Persistent depressive disorder

Persistent depressive disorder
Other names: Dysthymia, dysthymic disorder, chronic depression
The Old Guitarist by Pablo Picasso, depicting a state of sadness and incompletion
Pronunciation
  • Dysthymia
    /dɪsˈθaɪmiə/ dis-THY-mee-ə
SpecialtyPsychiatry
SymptomsLow mood, change in eating or sleeping, low energy, poor self esteem, trouble concentrating[1]
ComplicationsSubstance misuse, suicide[2][3]
Usual onsetChildhood or early adulthood[2]
DurationLong-term[3]
Risk factorsLoss of a parent, family history[2]
Diagnostic methodBased on symptoms after ruling out other possible causes[2]
Differential diagnosisHypothyroidism, drug misuse[2]
TreatmentCounseling, SSRIs[1]
Frequency3% (104 million as of 2015)[3][4]

Persistent depressive disorder (PDD), previously known as dysthymia and chronic major depression, is a prolonged depressed mood.[1][3] Other symptoms may include a change in eating or sleeping, low energy, poor self esteem, and trouble concentrating.[1] These symptoms are to a degree that significant distress or impairment occurs.[1] Episodes of major depressive disorder or suicide may occur.[5][3]

Risk factors include loss of a parent at a young age and family history.[2] Diagnosis is based on symptoms after ruling out other possible causes.[2] Symptoms must be present for at least two years in adults or one year in children for a diagnosis.[2] In the DSM-5, dysthymia and chronic major depression were combined to form persistent depressive disorder.[2]

Treatment is similar to major depressive disorder with the use of counselling and medications such as SSRIs.[1] About 1 to 6% of the population are affected at some point in time.[3] In 2015 about 104 million people were affected globally.[4] Onset is generally in childhood or early adulthood.[2] The term "dysthymia" came into use in the field of psychiatry in 1844 by Fleming.[1] It was first introduced in the DSM-II as a personality disorder and was later conceptualized as a disease state in the DSM-III.[1]

Signs and symptoms

Dysthymia characteristics include an extended period of depressed mood combined with at least two other symptoms which may include insomnia or hypersomnia, fatigue or low energy, eating changes (more or less), low self-esteem, or feelings of hopelessness. Poor concentration or difficulty making decisions are treated as another possible symptom. Mild degrees of dysthymia may result in people withdrawing from stress and avoiding opportunities for failure. In more severe cases of dysthymia, people may withdraw from daily activities.[6] They will usually find little pleasure in usual activities and pastimes. Diagnosis of dysthymia can be difficult because of the subtle nature of the symptoms and patients can often hide them in social situations, making it challenging for others to detect symptoms. Additionally, dysthymia often occurs at the same time as other psychological disorders, which adds a level of complexity in determining the presence of dysthymia, particularly because there is often an overlap in the symptoms of disorders.[7] There is a high incidence of comorbid illness in those with dysthymia. Suicidal behavior is also a particular problem with persons with dysthymia. It is vital to look for signs of major depression, panic disorder, generalised anxiety disorder, alcohol and substance misuse and personality disorder.[8]

Associated conditions

Dysthymia often co-occurs with other mental disorders. A "double depression" is the occurrence of episodes of major depression in addition to dysthymia. Switching between periods of dysthymic moods and periods of hypomanic moods is indicative of cyclothymia, which is a mild variant of bipolar disorder.

"At least three-quarters of patients with dysthymia also have a chronic physical illness or another psychiatric disorder such as one of the anxiety disorders, cyclothymia, drug addiction, or alcoholism".[9] Common co-occurring conditions include major depression (up to 75%), anxiety disorders (up to 50%), personality disorders (up to 40%), somatoform disorders (up to 45%) and substance abuse (up to 50%).[7] People with dysthymia have a higher-than-average chance of developing major depression.[10] A 10-year follow-up study found that 95% of dysthymia patients had an episode of major depression.[11] When an intense episode of depression occurs on top of dysthymia, the state is called "double depression."[10]

Double depression

Main article: Double depression

Double depression occurs when a person experiences a major depressive episode on top of the already-existing condition of dysthymia. It is difficult to treat, as sufferers accept these major depressive symptoms as a natural part of their personality or as a part of their life that is outside of their control. The fact that people with dysthymia may accept these worsening symptoms as inevitable can delay treatment. When and if such people seek out treatment, the treatment may not be very effective if only the symptoms of the major depression are addressed, but not the dysthymic symptoms.[12] Patients with double depression tend to report significantly higher levels of hopelessness than is normal. This can be a useful symptom for mental health services providers to focus on when working with patients to treat the condition.[10] Additionally, cognitive therapies can be effective for working with people with double depression in order to help change negative thinking patterns and give individuals a new way of seeing themselves and their environment.[12]

It has been suggested that the best way to prevent double depression is by treating the dysthymia. A combination of antidepressants and cognitive therapies can be helpful in preventing major depressive symptoms from occurring. Additionally, exercise and good sleep hygiene (e.g., improving sleep patterns) are thought to have an additive effect on treating dysthymic symptoms and preventing them from worsening.[12]

Causes

There are no known biological causes that apply consistently to all cases of dysthymia, which suggests diverse origin of the disorder.[7] However, there are some indications that there is a genetic predisposition to dysthymia: "The rate of depression in the families of people with dysthymia is as high as fifty percent for the early-onset form of the disorder".[9] Other factors linked with dysthymia include stress, social isolation, and lack of social support.[7]

In a study using identical and fraternal twins, results indicated that there is a stronger likelihood of identical twins both having depression than fraternal twins. This provides support for the idea that dysthymia is in part caused by heredity.

Pathophysiology

There is evidence that there may be neurological indicators of early onset dysthymia. There are several brain structures (corpus callosum and frontal lobe) that are different in women with dysthymia than in those without dysthymia. This may indicate that there is a developmental difference between these two groups.[13]

Another study, which used fMRI techniques to assess the differences between individuals with dysthymia and other people, found additional support for neurological indicators of the disorder. This study found several areas of the brain that function differently. The amygdala (associated with processing negative emotions such as fear) was more activated in dysthymia patients. The study also observed increased activity in the insula (which is associated with sad emotions). Finally, there was increased activity in the cingulate gyrus (which serves as the bridge between attention and emotion).[14]

A study comparing healthy individuals to people with dysthymia indicates there are other biological indicators of the disorder. An anticipated result appeared as healthy individuals expected fewer negative adjectives to apply to them, whereas people with dysthymia expected fewer positive adjectives to apply to them in the future. Biologically these groups are also differentiated in that healthy individuals showed greater neurological anticipation for all types of events (positive, neutral, or negative) than those with dysthymia. This provides neurological evidence of the dulling of emotion that individuals with dysthymia have learned to use to protect themselves from overly strong negative feelings, compared to healthy people.[15]

There is some evidence of a genetic basis for all types of depression, including dysthymia. A study using identical and fraternal twins indicated that there is a stronger likelihood of identical twins both having depression than fraternal twins. This provides support for the idea that dysthymia is caused in part by heredity.[16]

A new model has recently surfaced in the literature regarding the HPA axis (structures in the brain that get activated in response to stress)[17] and its involvement with dysthymia (e.g. phenotypic variations of corticotropin releasing hormone (CRH) and arginine vasopressin (AVP), and down-regulation of adrenal functioning) as well as forebrain serotonergic mechanisms.[18] Since this model is highly provisional, further research is still needed.

Diagnosis

The Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV), published by the American Psychiatric Association, characterizes dysthymic disorder.[19] The essential symptom involves the individual feeling depressed for the majority of days, and parts of the day, for at least two years. Low energy, disturbances in sleep or in appetite, and low self-esteem typically contribute to the clinical picture as well. Sufferers have often experienced dysthymia for many years before it is diagnosed. People around them often describe the sufferer in words similar to "just a moody person". Note the following diagnostic criteria:[20][21]

  1. During a majority of days for two years or more, the adult patient reports depressed mood, or appears depressed to others for most of the day.
  2. When depressed, the patient has two or more of:
    1. decreased or increased appetite
    2. decreased or increased sleep (insomnia or hypersomnia)
    3. Fatigue or low energy
    4. Reduced self-esteem
    5. Decreased concentration or problems making decisions
    6. Feelings of hopelessness or pessimism
  3. During this two-year period, the above symptoms are never absent longer than two consecutive months.
  4. During the duration of the two-year period, the patient may have had a perpetual major depressive episode.
  5. The patient has not had any manic, hypomanic, or mixed episodes.
  6. The patient has never fulfilled criteria for cyclothymic disorder.
  7. The depression does not exist only as part of a chronic psychosis (such as schizophrenia or delusional disorder).
  8. The symptoms are often not directly caused by a medical illness or by substances, including drug abuse or other medications.
  9. The symptoms may cause significant problems or distress in social, work, academic, or other major areas of life functioning.[19]

In children and adolescents, mood can be irritable, and duration must be at least one year, in contrast to two years needed for diagnosis in adults.

Early onset (diagnosis before age 21) is associated with more frequent relapses, psychiatric hospitalizations, and more co-occurring conditions.[7] For younger adults with dysthymia, there is a higher co-occurrence in personality abnormalities and the symptoms are likely chronic.[22] However, in older adults suffering from dysthymia, the psychological symptoms are associated with medical conditions and/or stressful life events and losses.[23]

Dysthymia can be contrasted with major depressive disorder by assessing the acute nature of the symptoms. Dysthymia is far more chronic (long lasting) than major depressive disorder, in which symptoms may be present for as little as 2 weeks. Also Dysthymia often presents itself at an earlier age than Major Depressive Disorder.[24]

Prevention

Though there is no clear-cut way to prevent dysthymia from occurring, some suggestions have been made. Since dysthymia will often first occur in childhood, it is important to identify children who may be at risk. It may be beneficial to work with children in helping to control their stress, increase resilience, boost self-esteem, and provide strong networks of social support. These tactics may be helpful in warding off or delaying dysthymic symptoms.[25]

Treatments

Persistent depressive disorder can be treated with psychotherapy and pharmacotherapy. The overall rate and degree of treatment success is somewhat lower than for non-chronic depression, and a combination of psychotherapy and pharmacotherapy shows best results.[26]

Therapy

Psychotherapy can be effective in treating dysthymia. There are many different types of therapy, and some are more effective than others.

  • The empirically most studied type of treatment is cognitive-behavioral therapy. This type of therapy is very effective for non-chronic depression, and it appears to be also effective for chronic depression.[26][27]
  • Cognitive behavioral analysis system of psychotherapy (CBASP) has been designed specifically to treat PDD. Empirical results on this form of therapy are inconclusive:[26] While one study showed remarkably high treatment success rates,[28] a later, even larger study showed no significant benefit of adding CBASP to treatment with antidepressants.[29]
  • Schema therapy and psychodynamic psychotherapy have been used for PDD, though good empirical results are lacking.[30][31]
  • Interpersonal psychotherapy has also been said to be effective in treating the disorder,[32] though it only shows marginal benefit when added to treatment with antidepressants.[26][33]

Medications

According to a 2014 meta-analysis, antidepressants are at least as effective for persistent depressive disorder as for major depressive disorder.[26] The first line of pharmacotherapy is usually SSRIs due to their purported more tolerable nature and reduced side effects compared to the irreversible monoamine oxidase inhibitors or tricyclic antidepressants. Studies have found that the mean response to antidepressant medications for people with dysthymia is 55%, compared with a 31% response rate to a placebo.[32] The most commonly prescribed antidepressants/SSRIs for dysthymia are escitalopram, citalopram, sertraline, fluoxetine, paroxetine, and fluvoxamine. It often takes an average of 6–8 weeks before the patient begins to feel these medications' therapeutic effects. Additionally, STAR*D, a multi-clinic governmental study, found that people with overall depression will generally need to try different brands of medication before finding one that works specifically for them. Research shows that 1 in 4 of those who switch medications get better results regardless of whether the second medication is an SSRI or some other type of antidepressant.

In a meta-analytic study from 2005, it was found that SSRIs and TCAs are equally effective in treating dysthymia. They also found that MAOIs have a slight advantage over the use of other medication in treating this disorder.[34] However, the author of this study cautions that MAOIs should not necessarily be the first line of defense in the treatment of dysthymia, as they are often less tolerable than their counterparts, such as SSRIs.[34]

Tentative evidence supports the use of amisulpride to treat dysthymia but with increased side effects.[35]

Combination treatment

A combination of antidepressant medication and psychotherapy has consistently been shown to be the most effective line of treatment for people diagnosed with dysthymia. Working with a psychotherapist to address the causes and effects of the disorder, in addition to taking antidepressants to help eliminate the symptoms, can be extremely beneficial. This combination is often the preferred method of treatment for those who have dysthymia. Looking at various studies involving treatment for dysthymia, 75% of people responded positively to a combination of cognitive behavioral therapy (CBT) and pharmacotherapy, whereas only 48% of people responded positively to just CBT or medication alone.

In a meta-analytic study from 2010, psychotherapy had a small but significant effect when compared to control groups. Psychotherapy was significantly less effective than pharmacotherapy in direct comparisons. However, the benefit of pharmacotherapy was limited to selective serotonin reuptake inhibitors (SSRIs) rather than tricyclic antidepressants (TCA). When pharmacotherapy alone was compared with combined treatment with pharmacotherapy plus psychotherapy, there was a strong trend in favour of combined treatment.[36]

A 2019 Cochrane review could not conclude with certainty that continued antidepressants was effective in preventing relapse or recurrence. The body of evidence was too small for any greater certainty although the study acknowledges that continued psychotherapy may be beneficial when compared to no treatment.[37]

Resistance

Because of dysthymia's chronic nature, treatment resistance is somewhat common.[26][32] In such a case, augmentation is often recommended. Such treatment augmentations can include lithium pharmacology, thyroid hormone augmentation, amisulpride, buspirone, bupropion, stimulants, and mirtazapine. Additionally, if the person also suffers from seasonal affective disorder, light therapy can be useful in helping augment therapeutic effects.[32]

Epidemiology

Globally dysthymia occurs in about 105 million people a year (1.5% of the population).[38] It is 38% more common in women (1.8% of women) than in men (1.3% of men).[38] The lifetime prevalence rate of dysthymia in community settings appears to range from 3 to 6% in the United States. However, in primary care settings the rate is higher ranging from 5 to 15 percent. United States prevalence rates tend to be somewhat higher than rates in other countries.[7]

See also

References

  1. 1 2 3 4 5 6 7 8 Patel, RK; Rose, GM (January 2020). "Persistent Depressive Disorder". PMID 31082096. {{cite journal}}: Cite journal requires |journal= (help)
  2. 1 2 3 4 5 6 7 8 9 10 Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). American Psychiatric Association. 2013. pp. 168-171. doi:10.1176/appi.books.9780890425596.156852. ISBN 978-0-89042-555-8. {{cite book}}: Cite has empty unknown parameter: |1= (help)
  3. 1 2 3 4 5 6 Schramm, E; Klein, DN; Elsaesser, M; Furukawa, TA; Domschke, K (September 2020). "Review of dysthymia and persistent depressive disorder: history, correlates, and clinical implications". The lancet. Psychiatry. 7 (9): 801–812. doi:10.1016/S2215-0366(20)30099-7. PMID 32828168.
  4. 1 2 GBD 2015 Disease and Injury Incidence and Prevalence, Collaborators. (8 October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC 5055577. PMID 27733282. {{cite journal}}: |first1= has generic name (help)
  5. ↑ "Depression". NIMH. May 2016. Archived from the original on 5 August 2016. Retrieved 31 July 2016.
  6. ↑ Niculescu, A.B.; Akiskal, H.S. (2001). "Proposed Endophenotypes of Dysthymia: Evolutionary, Clinical, and Pharmacogenomic Considerations". Molecular Psychiatry. 6 (4): 363–366. doi:10.1038/sj.mp.4000906. PMID 11443518.
  7. 1 2 3 4 5 6 Sansone, R. A. MD; Sansone, L. A. MD (2009). "Dysthymic Disorder: Forlorn and Overlooked?". Psychiatry. 6 (5): 46–50. PMC 2719439. PMID 19724735.
  8. ↑ Baldwin, Rudge S.; Thomas S. (1995). "Dysthymia: Options in Pharmacotherapy". Practical Therpeutics. 4 (6): 422 to 430. doi:10.2165/00023210-199504060-00005.
  9. 1 2 "Dysthymia". Harvard Health Publications. Harvard University. February 2005. Archived from the original (February 2005 issue of the Harvard Mental Health Letter) on 6 January 2010. Retrieved 12 December 2009.
  10. 1 2 3 "Double Depression: Hopelessness Key Component Of Mood Disorder". Science Daily. 26 July 2007. Archived from the original on 7 September 2008. Retrieved 17 July 2008.
  11. ↑ Klein, DN; Shankman, SA; Rose, S (2006). "Ten-year prospective follow-up study of the naturalistic course of dysthymic disorder and double depression". The American Journal of Psychiatry. 163 (5): 872–80. doi:10.1176/appi.ajp.163.5.872. PMID 16648329.
  12. 1 2 3 Double Depression: Definition, Symptoms, Treatment, and More Archived 2012-01-04 at the Wayback Machine. Webmd.com (2012-01-07). Retrieved on 2012-07-01.
  13. ↑ Lyoo, I.K., Kwon, J.S., Lee, S.J., Hann, M.H., Chang, C., Seo, Lee, S.I., and Renshaw, P.F. (2002). "Decrease in Genu of the Corpus Callosum in Medication-Naïve, Early-Onset Dysthymia and Depressive Personality Disorder". Biological Psychiatry. 52 (12): 1134–1143. doi:10.1016/S0006-3223(02)01436-1. PMID 12488058. S2CID 25677987.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ↑ Ravindran, A. V., Smith, A. Cameron, C., Bhatal, R., Cameron, I., Georgescu, T. M., Hogan, M. J. (2009). "Toward a Functional Neuroanatomy of Dysthymia: A Functional Magnetic Resonance Imaging Study". Journal of Affective Disorders. 119 (1–3): 9–15. doi:10.1016/j.jad.2009.03.009. PMID 19351572.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ↑ Casement, M. D.; Shestyuk, A. Y.; Best, J. L.; Casas, B. R.; Glezer, A.; Segundo, M. A.; Deldin, P. J. (2008). "Anticipation of Affect in Dysthymia: Behavioral and Neurophysiological Indicators". Biological Psychiatry. 77 (2): 197–204. doi:10.1016/j.biopsycho.2007.10.007. PMC 2709790. PMID 18063468.
  16. ↑ Edvardsen, J.; Torgersen, S.; Roysamb, E.; Lygren, S.; Skre, I.; Onstad, S.; and Oien, A. (2009). "Unipolar Depressive Disorders have a Common Genotype". Journal of Affective Disorders. 117 (1–2): 30–41. doi:10.1016/j.jad.2008.12.004. PMID 19167093.
  17. ↑ Schacter, Gilbert, Wegner (2011). Psychology (2nd ed.). Worth. pp. 631.{{cite book}}: CS1 maint: multiple names: authors list (link)
  18. ↑ J Griffiths; A V Ravindran; Z Merali; H Anisman (2000). "Dysthymia: a review of pharmacological and behavioral factors". Molecular Psychiatry. 5 (3): 242–261. doi:10.1038/sj.mp.4000697. PMID 10889527.
  19. 1 2 American Psychiatric Association, ed. (June 2000). Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR (4th ed.). American Psychiatric Publishing. ISBN 978-0-89042-024-9. Archived from the original on 2008-05-17.
  20. ↑ Turner, Samuel M.; Hersen, Michel; Beidel, Deborah C., eds. (2007). Adult Psychopathology and Diagnosis (5th ed.). Hoboken, New Jersey: John Wiley. ISBN 978-0-471-74584-6. OCLC 427516745.
  21. ↑ 300.4, ICD9, Accessed 2009 May 2
  22. ↑ "Persistent depressive disorder (dysthymia)". Mayo Clinic. December 2018. Archived from the original on 4 May 2020. Retrieved 10 May 2020.
  23. ↑ Bellino, S.; Patria, L.; Ziero, S.; Rocca, G.; Bogetto, F. (2001). "Clinical Features of Dysthymia and Age: a Clinical Investigation". Psychiatry Review. 103 (2–3): 219–228. doi:10.1016/S0165-1781(01)00274-8. PMID 11549409. S2CID 2502577.
  24. ↑ Goodman, S. H., Schwab-Stone, M., Lahey, B. B., Shaffer, D. and Jensen, P. S. (2000). "Major Depression and Dysthymia in Children and Adolescents: Discriminant Validity and Differential Consequences in a Community Sample". Journal of the American Academy of Child and Adolescent Psychiatry. 39 (6): 761–771. doi:10.1097/00004583-200006000-00015. PMID 10846311.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  25. ↑ Dysthymia (dysthymic disorder): Prevention Archived 2012-02-16 at the Wayback Machine. MayoClinic.com (2010-08-26). Retrieved on 2012-07-01.
  26. 1 2 3 4 5 6 Uher, R. (2014, July 31). Persistent Depressive Disorder, Dysthymia, and Chronic Depression: Update on Diagnosis, Treatment. Psychiatric Times, 31, 8, 1-3. Retrieved from https://www.psychiatrictimes.com/special-reports/persistent-depressive-disorder-dysthymia-and-chronic-depression-update-diagnosis-treatment Archived 2019-03-29 at the Wayback Machine
  27. ↑ Margarita Tartakovsky (2020), https://psychcentral.com/disorders/dysthymic-disorder-symptoms/persistent-depressive-disorder-dysthymia-treatment/ Archived 2020-09-18 at the Wayback Machine. psychcentral.com
  28. ↑ Keller MB, McCullough JP, Klein DN, et al. A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression (published correction appears in N Engl J Med. 2001;345:232). N Engl J Med. 2000;342:1462-1470.
  29. ↑ Kocsis JH, Gelenberg AJ, Rothbaum BO, et al. Cognitive behavioral analysis system of psychotherapy and brief supportive psychotherapy for augmentation of antidepressant nonresponse in chronic depression: the REVAMP Trial. Arch Gen Psychiatry. 2009;66:1178-1188.
  30. ↑ Herts KL, Evans S. Schema Therapy for Chronic Depression Associated with Childhood Trauma: A Case Study. Clinical Case Studies. September 2020. doi:10.1177/1534650120954275 Archived 2021-08-28 at the Wayback Machine
  31. ↑ "Archive copy". Archived from the original on 2021-08-28. Retrieved 2020-10-08.{{cite web}}: CS1 maint: archived copy as title (link)
  32. 1 2 3 4 Dysthymic Disorder~treatment at eMedicine
  33. ↑ Kriston L, von Wolff A, Westphal A, et al. Efficacy and acceptability of acute treatments for persistent depressive disorder: a network meta-analysis. Depress Anxiety. 2014 Jan 21; [Epub ahead of print].
  34. 1 2 Ballesteros, J (2005). "Orphan comparisons and indirect meta-analysis: A case study on antidepressant efficacy in dysthymia comparing tricyclic antidepressants, selective serotonin reuptake inhibitors, and monoamine oxidase inhibitors by using general linear models". Journal of Clinical Psychopharmacology. 25 (2): 127–31. doi:10.1097/01.jcp.0000155826.05327.c1. PMID 15738743. S2CID 844705.
  35. ↑ Komossa, K; Depping, AM; Gaudchau, A; Kissling, W; Leucht, S (8 December 2010). "Second-generation antipsychotics for major depressive disorder and dysthymia". The Cochrane Database of Systematic Reviews (12): CD008121. doi:10.1002/14651858.CD008121.pub2. PMID 21154393.
  36. ↑ Cuijpers, Pim; van Straten, Annemieke; Schuurmans, Josien; van Oppen, Patricia; Hollon, Steven D.; Andersson, Gerhard (2010). "Psychotherapy for chronic major depression and dysthymia: A meta-analysis". Clinical Psychology Review. 30 (1): 51–62. doi:10.1016/j.cpr.2009.09.003. PMID 19781837.
  37. ↑ Machmutow, Katja; Meister, Ramona; Jansen, Alessa; Kriston, Levente; Watzke, Birgit; Härter, Martin Christian; Liebherz, Sarah (20 May 2019). "Comparative effectiveness of continuation and maintenance treatments for persistent depressive disorder in adults". The Cochrane Database of Systematic Reviews. 5: CD012855. doi:10.1002/14651858.CD012855.pub2. ISSN 1469-493X. PMC 6526465. PMID 31106850. Archived from the original on 28 August 2021. Retrieved 23 July 2020.
  38. 1 2 Vos, T (Dec 15, 2012). "Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2163–96. doi:10.1016/S0140-6736(12)61729-2. PMC 6350784. PMID 23245607.
Classification
External resources
This article is issued from Offline. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.