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DEPRESSION OVERVIEW — Clinical depression is a medical condition that goes beyond everyday sadness. Depression may cause serious, long-lasting symptoms and often disrupts a person’s ability to perform routine tasks. The disorder is the most common psychiatric disorder worldwide. In the United States, about one in six people experiences a bout of clinical depression in their lifetime.
The treatment of depression is important because people with untreated depression have a lower quality of life, a higher risk of suicide, and worse physical outcomes if they have any medical conditions besides depression. In fact, people with depression are almost twice as likely to die as people without the condition. What’s more, depression affects not only the people with the disorder but also those around them.
This topic reviews the initial treatment of depression in adults. The clinical features and diagnosis of depression in adults are discussed separately, as are the diagnosis and treatment of depression in children and adolescents (See "Patient education: Depression in adults (Beyond the Basics)" and "Patient education: Depression in children and adolescents (Beyond the Basics)" and "Patient education: Depression treatment options for children and adolescents (Beyond the Basics)".)
More detailed information about depression is available by subscription. (See "Unipolar depression in adults: Clinical features" and "Unipolar major depression in adults: Choosing initial treatment" and "Unipolar depression in adults and initial treatment: General principles and prognosis" and "Severe antenatal unipolar major depression: Treatment" and "Unipolar depression in adults: Treatment of resistant depression" and "Unipolar depression in adults: Management of highly resistant (refractory) depression".)
DEFINITION OF DEPRESSION — When people talk about depression, they’re usually referring to what healthcare providers call “unipolar major depression” (or major depressive disorder). The diagnosis of unipolar major depression is discussed in detail elsewhere. (See "Patient education: Depression in adults (Beyond the Basics)".)
Briefly, to be diagnosed with unipolar major depression, a person must have five or more of the following symptoms present most of the day nearly every day for at least two weeks in a row. For the diagnosis, at least one symptom must be either depressed mood or loss of interest or pleasure.
●Loss of interest or pleasure in most or all activities
●Change in appetite or weight
●Insomnia or hypersomnia (sleeping too little or too much)
●Psychomotor agitation or retardation (restlessness or sluggishness)
●Fatigue or loss of energy
●Feelings of worthlessness or excessive guilt
●Recurrent thoughts of death or suicide
For the purposes of this discussion, we will use depression to mean unipolar major depression. There are other subtypes of depression, as well, but those are beyond the scope of this article.
TREATMENT FOR MAJOR DEPRESSION — For the initial treatment of depression, we suggest a combination of antidepressant medication and psychotherapy. Well-designed studies have shown that combination treatment is more effective than either treatment on its own. Nevertheless, either treatment can also be given alone, as studies have also shown that each is effective and comparable to the other.
Despite being comparably effective, one advantage of psychotherapy is that some of its benefits often persist even after active treatment ends. Psychotherapy may help people develop new coping skills as well as more adaptive ways of thinking about life problems. The same is not necessarily true of antidepressants; many who take antidepressants alone relapse after stopping them.
ANTIDEPRESSANTS — Individual medications are grouped into what healthcare providers call classes. All the medications within a particular class are chemically related and function in a similar way. The more commonly used medications are from the following classes:
●Selective serotonin reuptake inhibitors (SSRIs)
●Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Older, less commonly used, antidepressants include:
●Monoamine oxidase inhibitors (MAOIs) – People taking MAOIs should avoid or limit certain foods, which can interact with the medication and cause serious health problems (table 1).
Selecting an antidepressant — For people with mild to moderate depression who start treatment with an antidepressant, we suggest SSRIs. Among the different antidepressants, SSRIs offer as much benefit as other medications with the least amount of risk in terms of safety and side effects. They are the most widely prescribed class of antidepressants.
Reasonable alternatives to SSRIs include other second-generation antidepressants, namely serotonin-norepinephrine reuptake inhibitors, atypical antidepressants, and serotonin modulators (table 2). The antidepressants in these groups are—generally speaking—comparably effective.
Tricyclic antidepressants and monoamine oxidase inhibitors are typically not used as initial treatment because they can cause serious side effects and be dangerous (particularly in overdose).
Since all the second-generation antidepressants are roughly equivalent in terms of efficacy, healthcare providers select them based on other factors, such as:
●Each medication’s safety and side effect profile (table 2)
●The person’s specific symptoms or other illnesses
●The other medications the person is taking and whether they could interact with the chosen antidepressant
●Each medication’s ease of use (for example based on the number of pills the person must take each day)
●What the person prefers
●The cost of a medication and whether it is covered by insurance
●The person’s previous responses to antidepressants (during past bouts of depression)
●The response the person’s close family members have had to antidepressants
For example, for people who have trouble sleeping, healthcare providers often favor antidepressants known to promote sleep, such as mirtazapine. Similarly, for people who want to avoid the sexual side effects caused by many antidepressants, healthcare providers might favor bupropion, which is less likely to cause these side effects.
At this time, there is no evidence that using a genetic, psychological, or biological test to guide the choice of medication leads to better outcomes than the doctor using his or her knowledge and best judgment.
Side effects — The table lists the most common side effects for the main available antidepressants and how likely each set of side effects is to occur (table 3A-B). Some side effects (such as nausea) are common to many of the antidepressants, while others are more medication-specific. However, many side effects, including nausea, are often temporary and go away after a few days or weeks of use.
Dose — In general, healthcare providers tend to start their patients on low doses and slowly increase them as necessary. This helps minimize the likelihood of side effects.
How long before antidepressants take effect? — Antidepressants often take time to work, but many people start to feel better within one to two weeks. In fact, the people who see some benefit early on after starting an antidepressant appear to be the ones most likely to completely recover. That being said, it can take 6 to 12 weeks to see the full effect of an antidepressant, so healthcare providers generally wait that long to determine whether a particular medication or dose is effective. Still, if you’re not getting much or any relief from your symptoms after two to four weeks, it may make sense to change the plan. This might include increasing your dose, adding an additional medication, switching medication, or taking some other next step.
It’s important to keep in mind that each person’s response to antidepressants is different, and the medications take some time to take effect. If you are put on an antidepressant, give it a few weeks to start working. If you are having uncomfortable side effects, tell your healthcare provider. Some side effects go away over time, but others do not, and it might be possible to find a dose or alternate medication that causes fewer side effects. Finding the right medication (or combination of medications) and the right doses can take some trial and error, so try not to get discouraged.
PSYCHOTHERAPY — All forms of psychotherapy include support from a professional who is focused on helping you to make positive changes. There are many specific types of psychotherapy that are used to treat depression. Each works in a slightly different way, but all have been proven to help improve the symptoms of depression. What’s more, many psychotherapists use a combination of techniques when working with clients. Options include the following:
●Cognitive-behavioral therapy (CBT) – In CBT you work with a therapist to identify and reshape the thought and behavior patterns that contribute to your depression.
●Interpersonal psychotherapy – In interpersonal psychotherapy, you focus on your relationships, the way that you interact with other people in your life, and the different roles you play. Often you learn new ways to interact that can help improve those relationships
●Family and couples therapy – In family and couples therapy, you attend therapy sessions along with your partner or family members so that you can work together on the issues that are contributing to your depression.
●Problem solving therapy – In problem-solving therapy, you take a very practical and systematic approach to the problems in your life and find effective ways to solve them. If you are unemployed, for example, you work with your therapist to develop action steps you can accomplish as a way of achieving your goal of getting a job.
●Psychodynamic psychotherapy – In psychodynamic therapy, you might explore childhood or historic life events and work to reduce their influence by gaining insight into how they may be shaping your current behavior.
Selecting a psychotherapy — If there’s a particular form of psychotherapy that appeals to you more than another, ask the therapist you are thinking of working with whether he or she uses that form of therapy. Keep in mind, though, that the most important aspect of psychotherapy is the relationship and rapport you have with therapist you choose.
Clinician guided self-help — Instead of attending formal therapy sessions, some people opt to work on their own with a little guidance from a healthcare provider. This approach is called clinician guided self-help and involves the use of workbooks (hardcopy, compact disc, or internet-based), audiotapes, or videotapes. People who choose this approach check in periodically with their healthcare provider but the interactions are much more brief and infrequent compared with formal therapy.
Guided self-help can be a good choice for people who have mild depression and have no thoughts of death or suicide. People who fall into this category can even try self-help approaches on their own, without checking in with a healthcare provider, unless their symptoms start to get worse.
Psychotherapy compared with antidepressants — Research shows that psychotherapy is about as effective as antidepressants in treating most people with major depression. One advantage of psychotherapy is that its benefits often last even after treatment stops, whereas those of antidepressants wear off fairly quickly, once the antidepressant is stopped or tapered. For that reason, people who stop taking antidepressants may be more likely to relapse than those who stop psychotherapy. This is another reason why combining psychotherapy and antidepressants may be the best approach.
Relaxation, exercise, and positive activities — We suggest combining formal treatment with some add-on activities that may help to alleviate depression and any accompanying anxiety symptoms. Among these are relaxation techniques (such as progressive muscle relaxation) and exercise. We also suggest that people resume the activities they stopped doing because of their depression. People sometimes think that once their depression lifts, they’ll go back to doing those activities, but it turns out that resuming those activities—even while still depressed—may help turn the depression around.
Exercise in particular may have an especially positive effect on depression. Several studies suggest that exercise can ease depression. We suggest three to five exercise sessions per week, that last 45 to 60 minutes per session, for at least 10 weeks, and that involve aerobic exercise (such as walking, running, or cycling) or resistance training (upper and lower body weight lifting).
Anxiety and insomnia — Many people with depression also have problems with anxiety and sleeplessness. Antidepressants can help with both of those symptoms but sometimes take a while to start working. If you are very anxious or having a very hard time sleeping, your healthcare provider can prescribe medications to deal with both while you wait for your antidepressants start working. Relaxation exercises and psychotherapy may also help with accompanying anxiety and insomnia.
TREATMENT FOR SEVERE MAJOR DEPRESSION — For people with severe depression, we suggest a combination of antidepressant medication and psychotherapy. It’s also reasonable to try antidepressants alone. (Psychotherapy is generally not used alone for patients with severe depression.) Another reasonable treatment for severe depression is electroconvulsive therapy (ECT), particularly in people who are actively thinking about suicide and who may be in danger of following through on their plans. ECT is discussed at elsewhere (See "Patient education: Electroconvulsive therapy (ECT) (Beyond the Basics)".)
Severe depression — People with severe major depression have one or more of the following characteristics:
●They have thoughts of and plans for suicide or homicide.
●They have psychotic symptoms, such as delusions or hallucinations.
●They have a condition called catatonia, which involves being unable to move or talk normally.
●Their judgement is impaired such that people (including themselves) may be at risk for harm.
●Their basic functioning is impaired. For example, they may refuse to eat or drink which may lead to malnourishment or dehydration.
People with severe major depression usually need to be seen by a psychiatrist and sometimes need to be hospitalized.
Choosing an antidepressant — For the initial treatment of severe depression, we use serotonin-norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs). In people who have symptoms of psychosis (hallucinations, delusions), starting with an antidepressant and antipsychotic medication may be appropriate.
Some healthcare providers start with SNRIs because studies suggest that these medications are more likely than SSRIs to alleviate severe depression. A reasonable alternative to SNRIs or SSRIs is a medication called mirtazapine (brand name: Remeron). It, too, has been shown to be effective in treating severe depression.
Tricyclic antidepressants are another reasonable alternative for severe depression. However, tricyclics can be dangerous in overdose and cause serious side effects, so some healthcare providers prefer to avoid prescribing them until safer alternatives have been tried.
DEPRESSION AND PREGNANCY — Women who have depression and want to become pregnant or who develop depression while pregnant sometimes have a tough decision to make regarding the use of antidepressants. Taking antidepressants during pregnancy may slightly increase the risk of miscarriage, premature delivery, and low birth weight. Studies examining whether there has been an increased rate of birth defects associated with taking antidepressants in pregnancy have been inconsistent with some showing higher risk and others showing no increased risk. On the other hand, leaving depression untreated during pregnancy increases the risk of premature delivery, low birth weight, missed obstetrical appointments, anorexia, suicidality and other depressive symptoms, and substance (drug and alcohol) use disorders.
Given these risks, women must work with their healthcare providers to weigh the pros and cons of using antidepressants to treat depression during pregnancy.
The risks of antidepressants, generally speaking, are small, and they vary based on which specific medication is used, the dose, the duration of use, and when during the course of the pregnancy the medication is used. Still, because risks do exist, experts recommend avoiding antidepressants or minimizing their use during pregnancy whenever possible. Among the different choices, experts suggest that some medications, such as the SSRIs sertraline (brand name: Zoloft) and citalopram (brand name: Celexa) appear to confer the lowest risks to the fetus. However, you and your healthcare provider must look at your own set of circumstances and make the decision based on the risks and benefits unique to you.
Planning to become pregnant — Women who would like to become pregnant and are on antidepressants should discuss their plans with a healthcare provider. Women who are no longer depressed but are still taking antidepressants may want to consider going off them for their pregnancy. Studies show that women who stop antidepressants during pregnancy are more likely to relapse than women who continue medication. On the other hand, stopping the medications may lower risks to the baby.
Women who prefer to stay on antidepressants during pregnancy should work with their healthcare providers if the women want to switch to antidepressants that current literature suggests are the safest among the antidepressants for developing fetus. However, switching antidepressants may increase the risk of depression relapse.
Already pregnant — Here are the main recommendations regarding the treatment of depression in women who are already pregnant:
●Women who get pregnant while on antidepressants and want to go off them should do so slowly, not all at once, with guidance and input from a healthcare provider.
●For pregnant women with mild to moderate depression, experts suggest psychotherapy as initial treatment, rather than antidepressants. Antidepressants are a reasonable choice if psychotherapy is unsuccessful or not an option. Antidepressants are also a reasonable option for women who responded well to medications for past episodes of depression and for women with a history of severe depression.
●For pregnant women with severe depression, experts suggest selective serotonin reuptake inhibitors (SSRIs) as initial treatment, rather than other antidepressants. Among the SSRIs, experts consider sertraline or citalopram to be among the safest choices. Paroxetine is generally not recommended due to concerns about possible birth defects. Psychotherapy, in addition to antidepressants, may also be helpful.
●For pregnant women who are no longer depressed but who are taking antidepressants to prevent depression relapse, they should discuss with their healthcare provider whether to discontinue medications for the first trimester—during which the baby’s organs are formed. Oftentimes, healthcare providers will restart treatment during the second trimester when there is less risk to the fetus. Keep in mind that any time antidepressants are stopped, there is a chance of relapse; therefore, all such decisions about taking antidepressants should be discussed with a healthcare provider.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Patient education: Depression (The Basics)
Patient education: Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) (The Basics)
Patient education: Medicines for depression (The Basics)
Patient education: Electroconvulsive therapy (ECT) (The Basics)
Patient education: Post-traumatic stress disorder (The Basics)
Patient education: Postpartum depression (The Basics)
Patient education: When you have depression and another health problem (The Basics)
Patient education: Serotonin syndrome (The Basics)
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient education: Depression in adults (Beyond the Basics)
Patient education: Depression in children and adolescents (Beyond the Basics)
Patient education: Depression treatment options for children and adolescents (Beyond the Basics)
Patient education: Electroconvulsive therapy (ECT) (Beyond the Basics)
Patient education: Bipolar disorder (manic depression) (Beyond the Basics)
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Unipolar major depression in adults: Choosing initial treatment
Switching antidepressant medications in adults
Unipolar depression in adults: Assessment and diagnosis
Pediatric unipolar depression: Epidemiology, clinical features, assessment, and diagnosis
Unipolar major depression during pregnancy: Epidemiology, clinical features, assessment, and diagnosis
Diagnosis and management of late-life unipolar depression
Diagnosis of psychiatric disorders in patients with cancer
Management of psychiatric disorders in patients with cancer
Postpartum psychosis: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis
Treatment of postpartum psychosis
Seasonal affective disorder: Epidemiology, clinical features, assessment, and diagnosis
Unipolar depression in adults: Treatment of resistant depression
Comorbid anxiety and depression in adults: Epidemiology, clinical manifestations, and diagnosis
Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects
Serotonin-norepinephrine reuptake inhibitors (SNRIs): Pharmacology, administration, and side effects
Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects
Monoamine oxidase inhibitors (MAOIs) for treating depressed adults
Overview of electroconvulsive therapy (ECT) for adults
The following organizations also provide reliable health information.
●National Library of Medicine
●National Institute of Mental Health
●American Psychiatric Association
●American Psychological Association
●American Academy of Child and Adolescent Psychiatry
●Depression and Bipolar Support Alliance (DBSA)
●National Alliance on Mental Illness
ACKNOWLEDGMENT — We are saddened by the death of Wayne Katon, MD, who passed away in March 2015. UpToDate wishes to acknowledge Dr. Katon's past work as an author for this topic.
- Keller MB, Kocsis JH, Thase ME, et al. Maintenance phase efficacy of sertraline for chronic depression: a randomized controlled trial. JAMA 1998; 280:1665.
- Snow V, Lascher S, Mottur-Pilson C. Pharmacologic treatment of acute major depression and dysthymia. American College of Physicians-American Society of Internal Medicine. Ann Intern Med 2000; 132:738.
- Woelk H. Comparison of St John's wort and imipramine for treating depression: randomised controlled trial. BMJ 2000; 321:536.
- Blumenthal JA, Babyak MA, Moore KA, et al. Effects of exercise training on older patients with major depression. Arch Intern Med 1999; 159:2349.
- 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.
- 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; 32:2479.