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. 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. 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.
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. 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.
Worldwide it is estimated the prevalence of depression (including persistent depressive disorder/dysthymia) is approximately 12%. In the United States, the prevalence is slightly higher with the estimation of major depressive disorder being 17% and persistent depressive disorder being 3%. These findings vary depending on the methods of identification used (survey versus validated scales), and population studied. In general, the prevalence of the 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. 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. 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 ages greater than 65. Admittedly, estimates of depression may be low in the elderly due to increasing confounding physical disorders with age.
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 the mood. 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.
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.
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.
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. Validated screening tools for depression such as the patient health questionnaire can assist with screening and identification of depressed patients.
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. 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. 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. 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.
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.
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.
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.
Treatment of depression can involve a multidisciplinary team including a primary care provider 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 medications the patient is receiving. 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. A large majority of the management of persistent depressive disorder will likely occur in the primary care setting, and the collaborative care model will serve as one strategy to coordinate care.
|||Rhebergen D,Graham R, The re-labelling of dysthymic disorder to persistent depressive disorder in DSM-5: old wine in new bottles? Current opinion in psychiatry. 2014 Jan; [PubMed PMID: 24270481]|
|||Freeman HL, Historical and nosological aspects of dysthymia. Acta psychiatrica Scandinavica. Supplementum. 1994; [PubMed PMID: 7942068]|
|||Brieger P,Marneros A, Dysthymia and cyclothymia: historical origins and contemporary development. Journal of affective disorders. 1997 Sep; [PubMed PMID: 9298424]|
|||Brieger P,Marneros A, [The dysthymia concept: current and historical aspects--an overview]. Fortschritte der Neurologie-Psychiatrie. 1995 Oct; [PubMed PMID: 8529990]|
|||Sullivan PF,Neale MC,Kendler KS, Genetic epidemiology of major depression: review and meta-analysis. The American journal of psychiatry. 2000 Oct; [PubMed PMID: 11007705]|
|||Kendler KS,Gardner CO,Prescott CA, Toward a comprehensive developmental model for major depression in men. The American journal of psychiatry. 2006 Jan; [PubMed PMID: 16390898]|
|||Kessler RC,Ormel J,Petukhova M,McLaughlin KA,Green JG,Russo LJ,Stein DJ,Zaslavsky AM,Aguilar-Gaxiola S,Alonso J,Andrade L,Benjet C,de Girolamo G,de Graaf R,Demyttenaere K,Fayyad J,Haro JM,Hu Cy,Karam A,Lee S,Lepine JP,Matchsinger H,Mihaescu-Pintia C,Posada-Villa J,Sagar R,Ustün TB, Development of lifetime comorbidity in the World Health Organization world mental health surveys. Archives of general psychiatry. 2011 Jan; [PubMed PMID: 21199968]|
|||Kessler RC,Berglund P,Demler O,Jin R,Merikangas KR,Walters EE, Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of general psychiatry. 2005 Jun; [PubMed PMID: 15939837]|
|||Vandeleur CL,Fassassi S,Castelao E,Glaus J,Strippoli MF,Lasserre AM,Rudaz D,Gebreab S,Pistis G,Aubry JM,Angst J,Preisig M, Prevalence and correlates of DSM-5 major depressive and related disorders in the community. Psychiatry research. 2017 Apr; [PubMed PMID: 28142066]|
|||Seedat S,Scott KM,Angermeyer MC,Berglund P,Bromet EJ,Brugha TS,Demyttenaere K,de Girolamo G,Haro JM,Jin R,Karam EG,Kovess-Masfety V,Levinson D,Medina Mora ME,Ono Y,Ormel J,Pennell BE,Posada-Villa J,Sampson NA,Williams D,Kessler RC, Cross-national associations between gender and mental disorders in the World Health Organization World Mental Health Surveys. Archives of general psychiatry. 2009 Jul; [PubMed PMID: 19581570]|
|||Hasin DS,Goodwin RD,Stinson FS,Grant BF, Epidemiology of major depressive disorder: results from the National Epidemiologic Survey on Alcoholism and Related Conditions. Archives of general psychiatry. 2005 Oct; [PubMed PMID: 16203955]|
|||Kessler RC,Birnbaum H,Bromet E,Hwang I,Sampson N,Shahly V, Age differences in major depression: results from the National Comorbidity Survey Replication (NCS-R). Psychological medicine. 2010 Feb; [PubMed PMID: 19531277]|
|||Duman RS,Heninger GR,Nestler EJ, A molecular and cellular theory of depression. Archives of general psychiatry. 1997 Jul; [PubMed PMID: 9236543]|
|||Thase ME, Molecules that mediate mood. The New England journal of medicine. 2007 Dec 6; [PubMed PMID: 18057345]|
|||Nutt DJ,Baldwin DS,Clayton AH,Elgie R,Lecrubier Y,Montejo AL,Papakostas GI,Souery D,Trivedi MH,Tylee A, Consensus statement and research needs: the role of dopamine and norepinephrine in depression and antidepressant treatment. The Journal of clinical psychiatry. 2006; [PubMed PMID: 16848678]|
|||Sanacora G,Mason GF,Rothman DL,Behar KL,Hyder F,Petroff OA,Berman RM,Charney DS,Krystal JH, Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. Archives of general psychiatry. 1999 Nov; [PubMed PMID: 10565505]|
|||Koolschijn PC,van Haren NE,Lensvelt-Mulders GJ,Hulshoff Pol HE,Kahn RS, Brain volume abnormalities in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Human brain mapping. 2009 Nov; [PubMed PMID: 19441021]|
|||Uher R,Payne JL,Pavlova B,Perlis RH, Major depressive disorder in DSM-5: implications for clinical practice and research of changes from DSM-IV. Depression and anxiety. 2014 Jun; [PubMed PMID: 24272961]|
|||Korn CS,Currier GW,Henderson SO, [PubMed PMID: 10699517]|
|||Conigliaro A,Benabbas R,Schnitzer E,Janairo MP,Sinert R, Protocolized Laboratory Screening for the Medical Clearance of Psychiatric Patients in the Emergency Department: A Systematic Review. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2018 May; [PubMed PMID: 29266617]|
|||Ordas DM,Labbate LA, Routine screening of thyroid function in patients hospitalized for major depression or dysthymia? Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists. 1995 Dec; [PubMed PMID: 8721889]|
|||Kroenke K,Spitzer RL,Williams JB,Löwe B, The Patient Health Questionnaire Somatic, Anxiety, and Depressive Symptom Scales: a systematic review. General hospital psychiatry. 2010 Jul-Aug; [PubMed PMID: 20633738]|
|||Cuijpers P,Dekker J,Hollon SD,Andersson G, Adding psychotherapy to pharmacotherapy in the treatment of depressive disorders in adults: a meta-analysis. The Journal of clinical psychiatry. 2009 Sep; [PubMed PMID: 19818243]|
|||Cuijpers P,van Straten A,Warmerdam L,Andersson G, Psychotherapy versus the combination of psychotherapy and pharmacotherapy in the treatment of depression: a meta-analysis. Depression and anxiety. 2009; [PubMed PMID: 19031487]|
|||Linde K,Kriston L,Rücker G,Jamil S,Schumann I,Meissner K,Sigterman K,Schneider A, Efficacy and acceptability of pharmacological treatments for depressive disorders in primary care: systematic review and network meta-analysis. Annals of family medicine. 2015 Jan-Feb; [PubMed PMID: 25583895]|
|||Meister R,von Wolff A,Mohr H,Härter M,Nestoriuc Y,Hölzel L,Kriston L, Comparative Safety of Pharmacologic Treatments for Persistent Depressive Disorder: A Systematic Review and Network Meta-Analysis. PloS one. 2016; [PubMed PMID: 27187783]|
|||Meister R,Jansen A,Härter M,Nestoriuc Y,Kriston L, Placebo and nocebo reactions in randomized trials of pharmacological treatments for persistent depressive disorder. A meta-regression analysis. Journal of affective disorders. 2017 Jun; [PubMed PMID: 28363152]|
|||Cuijpers P,Karyotaki E,Weitz E,Andersson G,Hollon SD,van Straten A, The effects of psychotherapies for major depression in adults on remission, recovery and improvement: a meta-analysis. Journal of affective disorders. 2014 Apr; [PubMed PMID: 24679399]|
|||Cuijpers P,van Straten A,Andersson G,van Oppen P, Psychotherapy for depression in adults: a meta-analysis of comparative outcome studies. Journal of consulting and clinical psychology. 2008 Dec; [PubMed PMID: 19045960]|
|||Furukawa TA,Efthimiou O,Weitz ES,Cipriani A,Keller MB,Kocsis JH,Klein DN,Michalak J,Salanti G,Cuijpers P,Schramm E, Cognitive-Behavioral Analysis System of Psychotherapy, Drug, or Their Combination for Persistent Depressive Disorder: Personalizing the Treatment Choice Using Individual Participant Data Network Metaregression. Psychotherapy and psychosomatics. 2018; [PubMed PMID: 29847831]|
|||Hung CI,Liu CY,Yang CH, Persistent depressive disorder has long-term negative impacts on depression, anxiety, and somatic symptoms at 10-year follow-up among patients with major depressive disorder. Journal of affective disorders. 2019 Jan 15; [PubMed PMID: 30248637]|
|||Katon W,Ciechanowski P, Impact of major depression on chronic medical illness. Journal of psychosomatic research. 2002 Oct; [PubMed PMID: 12377294]|
|||Zeiss AM,Karlin BE, Integrating mental health and primary care services in the Department of Veterans Affairs health care system. Journal of clinical psychology in medical settings. 2008 Mar; [PubMed PMID: 19104957]|