Dysthymia
Synonyms and keywords: Dysthymic disorder; persistent depressive disorder; double depression

# Overview
Dysthymia is a mood disorder that falls on the depression spectrum.  It is characterized by the lack of enjoyment or pleasure, clinically referred to as anhedonia, that continues for an extended period. Dysthymia differs from major depression in that it is both longer-lasting and not as distressing. The symptoms of dysthymia are often underestimated by the patients and misdiagnosed by clinicians. Dysthymia can have a substantial impact on an individual's life by preventing effective functioning, disrupting sleep patterns, and interfering with activities of daily living (ADLs). It usually presents with mild symptoms on a day-to-day basis. Progressively, the disorder may take a more severe form, resulting in work impairment, social isolation, and high rates of suicide. Due to its chronicity and lesser severity, most of the patients suffering from dysthymia believe that it is a part of their character and do not seek treatment until it gets extremely disabling.

# Historical Perspective
- The historical origin of the term 'dysthymia' is Greek.
- In 1844, dysthymia was used first in psychiatry by C.F. Flemming. 
- In 1882, dysthymia was further described by Kahlbaum, and he differentiated it from the fluctuating mood of cyclothymia.
- In the Diagnostic and Statistical Manual of Mental Disorders (DSM), dysthymia as a clinical entity has undergone complex evolution from being considered a personality disorder to an affective disorder.

# Classification
- The Diagnostic and Statistical Manual of Mental Disorders (DSM-II) described chronic depression as a personality disorder.
- 'Dysthymic disorder' was the term used in DSM-III to describe depression present for more than two years.
- From the personality disorder of DSM-II,  DSM-III-R placed it under the affective category. 
- DSM-IV has classified chronic depression into dysthymic disorder and major depressive disorder, chronic type.
- Based on the age of onset, DSM-IV has divided dysthymic disorders into early (before 21 years) and late-onset (after 21 years) subtypes. 
- Early-onset dysthymic disorder is related to a higher familial burden of mood disorders and childhood adverse conditions. On the other hand, late-onset has an association with health issues and major losses.
- In DSM-IV, individuals having underlying dysthymic disorder who develop major depressive episodes are diagnosed as having both dysthymic disorder and major depressive disorder. So, DSM-IV has categorized dysthymic disorder and major depressive episodes as separate diagnoses instead of phases of a single disorder that fluctuates in severity over time.
- In spite of minor differences in the definitions of dysthymic disorder in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV)  and International Classification of Diseases Tenth Edition (ICD-l0), both the systems are competent to establish the diagnosis.
- Dysthymia and chronic major depression are both included under the new term 'persistent depressive disorder' in DSM-5.
- Since the introduction in DSM-III, the diagnostic validity of dysthymia is questioned. It is a heterogeneous diagnosis including various depressive and anxiety conditions. As persistent depressive disorder includes dysthymia as a component, the former is more likely to represent a heterogeneous domain diagnosis. It limits the identification of the preferred treatment options. 

# Pathophysiology
- Brain-derived neurotrophic factor (BDNF) has been found to play a major role in the long-term potentiation, functioning of neurons and therefore, affecting neuroplasticity. 
- Compared to controls, BDNF is significantly lower in individuals with dysthymia. 
- Interleukin-6 (IL-6)  levels are higher in dysthymic patients as compared to controls. Individuals with major depressive disorder also have higher levels of IL-6. 
- The expression of cytokines has also been found to have a role in the pathophysiology of dysthymia. Macrophage inflammatory protein-1 and Interferon--induced protein10 have a correlation with the response to treatment.
- The elevated Interleukin-1 associated with dysthymia fails to reach the normal range even after symptom resolution. It further suggests that IL-1 can be the trait marker of dysthymia and can help in early detection of the illness.

# Clinical Features
- The main features of dysthymia are
Low or irritable mood
Lack of interest in previously enjoyed activities
Loss of energy or easy fatigability
Increased or decreased appetite
Weight gain or loss
Excessive sleepiness or insomnia
Difficulty concentrating
Indecisiveness and having pessimistic thoughts
Negative self-image
- Low or irritable mood
- Lack of interest in previously enjoyed activities
- Loss of energy or easy fatigability
- Increased or decreased appetite
- Weight gain or loss
- Excessive sleepiness or insomnia
- Difficulty concentrating
- Indecisiveness and having pessimistic thoughts
- Negative self-image
- Dysthymia as compared to major depression, tends to be less intense and persists for a longer duration.
- Other than the variation in magnitude of severity, both these conditions exhibit similar symptomatology.
- To diagnose major depressive disorder, the symptoms should be present for a minimum duration of 14 days (2 weeks) whereas, dysthymia symptoms should be present for at least 2 years.
- The symptoms of dysthymia can grow into a full-blown episode of major depression. The intense episode often exists with the underlying feelings of low mood and this resulting condition is called "double depression"
- As compared to the general population, the people with dysthymia have a greater-than-average chance of developing major depression.
- While major depressive disorder mostly occurs in episodes, dysthymia lasts for longer periods, is consistent, and sometimes begins in childhood.  Therefore, persons with dysthymia tend to consider depression as a part of their character.
- Dysthymia and major depression, both are inheritable.
- Some individuals describe dysthymia as being under chronic stress.
- When treating cases, it is often difficult to distinguish if these people are actually under unusually high environmental stress or if the dysthymia causes them to be more psychologically stressed in a standard environment.

# Differential Diagnosis
The differential diagnosis of dysthymia includes the following: 
- Mood disorder secondary to general medical condition
- Major depressive disorder
- Recurrent depressive disorder
- Personality disorders
- Generalized Anxiety Disorder
- Mixed anxiety and depressive disorder
- Substance-induced mood disorder
- Neurasthenia
- Adjustment disorder
- Psychotic disorders

# Epidemiology and Demographics

## Prevalence
- The 12-month prevalence of dysthymia is approximately 500 per 100,000 (0.5%) of the overall population.

## Age
- Individuals of all age groups may develop dysthymia.
- Based on the age of onset, the etiology of dysthymia varies.
- The individuals with early onset dysthymia often have a history of physical or sexual abuse. They have also been found to have poor relationships with both the parents.
- Compared to adolescents, children display lesser variability in the symptoms of dysthymia.
- 'Anhedonia' is a common characteristic in adolescents with dysthymia. 
- In younger adults, dysthymia is related to the abnormalities of personality whereas, the elderly have a strong association with losses in life and other health-related issues. 

## Gender
- Dysthymia affects both men and women.
- The prevalence of dysthymia is more in women compared to men.
- The symptomatic profile is similar in males and females of the adolescent population. While comparing the symptoms of dysthymia in both genders, no specific symptom predominance has been noticed. 
- Gender differences have been noted in the elderly population.
- In elderly men, dysthymia is more related to lower educational levels and in those receiving nursing home/ institutional care. No relation has been found based on occupation or marital status.
- As opposed to this, in elderly females, dysthymia is predominant in older individuals (70 years +), married, and in those with higher education levels. It is not related to marital status, occupation, or form of health care received. 

## Race
- Dysthymia has a higher lifetime prevalence in individuals of Mexican American and African American backgrounds. This can be explained by a number of factors dominating these populations: 
Lower education level
Poverty
Hesitancy in seeking help
Lesser utilization of mental health services
Failure to comply with treatment
Various cultural beliefs
- Lower education level
- Poverty
- Hesitancy in seeking help
- Lesser utilization of mental health services
- Failure to comply with treatment
- Various cultural beliefs

# Risk Factors
Common risk factors in the development of dysthymia are:
- Genetic predisposition
- First-degree relatives with persistent depressive disorder
- Major depressive disorder in first-degree relatives
- Family history of other mood disorders
- Lower social integration
- Co-morbid substance use disorder
- Parental loss or separation
- Physical or sexual abuse
- Lower educational levels
- Polysomnographic abnormalities

# Natural History, Complications, and Prognosis
- Individuals with dysthymia have a higher risk of developing major depressive disorder in the future.
- Similar to adults, children and adolescents with dysthymia are also more likely to develop depression. 
- These children have a poor scholastic performance and deteriorating quality of life.
- Dysthymia has an impact on personal relationships, financial state as well as physical and mental well-being.
- Dysthymia is associated with higher suicide rates and significant disability.

## Prognosis
Overall, dysthymia has a worse prognosis than major depressive disorder. 
Poor prognostic factors related to dysthymia are: 
- Anxiety disorders
- Less education
- Conduct disorder
- Familial loading for chronic depression
- History of poor maternal relationship in childhood
- History of childhood sexual abuse
- Longer duration of symptoms
- Comorbid personality disorder
- Increased severity of the symptoms
- Higher levels of neuroticism
- Poorer global functioning

# Diagnostic Criteria

## DSM-5 Diagnostic Criteria for Dysthymia
- Persistent Depressive Disorder (Dysthymia) is diagnosed using DSM-5 Criteria.

# Treatment

## Medications

### Selective Serotonin Reuptake Inhibitors (SSRI)
- The most commonly prescribed anti-depressants for dysthymia are the selective serotonin reuptake inhibitors (SSRI), which include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), and citalopram (Celexa).
- SSRIs have a very high affinity for Serotonin (5-HT) receptors whereas low affinity for noradrenaline uptake receptors. They act by inhibiting the reuptake of 5-HT from the synaptic cleft, increasing its concentration and contributing to the therapeutic effect.
- The different SSRIs have variability in efficacy and side-effect profile, which requires thorough clinical consideration before prescribing them.
- SSRIs are easy to take and relatively safer compared with the other older forms of anti-depressants.

### Side Effects of SSRI
- SSRI are associated with some side effects like sleep disturbances, nausea, vomiting, sexual dysfunction, weight gain, cognitive disturbances and SSRI discontinuation syndrome.
- The sleep disturbances are more prominent initially in the treatment course. These are in the form of earlier onset of rapid eye movement (REM) sleep, increased duration of REM sleep, and lesser slow-wave sleep.
- The immediate adverse effects of SSRIs are due to increased concentration of serotonin at particular receptor subtypes in various parts of the brain. The post-synaptic receptor desensitization in these regions leads to tolerance to these side effects after some time. 

### Other medications
- Some patients do not respond to SSRIs or have to discontinue them due to inability to tolerate the adverse effects.
- Older antidepressants, such as a tricyclic antidepressant (TCA) or a monoamine oxidase inhibitor (MAOI) can be prescribed in such cases.
- TCAs have anticholinergic side-effects like weight gain, dry mouth, urinary retention, constipation, and blurry vision.
- Some individuals on TCA also develop sexual dysfunction, cardiac side-effects and orthostatic hypotension.
- These medications should be avoided in elderly patients.
- MAOIs can predispose to serotonin syndrome if used with SSRIs as an adjuvant therapy or if insufficient time is given for washout of SSRIs before switching to MAOIs. 
- A considerable approach to deal with this problem is to give at least a washout period of 14 days while switching from SSRIs to MAOIs or vice-versa.
- Fluoxetine has a longer half-life as compared to other SSRIs, therefore a longer washout period (a minimum of 5 weeks) is required to switch from Fluoxetine to another MAOI.
- Other antidepressants that can be used for treating dysthymia are bupropion (Wellbutrin), venlafaxine (Effexor), mirtazapine (Remeron), and duloxetine (Cymbalta).

## Psychotherapy
- Evidence suggests the combination of pharmacotherapy and psychotherapy provides the greatest improvement in dysthymia. 
- On the contrary, some studies point towards the inferiority of psychotherapy in treating dysthymia.
- There are different types of psychotherapies. The type of therapy chosen depends upon a number of factors like the nature of any stressful events, the availability of family and other social support, and personal preference.
- Psychotherapy focuses mainly on education about the disease model, correcting the underlying cognitive distortions, and building up support.
- Cognitive-behavioral therapy is designed to examine and help correct the faulty, self-critical thought patterns and correct the cognitive distortions that persons with mood disorders commonly experience.
- Psychodynamic, insight-oriented, or interpersonal psychotherapy (IPT) can find out the origin of the symptoms, address them appropriately, and explore the conflicts in important relationships which are further deteriorating the illness.
- IPT emphasizes resolving the conflict in current relationships that are exacerbating the depressive symptoms.
- Both CBT and IPT are effective for adolescents. Psychoeducation and psychosocial support provided to the parents of adolescents with dysthymia plays a very important role in the early and satisfactory response to these therapies.
- An adapted version for IPT is used for adolescents because they are in conflict with their parents as well as peers, limiting the outlet options for their emotional burden.