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.

White matter microstructure in boys with persistent depressive disorder.

BACKGROUND: Persistent depressive symptoms in children and adolescents are considered a risk factor for the development of major depressive disorder (MDD) later in life. Previous research has shown alterations in white matter microstructure in pediatric MDD but discrepancies exist as to the specific tracts affected. The current study aimed to improve upon previous methodology and address the question whether previous findings of lower fractional anisotropy (FA) replicate in a sample of children with persistent depressive disorder characterized by mild but more chronic symptoms of depression. METHODS: White matter microstructure was examined in 25 boys with persistent depressive disorder and 25 typically developing children. Tract specific analysis implemented with the Diffusion Tensor Imaging - ToolKit (DTI-TK) was used to probe fractional anisotropy (FA) in eleven major white matter tracts. RESULTS: Clusters within the left uncinate, inferior fronto-occipital and cerebrospinal tracts showed lower FA in the clinical group. FA in the left uncinate showed a negative association with self-reported symptoms of depression. CONCLUSIONS: The results demonstrate lower FA in several white matter tracts in children with persistent depressive disorder. These findings support the contention that early onset depression is associated with altered white matter microstructure, which may contribute to the maintenance and recurrence of symptoms.

Abnormal functional brain asymmetry in depression: evidence of biologic commonality between major depression and dysthymia.

Prior studies have found abnormalities of functional brain asymmetry in patients having a major depressive disorder (MDD). This study aimed to replicate findings of reduced right hemisphere advantage for perceiving dichotic complex tones in depressed patients, and to determine whether patients having "pure" dysthymia show the same abnormality of perceptual asymmetry as MDD. It also examined gender differences in lateralization, and the extent to which abnormalities of perceptual asymmetry in depressed patients are dependent on gender. Unmedicated patients having either a MDD (n=96) or "pure" dysthymic disorder (n=42) and healthy controls (n=114) were tested on dichotic fused-words and complex-tone tests. Patient and control groups differed in right hemisphere advantage for complex tones, but not left hemisphere advantage for words. Reduced right hemisphere advantage for tones was equally present in MDD and dysthymia, but was more evident among depressed men than depressed women. Also, healthy men had greater hemispheric asymmetry than healthy women for both words and tones, whereas this gender difference was not seen for depressed patients. Dysthymia and MDD share a common abnormality of hemispheric asymmetry for dichotic listening.

Estudio psicológico del trastorno distímico en la mujer / Psychological study of the dysthymic disorder in the woman

En este artículo estudiamos a dos mujeres distímicas a quiénes tratamos mediante psicoterapia y, a partir de ahí, se pusieron de manifiesto aquellos componentes “internos” que sustentan los síntomas depresivos. Estos mismos hallazgos se confirmaron en otras pacientes con idéntico diagnóstico. El resultado consistió en descubrir una desinserción sentimental respecto a sus parejas, permaneciendo con ellos sin separarse, al tiempo que van apareciendo insidiosamente las manifestaciones depresivas. Este desarrollo las lleva a la caída del “ideal de amor” al que aspiraban, que sostenía sus vidas y funcionaba como una “agarradera de la personalidad”. Tales apreciaciones ponen en cuestión las nociones clásicas acerca del “duelo” (AU)

In this article, we study two dysthymic women who we are treating with psychotherapy in order to reveal the inner components that maintain depressive symptoms. The same findings have been confirmed in other dysthymic patients. The result of the study consisted in discovering a sentimental separation from their love object, while the woman still lives with her partner and while the depressive symptoms are appearing insidiously. This development leads them to the deterioration in the “ideal of love” they sought, that supported their lives and served as an “anchor of their personality”. This point of view places classic notion about mourning into doubt (AU)

Patients with insomnia and subthreshold depression show marked worsening of insomnia after discontinuation of sleep promoting medication.

OBJECTIVE: To investigate whether the outcome of treatment with trazodone CR in primary insomnia differs between patients with and without subthreshold depression. METHODS: 14 patients (9 females, mean age 57.3 ± 13.3) with primary insomnia and increased Beck Depression Inventory (BDI) scores (>10) and 15 sex- and age-matched patients with primary insomnia and low BDI scores (≤ 10) were treated with trazodone CR 25-150 mg/d for 3 months and followed for 1 month after discontinuation of the medication. The Athens Insomnia Scale (AIS), Sheehan Disability Scale (SDS), and Clinical Global Impression scale (CGI) were completed at baseline, after each month of treatment and after the first week of run-out phase. Additional assessment tools comprised sleep diaries, the Leeds Sleep Evaluation Questionnaire (LSEQ) and actigraphic recordings. RESULTS: Subjective sleep time increased by 61.5 ± 72.3 min in the group with low BDI and 60.0 ± 59.4 min in the group with increased BDI at the end of the treatment phase. The significant improvements were also observed in the AIS, CGI, LSEQ and SDS. During the run-out phase the improvement was sustained in patients with low BDI, while AIS scores, sleep latency and total sleep time deteriorated in patients with increased BDI. CONCLUSIONS: Patients with subthreshold depression, even if the depressive symptoms do not fulfill the time criteria for depressive episode, show marked worsening of insomnia after discontinuation of sleep promoting medication.

Anhedonia is associated with poor health status and more somatic and cognitive symptoms in patients with coronary artery disease.

PURPOSE: The effectiveness of cardiac rehabilitation (CR) in patients with coronary artery disease (CAD) is moderated by negative emotions and clinical factors, but no studies evaluated the role of positive emotions. This study examined whether anhedonia (i.e. the lack of positive affect) moderated the effectiveness of CR on health status and somatic and cognitive symptoms. METHODS: CAD patients (n = 368) filled out the Hospital Anxiety and Depression Scale (HADS) to assess anhedonia at the start of CR, and the Short-Form Health Survey (SF-36) and the Health Complaints Scale (HCS) at the start of CR and at 3 months to assess health status and somatic and cognitive symptoms, respectively. RESULTS: Adjusting for clinical and demographic factors, health status improved significantly during the follow-up (F(1,357) = 10.84, P = .001). Anhedonic patients reported poorer health status compared with non-anhedonic patients, with anhedonia exerting a stable effect over time (F(1,358) = 34.80, P < .001). Somatic and cognitive symptoms decreased over time (F(1,358) = 3.85, P = .05). Anhedonics experienced more benefits in terms of somatic and cognitive symptoms over time (F(1,358) = 13.00, P < .001). CONCLUSION: Anhedonic patients reported poorer health status and higher levels of somatic and cognitive symptoms prior to and after CR. Somatic and cognitive symptoms differed as a function of anhedonia over time, but health status did not. Anhedonia might provide a new avenue for secondary prevention in CAD.

Toward a functional neuroanatomy of dysthymia: a functional magnetic resonance imaging study.

BACKGROUND: Dysthymia is a common mood disorder. Recent studies have confirmed the neurobiological and treatment response overlap of dysthymia with major depression. There are no previous published studies of functional magnetic resonance imaging (fMRI) in dysthymia. METHOD: fMRI was used to compare neural processing of 17 unmedicated dysthymic patients with 17 age, sex, and education-matched control subjects in a mood induction paradigm using the International Affective Pictures System (IAPS). RESULTS: Using a random effects analysis to compare the groups, the results revealed that the dysthymic patients had significantly reduced activation in the dorsolateral prefrontal cortex compared to controls. The dysthymic patients exhibited increased activation in the amygdala, anterior cingulate and insula compared to controls and these differences were more evident when processing negative than positive images. LIMITATIONS: This study included both early and late subtypes of dysthymia, and participants were only imaged at one time point, which may limit the generalizability of the results. CONCLUSIONS: The findings suggest the involvement of the prefrontal cortex, anterior cingulate, amygdala, and insula in the neural circuitry underlying dysthymia. It is suggested that altered activation in some of these neural regions may be a common substrate for depressive disorders in general while others may relate specifically to symptom characteristics and the chronic course of dysthymia. These findings are particularly striking given the history of this deceptively mild disorder which is still confused by some with character pathology.

Endofenotipos de Distimia: uso racional de psicofármacos / Endophenotypes of Dysthymia: rational use of psychiatric drugs

El trastorno distímico es una patología subdiagnosticada, que genera un malestar clínicamente significativo con deterioro social, laboral o de otras áreas importantes de la actividad de un individuo. La interrelación entre la genética y la influencia ambiental hace que surjan determinadas etiologías de un trastorno psiquiátrico, que se manifiestan con características clínicas diferentes. A éstas las llamamos ¶características endofenotípicas÷. El endofenotipo determinará también una genética psiquiátrica particular, resultante de la relación que haya entre éste y el pool génico del individuo en cuestión, como así también una respuesta a los fármacos utilizados durante el tratamiento. En la Distimia el afrontamiento maladaptativo es un síntoma central; genera sentimientos negativos llevando a la deserción, fracaso o aumento de la respuesta fisiológica al estrés. La diferente modalidad de afrontamiento, predominando o no la ansiedad como síntoma capital, genera dos endofenotipos de esta patología: Distimia Ansiosa (con ansiedad) y Distimia Anérgica (sin ansiedad). Entre los endofenotipos, las diferencias se reflejan en tratamientos específicos: para la Distimia Anérgica se debe modular el sistema noradrenalina/dopamina. Los IRSS no serían la primera elección. Sí, en cambio, fármacos como el bupropion, la venlafaxina, la amisulprida y los antidepresivos tricíclicos; en la Distimia Ansiosa, se deben utilizar antidepresivos que mejoren la neurotransmisión noradrenérgica/serotoninérgica; los Inhibidores de la Recaptación de la Serotonina y la Noradrenalina (SNRI) tienen una mejor respuesta que los Inhibidores Selectivos de la Recaptación de la Serotonina (IRSS), aunque estos también otorgan una buena alternativa.(AU)

Dysthymic disorder is an underdiagnosed pathology characterized by clinically significant distress, and impairment in the social, occupational, or other important areas of activity of an individual. The inter relationship between genetics and the environmental influence cause the emergence of certain etiologies from a psychiatric disorder, which manifest with different clinical characteristics. These are called "endophenotypic characteristics". The endophenotype will also determine a particular psychiatric genetics, which results from the relationship between it and the gene pool of the individual in question, as well as a response to the psychiatric drugs used during the treatment. Within dysthymia, maladaptive coping is a central symptom, it generates negative feelings that led to desertion, failure, or to an increase in the physiological response to stress. Each coping modality, whether anxiety prevails as the central symptom or not, generates two endophenotypes of this pathology: anxious dysthymia (dysthymia with anxiety) and Anergic Dysthymia (dysthymia without anxiety). Among the endophenotypes, differences are reflected in specific treatments: in the case of Anergic Dysthymia, the noradrenaline/dopamine system has to be modulated. SSRls would not be the firest choice, but rather, drugs such as bupropion, venlafaxine, amisulpride and tryciclic antidepressants, for the treatment of Anxious Dysthymia, antidepressants have to be used that imporve the noradrenergic/serotoninergic neurotransmission, Serotonin and Noradrenalin Reuptake inhibitors (SNRIs) have a better response than Selective Serotonin Repuptake Inhibitors (SSRIs) have a better response than Selective Serotonin Reuptake Inhibitors (SSRIs), although the latter also provide a good alternative.(AU)

Endofenotipos de Distimia: uso racional de psicofármacos / Endophenotypes of Dysthymia: rational use of psychiatric drugs

El trastorno distímico es una patología subdiagnosticada, que genera un malestar clínicamente significativo con deterioro social, laboral o de otras áreas importantes de la actividad de un individuo. La interrelación entre la genética y la influencia ambiental hace que surjan determinadas etiologías de un trastorno psiquiátrico, que se manifiestan con características clínicas diferentes. A éstas las llamamos “características endofenotípicas”. El endofenotipo determinará también una genética psiquiátrica particular, resultante de la relación que haya entre éste y el pool génico del individuo en cuestión, como así también una respuesta a los fármacos utilizados durante el tratamiento. En la Distimia el afrontamiento maladaptativo es un síntoma central; genera sentimientos negativos llevando a la deserción, fracaso o aumento de la respuesta fisiológica al estrés. La diferente modalidad de afrontamiento, predominando o no la ansiedad como síntoma capital, genera dos endofenotipos de esta patología: Distimia Ansiosa (con ansiedad) y Distimia Anérgica (sin ansiedad). Entre los endofenotipos, las diferencias se reflejan en tratamientos específicos: para la Distimia Anérgica se debe modular el sistema noradrenalina/dopamina. Los IRSS no serían la primera elección. Sí, en cambio, fármacos como el bupropion, la venlafaxina, la amisulprida y los antidepresivos tricíclicos; en la Distimia Ansiosa, se deben utilizar antidepresivos que mejoren la neurotransmisión noradrenérgica/serotoninérgica; los Inhibidores de la Recaptación de la Serotonina y la Noradrenalina (SNRI) tienen una mejor respuesta que los Inhibidores Selectivos de la Recaptación de la Serotonina (IRSS), aunque estos también otorgan una buena alternativa.

Dysthymic disorder is an underdiagnosed pathology characterized by clinically significant distress, and impairment in the social, occupational, or other important areas of activity of an individual. The inter relationship between genetics and the environmental influence cause the emergence of certain etiologies from a psychiatric disorder, which manifest with different clinical characteristics. These are called "endophenotypic characteristics". The endophenotype will also determine a particular psychiatric genetics, which results from the relationship between it and the gene pool of the individual in question, as well as a response to the psychiatric drugs used during the treatment. Within dysthymia, maladaptive coping is a central symptom, it generates negative feelings that led to desertion, failure, or to an increase in the physiological response to stress. Each coping modality, whether anxiety prevails as the central symptom or not, generates two endophenotypes of this pathology: anxious dysthymia (dysthymia with anxiety) and Anergic Dysthymia (dysthymia without anxiety). Among the endophenotypes, differences are reflected in specific treatments: in the case of Anergic Dysthymia, the noradrenaline/dopamine system has to be modulated. SSRls would not be the firest choice, but rather, drugs such as bupropion, venlafaxine, amisulpride and tryciclic antidepressants, for the treatment of Anxious Dysthymia, antidepressants have to be used that imporve the noradrenergic/serotoninergic neurotransmission, Serotonin and Noradrenalin Reuptake inhibitors (SNRIs) have a better response than Selective Serotonin Repuptake Inhibitors (SSRIs) have a better response than Selective Serotonin Reuptake Inhibitors (SSRIs), although the latter also provide a good alternative.

Benefits and risks of pharmacotherapy for dysthymia: a systematic appraisal of the evidence.

BACKGROUND: Dysthymia is a prevalent form of subthreshold depressive disorder, associated with considerable disability and high co-morbidity. This paper systematically appraises the evidence for the efficacy and acceptability of the pharmacological treatment for this condition. METHODS: Randomised, controlled trials evaluating the efficacy of drug therapies for dysthymia were included. A comprehensive search of the literature was performed, aiming to avoid publication bias. Pooled relative risks (RR) and 95% CIs were calculated with the Random Effect Model method. The number needed to treat (NNT) and number needed to harm (NNH) were estimated for statistically significant results. RESULTS: Twenty-five trials were included for the main comparisons. Regarding placebo-controlled trials (n = 16), similar results were obtained in terms of efficacy for different groups of drugs, such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and other drugs (sulpiride, amineptine, and ritanserin). The pooled RR for treatment response was 0.68 (95% CI 0.57-0.81) for TCA and the NNT was 4.3 (95% CI 3.2-6.5); 0.68 (95% CI 0.56-0.82) for SSRIs (NNT 5.1; 95% CI 3.9-7.7); 0.59 (95% CI 0.48-0.71) for MAOIs (NNT 2.9; 95% CI 2.2-4.3). Other drugs (amisulpride, amineptine and ritanserin) showed similar results. The equivalent efficacy between antidepressants as found in trials where active medications were compared confirmed the efficacy findings from placebo trials. In general, patients treated with a TCA were more likely to report adverse events, compared with placebo and SSRIs. CONCLUSIONS: Pharmacotherapy for dysthymia appears to be an effective short-term treatment for dysthymic disorder. Newer antidepressants are equally effective and have better acceptability than TCAs, although their higher cost must be balanced against this assumed advantage.

Decrease in genu of the corpus callosum in medication-naïve, early-onset dysthymia and depressive personality disorder.

BACKGROUND: The purpose of this study was to detect differences in regional areas of the corpus callosum (CC) in subjects with early-onset minor depression (dysthymia or depressive personality disorder) and healthy comparison subjects. Based on previous reports that have suggested reduced frontal lobe volume and reduced hemispheric lateralization in the frontal regions of the brain in depression, we hypothesized that the area of the CC that interconnects the frontal regions of the brain, i.e., the genu, will be smaller compared to that of healthy comparison subjects. METHODS: Forty female subjects with early-onset dysthymia or depressive personality disorder, as defined by the Structured Clinical Interview for DSM-III-R and the Diagnostic Interview for Depressive Personality, respectively, and age- and gender-matched healthy comparison subjects (n = 42) were recruited (age: 21.4 +/- 2.1 and 20.9 +/- 2.8 years, respectively). All subjects were psychotropic medications-naïve and right-handed. A 1.5T GE Sigma scanner was used to acquire 124 1.5-mm-thick contiguous coronal images. Midsagittal slice images were carefully selected from reconstructed magnetic resonance images both from native and stereotaxic space to measure seven regional areas of the CC. RESULTS: There were significant diagnosis by CC region interactions [F(6,480) = 4.06, p <.001; F(6,480) = 3.30, p =.003, native and stereotaxic space, respectively]. Early-onset minor depression subjects had a 9.9% (native space) and 6.9% (stereotaxic space) smaller genu of the CC compared to the healthy comparison subjects (the Newman-Keuls post hoc test, p =.005 and.019, native and stereotaxic space, respectively). Early-onset minor depression subjects also had a 7.8% smaller posterior midbody relative to the comparison subjects (the Newman-Keuls post hoc test, p =.033) only in the native space. Severity of current depressive symptoms or duration of illness did not correlate with the size of the genu or the posterior midbody parts of the CC. CONCLUSIONS: These results suggest frontal lobe structural, and possibly functional, abnormalities in the brain in young female adults with a milder spectrum of depression, i.e., DSM-IV early-onset dysthymia or depressive personality disorder. The present findings point out the possible role of frontal lobe abnormality in pathophysiology of early-onset minor depression.

[Late-onset dysthymic states]. / Pozdnie distimicheskie sostoianiia.

Sixty patients with dysthymic states which had emerged in later age of 60-80 years were examined. Two clinical types of dysthymic states were described: anergic (20 patients) and hypothymic (40 patients). Different comorbid mental disorders--obsessive-phobic (14 cases), somatoform (10), personality deviations (20) and psycho-organic (7)--were found to be characteristic of late-onset dysthymic states. According to developmental features, late dysthymia was primary (first manifested in the elderly) and secondary (develops after several depressive episodes). In diagnostic terms, the former is considered as "dysthymia" (F34.1 ICD-10) and the latter--as "recurrent depressive disorder" (F33).

The crucial role of frontostriatal circuits for depressive disorders in the postacute stage after stroke.

OBJECTIVE: This study analyzes lesion configuration in patients in the post-acute stage after first single unilateral stroke who suffered from depressive disorders. BACKGROUND: Recent studies indicate a biological origin of poststroke depressive disorders. Due to differences in times of investigation, methods applied, and patient selection, most data are not comparable. Furthermore, only a few studies of poststroke depression report detailed neuropsychologic assessments. METHODS: We investigated 20 consecutive patients who were diagnosed as depressive according to DSM-III-R criteria and exhibited no other severe illness, had no history of neurologic or psychiatric disease, and who were either not aphasic, or only mildly aphasic. A structured clinical interview, self-based and observer-based depression rating scales, a comprehensive neuropsychologic and neurologic examination and ADL-measurement were applied. Neuroradiologic analysis was based on standardized computed tomography scans. RESULTS: Nine of 10 subjects with left hemisphere strokes exhibited a major depression and 7 of 10 subjects with right hemisphere infarcts a minor depression. The most prominent neuropsychologic deficits were found in frontal lobe associated tasks. Type and severity of depression were not related to the severity of neurologic symptoms or impairment in activities of daily living. For both major and minor depression the maximal overlap of lesions was found in subcortical areas, including parts of the caudate nucleus, posterior parts of the putamen, and the deep white matter. CONCLUSIONS: The findings support the theory that poststroke depression is related to the dysfunction of (cortico-) striato-pallido-thalamic-cortical projections that modulate cortico-thalamo-cortical loop systems.

Amygdala enlargement in dysthymia--a volumetric study of patients with temporal lobe epilepsy.

BACKGROUND: Previous studies indicated an important role of the amygdala for emotional information processing. We investigated a possible relationship between amygdala volumes, aggressive behavior, and dysthymia, in patients with temporal lobe epilepsy (TLE). METHODS: Patients with TLE with and without aggression or dysthymia and healthy volunteers were assessed using quantitative MRI. Amygdala volumes were measured in a blinded fashion and corrected for total brain volumes. RESULTS: There was a highly significant enlargement of left and right amygdala volumes in patients with dysthymia (right side, p < .000; left side, p = .001). We found a significant positive correlation between left amygdala volumes (p = .02) and a trend towards positive correlation between right amygdala volumes and depression (p = .06), as measured with the Beck Depression Inventory. Amygdala volumes of females were significantly larger than those of males (left side: p = .005; right side: p = .06). CONCLUSIONS: This is the second report of a relationship between amygdala volumes and depressed mood, confirming an earlier finding in patients with bipolar disease, and the first study reporting a correlation between amygdala volumes and depression. Increased processing of emotional information might increase amygdala blood flow and subsequently, result in amygdala enlargement.