitors (MAOIs)

The neurotransmitters norepinephrine and serotonin are members of a class of compounds called monoamines. They are normally broken down in the body by the enzyme monoamine oxidase. MAOIs block this enzyme, raising the levels of norepinephrine and serotonin in the brain. That can relieve mood problems, anxiety, and other hallmarks of depression.

The two most commonly used MAOIs are tranylcypromine (Parnate) and phenelzine (Nardil). These drugs may be especially helpful if your depression includes features that are considered atypical, such as oversleeping rather than insomnia or weight gain rather than weight loss. They can also relieve the extreme anxiety of panic attacks.

As with other antidepressants, MAOIs have a variety of side effects. They can cause sedation, insomnia, and weight gain. MAOIs can also leave you feeling stimulated or restless. Dizziness sometimes occurs, which is particularly troubling to older adults who are more prone to disabling falls. In addition, a relatively small number of people taking MAOIs develop liver damage.

But the greatest source of inconvenience — and occasionally danger — is that people taking MAOIs must avoid eating a substance called tyramine. Normally, monoamine oxidase breaks down tyramine. If you are taking an MAOI, however, tyramine does not get broken down and can build to unsafe levels. In high concentrations, tyramine can cause a dangerous and rapid increase in blood pressure, and on rare occasions leads to a stroke. Therefore, if you take MAOIs, you must avoid foods that contain tyramine — such as yogurt, aged cheese, pickles, beer, and red wine.

Adding mood stabilizers

People who have problems with depression may also experience mood swings — like the ups and downs seen in various forms of bipolar disorder — so a mood stabilizer, such as lithium (Eskalith, Lithane, and others) or valproate (Depakote), may be added to treatment. Even if you don't have a tendency toward mood cycling, these medications can sometimes build on the effects of an antidepressant, improving your response.

Last updated:	January 23, 2007