Harvard Mental Health Letter

Managing chronic depression

Long-term treatment increases chances of response and remission.

For most patients, episodes of major depression last a limited amount of time. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) specifies that symptoms last at least two weeks, and treatment studies report a median duration of about 20 weeks. But for some patients, the condition becomes chronic — with symptoms lasting at least two years.

The differences between episodic and chronic depression encompass more than just duration. Studies show that, compared with episodic major depression, chronic depression causes more functional impairment, increases risk of suicide, and is more likely to occur in conjunction with other psychiatric disorders. Patients with chronic depression are also more likely than patients with episodic depression to report childhood trauma and a family history of mood disorders.

Because chronic depression lasts longer and tends to be more severe than episodic depression, treatment is more intensive. Relapse is also a challenge. About half of patients with chronic depression who respond to treatment (whether with antidepressants, psychotherapy, or a combination of the two) will suffer a relapse within one to two years if they stop treatment. For that reason, some type of maintenance therapy may be necessary.

Key points

  • By definition, in an episode of major depression, symptoms last at least two weeks. In chronic depression, they last at least two years.

  • Because chronic depression tends to be more severe than episodic depression, treatment is also more intensive.

  • Several subtypes of chronic depression exist, but they have similar long-term effects on health and quality of life.

Varieties of chronic depression

Before diagnosing a patient with chronic depression, it's important to rule out other medical conditions — such as thyroid disease or sleep disorders — that might be causing symptoms.

Several subtypes of chronic depression are described either in the DSM-IV or in the research literature. Although these subtypes differ in some respects, consensus is growing that they have similar long-term effects on health and quality of life.

Dysthymic disorder. The definition of dysthymic disorder has evolved, but the DSM-IV describes it as a type of chronic depression with symptoms that are not numerous or severe enough to meet the criteria for major depression. Dysthymic disorder affects about 6% of the general population at some point in their lives, and 36% of people seeking mental health treatment on an outpatient basis.

When dysthymic disorder occurs on its own (sometimes called "pure dysthymia"), its hallmark is depressed mood, accompanied by at least two additional symptoms of major depression. Some research suggests that dysthymic disorder may cause more cognitive symptoms, such as low self-esteem, difficulty making decisions or concentrating, and pervasive feelings of hopelessness, while major depression may cause more vegetative symptoms, such as poor appetite or overeating, insomnia or excessive sleep, and low energy or fatigue. However, dysthymic disorder seldom occurs on its own — major depression often follows on its heels.

Double depression. Although it is not described in the DSM-IV, the literature defines double depression as an episode of major depression that occurs at least two years after an adult patient — or one year after a child or adolescent — develops dysthymic disorder. More than 75% of patients with dysthymic disorder will experience double depression at some point in their lives. And 25% of patients who seek treatment for major depression will recall having had dysthymic disorder in the past. Researchers do not yet know whether dysthymic disorder is an early manifestation of major depression, or if they are separate disorders with overlapping symptoms.

Chronic major depression. Patients with chronic major depression continually meet the full DSM-IV criteria for a major depressive episode for at least two years. This situation is sadly common. About 20% of patients who develop major depression have not recovered in two years, while 12% have not recovered after five years.

Partial recovery. Some patients continue to experience subthreshold symptoms after treatment for major depression, or relapse within two months. While these less severe symptoms might suggest dysthymic disorder, the DSM-IV defines this pattern — residual symptoms remaining or occurring less than two years after an episode of major depression — as a major depressive episode in partial remission.

Antidepressant options

Controlled short-term clinical trials have evaluated both tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) for treatment of chronic depression. Most found that antidepressants were effective, and that no particular drug was better than another. Studies lasted from six to 12 weeks and reported that 45% to 55% of participants responded (usually defined as at least a 50% reduction in symptoms as measured by the Hamilton Depression Scale score). But only 25% to 35% of patients with chronic depression were able to achieve remission from the first drug — at least in the short term. This remission rate is similar to the results for patients with episodic major depression, as reported by the STAR*D trial.

It may be that patients with chronic depression need to take an antidepressant for an extended period before they experience any benefit. For example, three studies that continued active treatment for four months found that 30% to 40% of patients with chronic depression who were partial responders at the beginning of the treatment phase ended the studies in full remission.

Other studies report that long-term maintenance therapy reduces risk of relapse. Some clinicians therefore recommend that patients with chronic depression continue treatment for six to 12 months to increase chances of remaining in remission.


Although few studies have been published, most evidence supports a type of therapy designed specifically for chronic depression, known as Cognitive Behavioral Analysis System of Psychotherapy (CBASP). Limited evidence also supports tailored versions of cognitive behavioral therapy (CBT) or interpersonal therapy.

CBASP. This variation of CBT was developed by Dr. James P. McCullough at Virginia Commonwealth University. It is based on the premise that patients with chronic depression think, behave, and communicate in ways that make traditional therapy difficult. They tend to focus on themselves, may be uncooperative, and have difficulty controlling emotions. They also tend to view current situations either as a replay of a negative event in the past or a precursor to a similar situation in the future.

CBASP therapy involves exposing and challenging these perceptions and behaviors. For example, using a technique known as situational analysis, the therapist seeks to help a patient break down a distressing event into a sequence of events, and then find junctures where the outcome might have been different had the patient changed his or her behavior or reactions.

A randomized controlled study of 662 patients that compared CBASP, nefazodone (Serzone), or the combination found CBASP was as effective as the drug — with 48% of patients responding to either one alone. (Combining both boosted response rates to 73%.) A follow-up study, involving a subset of patients who responded to CBASP and continued treatment for another year, found monthly CBASP sessions helped prevent a recurrence.

CBT. This therapy helps patients reframe situations in more positive ways. Because patients with chronic depression may have entrenched feelings of hopelessness, however, CBT techniques may need to be more intensive than usual. One review suggested that therapy take place twice a week rather than once a week, and that it target behaviors or thought processes most amenable to change, increasing the chance that patients will see progress.

During therapy, a patient with chronic depression may make dramatic and self-defeating abstract statements, such as "I'm my own worst enemy," or "I'm a mess." It may help to keep the patient focused on specifics, such as details of a particular situation or problem.

Interpersonal therapy. The goal of interpersonal therapy in treating chronic depression is to change the way a patient perceives himself or herself — from being a person with a flawed character (an idea that can develop after years of depressed mood) to being someone with a chronic but treatable disease. Therapy also involves helping a patient to express anger productively, to become assertive, and to take social risks.

Only a few studies have evaluated the use of interpersonal therapy in chronic depression. This preliminary evidence suggests that it may be useful for some patients, but that it requires time and persistence.

Additional issues

Researchers are investigating ways to improve treatment by fine-tuning interventions for particular subsets of patients with chronic depression.

Some intriguing, if preliminary, research on the diverse origins of chronic depression suggests that a patient's individual medical history may help predict which treatments he or she might respond to. The theory is that there are two basic pathways to developing chronic depression: one in which family history of mood disorders creates genetic vulnerability, and the other characterized by an overly reactive stress response that originated with early childhood abuse or maltreatment. Early studies suggest that drug treatment is more effective for patients with a family history of mood disorders, while CBT may be more effective for those with a history of childhood adversity.

Other research suggests that hormones may affect response to treatment of chronic depression. A study comparing sertraline (Zoloft) with imipramine (Tofranil) for treatment of chronic depression found that women who were still menstruating were more likely than men or menopausal women to experience a worsening of symptoms during treatment — suggesting that hormones and premenstrual fluctuations might affect treatment.

A study in 23 middle-aged men with older-onset dysthymic disorder found that symptoms improved in 54% (7 of 13) who received testosterone injections, and in 10% (one in 10) who received placebo injections. This study suggests, as has other research, that late-onset chronic depression may be related to age-related hormonal changes.

And one study suggests that giving patients with chronic depression the type of treatment they want may improve outcomes. The study randomized 429 patients to treatment with nefazodone, CBASP, or the combination — but investigators also asked ahead of time which treatments the patients preferred.

At the end of the study, patients who wanted medication were twice as likely to achieve remission if they were assigned to the drug, and those who preferred psychotherapy were six times as likely to achieve remission on CBASP. In all, about half of the patients who received the treatment they wanted achieved remission — which suggests that one of the simplest ways to improve outcomes is to ask patients what type of treatment they prefer.

Gelenberg AJ, et al. "The State of Knowledge of Chronic Depression," Primary Care Companion to Journal of Clinical Psychiatry (2006): Vol. 8, No. 2, pp. 60–65.

Harvey AT, et al. "Acute Worsening of Chronic Depression During a Double-Blind, Randomized Clinical Trial of Antidepressant Efficacy: Differences by Sex and Menopausal Status," Journal of Clinical Psychiatry (June 2007): Vol. 68, No. 6, pp. 951–58.

Klein DN, et al. "Early Adversity in Chronic Depression: Clinical Correlates and Response to Pharmacotherapy," Depression and Anxiety (2009): Vol. 26, No. 8, pp. 701–10.

Kocsis JH. "Pharmacotherapy for Chronic Depression," Journal of Clinical Psychology (Aug. 2003): Vol. 59, No. 8, pp. 885–92.

McCullough JP, Jr. "Treatment for Chronic Depression Using Cognitive Behavioral Analysis System of Psychotherapy (CBASP)," Journal of Clinical Psychology (Aug. 2003): Vol. 59, No. 8, pp. 833–46.

Seidman SN, et al. "Effects of Testosterone Replacement in Middle-Aged Men with Dysthymia: A Randomized, Placebo-Controlled Clinical Trial," Journal of Clinical Psychopharmacology (June 2009): Vol. 29, No. 3, pp. 216–21.

Torpey DC, et al. "Chronic Depression: Update on Classification and Treatment," Current Psychiatry Reports (Dec. 2008): Vol. 10, No. 6, pp. 458–64.

For more references, please see www.health.harvard.edu/mentalextra.