While sadness touches all of our lives at different times, depression can have enormous depth and staying power. Being depressed has nothing to do with personal weakness; it’s about neural pathways, chemistry, and more.
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Features on Depression
Living Forward With Depression
by Harvard Medical School
If we were all carbon copies of one another, identifying the causes of depression and its proper treatment would be simpler. But unique differences in life experience, temperament, and biology make treatment a complex matter. No single treatment works for everyone. However, research suggests that many people benefit from a combination of medication and therapy (see "Drugs and therapy: A winning combination?").
Often, treatment is divided into three phases. Keep in mind, though, that there are no sharp lines dividing the phases, and very few people take a straight path through them.
On your road to treatment, your primary care doctor may be your first stop. A good primary care doctor can assess your symptoms with an eye to whether you have any underlying medical problems. If your doctor believes that depression is the main problem, he or she may suggest an antidepressant. Sometimes the initial response to the medication is good. If so, you may not need to go further.
However, if you don't respond well to the first medication, your doctor may refer you to a mental health professional, such as a psychiatrist, psychologist, social worker, or psychiatric nurse. Most primary care doctors aren't equipped to do a more detailed review of the mood problem or to take treatment further with psychotherapy or different medications.
You can also find a mental health professional through a local clinic or hospital or through recommendations from family members or friends. While some insurance plans leave the choice of therapist up to you, others limit you to professionals enrolled in their networks. Therefore, it's worthwhile to check with your insurer before choosing a doctor.
Since states have different requirements about who may hang out a shingle as a therapist, inquire about the therapist's training, and opt only for one who has been formally trained and certified (see "Ten questions to ask when choosing a therapist"). Some people like to meet with a few therapists before making the commitment to work with one. Even the most highly recommended person may not be the right match for you. Beginning therapy can be uncomfortable, but if a therapist's demeanor or office set-up puts you off, you needn't waste your time trying to make the situation work.
Often, medications are the first choice in treatment, especially if you're experiencing a severe depression or suicidal urges. Controlled studies have found that about 65%–85% of people get some relief from antidepressants, compared with 25%–40% of people taking a placebo (a pill with no biologically active ingredient). But the very same drug that works wonders for a friend may fail to ease your symptoms. You may need to try a few different medications to find the one that works best for you with as few side effects as possible. In some cases, a doctor may prescribe a combination of antidepressants or an antidepressant along with a drug to treat anxiety or distorted thinking. A drug combination may be more effective than either drug alone.
Doctors usually first prescribe medications from a class of drugs known as selective serotonin reuptake inhibitors (SSRIs). SSRIs include fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft). Although the side effects of each drug vary slightly from person to person, you have an equal chance of success on any of these drugs. If you don't have a good response to the first drug you try, you and your doctor may decide to switch to another.
Although in a few cases people report a change for the better as quickly as one or two weeks after beginning medication, more often it takes from two to six weeks for antidepressants to ease depression. The lag may reflect the time it takes the medications to affect processes inside the nerve cells and in brain circuits. It's frustrating but true that side effects may appear before the benefits of a drug become obvious. Once you start to feel better, though, it's important to take the medication for as long as it's prescribed to get a full response and avoid a relapse.
While you are using medications, the doctor prescribing them should regularly monitor the dosage and your response. All medical treatments have advantages and disadvantages, and a doctor cannot predict an individual's response to a given medication. While there's a good chance that an antidepressant will relieve your symptoms, there's also a possibility that you'll encounter side effects. So when you're about to embark on treatment, it's important to weigh the potential benefits against the risks. Thankfully, most side effects can be managed or reversed.
Poor response to an antidepressant is often due to an inadequate dose. If the medication doesn't seem to be working during the first phase of your treatment, don't be surprised if your doctor suggests increasing the prescribed amount.
Not everyone who takes a drug will be bothered by side effects. If you do experience some, the first step is to report them to your doctor. Your doctor may be able to suggest simple, helpful adjustments (see "Managing side effects"). Many side effects disappear once your body becomes accustomed to the medication. Or, if necessary, you can try a different dosage or drug.
Antidepressants are not habit-forming or addictive. However, if you are about to stop taking these medications, your body needs to readjust slowly, so your doctor may instruct you to reduce the dosage gradually. Even if you do this, you may experience uncomfortable or disturbing symptoms. Sometimes these symptoms are mistaken for a recurrence of the illness (see "Is it a relapse or not?").
While many antidepressants can be safely combined, some cannot. If you switch medications, you may need a washout period (a stretch of several weeks of taking no drugs) in order to prevent dangerous interactions between a new drug and the lingering effects of the previous one.
One day it may be possible to use biological markers and other indicators to predict exactly which antidepressant will work best for each person. Right now, though, psychiatrists and doctors who prescribe antidepressants choose a particular drug and dosage based on many factors.
Diagnosis. Certain drugs work better for specific symptoms and types of depression. For example, some antidepressants may be better when insomnia is an issue. The severity of your illness or the presence of anxiety, obsessions, or compulsions may also dictate the choice of one drug over another.
Age. As you age, your body tends to break down drugs more slowly. Thus, older patients may need a lower dosage. For children, only a few medications have been studied carefully.
Health. If you have certain health problems, it's best to avoid certain drugs. For this reason, it's important to discuss medical problems with a primary care doctor or psychiatrist before starting an antidepressant.
Medications, supplements, and diet. When combined with certain drugs or substances, antidepressants may not work as well, or they may have worrisome or dangerous side effects. For example, taking SSRIs with another type of antidepressant known as monoamine oxidase inhibitors (MAOIs) can be fatal. Combining the herbal remedy St. John's wort with an SSRI or an MAOI could lead to serious side effects, because this herb boosts serotonin. Likewise, mixing St. John's wort with other drugs — including certain drugs to control HIV infection, cancer medications, and birth control pills — might lower their effectiveness. Eating certain foods, such as cheeses and pickles, while taking an MAOI can raise your blood pressure to dangerously high levels.
Alcohol or drugs. Alcohol and other substances can cause depression and make antidepressants less effective. Doctors often treat alcohol or drug addiction first if they believe either is causing the depression. In many instances, simultaneous treatment for addiction and depression is warranted.
Mental health and medication history. Depending on the nature and course of your depression (for example, if your depression is long-lasting or difficult to treat), you may need a higher dosage or a combination of drugs. This may also be true if an antidepressant has stopped working for you, which may occur naturally or after you've stopped and restarted treatment with it.
No single treatment — whether a drug or a style of therapy — can beat depression in every case. But would you be better off with a combination of drugs and therapy? Research suggests the answer is yes.
A review of several studies considered data collected on nearly 600 people treated for major depression. The investigators found recovery was quicker and more likely to occur with interpersonal therapy plus an antidepressant compared with interpersonal or cognitive behavioral therapy alone. A study of more than 400 teens with major depression found similar results: Treatment with the antidepressant fluoxetine along with cognitive behavioral therapy worked better than either treatment alone.
Combination therapy may also help ward off recurrences. A three-year study reported in the Journal of the American Medical Association tracked recurrences of major depression in about 200 people ages 60 or older. Of those who received monthly interpersonal therapy and the medication nortriptyline, 80% avoided a recurrence. In contrast, only 57% of those who received the drug alone, 36% of those given just therapy, and a mere 10% in the placebo group did as well.
A study published in the Archives of General Psychiatry in 2004 found that one reason therapy and medication may complement each other is that they have effects on different parts of the brain.
However, if your depression is mild, research suggests that a combination of drugs and therapy is no better than cognitive behavioral therapy or interpersonal therapy alone.
Of course, it always makes sense to mull over all of your options. If one type of treatment alone isn't helping you, consider trying combination treatment.
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.
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.
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).
Selective serotonin reuptake inhibitors (SSRIs)
Generic name (brand name)
Side effects
citalopram (Celexa)
Nausea; diarrhea or constipation; weight loss or gain; anxiety; insomnia (occasionally drowsiness); headache; sweating; dry mouth; and sexual problems (see "Sexuality and SSRIs"). Bleeding problems are uncommon, but do sometimes occur.
escitalopram (Lexapro)
fluoxetine (Prozac)
fluvoxamine (Luvox)
paroxetine (Paxil)
sertraline (Zoloft)
Newer antidepressants
bupropion (Wellbutrin)
Anxiety; dry mouth; sweating; loss of appetite; sleep problems
Can trigger seizures and psychosis in people who have an underlying condition that makes them vulnerable to these problems
duloxetine (Cymbalta)
Nausea; dry mouth; dizziness; sexual problems; anxiety; loss of appetite; at higher doses, rise in blood pressure
mirtazapine (Remeron)
Drowsiness or sedation; constipation; dry mouth; increased appetite; weight gain
venlafaxine (Effexor)
Nausea; insomnia; dry mouth; dizziness; sleep problems; sexual problems; blurred vision; anxiety; loss of appetite; at higher doses, rise in blood pressure
Tricyclic antidepressants (TCAs)
amitriptyline (Elavil, Endep)
Dry mouth; blurred vision; dizziness when changing postures (for example, going from sitting to standing); drowsiness; weight gain; constipation; trouble urinating; disturbance of heart rhythm (arrhythmia)
clomipramine (Anafranil)
imipramine (Tofranil)
nortriptyline (Aventyl, Pamelor)
Monoamine oxidase inhibitors (MAOIs)
isocarboxazid (Marplan)
Dizziness when changing postures; diarrhea; nervousness or trembling; drowsiness; mild headache; weight gain, with cravings for sweets; disturbed sleep
Rarely: dangerously high blood pressure if foods containing tyramine are eaten; abnormal liver function
phenelzine (Nardil)
tranylcypromine (Parnate)
Note: All antidepressants may cause agitation and restlessness; involuntary movements, such as tics and tremors; and suicidal thoughts or behaviors, particularly in the first weeks of treatment. These side effects are rare.
Mood stabilizers
lithium carbonate (Eskalith, Lithonate)
Excessive thirst; frequent urination; memory problems and poor concentration; tremors; weight gain; drowsiness; diarrhea; occasional low-thyroid problems or, more rarely, heart or kidney problems over time
carbamazepine (Tegretol)
Fatigue; nausea; dizziness; unsteadiness; double or blurred vision
Rarely: lowered blood cell counts; impaired liver function
gabapentin (Neurontin)
Coordination problems; abnormal dreams or thinking; anemia; irregular heartbeat; agitation or nervousness
lamotrigine (Lamictal)
Fatigue; rash; headache; blurred or double vision; dizziness; nausea; memory or concentration problems
topiramate (Topamax)
Lack of coordination; dizziness; abdominal pain; fatigue; memory difficulties; nervousness; drowsiness; speech problems; nausea; tremors; sensations such as tingling, burning, or hypersensitivity; rapid movement of the eyes; upper respiratory infections; mood problems
Rarely: abdominal pain; weight loss
valproate (Depakote)
Nausea, indigestion, vomiting, or diarrhea; tremors; sedation; hair loss; increased appetite and weight gain
Rarely: impaired liver function; lowered blood cell counts; inflamed pancreas
Antipsychotics
clozapine (Clozaril)
Drowsiness; excess salivation; dry mouth; blurred vision; constipation; dizziness; transient fever; rapid heartbeat; seizures at higher doses; potentially dangerous drop in white blood cell counts, which requires frequent, regular monitoring
olanzapine (Zyprexa)
Drowsiness; weight gain; dry mouth; dizziness; weakness; upset stomach or constipation; anxiety or agitation; headache; fast heartbeat
Rarely: movement disorders; seizures; very low blood pressure
quetiapine (Seroquel)
Headache; drowsiness; dizziness; constipation; dry mouth; weight gain; rapid heart rate or low blood pressure; upset stomach; altered liver or thyroid function
Rarely: movement disorders; low blood cell counts; seizures
risperidone (Risperdal)
Drowsiness; anxiety; dizziness; constipation or diarrhea; nausea or stomach upset; rapid heart rate; increased dreaming; visual disturbances; weight gain
Rarely: movement disorders
Anti-anxiety medications
Benzodiazepines including:
alprazolam (Xanax)
clonazepam (Klonopin)
lorazepam (Ativan)
Clumsiness or unsteadiness; drowsiness; cognitive impairment; dizziness; headache; tolerance may develop
buspirone (BuSpar)
Chest pain; dizziness; headache; nausea
Note: For precautions regarding the use of these medications during pregnancy, see "Information for expectant and new mothers."
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.
One drawback to SSRIs is that they frequently dampen sexual response. One study suggested that as many as half of all people taking these medications may experience some sexual problems. In addition to reducing interest in sex, SSRIs can make it difficult to become aroused, sustain arousal, and reach orgasm. Some people taking SSRIs aren't able to have an orgasm at all. If you experience any sexual problems while taking an SSRI, talk with your doctor or therapist. In some cases, sexual difficulties may stem not from the medication, but rather from the underlying depression. If your medication is the problem, your doctor or therapist may suggest one of the following strategies:
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.
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.
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.
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.
Lithium is the most widely known medication used to treat bipolar disorder. Lithium helps stabilize moods. Other medications also have this effect — for example, some anticonvulsants (which are often used to combat seizures) also have mood-stabilizing properties. These mood stabilizers tend to be mainstays for treating bipolar disorder, but your doctor may recommend other medications as well. Depending on the nature of your illness, you may receive antipsychotic, antidepressant, or anti-anxiety medications.
Keep in mind that you may need to stay on some medication or combination of medications indefinitely to keep your mood stable. The likelihood of having a relapse when you go off medications is great, especially if you've had two or more episodes of mania or depression. Experts now believe that the more episodes of depression or mania you've experienced, the more intense and frequent your subsequent episodes may be. Therefore, for people with bipolar disorder, maintenance therapy is the best strategy.
Stabilizing mood is the chief goal of any treatment for bipolar disorder. By preventing manic and depressive episodes, these medications smooth out the highs and lows of this illness.
Lithium. Lithium is one of the oldest drugs used in psychiatry. Since the 1960s, it has proved very effective in preventing the mood swings of bipolar illness.
Common side effects of lithium include thirst, nausea, and tremors. While this medication can alter laboratory measures of kidney, heart, or thyroid function, studies of people who have taken lithium for many years are reassuring. Significant damage to the kidneys is quite rare, and changes to the heart noted on electrocardiograms are almost always benign. Long-term lithium use can cause thyroid problems in up to half the people who use it, but these problems can be treated.
There is a narrow dose range in which lithium is effective. Since doses that are too high can rapidly become toxic, doctors use periodic blood tests to monitor lithium levels in people taking this drug. Dehydration and diuretics (which are taken for high blood pressure) can increase the concentration of lithium in the blood, making the risk of toxicity greater. Early symptoms of toxicity include diarrhea, vomiting, drowsiness, weakness, and loss of coordination. Without treatment, toxicity can lead to confusion, agitation, unstable blood pressure, stupor, or coma. But these problems are quite rare if you know the risk and your doctor monitors your blood levels regularly.
Because lithium takes days or weeks to become effective in someone who is going through a manic phase, doctors often prescribe additional medications to help in the meantime.
While lithium has some drawbacks, a survey conducted by two large health plans indicates that it's better at preventing suicide than valproate, a newer drug that is increasingly replacing it in the treatment of bipolar disorder (see below). According to research appearing in the Journal of the American Medical Association in 2003, patients taking valproate had a 70% greater risk of a serious suicide attempt and nearly three times the risk of death by suicide. The difference amounted to one completed suicide per 1,000 patients annually. Valproate is at least as effective as lithium for mania, but lithium provides better protection against depression, the state in which bipolar patients are most likely to commit suicide. Other research shows that when patients stop taking lithium, the suicide rate rises for several months, although the effect can be minimized by lowering the dose gradually.
Anticonvulsants. Anticonvulsant drugs are named for their ability to treat seizure disorders, but doctors have recognized their value in treating mania and stabilizing moods.
One such drug, valproate, is so effective that some doctors turn to it first when treating bipolar disorder. While it isn't more effective than lithium, some doctors and patients find that its side effects seem easier to tolerate, and the dose is easier to adjust. For most people, blood tests are needed less frequently, and it isn't as toxic as lithium in overdose. It also may be better for some types of bipolar disorder — for example, when a person has very frequent mood cycles. However, there is evidence that lithium is better than valproate at lowering the risk of suicide for people with bipolar disorder (see "Lithium").
Common side effects include nausea, sedation, and weight gain. People who have liver disease should not take valproate without having their liver function carefully monitored.
Other anticonvulsants, including carbamazepine (Tegretol), lamotrigine (Lamictal), topiramate (Topamax), and gabapentin (Neurontin), have also proved useful in treating some people with mood disorders. (For more on these medications, see Table 1.) In addition, doctors commonly combine different mood stabilizers to treat people whose episodes are not controlled by a single drug; for example, a person might take two anticonvulsants, or an anticonvulsant along with lithium.
Antipsychotic medications play a role in treating bipolar illness in one of two ways. An antipsychotic can be helpful if distorted or psychotic thinking occurs as part of an episode of mania. And even in the absence of a thought disorder, the addition of an antipsychotic may help if you've tried mood stabilizers alone without great success.
Risperidone (Risperdal), olanzapine (Zyprexa), and quetiapine (Seroquel) are among the antipsychotics most often chosen (see Table 1). A newer medication pairs olanzapine with the antidepressant fluoxetine (see below).
In some cases, the drug clozapine (Clozaril) is most helpful. But because it sometimes suppresses white blood cells that the body uses to fight infection, doctors offer clozapine only to people who haven't responded to other treatments.
Because people with bipolar disorder are as likely to experience depression as mania, doctors may also prescribe antidepressants (see Table 1). One problem with using antidepressants to treat bipolar illness is that they can trigger a manic episode or cause a more rapid cycling of episodes. However, antidepressants can be helpful, and SSRIs and bupropion have been used safely for this purpose. Doctors have found that the mood stabilizer lamotrigine works well for people with bipolar disorder who are showing signs of depression. It tends not to cause the problems that antidepressants sometimes do.
A combination pill. A bipolar medication called Symbyax, introduced in early 2004, combines two medicines in one pill: the antidepressant fluoxetine and the antipsychotic drug olanzapine. The pill is touted as offering greater convenience, since some patients would have fewer pills to take. Plus, combining an antidepressant with an antipsychotic drug may be helpful for bipolar disorder, because antidepressants alone sometimes trigger mania in susceptible people. The addition of an antipsychotic drug can reduce that risk. However, some experts point out that this particular preparation has several drawbacks. Symbyax pills combine 6 milligrams (mg) or 12 mg of olanzapine with 25 mg or 50 mg of fluoxetine. These fixed amounts limit a doctor's ability to adjust the dose of each medication freely and make it harder to find the smallest effective dose for each drug. In addition, if a patient develops certain side effects, like weight gain or drowsiness, it won't be clear which drug is causing the problem. And since olanzapine alone comes in 5-mg doses and fluoxetine in 20-mg pills, it's not easy to convert to the combination pill after individual doses are established.
Finally, and perhaps most importantly, most patients who are treated for bipolar disorder aren't given these two medications in combination. In most cases, patients receive valproate or lithium alone. Then an antidepressant is added if those medications don't produce the desired effect. Combining an antidepressant with an antipsychotic is much less common.
Doctors may also prescribe anti-anxiety medications to help with the jitteriness, racing thoughts, and overall worry and distress that often accompany manic episodes. Typical choices are either an SSRI, buspirone (BuSpar), or one of the benzodiazepines, such as alprazolam (Xanax), clonazepam (Klonopin), or lorazepam (Ativan). Each of these benzodiazepines may differ slightly in how quickly it is absorbed by the body and how long its effects last. For more information on these medications, see Table 1 and talk to your doctor.
Depression can bring everything in your life — work, relationships, school, and even the most minor tasks — to a grinding halt, or, at the very least, gum up the works. The aim of psychotherapy is to relieve you of symptoms and to help you manage your problems better and live the healthiest, most satisfying life you can.
Some evidence suggests that by encouraging more constructive ways of thinking and acting, psychotherapy makes future bouts of depression less likely. Three schools of psychotherapy — cognitive behavioral therapy, interpersonal therapy, and psychodynamic therapy — play a primary role in combating depression.
Which type of psychotherapy works best? There's no simple answer. Just as people respond differently to different drugs, you might do better with one type of therapy than with another. Many people find that a blended approach — one that draws on elements of different schools of psychotherapy — suits them best.
Cognitive behavioral therapy aims to correct ingrained patterns of negative thoughts and behaviors. To accomplish this, you are taught to recognize distorted, self-critical thoughts, such as "I always screw up"; "People don't like me"; "It's all my fault." During cognitive behavioral therapy, your therapist may ask you to judge the truth behind these statements, to work to transform such automatic thoughts, and to recognize events that are beyond your control.
Along with cutting down on the number of negative thoughts, cognitive behavioral therapy also focuses on breaking jobs into smaller, more manageable pieces that set you up for success. You rehearse new ways of coping with problems and practice social skills that can help wean you from actions that provide a fertile breeding ground for depression, such as isolating yourself. Your therapist may assign you tasks to reinforce your learning. For example, you might keep a log of thoughts that occur as you try out your new skills. As negative patterns become clearer, you can learn to redirect them.
Interpersonal psychotherapy concentrates on the thornier aspects of your current relationships, both at work and at home. Weekly sessions over three or four months will help you identify and practice ways to cope with recurring conflicts. Typically, therapy centers on one of four specific problems:
Psychodynamic therapy focuses on how life events, desires, and past and current relationships affect your feelings and the choices you make. In this type of therapy, you and your therapist identify the compromises you've made to defend yourself against painful thoughts or emotions, sometimes without even knowing it. For example, someone with an overbearing parent may unconsciously find it difficult to risk developing intimate relationships, out of fear that all close relationships will involve a domineering partner. By becoming aware of links like this, you may find it easier to overcome such obstacles.
You and your therapist may talk about disruptions in your early life — perhaps the death of a parent, your parents' divorce, or other disappointments — to determine their effect on you. While the duration of psychodynamic therapy can be open-ended, a variation called brief dynamic therapy is limited to a specific amount of time (generally 12–20 weeks). It applies a similar lens to a specific emotional problem.
Group, family, or couples therapy may also be part of a plan for treating depression or bipolar disorder. Group therapy draws on support generated from people in the group and uses the dynamics among them, along with the leader's help, to explore shared problems. Family therapy and couples therapy also delve into human interactions. Like group therapy, the aim is to define destructive patterns — such as scapegoating one family member or enabling a spouse's alcohol abuse — and replace them with healthier ones. These therapies can uncover hidden issues and establish lines of communication. Family therapy is especially useful when one person is struggling with emotions that spill over into the family.
Whether you get a recommendation for a therapist from your primary care doctor, a friend, or your insurance company, finding out about his or her background and training can help you feel comfortable with your choice. Here are some questions to ask before settling on a therapist:
It's hard for a therapist to give precise answers to some of these questions, because no single therapist or type of treatment is best for everyone. But there are some general responses you should be looking for. The therapist should have formal training and certification, or be on the way to getting it. There's a tendency for mental health professionals to offer the particular type of psychotherapy that they do best. It's good if the person can describe the merits and drawbacks of different types of treatment, including ones they don't do.
The therapist should also let you know how he or she will monitor your progress. If you don't feel there's been improvement after several months, consider getting a second opinion.
Reality often fails to jibe with movies and books. While psychotherapy and antidepressants have garnered some positive fictional portrayals, electroconvulsive therapy (ECT) typically evokes only frightening pictures. More than 30 years after One Flew Over the Cuckoo's Nest won its Academy Awards, the images from the film linger in many people's minds. Yet ECT remains one of the most effective treatments for severe depression, with response rates of 80%–90% for people with major depression. ECT may also be used to treat mania when a person fails to respond to other treatments.
Despite its effectiveness, doctors usually reserve ECT for situations in which several drugs have failed. That's partly because of its technical complexity, and partly because of its negative image.
The discomfort of ECT is roughly equivalent to that of a minor surgical procedure. The purpose of ECT is to induce a seizure, which acts as the therapeutic agent. Before receiving treatment, a person is given general anesthesia. Then the doctor places electrodes on the patient's scalp and administers an electric current in a brief pulse that causes a seizure. Medicine is given to prevent the muscular effects of the seizure, so there are no obvious convulsions. The seizure is evident only because it registers on an electroencephalographic monitor. The procedure takes a few minutes, after which the person is roused from the anesthesia.
On average, 6–12 treatments are given over several weeks. Contrary to what some people might expect, when there is a good response, the improvement occurs gradually over the course of treatment, rather than all at once. Generally, the response occurs faster than with medications, making ECT a good treatment for severely depressed people who may be at very high risk for suicide.
In the best-case scenario, a prospective patient is well-educated about ECT. Usually, doctors and nurses explain the treatment in detail, and often patients watch videotapes of the procedure. Sometimes other people who have had ECT explain what the experience is like to further demystify it. Patients decide if they want to try ECT only after they have been fully informed about how the procedure works and what its risks and benefits are. Most states have clear safeguards against involuntary ECT treatment.
The most commonly discussed side effect of ECT is memory loss. Routinely, patients lose memories of events that occurred just before and soon after treatment. After the treatment concludes, some people will have difficulty remembering things that occurred during the course of treatment. Once all the treatments have ended, relatively few people have persistent memory problems. However, ECT may exaggerate problems in people already having memory trouble.
Other side effects are also fleeting. Some people feel a bit sedated or tired on the day of the procedure, or they might have a mild headache or nausea. However, these symptoms might come from the anesthesia rather than ECT itself. To date, no study has shown that ECT causes brain damage.
One drawback to ECT is a relapse rate of about 50% in people treated for severe depression. It may be even higher with so-called double depression (the combination of depression and dysthymia). To help avoid a relapse, a person who responds to ECT might also take an antidepressant medication or mood stabilizer. If dual treatment doesn't work, some people receive maintenance ECT on an outpatient basis about once a month. Some people with severe depression have done very well with this approach.
There are many different approaches to psychotherapy, but all good therapy shares some common elements. To start with, make sure that your therapist has a state license. While psychotherapy isn't always comfortable, you should feel reasonably at ease with your therapist. In the best case, the two of you will be, or will become, a good match. Of course, both of you must respect ethical and professional boundaries.
It's important that therapy provide some relief. Your therapist should not only offer reassurance and support, but also suggest a clear plan for how the therapy will proceed. You and your therapist should agree upon realistic goals for the therapy early on. While well-defined problems might be addressed relatively quickly, you may need to approach more difficult problems from many angles, which will take longer.
Since mood disorders can have a broad influence on relationships, work, school, and leisure activities, therapy should address these areas when — or if possible before — they become a problem. Therapy isn't just for uncovering painful thoughts, although that's part of the work. Good therapy also addresses how you can adjust, adapt, or function better. And it helps you understand the nature of your distress. You should feel that your therapist approaches the important issues in your life in a way that's unique to your needs, not from a one-size-fits-all perspective. Pertinent issues springing from your culture, sex, and age, as well as individual differences, should shape the direction therapy takes.
If a doctor other than your therapist prescribes antidepressants for you, the two should communicate. If they don't do so on their own, you may want to encourage collaboration by asking your therapist and doctor to speak regularly. Your therapist ought to understand the medication portion of your treatment, encourage you to take medications as prescribed, and help monitor your response.
Although it's not uncommon to feel stuck at times, don't persist for months with that feeling. Some difficult problems take a long time to unravel, but you should sense progress. If you don't, it's a sign that the match between you and either the technique or the therapist isn't right. If four to six months have gone by and you don't feel better, it's a good idea to consult another therapist.
Two newer treatments are geared toward people who haven't responded well to other, more traditional approaches. While they are somewhat similar to ECT, in that they rely on delivering impulses (electrical or magnetic) to achieve results, neither has the proven track record of ECT.
In the summer of 2005, the FDA approved a device known as a vagus-nerve stimulator as a treatment for adults with depression who haven't responded to four or more other therapies. Extending from the brain through the chest cavity, the vagus nerve helps control your breathing and is linked to the amygdala, hypothalamus, and other parts of the brain that modulate mood and anxiety. A vagus-nerve stimulator is a surgically implanted device similar to a pacemaker that delivers a small electrical impulse to this nerve for about 30 seconds every five minutes. Although vagus nerve stimulation (VNS) was initially developed as a method for controlling epilepsy, researchers found that it improved mood in some people.
The FDA based its approval on research showing that VNS was safe and effective. One study cited in the FDA approval documents showed that 31% of people getting VNS responded well to the treatment in the first 12 weeks of therapy and 45% did after one year. The most common side effects are cough and neck pain. Many people also find that their voice often becomes hoarse while the stimulator is delivering its impulse. Between impulses, though, the person's voice returns to normal.
Although the VNS device is on the market, VNS is a relatively untested treatment that has not yet been proved effective by randomized, controlled trials. For this reason, the consumer group Public Citizen petitioned the FDA not to approve it. The FDA has mandated that Cyberonics, the company that makes the device, conduct studies to monitor its effectiveness. For the most part, this treatment should be reserved for exceptional cases where many other therapies have been tried without success.
Another treatment for people whose depression has not responded to traditional therapy, called repetitive transcranial magnetic stimulation (rTMS), is also being tested in several centers. During rTMS, a donut-shaped wand passed along the surface of the scalp focuses magnetic pulses on a small part of the brain. This technique isn't invasive and doesn't cause seizures or require anesthesia, as ECT does. A person undergoing rTMS can sit comfortably in a chair and remain awake during the whole procedure, which takes 30–45 minutes. Usually, it is done once a day for 10 days.
Although results in trials are still inconsistent, the news from what now amounts to a large number of controlled studies is getting better. For example, in one study, using rTMS at different frequencies on different areas of the brain improved depression in people who had not responded to drugs. Researchers have also found weekly rTMS helpful to adults with bipolar disorder who are taking lithium.
Until doctors have a way to test people ahead of time to see which treatment will work for each individual, finding the right approach is a matter of trial and error. For some people, that process may be quick and simple: The first treatment used is successful, or only some minor tweaking of medications or dosages is needed. But for others, it takes a good deal of patience and willingness to try several different approaches before an effective treatment is found.
What might be a typical course of treatment if your depression doesn't respond well to the initial choice? If the first medication you try doesn't work after 6–12 weeks of treatment, your doctor may increase your dosage. If that doesn't work, he or she may suggest that you switch to another drug in the same class or a drug in a different class. Your doctor may also recommend adding psychotherapy if that hasn't been part of your treatment plan.
If you still don't respond to these therapies, your doctor may prescribe an additional medication, such as lithium, to be taken with the antidepressant. The next step may be trying ECT or light therapy. Newer therapies, such as vagus nerve stimulation or magnetic stimulation, are other options for you and your doctor to discuss.
Having to go through all of these steps may sound discouraging, but finding the treatment that works for you will be worth the effort. Also, keep in mind that there are some things you can do to improve your chances for success, including making sure you take medication as directed and keeping up with therapy appointments (see "Sticking with treatment").
Source: from Harvard Health Publications, Copyright © 2008 Harvard University. All rights reserved. Harvard Medical School does not endorse products. Used with permission of StayWell.Terms of UseMedical Disclaimer
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