Dysthymic Disorder

Back

Background

In the American Psychiatric Association’s Diagnostic and Statistical Manual, Fifth Edition (DSM-5), persistent depressive disorder (dysthymia) represents a consolidation of DSM-IV-defined chronic major depressive disorder and dysthymic disorder.[1] Persistent depressive disorder is a depressive mood disorder characterized by a chronic course and an early and inisidious onset (i.e., in childhood, adolescence, or early adulthood). Early onset (i.e., before age 21) is associated with higher risk for comorbid personality disorders and substance use disorders.

Although dysthymia was traditionally considered less severe than major depression, the consequences of dysthymia are increasingly recognized as grave; they include severe functional impairment, increased morbidity from physical disease, and increased risk of suicide. (See Prognosis.)

Anxious versus anergic dysthymia

Niculescu and Akisal proposed that dysthymia be divided into 2 subtypes: anxious dysthymia and anergic dysthymia. They described the subset of patients with anxious dysthymia as having pronounced symptoms of low self-esteem, undirected restlessness, and interpersonal rejection sensitivity. They also characterized these patients as help-seeking and more likely to make lower-lethality suicide attempts and to have a better response to selective serotonin reuptake inhibitors (SSRIs). Substances of choice for these patients include benzodiazepines, alcohol, marijuana, opiates, and possibly food. (See Treatment and Medication.)[2]

This group is compared with persons who have anergic dysthymia, characterized by low energy, hypersomnia, and anhedonia. Patients with anergic dysthymia, the authors suggest, may have a better response to treatment with agents that increase norepinephrine or dopamine. (See Treatment and Medication.)

Of note, an estimated 75% of people with dysthymia meet criteria for at least 1 major depressive episode, referred to as double depression.[3] Those with dysthymia who have depressive episodes tend to have longer periods of depression and spend less time fully recovered.[4] In a 10-year follow-up study of people with dysthymia, 75% experienced some (at least 2 mo) period of recovery from major depression; the mean time to recovery was 52 months from study entry. In this study, most (70%) of those who recovered experienced a relapse into another episode of depression, most commonly in the 3 years following recovery.[5]

Diagnostic criteria (DSM-5)

The specific DSM-5 criteria for persistent depressive disorder (dysthymia) are as follows:[1]

Depressed mood for most of the day, for more days than not, as indicated by either subjective account or observation by others, for at least 2 years. In children and adolescents, mood may be irritable and duration must be at least 1 year.

Presence, while depressed, of two (or more) of the following:

During the 2-year period (1 year for children and adolescents) of the disturbance, the individual has never been without symptoms in Criteria A and B for more than 2 months at a time.

Criteria for major depressive disorder may be continuously present for 2 years.

There has never been a manic episode or a hypomanic episode, and criteria have never been met for cyclothymic disorder.

The disturbance is not better explained by a persistent schizoaffective disorder, schizophrenia, delusional disorder, or other specified or unspecified schizophrenia spectrum and other psychotic disorders.

The symptoms are not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition (e.g., hypothyroidism).

The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

As with other depressive disorders, persistent depressive disorder (dysthymia) can be given further specifiers:

Etiology

The cause of dysthymia, although not clear, is likely multifactorial. A biopsychosocial formulation considering the interplay of family history and other genetic factors, medical problems, psychological make-up and coping strategies, and social stressors is helpful when considering the cause of dysthymia. Some examples of common contributing factors include the following:

Electroencephalogram (EEG) and polysomnogram data demonstrate that about 25% of people who have dysthymia have sleep changes similar to those of persons who have major depression, including shortened rapid eye movement (REM) latency, increased REM density, and poor sleep continuity.

Physiology of dysthymia

The involvement of serotonin and noradrenergic systems in dysthymia is suggested by the disease’s positive clinical responses to serotonergic and noradrenergic medications, such as SSRIs, serotonin/norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants.

Abnormalities in neuroendocrine systems, especially thyroid and hypothalamo-pituitary-adrenocortical (HPA) systems, have been linked to depressive disorders in general, although the HPA axis has not been adequately studied in dysthymic disorder.

Cytokines and inflammation have also been implicated in major depression; however, a link to dysthymia has not been clearly established.[9]

Epidemiology

Frequency

Best estimates are that the lifetime risk of significant depression exceeds 25%, with a point prevalence of about 5%. The lifetime community prevalence of dysthymia is 6%. Dysthymia affects an estimated 36% of patients in outpatient mental health treatment.

Demographics

Minimal research has been performed to define differences in frequency and symptoms between races. One study, the National Health and Nutrition Examination Survey III (NHANES III), found that dysthymia is more common among African Americans and Mexican Americans than among Caucasians.[10]

For major depressive disorders, females outnumber males, with a female-to-male ratio of 2:1 during their childbearing years. Before puberty and after menopause, the 2 sexes appear to be affected about equally. In elderly people, dysthymia is relatively more frequent in females, but dysthymia adversely affects survival in males more than in females.

Prognosis

Dysthymia is by definition chronic. Periods of depression or euthymia may occur during the course of the illness. A systematic review of epidemiologic studies found that 46–71% of persons with dysthymia reported remission at follow-up points ranging from 1–6 years.

Comorbidities, such as anxiety disorders and depressive personality disorder, are associated with lower recovery rates.[11, 12, 13, 14] Chronic stress is associated with more severe symptoms and a lower likelihood of recovery.[13]

With adequate treatment, substantial, prolonged improvement can be expected in most patients. Emphasis is increasing on the importance of striving for remission, rather than response, when treating depressive disorders, as is the strategy with other mood disorders.[15, 16]

Morbidity and mortality

Patients should be closely monitored for the emergence of major depression or bipolar disorder. Review of longitudinal studies showed that 76% of dysthymic children developed major depression and that 13% developed bipolar disorder over follow-up periods of 3–12 years.

Patients with dysthymia have a higher risk of employment problems, including decreased productivity and increased unemployment.[17] A study found that at 6 months, 14% of patients with dysthymia were newly unemployed, compared with 2% new unemployment in the control group and 3% new unemployment in a group with rheumatoid arthritis.[18]

Additional concerns in dysthymia include the following:

Patient Education

If possible, family members and other significant individuals should be helped to understand depression, to view the patient's complaints as symptoms of an illness, and to be sensitive to signs of major depression, with its risk of suicide. For example, an increase in irritability often heralds the progression from dysthymia to depression and may be apparent to people close to the patient before the patient is aware of the change.

The following websites contain additional patient information:

For patient education information, see the Depression Center, as well as Depression.

History

Patients with dysthymia often have a gloomy or negative outlook on life with an underlying sense of personal inadequacy. Compared with major depression, patients' histories tend to include more subjective symptoms, with fewer dramatic psychomotor disturbances or neurovegetative symptoms such as abnormal sleep, appetite, and libido. Some note a diurnal variation, with low energy, inertia, and anhedonia worst in the morning. People with dysthymia may exhibit decreased mental flexibility on neuropsychological testing.

To summarize, the most common symptoms include the following:

Alternative research criteria for dysthymic disorder also include irritability, excessive anger, and guilty brooding about the past.

A family history of a mood disorder is supporting evidence for the diagnosis. Of note, patients with dysthymia are more likely than patients with episodic major depression to have relatives with dysthymia or major depression.[23]

Although people with dysthymia often have social relationships, some research suggests that this population tends to invest most of their expendable energy into work, leaving little for social life or family and placing a strain on personal relationships.

As many as 15% of persons with dysthymia may have comorbid substance dependence. Since substance dependence can lead to symptoms similar to those caused by dysthymia, a detailed substance abuse history should always be obtained.

A physical and mental status examination is needed to confirm the diagnosis and to determine if comorbid diagnoses are present.

Although psychological tests, such as the Minnesota Multiphasic Inventory or the Rorschach, are not administered routinely in current clinical practice, these tests can be quite helpful for diagnostic purposes, ie, differential diagnosis.

Rating scales

The use of depression rating scales is recommended. Many rating scales, both self-administered and clinician rated, are available. The clinician-administered, 17-item Hamilton Rating Scale of Depression (HAM-D) and the self-report scales known as the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16), the Patient Health Questionnaire-9 (PHQ-9), and the Beck Depression Inventory (BDI) are all commonly used.

Simple enough to use on a routine basis, these scales offer diagnostic confirmation and provide a baseline against which change can be evaluated. Studies have emphasized the importance of these rating scales in detecting small changes that may indicate the initial phases of a treatment response.[24] However, use in dysthymia may be different from use in major depressive disorder.

Physical Examination

The mental status examination findings in a person with dysthymic disorder are similar to those seen in major depressive episodes.

Some depressed people are less attentive to their appearance, with decline in attention to dress or grooming. Speech may be slowed or show diminished emotional prosody. Mood is likely to be low, with a congruent affect.

Some observable signs of depressed affect include decreased eye contact, slumped posture, and diminished range of facial expression.

With dysthymia alone, one would expect the patient to retain the ability to convey his or her thoughts in a linear and logical manner and would not expect disorganization in speech or behavior.

Hallucinations or delusions would not be explained by dysthymia and should prompt consideration of other diagnoses.

A safety evaluation is an essential part of any mental status examination; the clinician should inquire about suicidal and homicidal thoughts and plans in persons with dysthymia as they would during any psychiatric examination.

Other thought content could be consistent with sad, hopeless, or guilty themes. One would not expect disruption of intellect, orientation, memory,[25] or abstraction from dysthymia alone.

A mental status examination for a person with dysthymia might include the following:

Physical findings

Although no physical findings are pathognomonic for dysthymia, an examination may reveal the following:

Laboratory Studies

The following lab tests may be carried out in the evaluation of patients with dysthymia:

Imaging Studies

While functional magnetic resonance imaging (fMRI) offers promise in the differential diagnosis of dysthymia, it remains strictly a research tool.

Single-photon emission computed tomography (SPECT) scanning is being offered commercially at some centers, but the existing database on depression may not be adequate, rendering this to likely be limited to an experimental study for the depressive spectrum.

Approach Considerations

Psychotherapy and medication management are effective treatment modalities for dysthymia, and combination treatment is common. Minimal data are available; however, a randomized trial that compared interpersonal psychotherapy, brief supportive psychotherapy, sertraline treatment alone, and sertraline treatment plus interpersonal psychotherapy found the greatest effect when sertraline and interpersonal therapy were combined.

Psychotherapy

Several types of therapy, including psychodynamic, cognitive behavioral, and interpersonal therapy, have been demonstrated in controlled studies to be effective in the treatment of depression and dysthymia.

Short- and long-term psychodynamic psychotherapy are effective for depressive disorders; in particular, they help in developing an individual’s understanding of their relationships and decrease maladaptive interpersonal interactions.[26, 27]

Cognitive behavioral therapy (CBT) is a structured, time-limited treatment that involves recognizing and restructuring cognitive processes leading to depression and noting the relationship between depressive cognitions, mood state, and the individual’s behavior. Cognitive strategies, such as reformulating distorted thinking, and behavioral strategies, such as daily activity scheduling, are effective for depressive symptoms.

Interpersonal therapy (IPT) is also a structured, time-limited treatment. This therapy focuses on current problems and the interpersonal context in which they occur. Success in solving interpersonal conflicts in IPT is associated with improved symptoms of dysthymia.[28, 29]

Although research in this area is limited, group therapy, including CBT and IPT groups, may be helpful for people with dysthymia.[30, 31]

Consultations

Close collaboration among all providers and treatment of any underlying or comorbid medical conditions are essential.

Activity

Studies suggest that individuals with depressed mood are helped by aerobic exercise 4–6 times per week and that any exercise is more helpful than none at all.

Prevention

No studies have focused on prevention, but social supports, adequate exercise, a rewarding occupation, and a generally healthy lifestyle may either be protective or else be evidence of a low propensity toward dysthymia.

Long-Term Monitoring

Inpatient care

Patients should be hospitalized when their psychiatric illness puts them at risk of harming themselves or another person or when it dangerously impairs their ability to care for themselves.

Follow-up and outpatient care

Because of the high rate of relapses from depression and from dysthymia, follow-up is important.

The patient who has recovered with pharmacotherapy should be encouraged to continue follow-up for at least 6 months before considering any medication taper.

Because of the chronic nature of dysthymia, long-term treatment with medications is often advisable. In cases where a medication loses its effectiveness, a new regimen should be considered.

Medication Summary

Antidepressants are effective in treating dysthymia; the mean response for any antidepressant in a review study was 55% among dysthymic patients (compared with 31% response for placebo). Doses are the same as those used for major depression. A systematic review of antidepressant treatment in dysthymia suggested that SSRIs, tricyclic antidepressants, and monoamine oxidase inhibitors (MAOIs) are all equally effective, but SSRIs may be slightly better tolerated. Success has also been reported with more noradrenergic agents such as mirtazapine (Remeron), nefazodone (Serzone), venlafaxine (Effexor), duloxetine (Cymbalta), and bupropion (Wellbutrin).

Comparisons of agents within or between classes have not been reported for dysthymia. A 2007 research summary by the Agency for Healthcare Research and Quality (AHRQ) identified no head-to-head trial comparing different second-generation antidepressants for treatment of dysthymia; comparison between placebo-controlled trials was stymied by significant differences in population characteristics.

The AHRQ noted that in a fair-quality placebo-controlled study, a subgroup of patients older than 60 years showed a significantly greater improvement on paroxetine than did those on placebo, whereas paroxetine was no more effective than placebo in a subgroup of patients younger than 60 years.[32]

While the older antidepressants, such as tricyclics and MAOIs, are effective, the SSRIs are the medications most commonly used for dysthymia, likely because of their relative safety and milder side-effect profile. Given that dysthymia is a chronic condition, tolerability is important to facilitate compliance over the long-term.

Little data exist for choosing one antidepressant over another unless (1) the risk of a particular adverse effect is to be avoided, (2) the patient has a history of prior response to a particular drug, or (3) a drug is known to have been effective for a member of the patient's family.

Of note, antidepressants may cause a temporary worsening of anxiety symptoms; lower doses, slower titration, or temporary use of benzodiazepines (if not contraindicated, for example, because of a substance use disorder) may mitigate anxiety and improve tolerability.

Physicians should be aware of the US Food and Drug Administration (FDA) black box warning regarding antidepressant treatment in children and younger adults and use appropriate caution when considering the risks and benefits of antidepressant treatment in these populations.

In December 2003, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) issued an advisory that most SSRIs are not suitable for use by persons younger than 18 years for treatment of "depressive illness." After review, this agency decided that the risks to pediatric patients outweigh the benefits of treatment with SSRIs, except fluoxetine (Prozac), which appears to have a positive risk-benefit ratio in the treatment of depressive illness in patients younger than 18 years.

In October 2003, the FDA issued a public health advisory regarding reports of suicidality in pediatric patients being treated with antidepressant medications for major depressive disorder. This advisory reported suicidality (ideation and attempts) in clinical trials of various antidepressant drugs in pediatric patients. The FDA has asked that additional studies be performed because suicidality was noted in treated and untreated patients with major depression and thus could not be definitively linked to drug treatment.

Treatment resistance is common in depression and dysthymia. Patients should be closely tracked for residual symptoms and, if symptoms have not remitted, a medication change or an augmentation should be considered to target full remission.[15] Data guiding antidepressant augmentation are drawn from studies in treatment-resistant major depression. The strongest data exists for lithium and thyroid hormone augmentation.

While thyroid dysfunction is common among people with depression and must be treated, thyroid hormone supplementation is an effective augmentation strategy even for patients with normal thyroid function.[33, 34] Buspirone, bupropion, stimulants, and mirtazapine are commonly used in clinical practice.

Bright-light therapy may be considered as an adjunct treatment, especially for patients who experience an exacerbation of symptoms during the winter. This therapy has been best studied in patients with seasonal affective disorder, but limited evidence supports its use in other depressive disorders.[35]

Citalopram (Celexa)

Clinical Context:  Citalopram is an SSRI used to treat depression. It is similar to fluoxetine, sertraline, and paroxetine. A highly selective reuptake inhibitor of serotonin, citalopram has little effect on other neurotransmitters.

Fluvoxamine (Luvox CR)

Clinical Context:  Fluvoxamine is a potent selective inhibitor of neuronal serotonin reuptake. It does not significantly bind to alpha-adrenergic, histamine, or cholinergic receptors and thus has fewer adverse effects than do tricyclic antidepressants. Fluvoxamine was approved initially for OCD but is effective in dysthymia.

Paroxetine (Paxil, Pexeva)

Clinical Context:  Paroxetine is a potent selective inhibitor of neuronal serotonin reuptake. It also has a weak effect on norepinephrine and dopamine neuronal reuptake. For maintenance therapy, adjust the dosage to maintain the patient on the lowest effective dosage, and reassess the patient periodically to determine the need for continued treatment, as is true for all SSRIs.

Fluoxetine (Prozac)

Clinical Context:  Fluoxetine, the best-studied drug, has a long half-life. It selectively inhibits presynaptic serotonin reuptake with minimal or no effect on the reuptake of norepinephrine or dopamine.

Sertraline (Zoloft)

Clinical Context:  Sertraline selectively inhibits presynaptic serotonin reuptake.

Escitalopram (Lexapro)

Clinical Context:  Escitalopram is an SSRI and an S-enantiomer of citalopram. It is used for the treatment of depression. The drug's mechanism of action is thought to be the potentiation of serotonergic activity in the CNS resulting from the inhibition of CNS neuronal reuptake of serotonin.

Class Summary

SSRIs potentiate the pharmacologic effects of serotonin (5-hydroxytryptamine [5-HT]) in the central nervous system (CNS).

Nortriptyline (Pamelor)

Clinical Context:  Nortriptyline has demonstrated effectiveness in the treatment of chronic pain. By inhibiting the reuptake of serotonin and/or norepinephrine by the presynaptic neuronal membrane, this drug increases the synaptic concentration of these neurotransmitters in the CNS. Pharmacodynamic effects such as the desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors also appear to play a role in its mechanisms of action.

Desipramine HCl (Norpramin)

Clinical Context:  Desipramine HCL may increase the synaptic concentration of norepinephrine in the CNS by inhibiting reuptake of norepinephrine by the presynaptic neuronal membrane. It may have effects in the desensitization of adenyl cyclase, down-regulation of beta-adrenergic receptors, and down-regulation of serotonin receptors.

Class Summary

The tricyclics are the prototypical antidepressants. Their anticholinergic (dry mouth) and antihistaminic (sedating) effects make noncompliance more of a problem than with the newer drugs. This is particularly a problem when the depressive symptoms are relatively mild. However, their very broad-based actions on a variety of neurotransmitters make them effective on occasions when SSRIs fail. Adverse effects with the so-called second-generation drugs generally are less of a problem.

Duloxetine (Cymbalta)

Clinical Context:  Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake. Its antidepressive action is theorized to be due to serotonergic and noradrenergic potentiation in the CNS.

Bupropion (Wellbutrin, Budeprion SR, Budeprion XL, Wellbutrin SR)

Clinical Context:  Bupropion inhibits neuronal dopamine reuptake, but it is also a weak blocker of serotonin and norepinephrine reuptake. A low incidence of sexual dysfunctions occurs with this medication. Bupropion binds to the nicotinic receptor and helps with smoking cessation.

Mirtazapine (Remeron, Remeron SolTab)

Clinical Context:  Mirtazapine is an antidepressant that is not chemically related to the tricyclics or to any other class of antidepressants. Its primary mechanism of action is antagonism at the central presynaptic alpha-2 receptors. The actions of the drug change as the dose is raised. Mirtazapine exhibits noradrenergic and serotonergic activity.

Venlafaxine (Effexor, Effexor XR)

Clinical Context:  Venlafaxine is structurally unrelated to other available antidepressants. It inhibits serotonin reuptake at select receptors, as well as the reuptake of norepinephrine.

Class Summary

The mixed serotonergic and noradrenergic drugs have effects on serotonin, norepinephrine, and, in some cases, dopamine and even on nicotinic acetylcholine systems. Because of the empirical nature of psychopharmacology, they may be used as first-line drugs or as follow-up agents when SSRIs fail.

T3, liothyronine (Cytomel, Triostat)

Clinical Context:  Liothyronine is a synthetic form of natural thyroid hormone T3 converted from T4. Its duration of activity is short and allows for quick dosage adjustments in the event of overdosage. Liothyronine may need to be administered as often as 4 times daily. In its active form, the drug influences the growth and maturation of tissues.

The dose should be one quarter of the T4 dose, according to some; others recommend administering liothyronine alone.

T3/T4 combinations (Armour Thyroid, Westhroid, Nature-Throid)

Clinical Context:  These are mixtures of 1 part T3 to 4 parts T4; they carry the same advice and warnings that the 2 hormones do when administered separately. For desiccated thyroid, 1 grain (60 mg) contains 38 mcg T4 and 9 mcg T3. Thyrolar 1 contains 50 mcg T4 and 12.5 mcg T3.

Class Summary

These drugs are administered as an augmentation strategy. They may convert nonresponders (to antidepressants) to responders by increasing receptor sensitivity and enhancing the effects of antidepressants, particularly tricyclic antidepressants.

Author

Jerry L Halverson, MD, Medical Director of Rogers Memorial Hospital at Oconomowoc; Voluntary Clinical Assistant Professor, Department of Psychiatry, University of Wisconsin School of Medicine and Public Health; Clinical Assistant Professor of Psychiatry, Department of Psychiatry and Behavioral Sciences, Medical College of Wisconsin

Disclosure: Nothing to disclose.

Chief Editor

David Bienenfeld, MD, Professor, Departments of Psychiatry and Geriatric Medicine, Wright State University, Boonshoft School of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Sarah C Langenfeld, MD Assistant Professor, Department of Psychiatry, University of Massachusetts Medical School; Attending Psychiatrist, Community HealthLink

Sarah C Langenfeld, MD is a member of the following medical societies: American Medical Association, American Psychiatric Association, and Massachusetts Medical Society

Disclosure: Nothing to disclose. Rebecca S Lundquist, MD Consulting Staff, Department of Psychiatry, UMass Memorial Medical Center

Rebecca S Lundquist, MD is a member of the following medical societies: American Psychiatric Association

Disclosure: Pfizer Salary Employment; Biogen Salary Employment

Alan D Schmetzer, MD Professor Emeritus, Interim Chairman, Vice-Chair for Education, Associate Residency Training Director in General Psychiatry, Fellowship Training Director in Addiction Psychiatry, Department of Psychiatry, Indiana University School of Medicine; Addiction Psychiatrist, Midtown Mental Health Cener at Wishard Health Services

Alan D Schmetzer, MD is a member of the following medical societies: American Academy of Addiction Psychiatry, American Academy of Clinical Psychiatrists, American Academy of Psychiatry and the Law, American College of Physician Executives, American Medical Association, American Neuropsychiatric Association, American Psychiatric Association, and Association for Convulsive Therapy

Disclosure: Eli Lilly & Co. Grant/research funds Other

Brian R Szetela, MD Assistant Professor, Department of Psychiatry, University of Massachusetts Medical School; Consulting Psychiatrist, Psychiatric Consultation - Liaison Service, University of Massachusetts Memorial Medical Center

Brian R Szetela, MD is a member of the following medical societies: American Psychiatric Association, American Society of Addiction Medicine, and Association for Convulsive Therapy

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References

  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Washington, DC: American Psychiatric Association; 2013.
  2. Niculescu AB 3rd, Akiskal HS. Proposed endophenotypes of dysthymia: evolutionary, clinical and pharmacogenomic considerations. Mol Psychiatry. 2001 Jul. 6(4):363-6. [View Abstract]
  3. Keller MB, Harrison W, Fawcett JA, Gelenberg A, Hirschfeld RM, Klein D, et al. Treatment of chronic depression with sertraline or imipramine: preliminary blinded response rates and high rates of undertreatment in the community. Psychopharmacol Bull. 1995. 31(2):205-12. [View Abstract]
  4. Klein DN, Schwartz JE, Rose S, Leader JB. Five-year course and outcome of dysthymic disorder: A prospective, naturalistic follow-up study. Am J Psychiatry. 2000 Jun. 157(6):931-9. [View Abstract]
  5. Klein DN, Shankman SA, Rose S. Ten-year prospective follow-up study of the naturalistic course of dysthymic disorder and double depression. Am J Psychiatry. 2006 May. 163(5):872-80. [View Abstract]
  6. Kelly O, Matheson K, Ravindran A, Merali Z, Anisman H. Ruminative coping among patients with dysthymia before and after pharmacotherapy. Depress Anxiety. 2007. 24(4):233-43. [View Abstract]
  7. Hermens ML, van Hout HP, Terluin B, van der Windt DA, Beekman AT, et al. The prognosis of minor depression in the general population: a systematic review. Gen Hosp Psychiatry. 2004 Nov-Dec. 26(6):453-62. [View Abstract]
  8. Johnson JG, Cohen P, Kasen S, Brook JS. Personality disorder traits associated with risk for unipolar depression during middle adulthood. Psychiatry Res. 2005 Sep 15. 136(2-3):113-21. [View Abstract]
  9. Ho PS, Yen CH, Chen CY, Huang SY, Liang CS. Changes in cytokine and chemokine expression distinguish dysthymic disorder from major depression and healthy controls. Psychiatry Res. 2017 Feb. 248:20-27. [View Abstract]
  10. Riolo SA, Nguyen TA, Greden JF, King CA. Prevalence of depression by race/ethnicity: findings from the National Health and Nutrition Examination Survey III. Am J Public Health. 2005 Jun. 95(6):998-1000. [View Abstract]
  11. Shankman SA, Klein DN. The impact of comorbid anxiety disorders on the course of dysthymic disorder: a 5-year prospective longitudinal study. J Affect Disord. 2002 Jul. 70(2):211-7. [View Abstract]
  12. Laptook RS, Klein DN, Dougherty LR. Ten-year stability of depressive personality disorder in depressed outpatients. Am J Psychiatry. 2006 May. 163(5):865-71. [View Abstract]
  13. Hayden EP, Klein DN. Outcome of dysthymic disorder at 5-year follow-up: the effect of familial psychopathology, early adversity, personality, comorbidity, and chronic stress. Am J Psychiatry. 2001 Nov. 158(11):1864-70. [View Abstract]
  14. Markowitz JC, Skodol AE, Petkova E, Xie H, Cheng J, Hellerstein DJ, et al. Longitudinal comparison of depressive personality disorder and dysthymic disorder. Compr Psychiatry. 2005 Jul-Aug. 46(4):239-45. [View Abstract]
  15. Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov. 163(11):1905-17. [View Abstract]
  16. Rush AJ, Kraemer HC, Sackeim HA, et al. Report by the ACNP Task Force on response and remission in major depressive disorder. Neuropsychopharmacology. 2006 Sep. 31(9):1841-53. [View Abstract]
  17. Adler DA, Irish J, McLaughlin TJ, Perissinotto C, Chang H, Hood M, et al. The work impact of dysthymia in a primary care population. Gen Hosp Psychiatry. 2004 Jul-Aug. 26(4):269-76. [View Abstract]
  18. Lerner D, Adler DA, Chang H, Lapitsky L, Hood MY, Perissinotto C. Unemployment, job retention, and productivity loss among employees with depression. Psychiatr Serv. 2004 Dec. 55(12):1371-8. [View Abstract]
  19. Barbui C, Motterlini N, Garattini L. Health status, resource consumption, and costs of dysthymia. A multi-center two-year longitudinal study. J Affect Disord. 2006 Feb. 90(2-3):181-6. [View Abstract]
  20. Bernal M, Haro JM, Bernert S, Brugha T, de Graaf R, Bruffaerts R, et al. Risk factors for suicidality in Europe: results from the ESEMED study. J Affect Disord. 2007 Aug. 101(1-3):27-34. [View Abstract]
  21. Bakken K, Vaglum P. Predictors of suicide attempters in substance-dependent patients: a six-year prospective follow-up. Clin Pract Epidemol Ment Health. 2007. 3:20. [View Abstract]
  22. Casement MD, Shestyuk AY, Best JL, Casas BR, Glezer A, Segundo MA, et al. Anticipation of affect in dysthymia: behavioral and neurophysiological indicators. Biol Psychol. 2008 Feb. 77(2):197-204. [View Abstract]
  23. Klein DN, Shankman SA, Lewinsohn PM, Rohde P, Seeley JR. Family study of chronic depression in a community sample of young adults. Am J Psychiatry. 2004 Apr. 161(4):646-53. [View Abstract]
  24. Keitner GI, Ryan CE, Solomon DA. Realistic expectations and a disease management model for depressed patients with persistent symptoms. J Clin Psychiatry. 2006 Sep. 67(9):1412-21. [View Abstract]
  25. Airaksinen E, Larsson M, Lundberg I, Forsell Y. Cognitive functions in depressive disorders: evidence from a population-based study. Psychol Med. 2004 Jan. 34(1):83-91. [View Abstract]
  26. Leichsenring F, Hiller W, Weissberg M, Leibing E. Cognitive-behavioral therapy and psychodynamic psychotherapy: techniques, efficacy, and indications. Am J Psychother. 2006. 60(3):233-59. [View Abstract]
  27. Leichsenring F, Leibing E. Psychodynamic psychotherapy: a systematic review of techniques, indications and empirical evidence. Psychol Psychother. 2007 Jun. 80:217-28. [View Abstract]
  28. Markowitz JC, Bleiberg KL, Christos P, Levitan E. Solving interpersonal problems correlates with symptom improvement in interpersonal psychotherapy: preliminary findings. J Nerv Ment Dis. 2006 Jan. 194(1):15-20. [View Abstract]
  29. Markowitz JC, Kocsis JH, Bleiberg KL, Christos PJ, Sacks M. A comparative trial of psychotherapy and pharmacotherapy for "pure" dysthymic patients. J Affect Disord. 2005 Dec. 89(1-3):167-75. [View Abstract]
  30. Bolton P, Bass J, Neugebauer R, Verdeli H, Clougherty KF, Wickramaratne P. Group interpersonal psychotherapy for depression in rural Uganda: a randomized controlled trial. JAMA. 2003 Jun 18. 289(23):3117-24. [View Abstract]
  31. Johnson JE, Zlotnick C. A pilot study of group interpersonal psychotherapy for depression in substance-abusing female prisoners. J Subst Abuse Treat. 2008 Jun. 34(4):371-7. [View Abstract]
  32. Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression. Accessed: May 19, 2009. AHRQ: Agency for Healthcare Research and Quality. Jan. 24, 2007. Available at http://www.effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productid=61
  33. Carvalho AF, Cavalcante JL, Castelo MS, Lima MC. Augmentation strategies for treatment-resistant depression: a literature review. J Clin Pharm Ther. 2007 Oct. 32(5):415-28. [View Abstract]
  34. Lifschytz T, Segman R, Shalom G, Lerer B, Gur E, Golzer T, et al. Basic mechanisms of augmentation of antidepressant effects with thyroid hormone. Curr Drug Targets. 2006 Feb. 7(2):203-10. [View Abstract]
  35. Tuunainen A, Kripke DF, Endo T. Light therapy for non-seasonal depression. Cochrane Database Syst Rev. 2004. CD004050. [View Abstract]
  36. McCullough JP Jr, Klein DN, Borian FE, Howland RH, Riso LP, Keller MB, et al. Group comparisons of DSM-IV subtypes of chronic depression: validity of the distinctions, part 2. J Abnorm Psychol. 2003 Nov. 112(4):614-22. [View Abstract]
  37. Kessing LV. Epidemiology of Subtypes of Depression. Acta Psychiatr Scand. 2007. 115 (Suppl 433):85-89.
  38. Murphy JA, Byrne GJ. Prevalence and correlates of the proposed DSM-5 diagnosis of Chronic Depressive Disorder. J Affect Disord. 2012 Feb 29. [View Abstract]
  39. Olfson M, Liu SM, Grant BF, Blanco C. Influence of comorbid mental disorders on time to seeking treatment for major depressive disorder. Med Care. 2012 Mar. 50(3):227-32. [View Abstract]
  40. Ryder AG, Schuller DR, Bagby RM. Depressive personality and dysthymia: evaluating symptom and syndrome overlap. J Affect Disord. 2006 Apr. 91(2-3):217-27. [View Abstract]
  41. Masi G, Millepiedi S, Mucci M, Pascale RR, Perugi G, Akiskal HS. Phenomenology and comorbidity of dysthymic disorder in 100 consecutively referred children and adolescents: beyond DSM-IV. Can J Psychiatry. 2003 Mar. 48(2):99-105. [View Abstract]
  42. Hellerstein DJ, Batchelder S, Miozzo R, Kreditor D, Hyler S, Gangure D. Citalopram in the treatment of dysthymic disorder. Int Clin Psychopharmacol. 2004 May. 19(3):143-8. [View Abstract]

The various outcomes of dysthymia.