An update on the pharmacotherapeutic strategies for the treatment of dysthymic disorder: a systematic review.

INTRODUCTION: Longer treatment times, more comorbidity, more severe impairments in social, psychological, and emotional functioning, increased healthcare use, and more hospitalizations are all factors that are related to dysthymia. Given the significant prevalence of dysthymia (including persistent depressive disorder) worldwide, its comorbidity with several mental disorders, and the detrimental effects of these comorbidities, it is important to conduct a systematic review to compare the effects of pharmacological acute and maintenance treatments for dysthymia with placebo and standard care in the last 10 years, based on the publication of DSM5. AREAS COVERED: This systematic review was performed according to PRISMA guidelines. Databases, including PubMed and Cochrane Central Register of Controlled Trials, were searched to assess the effects of pharmacological acute and maintenance treatments for dysthymia in comparison with placebo and treatment as usual. EXPERT OPINION: Our review shows that SSRIs and SNRIs present efficacy for dysthymia treatment, and L-Acetylcarnitine should be investigated further for this condition in elderly patients. The comparison of antidepressant medication versus placebo showed coherent results based on three studies favoring pharmacotherapy as an effective treatment for participants with dysthymia. However, the scarcity of research on continuation and maintenance therapy in people with dysthymia highlights the need for more primary research.

Efficacy of amisulpride for depressive symptoms in individuals with mental disorders: A systematic review and meta-analysis.

BACKGROUND: Depressive symptoms occur in several psychiatric disorders, often in the absence of a formal diagnosis of depression. We aimed to evaluate the efficacy and the tolerability of amisulpride, both alone and as augmentation therapy, in the treatment of depressive symptoms in individuals with any major psychiatric disorder. METHODS: We searched PubMed, Embase, PsycINFO, GreyLit, OpenGrey and ProQuest up to March 2020 for randomised controlled trials focussing on the treatment of an acute depressive episode in any major psychiatric disorder. A random-effect meta-analysis was performed to synthesize the findings on depressive symptoms (primary outcome), response rate and tolerability. RESULTS: We retrieved 11 studies including 2065 patients with a diagnosis of dysthymia (eight studies), major depression (one study) or schizophrenia (two studies). Amisulpride 50 mg/day was associated with a larger reduction of depressive symptoms compared to placebo (standardised mean difference [SMD] = -0.70, CI 95% -0.92, -0.49; I2  = 0.0%), and was found to be comparable to selective serotonin reuptake inhibitors (SSRIs; SMD = -0.08, CI 95% -0.23, 0.06, I2  = 0.0%), amineptine, imipramine and amitriptyline in the treatment of dysthymia (three studies, not pooled). In individuals with schizophrenia, amisulpride administered at higher doses (>400 mg/day) was comparable to olanzapine and risperidone (two studies, not pooled). In terms of tolerability, amisulpride was superior to placebo for dysthymia (odds ratio [OR] = 3.94, CI 95% 1.07, 14.48; I2  = 0.0) and comparable with SSRIs (OR = 0.94, CI 95% 0.55, 1.62; I2  = 0.0%). CONCLUSION: Treatment with amisulpride could be a valid choice for selected individuals with dysthymia or depressive symptoms in the context of schizophrenia. More studies on the efficacy and tolerability of amisulpride are needed to draw firm conclusions on its potential benefits in other psychiatric disorders.

Prevalence of depressive disorders and treatment in China: a cross-sectional epidemiological study.

BACKGROUND: In China, depressive disorders have been estimated to be the second leading cause of years lived with disability. However, nationally representative epidemiological data for depressive disorders, in particular use of mental health services by adults with these disorders, are unavailable in China. The present study, part of the China Mental Health Survey, 2012-15, aims to describe the socioeconomic characteristics and the use of mental health services in people with depressive disorders in China. METHODS: The China Mental Health Survey was a cross-sectional epidemiological survey of mental disorders in a multistage clustered-area probability sample of adults of Chinese nationality (≥18 years) from 157 nationwide representative population-based disease surveillance points in 31 provinces across China. Trained investigators interviewed the participants with the Composite International Diagnostic Interview 3.0 to ascertain the presence of lifetime and 12-month depressive disorders according to DSM-IV criteria, including major depressive disorder, dysthymic disorder, and depressive disorder not otherwise specified. Participants with 12-month depressive disorders were asked whether they received any treatment for their emotional problems during the past 12 months and, if so, the specific types of treatment providers. The Sheehan Disability Scale (SDS) was used to assess impairments associated with 12-month depressive symptoms. Data-quality control procedures included logic check by computers, sequential recording check, and phone-call check by the quality controllers, and reinterview check by the psychiatrists. Data were weighted according to the age-sex-residence distribution data from China's 2010 census population survey to adjust for differential probabilities of selection and differential response, as well as to post-stratify the sample to match the population distribution. FINDINGS: 28 140 respondents (12 537 [44·6%] men and 15 603 [55·4%] women) completed the survey between July 22, 2013, and March 5, 2015. Ethnicity data (Han or non-Han) were collected for only a subsample. Prevalence of any depressive disorders was higher in women than men (lifetime prevalence odds ratio [OR] 1·44 [95% CI 1·20-1·72] and 12-month prevalence OR 1·41 [1·12-1·78]), in unemployed people than employed people (lifetime OR 2·38 [95% CI 1·68-3·38] and 12-month OR 2·80 [95% CI 1·88-4·18]), and in people who were separated, widowed, or divorced compared with those who were married or cohabiting (lifetime OR 1·87 [95% CI 1·39-2·51] and 12-month OR 1·85 [95% CI 1·40-2·46]). Overall, 574 (weighted % 75·9%) of 744 people with 12-month depressive disorders had role impairment of any SDS domain: 439 (83·6%) of 534 respondents with major depressive disorder, 207 (79·8%) of 254 respondents with dysthymic disorder, and 122 (59·9%) of 189 respondents with depressive disorder not otherwise specified. Only an estimated 84 (weighted % 9·5%) of 1007 participants with 12-month depressive disorders were treated in any treatment sector: 38 (3·6%) in speciality mental health, 20 (1·5%) in general medical, two (0·3%) in human services, and 21 (2·7%) in complementary and alternative medicine. Only 12 (0·5%) of 1007 participants with depressive disorders were treated adequately. INTERPRETATION: Depressive disorders in China were more prevalent in women than men, unemployed people than employed, and those who were separated, widowed, or divorced than people who were married or cohabiting. Most people with depressive disorders reported social impairment. Treatment rates were very low, and few people received adequate treatment. National programmes are needed to remove barriers to availability, accessibility, and acceptability of care for depression in China. FUNDING: National Health Commission and Ministry of Science and Technology of People's Republic of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

The use of biofeedback intervention in the improvement of depression levels: a randomised trial.

OBJECTIVE: To evaluate the use of biofeedback intervention in the levels of depression. The main hypothesis tested if the use of biofeedback improves depression levels compared to the control group. METHODS: A randomised clinical trial. The final sample was composed of 36 participants (18 in the experimental group, receiving 6 training, once a week, with biofeedback; and 18 in the control group, who received conventional treatment in the service).Outcome measures were assessed in two stages: pre-test and post-test. The research used the following instruments: demographic survey data, Mini International Neuropsychiatric Interview 5.0.0 and Beck Depression Inventory (BDI). The factors and variables were presented in terms of descriptive and inferential statistics. Fisher's exact test (p < 0.05) was used to verify the existence of an association between the counting variables. The multinomial logistic regression model was adopted, and the Logit link function was used, as the software RStudio version 3.6.2. RESULTS: The factors that remained in the final model were group, sex, partner, atypical antidepressant, benzodiazepines, mood stabiliser, antiepileptic and antihistamine, according to the levels of depression based on the BDI. The group that did not receive biofeedback intervention had 16 times more chances of increasing the depression levels compared to participants in the experimental group. CONCLUSION: The use of biofeedback reduces depression, thus, representing a complementary alternative for the treatment of moderate and severe depression, and dysthymia.

Treatment of double depression: A meta-analysis.

BACKGROUND: Double depression (DD), the co-existence of DSM-IV major depressive disorder (MDD) and dysthymia, is a poorly known and sparsely studied phenomenon. Nevertheless, it is prevalent in clinical samples of patients with depression. Thus, it is important to understand the efficacy of its treatment. METHODS: We conducted a meta-analysis of studies in which antidepressant medication was used to treat depression. Systematic searches in bibliographical databases resulted in 11 samples, including 775 patients that met inclusion criteria. RESULTS: The overall effect size indicating the differences in depressive symptoms before and after pharmacotherapy was 1.81 (95% CI: 1.47, 2.16), suggesting that individuals with depression exhibited a significant reduction in their depressive symptoms following treatment. Importantly, a moderation analysis indicated that a higher proportion of individuals with DD within a sample was associated with lower effect sizes. Publication bias did not pose a major threat to the stability of the findings. LIMITATIONS: High observed heterogeneity indicated substantial variability in effect sizes and elucidation of the potential moderators of treatment outcome was limited due to a paucity of relevant data. CONCLUSIONS: Pharmacotherapy seems to be effective in treating DD, but DD may be more difficult to treat than either MDD or dysthymia alone. More research specifically focusing on the treatment of DD with larger sample sizes using randomized control trials is needed to make a firm conclusion.

Antidepressants Reduced Risk of Mortality in Patients With Diabetes Mellitus: A Population-Based Cohort Study in Taiwan.

CONTEXT: The effect of antidepressant (ATD) use on mortality in patients with diabetes mellitus (DM) has not yet been sufficiently studied, although comorbid depression is common in this population. OBJECTIVE: To explore the impact of ATDs on mortality among DM patients. DESIGN: A retrospective cohort study in a national database. SETTING: This population-based study used the National Health Insurance Research Database in Taiwan. Since 2000, we identified 53,412 cases of newly diagnosed patients with DM and depression. Patient cases were followed for assessing mortality until 2013. MAIN OUTCOME MEASURE: The association between mortality and ATD use was explored adjusting for cumulative dosing. RESULTS: Using the time-dependent Cox regression model, ATD use was associated with significantly reduced mortality among patients with DM [in the highest dose group: hazard ratio (HR), 0.65; 95% CI, 0.59 to 0.71]. Further analysis showed that differences in mortality existed across ATD categories: selective serotonin reuptake inhibitors (HR, 0.63; 95% CI, 0.56 to 0.71), serotonin-norepinephrine reuptake inhibitors (HR, 0.58; 95% CI, 0.44 to 0.78), norepinephrine-dopamine reuptake inhibitors (HR, 0.20; 95% CI, 0.07 to 0.63), mirtazapine (HR, 0.60; 95% CI, 0.45 to 0.82), tricyclic/tetracyclic antidepressants (HR, 0.73; 95% CI, 0.54 to 0.97), and trazodone (HR, 0.52; 95% CI, 0.29 to 0.91). However, reversible inhibitor of monoamine oxidase A (RIMA) was found to be associated with an increase, rather than a decrease, in total mortality (HR, 1.48; 95% CI, 1.09 to 1.99). CONCLUSION: Most ATDs, but not RIMA, were associated with significantly reduced mortality among a population with comorbid DM and depression.

Current pharmacotherapeutic approaches for dysthymic disorder and persistent depressive disorder.

Introduction: Persistent Depressive Disorder (PDD) is a nosological entity introduced with DSM-5, encompassing numerous different conditions including Dysthymia, recurrent Major Depressive Disorder, Double Depression and Chronic Major Depression. PDD is a particularly significant cause of disease burden in the general population. Areas covered: In the present paper, the authors explore the controversies surrounding the definition of PDD, the current approach to its treatment endorsed by the major scientific bodies, along with the available evidence on the efficacy of said treatments. Expert opinion: Clinicians need to be particularly vigilant and always gather a thorough history. In this diagnostic group, there is a relevant risk of having an undiagnosed Bipolar Disorder as affected individuals typically fail to recognize the pathological components of hypomanic episodes. In this setting, it is crucial to reconsider the diagnosis and to frequently verify compliance with the treatment plan. Numerous technological advances, particularly in the neuroimaging field, offer new insight and new challenges in defining the pathophysiological mechanisms of depressive syndromes. In the future, these advances may offer guidance towards an improved treatment approach and diagnostic process.

Antidepressants for the treatment of depression in people with cancer.

BACKGROUND: Major depression and other depressive conditions are common in people with cancer. These conditions are not easily detectable in clinical practice, due to the overlap between medical and psychiatric symptoms, as described by diagnostic manuals such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). Moreover, it is particularly challenging to distinguish between pathological and normal reactions to such a severe illness. Depressive symptoms, even in subthreshold manifestations, have been shown to have a negative impact in terms of quality of life, compliance with anti-cancer treatment, suicide risk and likely even the mortality rate for the cancer itself. Randomised controlled trials (RCTs) on the efficacy, tolerability and acceptability of antidepressants in this population are few and often report conflicting results. OBJECTIVES: To assess the efficacy, tolerability and acceptability of antidepressants for treating depressive symptoms in adults (aged 18 years or older) with cancer (any site and stage). SEARCH METHODS: We searched the following electronic bibliographic databases: the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 6), MEDLINE Ovid (1946 to June week 4 2017), Embase Ovid (1980 to 2017 week 27) and PsycINFO Ovid (1987 to July week 4 2017). We additionally handsearched the trial databases of the most relevant national, international and pharmaceutical company trial registers and drug-approving agencies for published, unpublished and ongoing controlled trials. SELECTION CRITERIA: We included RCTs comparing antidepressants versus placebo, or antidepressants versus other antidepressants, in adults (aged 18 years or above) with any primary diagnosis of cancer and depression (including major depressive disorder, adjustment disorder, dysthymic disorder or depressive symptoms in the absence of a formal diagnosis). DATA COLLECTION AND ANALYSIS: Two review authors independently checked eligibility and extracted data using a form specifically designed for the aims of this review. The two authors compared the data extracted and then entered data into Review Manager 5 using a double-entry procedure. Information extracted included study and participant characteristics, intervention details, outcome measures for each time point of interest, cost analysis and sponsorship by a drug company. We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We retrieved a total of 10 studies (885 participants), seven of which contributed to the meta-analysis for the primary outcome. Four of these compared antidepressants and placebo, two compared two antidepressants, and one three-armed study compared two antidepressants and placebo. In this update we included one additional unpublished study. These new data contributed to the secondary analysis, while the results of the primary analysis remained unchanged.For acute-phase treatment response (6 to 12 weeks), we found no difference between antidepressants as a class and placebo on symptoms of depression measured both as a continuous outcome (standardised mean difference (SMD) -0.45, 95% confidence interval (CI) -1.01 to 0.11, five RCTs, 266 participants; very low certainty evidence) and as a proportion of people who had depression at the end of the study (risk ratio (RR) 0.82, 95% CI 0.62 to 1.08, five RCTs, 417 participants; very low certainty evidence). No trials reported data on follow-up response (more than 12 weeks). In head-to-head comparisons we only retrieved data for selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants, showing no difference between these two classes (SMD -0.08, 95% CI -0.34 to 0.18, three RCTs, 237 participants; very low certainty evidence). No clear evidence of a beneficial effect of antidepressants versus either placebo or other antidepressants emerged from our analyses of the secondary efficacy outcomes (dichotomous outcome, response at 6 to 12 weeks, very low certainty evidence). In terms of dropouts due to any cause, we found no difference between antidepressants as a class compared with placebo (RR 0.85, 95% CI 0.52 to 1.38, seven RCTs, 479 participants; very low certainty evidence), and between SSRIs and tricyclic antidepressants (RR 0.83, 95% CI 0.53 to 1.30, three RCTs, 237 participants). We downgraded the certainty (quality) of the evidence because the included studies were at an unclear or high risk of bias due to poor reporting, imprecision arising from small sample sizes and wide confidence intervals, and inconsistency due to statistical or clinical heterogeneity. AUTHORS' CONCLUSIONS: Despite the impact of depression on people with cancer, the available studies were very few and of low quality. This review found very low certainty evidence for the effects of these drugs compared with placebo. On the basis of these results, clear implications for practice cannot be deduced. The use of antidepressants in people with cancer should be considered on an individual basis and, considering the lack of head-to-head data, the choice of which agent to prescribe may be based on the data on antidepressant efficacy in the general population of individuals with major depression, also taking into account that data on medically ill patients suggest a positive safety profile for the SSRIs. To better inform clinical practice, there is an urgent need for large, simple, randomised, pragmatic trials comparing commonly used antidepressants versus placebo in people with cancer who have depressive symptoms, with or without a formal diagnosis of a depressive disorder.

Evidence for neuroplastic compensation in the cerebral cortex of persons with depressive illness.

We yoked anatomical brain magnetic resonance imaging to a randomized, double-blind, placebo-controlled trial (RCT) of antidepressant medication for 10-week's duration in patients with dysthymia. The RCT study design mitigated ascertainment bias by randomizing patients to receive either duloxetine or placebo, and it supported true causal inferences about treatment effects on the brain by controlling treatment assignment experimentally. We acquired 121 anatomical scans: at baseline and end point in 41 patients and once in 39 healthy controls. At baseline, patients had diffusely thicker cortices than did healthy participants, and patients who had thicker cortices had proportionately less severe symptoms. During the trial, symptoms improved significantly more in medication-compared with placebo-treated patients; concurrently, thicknesses in medication-treated patients declined toward values in healthy controls, but they increased slightly, away from control values, in placebo-treated patients. Changes in symptom severity during the trial mediated the association of treatment assignment with the change in thickness, suggesting that the beneficial effects of medication on symptom severity were at least partially responsible for normalizing cortical thickness. Together our findings suggest that baseline cortical hypertrophy in medication-free patients likely represented a compensatory, neuroplastic response that attenuated symptom severity. Medication then reduced symptoms and lessened the need for compensation, thereby normalizing thickness. This is to the best of our knowledge the first study to report within an RCT a differential change in cortical morphology during medication treatment for depressive illness and the first to provide within an RCT in vivo evidence for the presence of neuroanatomical plasticity in humans.

Escitalopram Induced SIADH in an Elderly Female: A Case Study.

Hyponatraemia is a well-established and potentially, a life-threatening adverse effect of selective serotonin receptor uptake inhibitors (SSRI). However, its occurrence secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH) with escitalopram, has been reported extremely sporadically. The reporting of such rare, but life-threatening adverse effects of escitalopram assumes immense significance in light of the fact that SSRIs presently form the mainstay of treatment of depressive disorders. Here, we report a case where a 58 year old diabetic lady, when initiated on escitalopram for dysthymia developed severe hyponatraemia within 2 weeks. Further, we discuss other relevant cases that have been reported in the past with an eye on the management of SIADH and hyponatraemia.

[Influence of depression on the initial diagnosis and the evolution of cognitive impairment]. / Influencia de la depresion en el diagnostico inicial y evolutivo del deterioro cognitivo.

INTRODUCTION: Depression and cognitive impairment maintain a close and complex relationship, which could be modified by pharmacological treatment. AIM: To analyze the influence of depression and antidepressive medication on the initial diagnosis and the evolution of cognitive impairment. PATIENTS AND METHODS: All the patients derived to a Neurology clinic due to complaints or suspicion of cognitive impairment, during a period of nine years, were studied. The influence of demographic and depression-related variables on initial cognitive diagnosis, cognitive-functional situation and 1-year evolution were analyzed. RESULTS: A total of 582 patients were included (mean age: 77.6 ± 7.0; 64.9% women). Frequency of current and past depression were, respectively, 25.4% and 17.2%. In addition, 20.6% of the patients were taking antidepressant medication and 31.2% were on anxiolytic/hypnotic treatment. One-year follow-up visit was available in 320 (59.8%) of patients. In the adjusted analysis, anxiolytic/hypnotic treatment was associated with a worse cognitive-functional situation in the initial visit, while past depression and presence of dystimia were associated with a favorable evolution (p < 0.05). CONCLUSIONS: Past or current depression are not associated with bad prognosis in patients derived to neurologist due to possible cognitive impairment.

TITLE: Influencia de la depresion en el diagnostico inicial y evolutivo del deterioro cognitivo.Introduccion. La depresion y el deterioro cognitivo mantienen una estrecha y compleja relacion, que podria verse alterada por el tratamiento antidepresivo. Objetivo. Analizar la influencia de la depresion y del tratamiento antidepresivo en el diagnostico cognitivo inicial y evolutivo de los pacientes remitidos a neurologia por quejas o sospecha de deterioro cognitivo. Pacientes y metodos. Se estudio a todos los pacientes remitidos a una consulta de neurologia por quejas o sospecha de deterioro cognitivo durante un periodo de nueve años. Se analizo la influencia de las variables demograficas y de las variables relacionadas con la depresion en el diagnostico cognitivo y en la situacion cognitivo-funcional inicial y tras un año de seguimiento. Resultados. Se incluyo a 582 pacientes (edad media: 77,6 ± 7 años; mujeres, 64,9%). La frecuencia de depresion actual o en el pasado era, respectivamente, del 25,4% y 17,2%. El 20,6% de los pacientes recibia tratamiento con farmacos antidepresivos y el 31,2% tomaba ansioliticos/hipnoticos. Se dispuso de seguimiento al cabo de un año en 320 pacientes (59,8%). En el analisis ajustado, el tratamiento ansiolitico/hipnotico se asocio a una peor situacion cognitiva y funcional inicial, mientras que la depresion en el pasado y la presencia de distimia en la visita inicial se asociaron a una evolucion favorable (p < 0,05). Conclusiones. La depresion pasada o actual no es un factor de mal pronostico en los pacientes remitidos al neurologo por posible deterioro cognitivo.

Incremental Benefit-Cost of MOMCare: Collaborative Care for Perinatal Depression Among Economically Disadvantaged Women.

OBJECTIVE: Effectiveness of collaborative care for perinatal depression has been demonstrated for MOMCare, from early pregnancy up to 15 months postpartum, for Medicaid enrollees in a public health system. MOMCare had a greater impact on reducing depression and improving functioning for women with comorbid posttraumatic stress disorder (PTSD) than for those without PTSD. This study estimated the incremental benefit and cost and the net benefit of MOMCare for women with major depression and PTSD. METHODS: A randomized trial (September 2009 to December 2014) compared the MOMCare collaborative care depression intervention (choice of brief interpersonal psychotherapy or pharmacotherapy or both) with enhanced maternity support services (MSS-Plus) in the public health system of Seattle-King County. Among pregnant women with a probable diagnosis of major depression or dysthymia (N=164), two-thirds (N=106) met criteria for probable PTSD. Blinded assessments at three, six, 12, and 18 months postbaseline included the Symptom Checklist-20 depression scale and the Cornell Services Index. Analyses of covariance estimated gain in depression free days (DFDs) by intervention and PTSD status. RESULTS: When the analysis controlled for baseline depression severity, women with probable depression and PTSD in MOMCare had 68 more depression-free days over 18 months than those in MSS-Plus (p<.05). The additional depression care cost per MOMCare participant with comorbid PTSD was $1,312. The incremental net benefit of MOMCare was positive if a DFD was valued at ≥$20. CONCLUSIONS: For women with probable major depression and PTSD, MOMCare had significant clinical benefit over MSS-Plus, with only a moderate increase in health services cost.

Do social functioning and symptoms improve with continuation antidepressant treatment of persistent depressive disorder? An observational study.

OBJECTIVE: To determine efficacy of continued treatment with the serotonin norepinephrine reuptake inhibitor duloxetine on symptom reduction and functional improvement in outpatients with dysthymia. METHOD: Fifty outpatients with DSM-IV-TR diagnosed dysthymia who had participated in a 10 week double-blind, placebo-controlled study of duloxetine received open treatment for three months. Nineteen duloxetine responders continued duloxetine, 24 patients initially treated with placebo started open duloxetine treatment, and 7 duloxetine non-responders were treated with desvenlafaxine or bupropion, selected by clinician choice. RESULTS: Patients continuing duloxetine maintained symptom improvement, 84% meeting response and 63% remission criteria at week 22. Patients initially treated with placebo showed similarly high levels of response (83%) and remission (62%) at week 22, and most duloxetine non-responders subsequently responded to other antidepressants. Duloxetine-continuation patients improved modestly between weeks 10 and 22 on measures of social and cognitive functioning and temperament. Despite this improvement concurrently across several functional domains, 66.7% of patients continuing duloxetine remained in the impaired range of functioning according to the Social Adjustment Scale (SAS). CONCLUSIONS: Continued duloxetine treatment appears to be effective in maintaining symptom response in dysthymic disorder, and has positive effects on social functioning. However, the majority of patients do not show normalization of functioning, even when controlling for remission status. Additional treatments should be considered to target residual impairments in social functioning in mood remitted patients with persistent depressive disorder.

Changes in cytokine and chemokine expression distinguish dysthymic disorder from major depression and healthy controls.

An important area of uncertainty is the inflammatory degree to which depression occurring as part of dysthymic disorder may differ from major depression. Using a 27-plex cytokine assay, we analyzed the serum of 12 patients with dysthymic disorder, 12 with major depression, and an age-, sex-, and body mass index-matched control group of 20 healthy volunteers. We observed that patients with dysthymic disorder exhibited aberrant cytokine and chemokine expression compared with healthy controls and patients with major depression. The levels of interferon-γ-induced protein 10 highly predicted dysthymic disorder. Network analyses revealed that in patients with dysthymic disorder, the vertices were more sparsely connected and adopted a more hub-like architecture, and the connections from neighboring vertices of interleukin 2 and eotaxin-1 increased. After treatment with the same antidepressant, there was no difference between dysthymic disorder and major depression regarding any of the cytokines or chemokines analyzed. For dysthymic disorder, changes in the levels of interferon-γ-induced protein 10 and macrophage inflammatory protein-1α correlated with depression improvement. The findings suggest that the cytokine milieu in dysthymic disorder differs either at the level of individual expression or in network patterns. Moreover, chemokines play an important role in driving the pathophysiology of dysthymic disorder.

Systematic Review of Clinical Practice Guidelines for Failed Antidepressant Treatment Response in Major Depressive Disorder, Dysthymia, and Subthreshold Depression in Adults.

OBJECTIVE: This systematic review critically evaluated clinical practice guidelines (CPGs) for treating adults with major depressive disorder, dysthymia, or subthreshold or minor depression for recommendations following inadequate response to first-line treatment with selective serotonin reuptake inhibitors (SSRIs). METHOD: Searches for CPGs (January 2004 to November 2014) in English included 7 bibliographic databases and grey literature sources using CPG and depression as the keywords. Two raters selected CPGs on depression with a national scope. Data extraction included definitions of adequate response and recommended treatment options. Two raters assessed quality using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. RESULTS: From 46,908 citations, 3167 were screened at full text. From these 21 CPG were applicable to adults in primary care and outpatient settings. Five CPGs consider patients with dysthymia or subthreshold or minor depression. None provides recommendations for those who do not respond to first-line SSRI treatment. For adults with MDD, most CPGs do not define an "inadequate response" or provide specific suggestions regarding how to choose alternative medications when switching to an alternative antidepressant. There is variability between CPGs in recommending combination strategies. AGREE II ratings for stakeholder involvement in CPG development, editorial independence, and rigor of development are domains in which depression guidelines are often less robust. CONCLUSIONS: About half of patients with depression require second-line treatment to achieve remission. Consistency and clarity in guidelines for second-line treatment of depression are therefore important for clinicians but lacking in most current guidelines. This may reflect a paucity of primary studies upon which to base conclusions.

Collaborative Care for Perinatal Depression Among Socioeconomically Disadvantaged Women: Adverse Neonatal Birth Events and Treatment Response.

OBJECTIVE: The study examined the effectiveness of a perinatal collaborative care intervention in moderating the effects of adverse neonatal birth events on risks of postpartum depressive symptoms and impaired functioning among women of lower socioeconomic status with antenatal depression. METHODS: A randomized controlled trial with blinded outcome assessments was conducted in ten public health centers, comparing MOMCare (choice of brief interpersonal psychotherapy, pharmacotherapy, or both) with intensive maternity support services (MSS-Plus). Participants had probable diagnoses of major depressive disorder or dysthymia during pregnancy. Generalized estimating equations estimated differences in depression and functioning measures between groups with and without adverse birth events within the treatment arms. A total of 160 women, 43% of whom experienced at least one adverse birth event, were included in the analyses. RESULTS: For women who received MOMCare, postpartum depression scores (measured with the Symptom Checklist-20) did not differ by whether or not they experienced an adverse birth event (mean±SD scores of .86±.51 for mothers with an adverse birth event and .83±.56 for mothers with no event; p=.78). For women who received MSS-Plus, having an adverse birth event was associated with persisting depression in the postpartum period (mean scores of 1.20±.0.61 for mothers with an adverse birth event and .93±.52 for mothers without adverse birth event; p=.04). Similar results were seen for depression response rates and functioning. CONCLUSIONS: MOMCare mitigated the risk of postpartum depressive symptoms and impaired functioning among women of low socioeconomic status who had antenatal depression and who experienced adverse birth events.

Prescribing patterns of psychotropic medications and clinical features in patients with major depressive disorder with and without comorbid dysthymia in China.

INTRODUCTION: Little has been reported about the demographic and clinical features of major depressive disorder (MDD) with comorbid dysthymia in Chinese patients. This study examined the frequency of comorbid dysthymia in Chinese MDD patients together with the demographic and clinical correlates and prescribing patterns of psychotropic drugs. METHODS: Consecutively collected sample of 1178 patients with MDD were examined in 13 major psychiatric hospitals in China. Patients' demographic and clinical characteristics and psychotropic drugs prescriptions were recorded using a standardized protocol and data collection procedure. The diagnosis of dysthymia was established using the Mini International Neuropsychiatric Interview. Medications ascertained included antidepressants, antipsychotics, benzodiazepines, and mood stabilizers. RESULTS: One hundred and three (8.7%) patients fulfilled criteria for dysthymia. In multiple logistic regression analyses, compared to non-dysthymia counterparts, MDD patients with dysthymia had more depressive episodes with atypical features including increased appetite, sleep, and weight gain, more frequent lifetime depressive episodes, and less likelihood of family history of psychiatric disorders. There was no significant difference in the pattern of psychotropic prescription between the 2 groups. CONCLUSIONS: There are important differences in the demographic and clinical features of comorbid dysthymia in Chinese MDD patients compared with previous reports. The clinical profile found in this study has implications for treatment decisions.

Pharmacogenetics of citalopram-related side effects in children with depression and/or anxiety disorders.

Pharmacogenetic approach to antidepressant (AD) response is a promising avenue toward individualizing AD treatment. This is particularly relevant in pediatric populations because of concerns about the suicide risk of serotonin selective reuptake inhibitors (SSRIs), resulting in a black-box warning. However, to date, no specific gene or polymorphism has been consistently implicated as a marker of AD side effect (SE) in the pediatric population. The aim of this study was to examine the association between polymorphisms in genes related to the serotonergic system and citalopram SE's in children and adolescents with major depressive disorder (MDD)/dysthymia and/or anxiety disorders. Outpatients (N = 87, 44 % males), aged 7-18 years with a DSM-IV-TR diagnosis of MDD/dysthymia and/or an anxiety disorder were treated in an 8-week open trial with 20-40 mg/day of citalopram. SE's were rated using a questionnaire devised specifically for this study. Association analysis between known/candidate genetic variants in three genes (5-HTR2A, 5-HTR1Dß, 5-HTR2C) and SE's was conducted. Agitation was more common in boys than girls (male:female 42.1 vs. 18.7 %, χ 2 = 5.61, df = 1, p = 0.018). Subjects with 5-HTR1Dß CC genotype showed more agitation vs. both CG and GG genotypes (CC:CG:GG 71.4 vs. 33.3 vs. 18.1 %, χ 2 = 8.99, df = 2, p = 0.011). The 5-HTR1Dß CC genotype was associated with more reports of agitation. It has been suggested that agitation may be an intermediate phenotype to suicidal behavior. Thus, it seems that 5-HTR1Dß polymorphism may be involved in citalopram-related agitation in children and adolescents treated for depression and/or anxiety.