Depression treatment options for adults
Patient information: Depression treatment options for adults
Author
Wayne Katon, MD
Paul Ciechanowski, MD Section Editor
Thomas L Schwenk, MD Deputy Editor
Leah K Moynihan, RNC, MSN
H Nancy Sokol, MD
DEPRESSION OVERVIEW — Depression is a treatable condition. However, many people are reluctant to accept a diagnosis of depression and pursue treatment. A person may worry about the social stigma of depression, and may be embarrassed to discuss the need for treatment with family or friends. In addition, some people do not understand that physical problems such as aches and pains, fatigue, and difficulty sleeping can be caused by depression.
Fortunately, early and successful treatment of depression shortens the duration of illness, reduces the likelihood of persistent symptoms, and reduces the likelihood of a relapse.
The treatment of depression may include psychotherapy (counseling), drug therapy, or some combination of these therapies. In many cases, depression can be treated by a primary care provider.
This topic review discusses the treatment options available for adults with depression. A topic review that discusses the cause, symptoms, and diagnosis of depression is available separately. (See “Patient information: Depression in adults” and see “Patient information: A guide to depression”).
PREVENTING SUICIDE — Suicide is a tragic and preventable consequence of severe depression. If a clinician suspects that you are depressed, he or she will often ask about suicidal thoughts. It is absolutely imperative to tell your clinician if you have thoughts about harming yourself or ending your life. If you are concerned that you or someone you know is at risk of hurting him or herself or others, you should do one of the following:
Call a health care provider for advice or an urgent appointment
Take the person to the local emergency department
Call the National Suicide Prevention Lifeline (www.suicidepreventionlifeline.org) at 1-800-273-TALK (8255).
A person who is at immediate risk for attempting suicide requires emergency evaluation and prompt treatment for depression (if depression precipitated the suicidal thoughts). This may include hospitalization, antidepressant medication, and intensive therapy.
ANTIDEPRESSANTS VERSUS PSYCHOTHERAPY — People with severe depression generally require one or more antidepressant medications to treat their symptoms, sometimes along with psychotherapy. Combination therapy (counseling and antidepressant medication) may be especially helpful for those who have severe depression or a history of recurrent depression. Mild or moderate depression can probably be treated with either drug therapy or psychotherapy. There are no clear predictors of which therapy is a better choice for any given individual.
PSYCHOTHERAPY TO TREAT DEPRESSION — Psychotherapy (sometimes called therapy or counseling) is a process during which a person talks to a healthcare professional about their feelings, relationships, and worries. During a therapy session, the patient and therapist can discuss alternate ways of thinking or feeling about a situation, which often helps the patient to cope with depressive symptoms, improve social skills, and increase self-confidence.
There are several different types of psychotherapy. Therapy sessions are usually conducted in the therapist’s office once per week for 30 to 60 minutes. In the early stages of treatment, two or more sessions per week may be recommended. As the treatment progresses, the frequency of meetings can sometimes be reduced to once per week or every other week. The patient and therapist should work together to determine the optimal schedule.
The initial therapy sessions often focus on trying to understand why you are depressed, and may include simple homework activities to identify the factors that may be contributing to depression. Although psychotherapy can improve symptoms of depression within several weeks, the greatest benefit of therapy may not be seen for 8 to 10 weeks or longer.
Psychotherapy can be provided by any licensed healthcare professional who has appropriate training, including a psychologist, psychiatrist, clinical social worker, or clinical nurse specialist.
People with severe depression and those at risk for suicide are often hospitalized in a psychiatric facility for a short period of time. During the hospitalization, the person usually meets with a psychiatrist to manage medications and a psychologist or counselor for therapy sessions. Other activities, such as group therapy sessions and physical exercise, are often encouraged.
ANTIDEPRESSANT MEDICATIONS — If your therapist feels that you need an antidepressant medication, you may be referred to a psychiatrist or your primary care provider. A psychiatrist is a medical doctor with specialized training in the treatment of mental health issues. In some cases, a psychiatrist provides counseling and prescribes medications if needed; in other cases, a therapist provides counseling and a psychiatrist prescribes medication.
Therapy with an antidepressant medication helps reestablish the normal balance of chemicals in the brain. Several different classes of antidepressants effectively relieve the symptoms of depression.
Time required for a response — Some people respond to antidepressant medication after about two weeks, but for most, the full effect is not seen until four to six weeks or longer. During the first few weeks, the dose is usually increased gradually. The person usually sees the medical provider (the psychiatrist or primary care provider) once every one or two weeks for the first few weeks, then less frequently; if problems develop at any point, more frequent visits may be recommended.
By six to eight weeks after starting an antidepressant medication, it is usually possible to determine if the medication is effective. If your symptoms have improved somewhat during this time, the dose of the medication may be increased. If there has been no improvement in symptoms, an alternate antidepressant medication may be recommended.
Duration — In most cases, antidepressant medications are recommended for at least six to nine months. This amount of time varies greatly depending upon your situation. The decision to stop antidepressant medication should be shared between you and your provider.
People who experience depression as a result of an event (such as a major stress or loss), should continue taking antidepressant medication until the emotional response to the event has been fully addressed.
When antidepressants are stopped, they should be tapered slowly over two to four weeks to minimize the potential side effects associated with abruptly stopping medication. Side effects associated with stopping medication quickly can include jitteriness, dizziness, nausea, fatigue, muscle aches, chills, anxiety, and irritability. Although these symptoms are not dangerous and usually improve over one to two weeks, they can be quite distressing and uncomfortable.
In people with major depression, a relapse in symptoms is relatively common after stopping treatment with an antidepressant; in some cases, longer term treatment is recommended (see “Maintenance drug therapy” below)
Maintenance drug therapy — Maintenance antidepressant therapy (long-term drug therapy) may be appropriate for people who are at risk for a relapse of depression. One study found that 37 percent of people who were treated for depression experienced a relapse within 12 months of stopping antidepressant therapy [2] . Maintenance therapy may last from one year to indefinitely, depending upon the individual’s situation.
Therapy with other medications — In some people, depression is accompanied by other psychiatric conditions, such as panic attacks or mania. Clinicians may therefore recommend using combination therapy, including an antidepressants and one or more antipsychotic, antianxiety, mood-stabilizing, or anticonvulsant medications.
CHOICE OF ANTIDEPRESSANTS — Many different classes of antidepressants are effective for relieving depression [3] . Thus, the choice among antidepressants depends upon other factors, including if the person has other medical conditions, takes medications that could interact with the antidepressant, and the impact of potential antidepressant side effects.
When considering use of an antidepressant, is important to do the following:
Discuss the expected benefits before starting treatment
Be aware of possible side effects of antidepressants
Follow the instructions for the dose and timing
Avoid combining antidepressants unless you are instructed to do so
Selective serotonin reuptake inhibitors (SSRIs) — Drugs in this class include fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), fluvoxamine (Luvox®), and escitalopram (Lexapro®) (show table 1).
The selective serotonin reuptake inhibitors (SSRIs) increase brain levels of the neurochemical serotonin. Low levels of serotonin may be one cause of depression.
Side effects — Compared with most other antidepressants, the SSRIs have relatively few side effects. The most common side effects include jitteriness, restlessness, agitation, headache, diarrhea and nausea, and insomnia.
Sexual side effects (loss of sexual desire, diminished arousal, and difficulty having an orgasm) may also occur with prolonged use of the SSRIs; however, adding another drug (such as bupropion [Wellbutrin®] or buspirone [BuSpar®]) can sometimes relieve these sexual side effects. (See “Patient information: Sexual problems in men” and see “Patient information: Sexual problems in women”).
Serotonin syndrome — A more serious potential side effect of SSRIs is serotonin syndrome. Symptoms of serotonin syndrome can include agitation, confusion, and overheating (hyperthermia). This can occur with high doses of an SSRI or if an SSRI is taken in combination with another antidepressant medication called a monoamine oxidase inhibitor (MAOI).
There is a very small risk of serotonin syndrome when an SSRI is combined with a class of migraine medications called triptans (eg, sumatriptan (Imitrex®), zolmitriptan (Zomig®), naratriptan (Amerge®), rizatriptan (Maxalt®), almotriptan (Axert®), eletriptan (Relpax®) and frovatriptan (Frova®)). Many headache experts feel that it is safe to use an SSRI and a triptan in combination as long as the person is monitored for symptoms.
Mirtazapine — Mirtazapine (Remeron®) is a newer antidepressants. This drug changes the levels of several neurochemicals in the brain, including serotonin. Mirtazapine has antianxiety and sedative effects and may be especially effective in people with depression who have symptoms of anxiety and insomnia.
The side effects of mirtazapine include sedation, which is more common at lower drug doses. Other side effects include increased appetite, weight gain, and dry mouth (show table 1). Mirtazapine is less likely than other antidepressants to have sexual side effects.
Bupropion — Bupropion (Wellbutrin®) is an antidepressant that changes the level of several neurochemicals in the brain but does not appear to have any direct effect on levels of serotonin. Bupropion has a mild stimulant action and may be especially effective in people with depression who have fatigue or poor concentration.
Bupropion has few side effects, but it has been associated with seizures in people with eating disorders; it is not recommended for people who have bulimia or anorexia. The drug carries a small risk of seizures in other people. Other side effects of bupropion may include mild anxiety or insomnia and decreased appetite with weight loss (show table 1). Unlike other antidepressants, bupropion does not have sexual side effects. It is sometimes used at low doses to help counter the sexual side effects of other antidepressants.
Serotonin norepinephrine reuptake inhibitors — The serotonin norepinephrine reuptake inhibitors venlafaxine (Effexor®) and duloxetine (Cymbalta®) alter levels of several different neurochemicals in the brain. For unknown reasons, these drugs may be especially effective in people who have a poor response to other antidepressants. Duloxetine may be of benefit in persons with depression as well as pain from medical (eg, arthritis) or orthopaedic (eg, spinal disc disease) conditions, although there have not been studies comparing duloxetine to other antidepressants for this purpose.
Common side effects include nausea, dizziness, insomnia, sedation, and constipation. Rarely, these drugs also cause increased sweating (show table 1). People taking venlafaxine should have regular blood pressure checks since it may cause blood pressure to rise.
Tricyclic antidepressants — The tricyclic antidepressants alter levels of several different neurochemicals in the brain. Drugs in this class include imipramine (Tofranil®), amitriptyline (Elavil®), desipramine (Norpramin®), nortriptyline (Pamelor®), and clomipramine (Anafranil®).
Because of the numerous side effects associated with these drugs and the availability of newer antidepressants, the tricyclic antidepressants are less commonly used as first-line antidepressant therapy.
The side effects of tricyclic antidepressants may include dry mouth, blurred vision, constipation, nausea, difficulty urinating, drowsiness, weight gain, sexual problems, and rapid heart beat. In older adults, the side effects may include memory impairment, confusion, and hallucinations. Some people with heart diseases may not be able to take tricyclic antidepressants. Nevertheless, many patients use these drugs safely, and their antidepressant activity is equivalent to that of antidepressants from other classes.
Monoamine oxidase (MAO) inhibitors — The monoamine oxidase (MAO) inhibitors were the first drugs used to treat depression. These drugs block an enzyme that breaks down neurochemicals. Drugs in this class include tranylcypromine (Parnate®) and phenelzine (Nardil®).
The MAO inhibitors are usually not a first choice for the treatment of depression, but they may be especially effective for the treatment of atypical depression and depression that does not respond to other drugs. Side effects of MAO inhibitors may include dizziness, dry mouth, gastrointestinal upset, difficulty urinating, headache, unpredictable muscle contractions, and afternoon fatigue.
People who take MAO inhibitors for depression must avoid foods and beverages that contain tyramine. These include fermented cheeses; imported beer; Chianti and some other wines; champagne; soy sauces; avocados; bananas; overripe or spoiled food; and any fermented, smoked, or aged fish or meat. People who accidentally consume tyramine while taking MAO inhibitors may experience severe high blood pressure.
Trazodone — Trazodone (Desyrel®) is a drug that is sometimes used to treat depression. However, it is not as effective as other antidepressant drugs and can cause side effects. As a result, trazodone is usually not a first choice for the treatment of depression.
The most common side effect of trazodone is sedation; other side effects may include lightheadedness upon standing and nausea. A rare but potentially serious side effects of trazodone is irregular heart beat and priapism (a persistent erection that requires medical treatment).
OTHER TREATMENT OPTIONS FOR DEPRESSION — Several other treatment options may alleviate depression in some people.
St. John’s wort — St. John’s wort (Hypericum perforatum) appears to alter levels of several neurochemicals in the brain. Studies suggest that for the treatment of mild to moderate depression, St. John’s wort is more effective than a placebo and as effective as tricyclic antidepressants, with fewer side effects [4] . However, the long-term effectiveness of St. John’s wort is unknown.
St. John’s wort is not approved by the United States Food and Drug Administration for the treatment of depression. Because the composition of St. John’s wort products varies widely, some products may be less effective than others for relieving depression. The products that are most likely to be effective are those that are standardized at 0.3 percent hypericin. The dose in most studies is 300 mg three times per day, although doses as low as 250 mg twice per day may be effective.
The side effects of St. John’s wort may include stomach upset, dizziness or confusion, tiredness, and dry mouth. Rarely, some people who take St. John’s wort notice that their skin becomes extremely sensitive to sunlight. The long-term safety of St. John’s wort is unknown.
It is important to tell your clinician if you use St. John’s wort. This herb can reduce the effectiveness of drugs used to treat a variety of other medical conditions, including hormonal methods of birth control (eg, pills). Of particular concern are interactions with medications used to treat HIV and cancer. In general, patients on chemotherapy or antiviral therapy for HIV should not take St. John’s wort. Furthermore, St. John’s wort should not be used in combination with other antidepressants, particularly the selective serotonin reuptake inhibitors (SSRIs).
Studies suggest that pregnant or breast-feeding women should not take St. John’s wort. There are some concerns that the herb may lower fertility. St. John’s wort is inappropriate for people with severe depression who are at risk for suicide.
A good source for updated information about St. John’s wort can be found at the National Center for Complementary and Alternative Medicine, a branch of the National Institutes of Health (www.nccam.nih.gov/health/stjohnswort/).
Electroconvulsive therapy (ECT) — During electroconvulsive therapy (ECT), an electrical current is passed through the brain, triggering a seizure. For unknown reasons, the seizure helps to restore the normal balance of neurochemicals in the brain. ECT is especially effective for people with depression who also have delusions (powerful, irrational beliefs) and for people who have severe depression despite maximal drug therapy. ECT can be used in pregnant women or in persons who cannot tolerate antidepressant medications, and is especially useful in persons who need a rapid-onset antidepressant treatment. (See “Medical consultation for electroconvulsive therapy”).
Patients who undergo ECT are given general anesthesia to induce sleep and prevent discomfort. Patients are monitored carefully before, during, and after the treatment. Side effects of this therapy include brief confusion and memory loss. Although ECT has been negatively portrayed in the media, this therapy often provides rapid and dramatic relief of depression and has very few side effects. Most people who undergo ECT find it a helpful treatment for their depression.
More detailed information about ECT is available on the American Psychiatric Association’s web site, http://www.psych.org/Departments/APIREandResearch/ResearchTraining/clin_res/index.aspx.
Repetitive transcranial magnetic stimulation (rTMS) — During repetitive transcranial magnetic stimulation (rTMS), a powerful magnetic field is used to stimulate the brain. This therapy does not require anesthesia or cause any confusion or memory loss. The effectiveness of rTMS for the treatment of depression is still being studied.
Exercise — Exercise can improve depressive symptoms, although the effects occur more slowly than with antidepressant drugs. One study found that the depression-relieving benefit of exercise was equal to that of a selective serotonin reuptake inhibitor (SSRI) after 16 weeks [5] .
Light therapy — Light therapy can relieve the depression of seasonal affective disorder (SAD), which typically occurs during the winter months. Seasonal affective disorder is discussed separately. (See “Seasonal affective disorder”).
Light therapy is usually done with a specially designed light box. The usual dose of light therapy is 10,000 lux, beginning with one 10 to 15 minute session per day, gradually increasing to 30 to 45 minutes per day depending upon response. It may take four to six weeks of light therapy to see a response, although some patients improve within days. Therapy is continued until sufficient daily light exposure is available through other sources, typically from springtime sun.
ANTIDEPRESSANTS AND PREGNANCY — Women who are taking antidepressants and considering pregnancy should talk with their healthcare provider. A woman who takes an antidepressant and discovers she is pregnant should not stop her medication suddenly. Instead, she should speak with her healthcare provider to determine if she should continue, change to another medication, or slowly taper her medication.
The decision to take an antidepressant during pregnancy is difficult due to the potential risks to the mother (if she is not treated or undertreated), her developing baby, and her family. All of the risks and benefits should be discussed with a knowledgeable and experienced healthcare provider, who can help to decide which treatment, if any, is best.
Issues to consider include the following:
Paroxetine (Paxil®) and sertraline (Zoloft®) have been associated with an increased risk of birth defects in babies whose mothers took the drug during the first 13 weeks of pregnancy.
Infants of women who took paroxetine or fluoxetine (Prozac®) during the last 13 weeks of pregnancy have an increased risk of temporary behavior changes. These behavior changes can include tremors or a slightly increased breathing rate, but rarely include more serious problems. Behavior changes usually disappear one to two weeks after birth.
Exposure to tricyclic antidepressants can also cause temporary behavior changes in newborns. If a TCA is required, desipramine and nortriptyline are preferred due to fewer side effects in the fetus.
SSRIs have also been associated with an increased risk of a serious lung problem called persistent pulmonary hypertension of the newborn. The risk is probably small and needs to be considered along with the potentially greater risk to the fetus and mother if the mother’s depression is untreated.
Monoamine oxidase inhibitors (MAOIs) (eg, phenelzine, tranylcypromine) are not recommended for use in pregnant women because animal studies have shown that MAOI exposure may limit the fetus’ growth; there are insufficient data to know if MAOIs have the same effect in humans.
Other antidepressant medications (eg, trazodone, bupropion, mirtazapine) are not recommended as a first line depression treatment because long-term safety data are not available.
There have been no reports of long-term developmental or behavioral problems in children who were exposed to antidepressants during their mother’s pregnancy.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Institute of Mental Health
(www.nimh.nih.gov)
American Psychiatric Association
(www.psych.org)
American Psychological Association
(www.apa.org)
American Academy of Child and Adolescent Psychiatry
(www.aacap.org)
Depression and Bipolar Support Alliance (DBSA)
(www.DBSAlliance.org)
National Foundation For Depressive Illness
(www.depression.org)
National Mental Health Association
(www.nmha.org)
National Alliance for the Mentally Ill
(www.nami.org)
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REFERENCES
1 Depression Guideline Panel. Depression in Primary Care: Treatment of Major Depression: Clinical Practice Guideline. US Dept of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research. AHCPR publication 93-0551, Rockville, MD 1993.
2 Keller, MB, Koesis, JH, Thase, ME, et al. Maintenance phase efficacy of sertraline for chronic depression: A randomized controlled trial. JAMA 1998; 280:1665.
3 Snow, V, Lascher, S, Mottur-Pilson, C. Pharmacologic treatment of acute major depression and dysthymia. Ann Intern Med 2000; 132:738.
4 Woelk, H for the Remotiv/Imipramine Study Group. Comparison of St. John’s wort and imipramine for treating depression: Randomised controlled trial. BMJ 2000; 321:536.
5 Blumenthal, JA, Babyak, MA, Moore, KA, et al. Effects of exercise training on older patients with major depression. Arch Intern Med 1999; 159:2349.
6 Trivedi, MH, Rush, AJ, Gaynes, BN, et al. Maximizing the Adequacy of Medication Treatment in Controlled Trials and Clinical Practice: STAR*D Measurement-Based Care. Neuropsychopharmacology 2007. [Epub ahead of print].
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