The various outcomes of dysthymia.
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.)
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]
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:
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.
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]
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.
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.
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]
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:
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.
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.
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.
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:
Although no physical findings are pathognomonic for dysthymia, an examination may reveal the following:
The following lab tests may be carried out in the evaluation of patients with dysthymia:
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.
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.
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]
Close collaboration among all providers and treatment of any underlying or comorbid medical conditions are essential.
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.
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.
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.
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.
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]
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.
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.
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.
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.
Clinical Context: Sertraline selectively inhibits presynaptic serotonin reuptake.
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.
SSRIs potentiate the pharmacologic effects of serotonin (5-hydroxytryptamine [5-HT]) in the central nervous system (CNS).
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.
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.
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.
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.
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.
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.
Clinical Context: Venlafaxine is structurally unrelated to other available antidepressants. It inhibits serotonin reuptake at select receptors, as well as the reuptake of norepinephrine.
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.
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.
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.
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.
The various outcomes of dysthymia.
