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Persistent Depressive Disorder

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Last Update: June 26, 2023.

Continuing Education Activity

Persistent depressive disorder, also known as dysthymia or chronic major depression, is a poorly understood condition for which the diagnostic criteria are constantly evolving. In the past, this condition was considered a personality disorder, which connotes a permanent, pervasive nature. However, it is likely better conceptualized as a temporary state that can change. This activity reviews the new diagnostic criteria and treatment considerations for persistent depressive disorder and highlights the role of the interprofessional team in managing patients with this condition.


  • Outline the etiology of persistent depressive disorder.
  • Identify the diagnostic criteria for persistent depressive disorder.
  • Describe the management considerations for persistent depressive disorder.
  • Explain the importance of improving coordination between interprofessional team members to enhance the delivery of care and optimize outcomes for patients with persistent depressive disorder.
Access free multiple choice questions on this topic.


Persistent depressive disorder is a newly coined term in the DSM-5 to capture what was originally known as dysthymia and chronic major depression.  This disorder has been poorly understood, and its classification has evolved due to the complicated and ever-evolving nature of the nosology of depressive disorders.[1]  In the past, this disease was considered a depressed personality state, but it is likely better conceptualized as a disease state rather than a personality disorder (permanent, pervasive way of approaching the world).  This change is reflected in the history of the diagnosis as the DSM-II originally identified it as a personality disorder.  It was not until the DSM-III that dysthymic disorder was defined as a mild chronic depression lasting longer than 2 years.[2]  The origin of the word dysthymia dates back to its Greek roots, with the first use of the word referring to psychiatry occurring by CF Fleming around 1844.[3][4] 


The etiology of depressed states continues to evolve with the modernization and advancement of medicine. Generally, there is a commonly accepted biopsychosocial conceptualization of depression that postulates that depression is a multifactorial disease state brought on by biological, social, and psychological factors.[5]  An in-depth discussion regarding the etiology of depression is beyond the scope of this article, given the numerous risk factors associated with depression and the range of theorized causes, and various continuing areas of research. However, there are specific risk factors for a persistent depressive disorder that include but are not limited to genetics, epigenetics, prior mental illness, neuroticism, high anxiety states, sense of self-worth, psychological health, trauma, life stressors, and social determinants of health.[6] 


Worldwide it is estimated the prevalence of depression (including persistent depressive disorder/dysthymia) is approximately 12%.[7]  In the United States, the prevalence is slightly higher, with the estimation of major depressive disorder being 17% and persistent depressive disorder being 3%.[8]  These findings vary depending on the methods of identification used (survey versus validated scales) and the population studied.  In general, the prevalence of major depressive disorder is higher than that of persistent depressive disorder, suggesting that the disease course of depression naturally is more often to relapse and remit rather than remain present chronically over an extended time. A study of an urban population of 3720 patients suggests that the prevalence was 15.2% for persistent depressive disorder with persistent major depressive episode (MDE), 3.3% for persistent depressive disorder with pure dysthymia, and 28.2% for major depressive disorder.[9]  In general, when it comes to gender, the prevalence of persistent depressive disorder is two times higher in females than in males, and this is fairly consistent both worldwide and in the US.[10][11]  While frequency in age groups for persistent depressive disorder is less clear given the recent changes to the condition, in general, depression rates tend to decrease with increasing age, especially age greater than 65. Admittedly, estimates of depression may be low in the elderly due to increasing confounding physical disorders with age.[12]


The pathophysiology of persistent depressive disorder and depression continues to be a major area of research.  There is a complex interplay between neurotransmitters and receptors that affect the brain chemistry of mood. Serotonin is often the implicated neurotransmitter and target of pharmacologic intervention, but researchers have identified other neurotransmitters such as dopamine, epinephrine, norepinephrine, GABA, and glutamate as affecting mood.[13][14][15][16]  There are significant areas of the brain that also demonstrate significant volume reduction in depression.  The frontal areas of the brain (especially the anterior cingulate and the orbitofrontal cortex), as well as the hippocampus, showed large to moderate volume reductions.[17]

History and Physical

A careful history is crucial to any psychiatric interview, especially one for diagnostic purposes.  Eliciting symptomatology, severity, and the temporal course helps determine the appropriate DSM diagnosis.  Persistent depressive disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington 2013.) is as follows:

The patient must have a depressed mood for at least 2 years.  For children or adolescents, the mood can be irritable instead of depressed, and the time requirement is 1 year.  For both groups, symptoms cannot be absent for greater than 2 months. In addition to depressed/irritable mood, at least 2 of the following symptoms have to be present.  

  1. Poor appetite or overeating
  2. Insomnia or hypersomnia
  3. Low energy/fatigue
  4. Low self-esteem
  5. Poor concentration/decision making
  6. Hopelessness

Note, the DSM-5 has consolidated chronic major depression and dysthymia from DSM-IV into persistent depressive disorder; this means that a patient may meet the criteria for persistent depressive disorder and major depressive disorder at the same time. The DSM-5 has identified specifiers to determine if the persistent depressive disorder is with a pure dysthymic syndrome or with a persistent major depressive episode and whether an episode is current or not.  As always, the above symptoms must cause significant distress and impairment in critical areas of functioning to meet the threshold for diagnosis.[18]  


A thorough assessment of patients presenting with mental health symptoms involves ruling out medical and biological causes of symptomatology.  Current and past medical history, as well as current medications, should be part of the psychiatric evaluation to provide context to symptoms.  While routine laboratory screening of an otherwise healthy patient with symptoms of depression is of questionable diagnostic value, the following tests are commonly ordered to support medical decision-making: complete blood count, chemistry panels, urine pregnancy, urine toxicology, and TSH.  Symptoms and patient history often guide additional testing.[19][20][21]  Validated screening tools for depression, such as the patient health questionnaire, can assist with screening and identification of depressed patients.[22] 

Treatment / Management

In general, the treatment and management of persistent depressive disorder do not vary significantly from the treatment and management of a major depressive disorder.  While there may be differences in the individualization of treatment plans based on symptom number, severity, and chronicity, the general principles of pharmacotherapy and psychotherapy remain the same.  It is also commonly accepted and well-validated that a combination of pharmacotherapy and psychotherapy is more effective than either treatment independently.[23][24]  If antidepressant therapy is indicated, an SSRI (selective serotonin reuptake inhibitor) is the first line typically given the overall efficacy and tolerability of the class.  While other classes such as SNRIs (serotonin-norepinephrine reuptake inhibitor) and atypical antidepressants have also shown efficacy, specific antidepressant selection and management of treatment-resistant depression is beyond the scope of this article.[25][26][27]  Psychotherapy selection and type offered is less important (due to similar efficacies) than universal principles such as strong therapeutic rapport, but CBT (cognitive behavioral therapy) and interpersonal therapy appear to be the most commonly studied for the treatment of depression.[28][29]  The cognitive-behavioral analysis system of psychotherapy (CBASP) is a newer modality and the only psychotherapy specifically developed for the management of chronic depression, but it has yet to become standard of care.[30]

Differential Diagnosis

Differential diagnoses for persistent depressive disorder include ruling out medical/organic causes as well as screening for other DSM diagnoses, including major depression, bipolar, psychotic disorders, substance-induced states, and personality disorders. 


Depression, in general, has a substantial impact on both morbidity and mortality and a common cause of global disease burden and disability worldwide. Persistent depressive disorder represents a disorder of chronic depression, and outcomes and prognosis are similar if not worse than those of major depressive disorder depending on whether or not the disorder represents dysthymia or chronic major depression. Outcomes of a 10-year study suggest that persistent depressive disorder is independently associated with greater severity of depression, anxiety, and somatic symptoms in comparison to major depressive disorder.[31] 


Complications of untreated depression are similar to those complications of other untreated mental illnesses. It is commonly accepted that untreated depression broadly impacts healthcare resulting in increased healthcare costs as well as decreased medication adherence and treatment compliance in those with medical problems. In multiple studies, depression has been shown to lead to additive functional impairment and increase symptom burden in those with chronic medical illnesses. Additionally, there is evidence suggesting that depression increases mortality.[32] 

Deterrence and Patient Education

Patient education is crucial in patients with persistent depressive disorder.  An informed patient is more likely to have a better understanding of the causes and treatment for their depressive condition and therefore a greater likelihood of a better outcome due to improved treatment compliance.  

Enhancing Healthcare Team Outcomes

Treatment of depression can involve an interprofessional team, including a primary care provider and other specialists. Special attention is necessary for the provider managing psychiatric medications and the therapist providing therapy to ensure open and direct lines of communication to ensure that the patient is receiving the best care possible. Furthermore, the mental health provider must maintain a general understanding of the patient's overall health to ensure that psychiatric medications are not interacting with other drugs the patient is receiving; this is where a consult with a board-certified psychiatric pharmacist can be of great value. Psychiatric health nursing staff can also coordinate with the team members, providing patient resources, answering questions, and monitoring patient progress while watching for signs of adverse drug reactions, which will be reported to appropriate team staff members promptly if encountered. The collaborative care model is a newer model of care designed to improve healthcare outcomes that involve initiating mental health care in the primary care setting utilizing behavioral health specialists and care coordination with nurse case managers and providers.[33] A large majority of the management of persistent depressive disorder will likely occur in the primary care setting, and the collaborative, interprofessional care model will serve as one strategy to coordinate care. [Level 5] 

Review Questions


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Disclosure: Raj Patel declares no relevant financial relationships with ineligible companies.

Disclosure: Gregory Rose declares no relevant financial relationships with ineligible companies.

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