AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Background

Dysthymic disorder is a depressive mood disorder characterized by a chronic course and an insidious onset. Many people with dysthymia report that they have been depressed all of their lives and have an outlook colored by chronic depression.

The current consensus is that major depressive disorder, dysthymia, double depression (a major depressive episode superimposed upon underlying dysthymia), and some apparently transient dysphorias all are manifestations of the same disease process. These varieties of depressive mood states share similar symptoms and respond to similar medications and psychotherapeutic approaches.

By definition, dysthymia is a chronic mood disorder, with a duration of at least 2 years in adults and 1 year in adolescents and children. It is manifested as depressed mood for most of the day, occurring more days than not, and accompanied by at least 2 of the following symptoms:

• Poor appetite or overeating
• Insomnia or hypersomnia
• Low energy or fatigue
• Low self-esteem
• Poor concentration
• Difficulty making decisions
• Feelings of hopelessness.

To diagnose dysthymia, manic episodes must not have occurred, and major depressive episodes must not have occurred in the first 2 years of the illness (1 year in children). The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV TR) allows transient euthymic episodes (periods of normal mood) of up to 2 months during the course of dysthymia.

Dysthymia should be differentiated from major depression. In contrast to dysthymia, major depression is diagnosed if 5 or more of the following symptoms have been present most of the day, every day, for the past 2 weeks:

• Depressed mood
• Loss of interest or pleasure in usual activities
• Significant weight loss or gain
• Insomnia or hypersomnia
• Psychomotor agitation or retardation
• Fatigue or loss of energy
• Feelings of worthlessness or excessive or inappropriate guilt
• Diminished ability to think or concentrate
• Recurrent thoughts of death or suicide

For major depression to be diagnosed, depressed mood and/or significant loss of interest or pleasure in activities must be present. Differentiating dysthymia from major depression may become challenging, for example, when considering cases when major depression has been treated to the point where only a limited number of symptoms remain.

Several specifiers are used to subclassify dysthymia in the DSM-IV-TR. These include early onset if symptoms began before age 21 years; late onset if symptoms began at age 21 years or later; and dysthymia with atypical features if symptoms include increased appetite or weight gain, hypersomnia, a feeling of leaden paralysis, and extreme sensitivity to rejection.

Although dysthymia is often considered less severe than a major depression, the consequences of dysthymia without major depression are grave and include severely impaired functioning, increased morbidity from physical disease, and increased risk of suicide.

Pathophysiology

The pathophysiology of dysthymia has not been clearly established.

Abnormalities in neuroendocrine systems, especially thyroid and hypothalamo-pituitary-adrenocortical (HPA) systems, have been linked to depressive disorders in general; the HPA axis has not been adequately studied in dysthymic disorder. Research into the role of a variety of cytokines has not as of yet yielded a clear explanatory model.

Involvement of serotonin and noradrenergic systems is suggested by positive clinical responses to selective serotonin reuptake inhibitors (SSRIs) and noradrenergic uptake inhibitors.

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

Frequency

United States

Best estimates are that the lifetime risk of significant depression exceeds 25%, with a point prevalence of about 5%. Dysthymia appears to have a lifetime prevalence of about 6%.

Mortality/Morbidity

Mortality is reflected not only in the death rate from suicide but also increased morbidity and mortality from a variety of physical illnesses when the patient has comorbid dysthymia.

Race

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.

Sex

For major depressive disorders, females outnumber males, with a female-to-male ratio of 2:1 during their childbearing years. However, according to Cyranowski et al (2000), both 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.

Age

Most often, patients with dysthymia recall unexplained unhappiness in preadolescent childhood. Whether DSM-IV-TR adequately addresses dysthymia in children and adolescents is a matter of some controversy (Masi, 2003).

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

History

Patients with dysthymia tend to have a gloomy outlook on life with an underlying sense of personal inadequacy. Some debate exists as to whether chronic subthreshold depressive symptoms should be classified as mood disorders or personality disorders. That dysthymia can improve with treatment is somewhat suggestive of a mood disorder while the persistence of the state contributes to the notion of personality dysfunction.

When compared to major depression, patients' histories tend to focus more on subjective symptoms with fewer apparent dramatic psychomotor disturbances or complaints about sleep, appetite, and libido. Some do 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.

The most common symptoms include the following:

• A negative, pessimistic, or gloomy outlook
• Depressed mood (insufficient for a diagnosis of major depressive disorder)
• Restlessness
• Anxiety (insufficient for a diagnosis of generalized anxiety disorder)
• Neurovegetative symptoms (eg, disturbed sleeping and feeding behaviors, lethargy), usually less marked than those seen in a major depressive episode
• Loss of pleasurable feelings (anhedonia)
• Tend to spend little time engaged in leisure activities
• Alternative research criteria for dysthymic disorder also include irritability, excessive anger, and guilty brooding about the past.
• A history of mania precludes the diagnosis of dysthymia
• 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.
• 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 those relationships.
• Since as many as 15% of those with dysthymia may have comorbid substance dependence and since substance dependence can lead to symptoms similar to those caused by dysthymia, a detailed substance abuse history should always be obtained.
• Niculescu and Akisal proposed that dysthymia be divided into 2 subtypes: anxious dysthymia and anergic dysthymia.
• • They describe a subset of patients with anxious dysthymia with pronounced symptoms of low self-esteem, undirected restlessness, and interpersonal rejection sensitivity. They propose that these patients are help-seeking and may be more likely to make lower-lethality suicide attempts. Substances of choice for these patients include benzodiazepines, alcohol, marijuana, opiates, and possibly food. SSRIs may be effective for this group of patients.
  • They contrast this group to those with anergic dysthymia with low energy, hypersomnia, and anhedonia. This group, they suggested, may have a better response to treatment with agents that increase norepinephrine or dopamine.

Physical

No physical findings are pathognomonic for dysthymia; however, examination may reveal the following:

• Evidence of weight gain or loss
• Low body temperature, brittle nails and hair, slow reflexes, and other symptoms of hypothyroidism suggest thyroid dysfunction.
• A mental status examination is needed to confirm the diagnosis and to determine if comorbid diagnoses are present.
• • Some clinicians use psychological tests, such as the Minnesota Multiphasic Inventory or the Rorschach, for diagnostic purposes.
  • Many symptom checklists are easy to use on a routine basis, offer diagnostic confirmation, and provide a baseline against which change can be evaluated.
• The mental status examination may show findings similar to those seen in other depressive disorders. For example, 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 not expect the person to retain the ability to convey their 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 important part of any mental status examination; inquiring about suicidal thoughts and plans in those with dysthymia is important.

Causes

The cause of dysthymia is not clear. Several possible predisposing factors exist, which together may cause dysthymia.

• Genetic predisposition
• Chronic stress (eg, particularly with feelings of hopelessness and/or helplessness)
• Psychosocial factors, such as social isolation
• Persons diagnosed with antisocial, borderline, dependent, depressive, histionic, or schizotypal personality traits are at an increased risk for developing dysthymic disorder.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Other Problems to be Considered

Substance abuse or dependence
Adjustment disorders
Grief

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Lab Studies

• Complete blood count
• Thyroid function tests
• Homocysteine and methylmalonic acid levels may be better in detecting folate/vitamin B-12–responsive dysthymia than folate and vitamin B-12 levels themselves.
• Hypothalamic-pituitary-adrenal axis dysfunction is evident in major depression. The HPA axis has not been adequately studied in dysthymia to determine if dysregulation also exists in this disorder.

Imaging Studies

• While fMRI offers promise in the differential diagnosis of dysthymia, it remains strictly a research tool.
• Single-photon emission computed tomography (SPECT) is being offered commercially at some centers, but the existing database on depression seems too scant for this to be more than an experimental study for the depressive spectrum at this time.

Other Tests

• Projective tests (Rorschach) or standardized inventories (Minnesota Multiphasic Inventory) can be helpful.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Medical Care

Treatment of any underlying medical conditions is essential.

• In the absence of a treatable medical condition, psychotherapy is an important component of treatment. Both cognitive behavior therapy and interpersonal psychotherapy have been demonstrated in controlled studies to be effective in the treatment of depression and dysthymia.
• • Cognitive behavioral therapy is a structured time-limited treatment that involves recognizing cognitive processes leading to depression and restructuring the emotional response to counterproductive depressive cognitions.
  • Interpersonal therapy 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 interpersonal therapy is associated with improved symptoms of dysthymia.
• Little evidence exists comparing the efficacy of therapy alone to medication alone. One randomized trial that compared interpersonal psychotherapy, brief supportive psychotherapy, sertraline medication treatment alone, and sertraline plus interpersonal psychotherapy found the greatest effect when sertraline and interpersonal therapy were combined.

Activity

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

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Antidepressant medications are helpful in the treatment of dysthymia. In a review of medication trials, the mean response for any antidepressant was 55% (compared with 31% response for placebo). Trials comparing one class of antidepressant to another and trials comparing selective serotonin reuptake inhibitors (SSRIs) to one another have not been performed. Review of data compiled for a systematic review suggests that SSRIs, tricyclic antidepressants, and monoamine oxidase inhibitors are all equally effective, but SSRIs may be slightly better tolerated.

After starting medication, even modest improvement often allows the patient to make better use of other helpful therapy such as psychotherapy or exercise.

While the older antidepressants such as the first- and second-generation tricyclics and monoamine oxidase inhibitors (MAOIs) are effective, the SSRIs are the medications most commonly used for dysthymia. Success has also been reported with more noradrenergic agents such as desipramine (Norpramin), mirtazapine (Remeron), nefazodone (Serzone), venlafaxine (Effexor), and bupropion (Wellbutrin). In treating dysthymia, it is particularly important to find a drug with minimal adverse effects for the particular patient. Because the illness is chronic, long-term compliance is a particular concern.

In patients with a childhood history of attention deficit disorder and in elderly patients, short-acting stimulants, such as the amphetamines and methylphenidate (Ritalin), can be of value.

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) if a drug is known to have been effective for a member of the patient's family. One particular caution should be kept in mind when using SSRIs in dysthymia with comorbid anxiety. Starting with a dose that is too high (which may be a "usual" starting dose but too high for that individual patient) or increasing the dose too quickly can produce a temporary worsening of anxiety and consequent patient noncompliance. The various algorithms for the selection of antidepressants, and for augmenting them, apply in the case of dysthymia as well.

As a related point, the US Food and Drug Administration (FDA) defined efficacy by response (50% improvement) rather than recovery from depressive states. The dysthymia that remains after response to an antidepressant has led some to speculate that treatment has uncovered an underlying and unresponsive dysthymia. More current thinking considers the residual depressive symptoms evidence of inadequate treatment and recommends augmenting strategies aimed at full remission.

Selective serotonin reuptake inhibitors

The drugs differ from one another mostly in terms of half-life and, to some extent, in adverse effects. They have slightly different patterns of actions on neurotransmitters. Thus, patients may respond to one SSRI and not to another.

SSRIs are generally preferred over the other classes of antidepressants because of their more benign side effect profile, which may promote better compliance. SSRIs do not have the cardiac arrhythmia risk associated with tricyclic antidepressants. Arrhythmia risk is especially pertinent in overdose, and suicide risk must always be considered when treating a person with mood disorder.

Physicians are advised to be aware of the following information and use appropriate caution when considering treatment with SSRIs in the pediatric population.

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 (both ideation and attempts) in clinical trials of various antidepressant drugs in pediatric patients. The FDA has asked that additional studies be performed because suicidality occurred in both treated and untreated patients with major depression and thus could not be definitively linked to drug treatment.

Thyroid supplements

Hypothyroidism commonly is associated with dysthymia, and treatment usually involves administering a thyroxine (T4), which the body converts to the active triiodothyronine (T3). However, the effects on mood are better when a T3 also is used, and a 4:1 T4-to-T3 ratio has been recommended. Some patients have essentially normal thyroid panels but respond very well to T3/T4 administration. This has been noted in the use of thyroid supplementation to augment response to an antidepressant and in the use of thyroid supplementation alone. The dangers of osteoporosis, cardiac arrhythmias, and rebound hypothyroidism upon stopping thyroid supplements have been discussed, and the consensus seems to be that these dangers are more theoretical than practical.

Miscellaneous mixed serotonergic and noradrenergic drugs

The reason altering central monoamines is therapeutic for depression remains somewhat of a mystery, but while about 60% respond to any antidepressant, some patients respond to one and not to another. Failing with a serotonergic drug suggests trying one of the more noradrenergic drugs, although studies have not been performed to provide objective data in support of this approach.

Drug Category: Selective serotonin reuptake inhibitors

Potentiate the pharmacological effects of serotonin (5-HT) in the CNS.

Drug Name	Fluvoxamine (Luvox)
Description	Potent selective inhibitor of neuronal serotonin reuptake. Does not significantly bind to alpha-adrenergic, histamine, or cholinergic receptors and thus has fewer adverse effects than tricyclic antidepressants. Approved initially for OCD, but effective in dysthymia. Expensive.
Adult Dose	50 mg PO initially as a single hs dose, increase dose in 50-mg increments q4-7d as tolerated until maximum therapeutic benefit achieved, divide total daily dose into 2 doses; if doses are unequal, administer larger dose hs; not to exceed 300 mg/d
Pediatric Dose	Consult child psychiatrist if SSRI treatment of pediatric patient considered
Contraindications	Documented hypersensitivity; administration within 14 d of receiving MAOI
Interactions	Fluvoxamine potentiates effect of triazolam and alprazolam and thus, when taking them concurrently, reduce dose by at least 50%; reduce theophylline dose by one third; monitor plasma levels if taking concurrently with fluvoxamine; alcohol, cimetidine, sertraline, phenothiazines, and warfarin increase toxicity of fluvoxamine
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Use with caution if history of mania or hypomania; should not be given within 2 wk of MAOI; common adverse effects include insomnia, sexual dysfunction, nausea, diarrhea, sweating, fatigue, and somnolence or agitation; caution in liver dysfunction or cardiovascular disease and history of seizures or suicide attempts

Drug Name	Paroxetine (Paxil)
Description	Potent selective inhibitor of neuronal serotonin reuptake. Also has a weak effect on norepinephrine and dopamine neuronal reuptake. For maintenance therapy, adjust dosage to maintain patient on lowest effective dosage, and reassess patient periodically to determine need for continued treatment.
Adult Dose	10 mg/d PO initial therapy; increase in 10-mg/d increments, if necessary; dose changes should occur at intervals of at least 1 wk; 10-60 mg/d usual dose range; not to exceed 60 mg/d
Pediatric Dose	Consult child psychiatrist if SSRI treatment of pediatric patient considered
Contraindications	Documented hypersensitivity; administration within 14 d of receiving MAOI
Interactions	Phenobarbital and phenytoin decrease effects of paroxetine; alcohol, cimetidine, sertraline, phenothiazines, and warfarin increase toxicity of paroxetine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Use with caution if history of mania or hypomania; should not be given within 2 wk of MAOI; common adverse effects include insomnia, sexual dysfunction, nausea, diarrhea, sweating, fatigue, and somnolence or agitation; caution in history of seizures, renal disease, and cardiac disease

Drug Name	Fluoxetine (Prozac)
Description	Best-studied drug. Has a long half-life. Selectively inhibits presynaptic serotonin reuptake with minimal or no effect in reuptake of norepinephrine or dopamine.
Adult Dose	20 mg/d PO in am, increase after several wk by 20 mg/d; not to exceed 80 mg/d
Pediatric Dose	Consult child psychiatrist if SSRI treatment of pediatric patient considered
Contraindications	Documented hypersensitivity; concurrently taking MAOIs or receiving MAOIs in the last 2 wk
Interactions	Increases toxicity of diazepam and trazodone by decreasing clearance; also increases toxicity of MAOIs and highly protein-bound drugs
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Use with caution if history of mania or hypomania; should not be given within 2 wk of MAOI; common adverse effects include insomnia, sexual dysfunction, nausea, diarrhea, sweating, fatigue, and somnolence or agitation; caution in hepatic impairment and history of seizures

Drug Name	Sertraline (Zoloft)
Description	Selectively inhibits presynaptic serotonin reuptake.
Adult Dose	50 mg/d PO in am with 50-mg/d increments q2-3d to 100 mg/d, if tolerated; not to exceed 200 mg/d
Pediatric Dose	Consult child psychiatrist if SSRI treatment of pediatric patient considered
Contraindications	Documented hypersensitivity
Interactions	Increases toxicity of MAOIs, diazepam, tolbutamide, and warfarin
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Use with caution if history of mania or hypomania; should not be given within 2 wk of MAOI; common adverse effects include insomnia, sexual dysfunction, nausea, diarrhea, sweating, fatigue, and somnolence or agitation; caution in preexisting seizure disorders and in those who have experienced a recent myocardial infarction, have unstable heart disease, and hepatic or renal impairment

Drug Name	Escitalopram (Lexapro)
Description	SSRI and S-enantiomer of citalopram. Used for the treatment of depression. Mechanism of action is thought to be potentiation of serotonergic activity in CNS resulting from inhibition of CNS neuronal reuptake of serotonin.
Adult Dose	10 mg PO qd initially; if needed, may increase to 20 mg/d after 1 wk
Pediatric Dose	Consult child psychiatrist if SSRI treatment of pediatric patient considered
Contraindications	Documented hypersensitivity; administration within 14 d of receiving MAOI
Interactions	Primarily metabolized by CYP450 3A4 and 2C19; coadministration with alcohol or other centrally acting drugs increases CNS depression; cimetidine increases AUC and maximum serum concentration; coadministration with sumatriptan and SSRIs has caused weakness and hyperreflexia
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Use with caution if history of mania or hypomania; should not be given within 2 wk of MAOI; common adverse effects include insomnia, sexual dysfunction, nausea, diarrhea, sweating, fatigue, and somnolence or agitation; caution with history of seizures, suicide

Drug Category: Tricyclic antidepressants

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.

Drug Name	Desipramine HCl (Norpramin)
Description	May increase synaptic concentration of norepinephrine in CNS by inhibiting reuptake by presynaptic neuronal membrane. May have effects in the desensitization of adenyl cyclase, down-regulation of beta-adrenergic receptors, and down-regulation of serotonin receptors.
Adult Dose	75 mg/d PO initially in equally divided doses, increase gradually prn, but do not exceed 300 mg/d For elderly patients, 25-100 mg/d PO; not to exceed 150 mg/d
Pediatric Dose	Consult child psychiatrist if antidepressant treatment of pediatric patient considered
Contraindications	Documented hypersensitivity; narrow-angle glaucoma; recent postmyocardial infarction; patients currently receiving MAOIs, fluoxetine, or who took them in the previous 2 wk
Interactions	Decreases antihypertensive effects of clonidine but increases effects of sympathomimetics and benzodiazepines; effects of desipramine increase with phenytoin and carbamazepine
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in cardiovascular disease, conduction disturbances, seizure disorders, urinary retention, hyperthyroidism, and patients receiving thyroid replacement

Drug Category: Thyroid supplements

Increase serum levels of thyroid hormone. May convert nonresponders (to antidepressants) to responders by increasing receptor sensitivity and enhancing effects of antidepressants, particularly, tricyclic antidepressants.

Drug Name	T3/T4 combinations (Armour Thyroid, Thyrolar)
Description	Mixtures of 1 part T3 to 4 parts T4 and carry the same advice and warnings as the 2 hormones 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.
Adult Dose	Base dosing on corresponding dosing regimens for liothyronine or levothyroxine
Pediatric Dose	Consult child psychiatrist
Contraindications	Documented hypersensitivity; uncorrected adrenal insufficiency; hyperthyroid conditions
Interactions	Cholestyramine may decrease liothyronine absorption; estrogens may decrease the response to thyroid hormone therapy in patients with nonfunctioning thyroid glands; effect of anticoagulants is potentiated by liothyronine; activity of some beta-blockers may decrease when the hypothyroid patient is converted to a euthyroid state
Pregnancy	A - Safe in pregnancy
Precautions	Caution when administering to patients with angina pectoris or cardiovascular disease; monitor thyroid status periodically

Drug Category: Miscellaneous mixed serotonergic and noradrenergic drugs

Because norepinephrine is involved in depression as well as serotonin, arguments exist. These drugs have effects on serotonin and norepinephrine and, in some cases, on dopamine and even nicotinic acetylcholine systems. Because of the empirical nature of psychopharmacology, they may be used as first-line agents or as follow-up agents when SSRIs fail.

Drug Name	Mirtazapine (Remeron, Remeron SolTab)
Description	Antidepressant that is not chemically related to tricyclic or any other class of antidepressants. Primary mechanism of action of mirtazapine is antagonism at central presynaptic alpha-2 receptors. Actions of drug change as dose is raised. Exhibits both noradrenergic and serotonergic activity.
Adult Dose	15-45 mg PO qd
Pediatric Dose	Consult child psychiatrist if antidepressant treatment of pediatric patient considered
Contraindications	Documented hypersensitivity; agranulocytosis
Interactions	May increase effect of CNS depressants; taken within 14 d of MAOIs may trigger hypertensive crisis
Pregnancy	C - Safety for use during pregnancy has not been established
Precautions	Discontinue therapy if sore throat, fever, stomatitis, or other signs of infection and neutropenia develop; use with caution if history of mania or hypomania; should not be given within 2 wk of MAOI

Drug Name	Venlafaxine (Effexor, Effexor XR)
Description	Structurally unrelated to other available antidepressants. Inhibits serotonin reuptake at select receptors and reuptake of norepinephrine.
Adult Dose	IR: 75 mg/d PO divided bid, may increase by 75 mg/d PO at 4-d intervals prn; not to exceed 375 mg/d administered in 3 divided doses ER: 75 mg PO qd Alternatively: 37.5 mg PO qd for 4-7 d initial, then increase to 75 mg/d, may increase by 75 mg/d PO at 4-d intervals prn; not to exceed 225 mg PO qd
Pediatric Dose	Consult child psychiatrist if antidepressant treatment of pediatric patient considered
Contraindications	Documented hypersensitivity
Interactions	Increased risk of serotonin syndrome with coadministration of SSRI or MAOI
Pregnancy	C - Safety for use during pregnancy has not been established
Precautions	Monitor for hypertension

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Further Inpatient Care

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

Further Outpatient Care

• Because of the high rate of relapses both from depression and 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.

Deterrence/Prevention

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

Complications

• Patients should be closely monitored for the emergence of major depression or bipolar disorder. Review of longitudinal studies shows 76% of dysthymic children develop major depression and 13% develop bipolar disorder over follow-up periods of 3-12 years.
• Increased mortality and morbidity from unrelated physical illnesses
• Suicide, attempted or successful
• Patients with dysthymia have a higher risk of employment problems, including decreased productivity and increased unemployment. 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.

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% with dysthymia report remission at follow-up points ranging from 1-6 years.
• With adequate treatment, substantial, prolonged improvement can be expected in most patients. Some have suggested that with a tenacious effort to find the best combination of drugs and psychotherapies, as many as 90% of patients can be expected to recover.

Patient Education

• If possible, families 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.
• For excellent patient education resources, visit eMedicine's Depression Center and Endocrine System Center. Also, see eMedicine's patient education articles Depression and Thyroid Problems.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Media file 1:  The various outcomes of dysthymia.
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Media type:  Graph

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

• Adler DA, Irish J, McLaughlin TJ, et al. The work impact of dysthymia in a primary care population. Gen Hosp Psychiatry. Jul-Aug 2004;26(4):269-76.
• Airaksinen E, Larsson M, Lundberg I. Cognitive functions in depressive disorders: evidence from a population-based study. Psychol Med. Jan 2004;34(1):83-91. [Medline].
• American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. 2000.
• Angst J, Merikangas K. The depressive spectrum: diagnostic classification and course. J Affect Disord. Aug 1997;45(1-2):31-9; discussion 39-40. [Medline].
• Askinazi C, Weintraub RJ, Karamouz N. Elderly depressed females as a possible subgroup of patients responsive to methylphenidate. J Clin Psychiatry. Sep 1986;47(9):467-9. [Medline].
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Article Last Updated: Jul 13, 2006