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Authors: Randy A. Sansone, MD, Professor, Departments of Psychiatry and Internal Medicine, Wright State University, Dayton, Ohio, and Director of Psychiatry Education, Kettering Medical Center, Kettering, Ohio; and Lori A. Sansone, MD, private practice, Alliance Physicians, Kettering Medical Center, Bellbrook, Ohio.
Editor’s Note—While acute depression is easily diagnosed in the primary care setting,1 there is a more elusive member of the depression family that tends to be under-diagnosed2 and under-treated.3 Dysthymic disorder (DD), or chronic depression, has less dramatic and intense symptoms compared with major depression, which may explain its tendency to go clinically unnoticed. However, the morbidity can be considerable and may include greater use of health care services, adverse effects on the course of medical illness, and the risk of suicide. When diagnosed, DD can be challenging to treat and may require consultation with a psychiatrist. In the following article, we review the various clinical facets of this perplexing disorder, including various strategies for treatment.
Symptom Profile. DD is a chronic, smoldering depression of at least 2 year’s duration.4 In one study, the mean duration of DD was found to be 30 years.3 The symptoms can be fairly subtle and are characterized by cognitive, social, and motivational features rather than the neurovegetative signs observed in acute depression.5 In addition, the dysphoric mood may be punctuated by brief periods of normal mood, up to 2 months over a 2-year period. In one study, euthymic periods among dysthymics were found to vary from 2 to 30 days, with a mean of 8 days.6 The fleeting euthymia may result in the misinterpretation of symptoms by both the patient (eg, "How could I be depressed? I felt fine last week!") and physician.
Despite symptoms that are often described as mild-to-moderate in intensity, the morbidity of DD can be substantial. In addition, medical illness and drugs (eg, beta blockers) can physiologically contribute to the patient’s symptoms as well as stressful life events.7 The Diagnostic and Statistic Manual (DSM)-IV4 criteria for DD are shown in Table 1 and a symptom comparison between DD and major depression is shown in Table 2.
|Table 1. DSM-IV Criteria for Dysthymic Disorder4|
|•||Depressed mood for most of the day for at least 2 years (1 year for children)|
|•||Two or more of the following symptoms: poor appetite or overeating, insomnia or hypersomnia, low energy or fatigue, low self-esteem, poor concentration or difficulty making decisions, feelings of hopelessness|
|•||During the 2-year period, no symptom-free period for more than 2 months at a time|
|•||No major depression during the first 2 years|
|•||No prior history of manic/hypomanic episodes or cyclothymia|
|•||Symptoms not exclusive to a chronic psychotic disorder|
|•||Symptoms not due to direct effects of substance use or a general medical condition|
|•||Symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning|
|Table 2. A Comparison of Dysthymic Disorder and Major Depression|
|Features||Dysthymic Disorder||Major Depression|
|Onset||Insidious||Fairly well defined|
|Symptoms||Cognitive, social, motivational||Vegetative, psychomotor|
|Euthymic periods||Up to 2 months or 10% of the year||Rarely present|
|Symptom duration||At least 2 years||At least 2 weeks|
|Symptom presence||Waxing and waning||Fairly sustained, discrete episodes|
|Patient/family recognition||Relatively lower||Relatively higher|
Early Onset vs. Late Onset DD. In the diagnostic approach to DD, symptom onset before age 21 is described as "early onset," and after age 21, "late onset" DD.4 Compared with late onset, early onset DD is consistently associated with a higher prevalence of comorbid (ie, co-existing) personality disorder.8,9 This association has been verified in psychiatric as well as primary care populations.10 There also appears to be a higher prevalence of substance use disorders among early onset dysthymic patients.9
Evolution of DSM Dysthymic Disorder
C.F. Flemming coined the term "dysthymia" in 1844.11 However, DD did not attain official DSM status until the appearance of the third edition in 1980. The emergence of the DSM-III12 DD diagnosis coincided with the collapse and loss of several other diagnostic entities in earlier DSM editions that were characterized by chronic dysphoria, including depressive neurosis and depressive personality. In the aftermath of this diagnostic consolidation, DD may actually represent a heterogeneous group of various types of chronic depressive disorders. Because of this, several investigators have questioned the diagnostic validity of the disorder.13,14 For example, researchers continue to question genuine differences between DD and a proposed DSM diagnosis listed in the Appendix of DSM-IV,4 depressive personality disorder.15,16 In addition, some researchers have found few differences between DD alone and in combination with major depression.17 These observations suggest that DD may be either a designation for several different types of chronic depression (ie, it exhibits etiological heterogeneity) or it is a disorder that is fairly fluid with other mood disorders (ie, part of a depressive disorder spectrum).
Community Samples. According to the Epidemiological Catchment Area Study,18 the prevalence of DD in the general population is around 3%. In a more recent study, the National Comorbidity Survey,19 the lifetime prevalence was 4.8% among men and 8% among women (total of 6.4%). In accordance with the observed gender patterns for all diagnostic types of depression, the prevalence appears greater among women compared with men, with a nearly 2:1 ratio.
Health Care Samples. Compared with community samples, the prevalence of DD appears to be higher in health care settings. For example, in mental health settings, up to one third of patients suffer from DD.20 In US and international primary care settings, 5-15%21 and 2.1%22 of individuals, respectively, suffer from DD. With regard to all types of depression, chronic depression is diagnosed in nearly one third of cases.23
Age. The prevalence of DD was found to be 3.4% among adolescents24 and 3.5% in very elderly patients (mean age, 70.5 years).25 Among the elderly, DD may emerge in middle or late life,26 and it appears to be overrepresented in those affected by dementia.25
As with many psychiatric disorders, the explicit etiology of DD is unknown. Given its possible heterogeneous nature, there may be multidetermined causes for this disorder.
Biological Abnormalities. Several biological abnormalities have been identified in study populations suffering from DD. These include dysfunctions in the serotonergic system,27,28 an elevated production of interleukin-1 in mitogen-stimulated lymphocytes,29 and altered platelet monoamine oxidase (MAO) activity, which was found to be lower among females but not males with DD.30
Other biological findings have been unremarkable. For example, adrenocorticotropic hormone (ACTH) responses among those with DD are not noteworthy and cortisol measurements following dexamethasone suppression do not appear to differentiate dysthymics from healthy subjects.31
Family Studies. The relatives of those with DD appear to have significantly higher rates of the disorder themselves,32 as well as other depressive33 and various personality disorders.34
Summary. The biological findings do not clearly indicate or suggest a consistent or specific etiology, and some of the findings are unexpected (eg, the dexamethasone suppression results and gender differences with regard to platelet MAO activity). Family studies consistently suggest higher rates of psychopathology among members, particularly in the area of mood and personality disorders. These findings may suggest a possible nonspecific psychological vulnerability to DD, either from a genetic (biological) or early developmental (familial) perspective.
DD rarely exists as a freestanding psychiatric disorder.35 It is highlighted or characterized by its significant comorbidity with other psychiatric and medical disorders.
Comorbid Psychiatric Disorders. Comorbid mood disorders appear most prevalent among dysthymics, with major depression occurring in up to 70%.20 The combination of DD and major depression is referred to as "double depression" and can be difficult to treat. For some individuals, these superimposed major depressions may be related to new-onset life events in the context of an ongoing chronic stressor.7
In examining gender differences with regard to double depression, Kornstein and colleagues36 found that women were less likely to be married, had an earlier age of onset, and reported more extensive family histories of affective disorder. Compared with men, women were also more likely to report sleep and psychomotor changes, somatic symptoms, and a greater severity of illness.
In addition to mood disorders, comorbid anxiety disorders are prevalent. For example, in a large sample of primary care patients with DD, 90% screened positive for Axis I disorders, including major depression as well as panic disorder, simple phobia, and generalized anxiety disorder.37 Up to 15% of dysthymics have social phobia.40 This finding may be related to the personality profiles found among some individuals, particularly those suffering from avoidant and Cluster C personality disorders.
Several studies have examined Axis II comorbidity profiles between acute vs. chronic depressives, and, as expected, the chronic depressives demonstrate a higher prevalence of personality disorder,8 particularly among those with early onset DD.8-10 Associated personality disorders include avoidant, dependent, self-defeating, and borderline personality disorders.20,39 In a Dutch study, Cluster A personality disorders (eg, paranoid, schizoid, schizotypal) were the predominant Axis II disorders among a dysthymic sample.40
Finally, substance abuse is a comorbid risk for many psychiatric disorders, including DD. The treatment of DD is not likely to be successful without addressing this issue, when present.
Comorbid Medical Disorders. A variety of medical conditions appear to be associated with DD,38 including neurological disorders (eg, stroke, multiple sclerosis), HIV, postcardiac transplantation, thyroid disorders, and several psychophysiological disorders (eg, fibromyalgia, chronic fatigue syndrome). Despite the intuitive assumption that chronic medical conditions should be associated with chronic depression, there appears to be a low prevalence of DD among patients with cancer.38 While the relationship between medical conditions and DD remains unknown, possibilities include illness-induced neurotransmitter dysfunction, DD functioning as a risk factor for the subsequent development of medical illness, pharmacological treatment of the medical illness causing DD, and/or a complicated reinforcing cycle between the mood and medical disorder.
Comorbidity Among the Elderly. Several studies have examined comorbidity patterns among elderly dysthymics. Compared with more typical ages of onset, it appears that midlife onset of DD has less psychiatric comorbidity and more relationship to life stresses, particularly medical illnesses.26,41,42 Among elderly dysthymics with personality disorder (about one third of this subgroup of dysthymics), obsessive-compulsive personality disorder may be most common, followed by avoidant personality disorder.43
Index of Suspicion. It is fairly well established that DD tends to be under-diagnosed, most likely because the symptoms are typically less dramatic compared with acute depression or other types of psychopathology (eg, panic attacks, hallucinations). Therefore, clinicians need to maintain an awareness of its potential presence based upon comorbidity probabilities. Because of the high comorbidity between DD and major depression, all evaluations of acute depression should entail a query for chronic depression. The other high-yield Axis I disorders are anxiety disorders including generalized anxiety disorder and social phobia. Suspicions of underlying personality disorder may also trigger an evaluation for DD as well as the previously noted medical conditions.
Assessment Approach. There are several ways to approach assessment. One approach is to explore the presence of depression over the past 2 years (ie, "Over the past 2 years, what percent of the time have you suffered from depression?"). Diagnostic confirmation is the presence of depression for 90% or more of the time. This initial inquiry might be followed by, "It sounds like this depression has been persistent—how far back do the symptoms go?" This question will determine whether the DD is early or late onset. Because the symptoms are more cognitive/social/motivational in nature, they are usually fairly easy to confirm after the time frame of the depression is established.
In our experience, the assessment of DD can be complicated if the symptoms are severe in intensity or complicated by major depression. We have found that drawing diagrams can facilitate the patient’s awareness and identification of the 2 types of depression, if present (see Figure). This approach may also determine whether the major depression, if present, is recurrent.
Figure. A Diagrammatic Comparison of Major
Depression and Dysthymia
As for psychological tools, we are only aware of 1 specific measure for DD—the Cornell Dysthymia Rating Scale.44 On review of this scale, it appears to be more practical for following depressive symptoms and their response to treatment rather than actually diagnosing DD. In addition, further validation of the scale is needed,44 thus limiting its use in the clinical setting. While not designed for the diagnosis of DD, the Beck Depression Inventory45 and the Zung Self-Rating Depression Scale46 can be used to follow symptom response to treatment.
Antidepressants. Given all of the ambiguities surrounding the etiology and diagnostic "purity" of DD, one observation is consistent—antidepressants alleviate the symptoms.47 Indeed, selective serotonin reuptake inhibitors (SSRIs),48-52 venlafaxine,53-55 bupropion,56 nefazodone,57 mirtazepine,58 tricyclics,59 and monoamine oxidase inhibitors60 have each empirically resulted in reductions in depressive symptoms. Therefore, it seems that there are no significant differences in efficacy between and within various classes of antidepressant drugs.60,61
Given that the majority of antidepressant types demonstrate efficacy, the selection of an initial antidepressant is likely to be based on tolerability and dosing frequency. Given these parameters, SSRIs are often an initial choice. Because DD is often comorbid with other psychiatric and medical disorders, SSRIs have the additional advantage of being fairly panoramic in their clinical indications and efficacy. In this regard, they are recognized in the treatment of depression and anxiety, social phobia, panic attacks, impulsivity, worry and rumination, posttraumatic stress disorder, and obsessive-compulsive disorder.62 This broad-spectrum clinical efficacy is not currently recognized for other types of antidepressants.
The side effects of SSRIs are minimal and may include headaches, nausea, sexual dysfunction (eg, decreased libido, delayed orgasm), psychomotor effects (eg, activation or sedation), and varying potentials for P-450 drug interactions.63 Because of few cognitive or cardiovascular effects, the SSRIs are relatively well tolerated in medically ill patients.
When using SSRIs, there are some important differences to note among them. With regard to side effects, fluoxetine may cause overactivation, insomnia, restlessness, and weight loss. Sertraline may cause loose stools. Paroxetine has some anticholinergic activity64 and tends to cause dry mouth and constipation. Fluvoxamine has extensive potential drug interactions through the P-450 isoenzyme system.65 Finally, citalopram is potentially lethal in solo overdose (ie, the absence of other drugs).66 Only citalopram has been determined as safe in patients prescribed coumadin.67
Other antidepressants may be considered in dysthymic patients. For example, venlafaxine extended release is administered once per day, does not interfere with coumadin management, and has diverse neurotransmitter effects.68 Potential limitations of venlafaxine include nausea and elevation of diastolic blood pressure. Like SSRIs, abrupt cessation of venlafaxine may precipitate a discontinuation syndrome (eg, dizziness, dysphoria, irritability, sleep disturbance), which, while not medically dangerous, can cause discomfort.69 Treatment of discontinuation syndrome, as well as prevention, entails gradual tapering of the medication, the rate that depends on the duration of antidepressant exposure.
Several antidepressants have features that may complicate treatment. For example, mirtazapine is associated with weight gain and somnolence, with the latter effect being more pronounced at lower rather than higher doses. Trazodone may cause the very rare occurrence of priapism (prolonged, painful erection that requires medical management).70 Bupropion may lower the seizure threshold, is contraindicated in patients with histories of seizures or eating disorders, and should be used with caution in patients with neurological compromise or head injury. Nefazodone undergoes a complex metabolism in the liver (ie, potentially prolonged overall half-life in patients with hepatic compromise) and has precipitated hepatic failure requiring liver transplantation in a small number of patients.71 Tricyclic antidepressants have anticholinergic effects that can exacerbate confusional states and cause cardiovascular symptoms (eg, tachycardia, lightheadedness). Tricyclics are also extremely dangerous in overdose because of their effects on cardiac conduction.72
Suggested Guidelines for Using Antidepressants in Dysthymia. While many investigators report favorable responses with antidepressants in the treatment of DD,73,74 others have noticed mild-to-moderate responses, at best.75,76 These seemingly unpredictable outcomes are probably related to the heterogeneity found among dysthymics. In our experience, those with early onset DD and comorbid personality disorder tend to fare less well, while those with late onset DD and healthy premorbid functioning may achieve impressive remissions with a single agent.
When prescribing, we suggest initiating antidepressant medication at low doses (eg, 12.5 mg of sertraline, 10 mg of citalopram) to determine patient tolerability. Either the presence of a personality disorder or medical condition may result in sensitivity to antidepressant medication. The dosage may then be titrated every 4-7 days, as tolerated, with individual adjustments as necessary (eg, for sertraline, 12.5 mg, then 25 mg, then 37.5 mg, then 50 mg). Some patients may benefit from titration of antidepressants to higher-than-usual doses, although side effects may be a limiting factor.
We suggest a 3-month drug trial (ie, the time period required to see if the medication actually works).77 Keep in mind that DD is a chronic form of depression and, in most individuals, it demonstrates a sluggish response to medication intervention. At the 3-month mark, a 30% or more reduction in overall symptoms is reasonable, and with ongoing treatment, improvement in symptoms continues in many cases.77 Full remission is the intended treatment goal, including not only improvements in depressive symptoms but social functioning as well.
The course of treatment for DD remains unknown. We recommend at least a 2-year course for symptoms that are recent onset. For longstanding symptoms, lifelong treatment may be indicated. This will entail the ongoing prescription of antidepressants. Therefore, the documentation of DD in the medical record is particularly important for insurance purposes as it justifies ongoing antidepressant treatment.
Augmentation Strategies. Many patients do not achieve full remission of symptoms during treatment with a single agent. When there has been a partial response to a single antidepressant, the clinician may want to consider an augmentation strategy (ie, adding a second psychotropic drug to the first). For patients in the primary care setting, the most uncomplicated augmentation medications, in our opinion, are buspirone78,79 or gabapentin.80 Although these drugs have undergone limited empirical evaluation as augmentation agents, they are being increasingly used for this purpose.
Buspirone may be favored as a first choice when there is a prominent anxiety component. Note that buspirone in combination with an SSRI runs the risk of serotonin syndrome, although we have never observed this potential complication in practice. Gabapentin is particularly useful for mood lability, impulsivity, and affective instability (eg, rage reactions). Note that gabapentin is potentially teratogenic and initially somewhat sedating but has few drug interactions (renal excretion) and does not require initial laboratory studies or ongoing serum levels.
Both of these drugs are dosed twice per day, and we suggest beginning at lower doses and slowly titrating upward (eg, beginning buspirone at 5 mg/d for 4 days with 5 mg increases every 4 days to a daily dose of 10-40 mg/d; beginning gabapentin at 100 mg/d for 4 days with 100 mg increases every 4-7 days as tolerated to a daily dose of 600-1200 mg/d).81
Augmentation effects may occur within 2 weeks, but we advise 6-week trials. Clinicians typically elect 1 augmenting medication for trial, and if ineffective, undertake the second augmenting medication. (See Table 3.)
|Table 3. Summary of Prescribing Guidelines for the Treatment of Dysthymia|
|•||Consider SSRIs as first-line antidepressants.|
|•||Consider venlafaxine extended-release as second-line.|
|•||Begin with low doses and attempt to titrate to standard dose.|
|•||If not able to titrate to standard dose, continue with current dose.|
|•||Maintain drug-evaluation trial for 12 weeks.|
|•||Observe for 30% or more reduction in symptoms at 3 months.|
|•||Consider new drug in nonresponders (ie, another SSRI or venlafaxine extended release for second or third trial, or another type of antidepressant if undergoing third or fourth trial).|
|•||For partial responders, consider increasing dose of primary antidepressant, or augmentation strategy with either buspirone or gabapentin.|
Psychotherapy Intervention. Psychotherapy interventions have been promising including individual psychotherapy,82 interpersonal psychotherapy,83,84 cognitive-behavioral therapy,85 and group therapy.86 Whether these various adjunctive interventions have genuine specificity for DD is unknown. It is possible that what is being observed is the generic effectiveness of a psychotherapeutic intervention. At any rate, in the primary care setting, supportive psychotherapy in combination with antidepressant medication may be beneficial.
Psychotherapy should be particularly considered for those patients undergoing extreme psychosocial stressors (eg, medical illness, bereavement) or suffering from interpersonal difficulties secondary to personality disorder. Not all patients are candidates for psychotherapy, and a consultation with a mental health professional may assess the viability of this option.
Psychiatric Consultation. Psychiatric consultation might be considered when several antidepressant trials have been attempted, without success, in addition to an augmentation strategy. The psychiatric consultant may consider other types of more complex augmentation strategies (eg, methylphenidate,87 other anticonvulsants, lithium, and even low-dose antipsychotics in nonpsychotic patients88) as well as recommend other adjunctive psychotherapy interventions.
As expected, because of the etiological heterogeneity in DD, outcomes vary. Angst and colleagues89 found that DD, alone, could be very severe and that overall quality of life at follow-up was low.90 Klein and colleagues91 found that over a 5-year follow-up period, the recovery rate was about 50% and the relapse rate following recovery was high (45%). At 30-month follow-up, Klein et al92 also reported that recovery from early onset DD was only 40%, with nearly 50% of individuals meeting the full criteria for DD. Durbin and colleagues93 determined that poorer outcome was associated with a history of sexual abuse, poor relationships with both parents (ie, biparental failure), and family histories of substance abuse and Cluster C personality disorders.
As expected, medication studies have been limited by the typically brief follow-up periods. Friedman and colleagues94 found that after antidepressant treatment, only 24% of patients achieved normal levels of social functioning. Other studies95 describe more optimistic results—up to an overall response rate of 76% to medication. Undoubtedly, these differences reflect different populations of dysthymic patients.
In our experience, robust responses are usually encountered among older patients with midlife onset of DD and no premorbid or current psychiatric comorbidity. On the other hand, less dramatic responses are usually encountered in patients with early onset, longstanding DDs that are complicated by extensive comorbidity including personality disorder. Many of these latter cases entail early histories of abuse, including sexual, physical, and/or emotional abuse, coupled with emotional nonavailability of parents.
DD is a formidable chronic depression highlighted by its etiological heterogeneity, psychiatric and medical comorbidity, and significant morbidity. Clinical suspicion is important in the detection of this, at times, elusive disorder. Treatment with antidepressants, including the consideration of an augmentation strategy, is the recommended initial approach in the primary care setting. Psychiatric consultation should be considered for nonresponders. While the outcome of DD appears highly variable, comorbidity clearly tempers outcome as well as family histories of inadequate parenting and psychopathology. Continued research regarding intervention strategies is sorely needed to enhance the treatment outcomes for this difficult group of depressive patients.
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