Diagnosis and treatment of dysthymia in children and adolescents

Dysthymic disorder is a chronic depressive condition occurring in 0.6-4.6% of children and 1.6-8.0% of adolescents. Although symptoms are less severe than those observed in major depression, childhood-onset dysthymic disorder is characterised by a persistent and long-term depressed or irritable mood (mean episode duration 3-4 years), a worse outcome than major depression and, frequently, comorbid disorders (in around 50% of patients). Long-lasting depressive symptoms seem responsible for long-term disabling consequences on social skill learning, psychosocial functioning and consequent professional life, probably contributing to a higher risk of relapse or development of major depression. Consistently, the first episode of major depression occurs 2-3 years after the onset of dysthymic disorder, suggesting that the latter is one of the gateways to recurrent mood disorders. The primary aims of treatment for dysthymic disorder should be to resolve depressive symptoms, reduce the risk of developing other mood disorders over time and strengthen psychosocial functioning, especially in children and adolescents, in order to prevent the potentially serious sequelae of this disorder. As children with dysthymia often have multiple problems, interventions should involve multiple levels and measures: individual psychotherapy, family therapy/education and pharmacological treatment. Psychotherapeutic techniques, such as cognitive-behaviour therapy and interpersonal therapy, have been found to be efficacious interventions in treating children and adolescents with mild to moderate depression in studies including patients with either dysthmia or double depression. SSRIs are the first-line drug treatment for children and adolescents because of their safety, adverse effect profile and ease of use (the safety of paroxetine is currently under investigation). Several nonblind studies have shown the efficacy and good tolerability of SSRIs in children and adolescents with dysthymic disorder, but further research is needed to confirm their efficacy and that of newer antidepressants in the treatment of this disorder. Regardless of whether psychotherapeutic or medical treatments are planned, according to clinical experience, psychoeducational interventions and psychosocial support should be provided to parents and other caregivers during the acute treatment phase to help manage the child's irritable mood and foster a therapeutic alliance and better compliance with treatment. Unfortunately, no studies have focused on continuation treatment of paediatric dysthymic disorder. Given the chronicity, recurrence, psychosocial consequences and peculiar response pattern to treatment of dysthymic disorder, establishing effective 'acute' and 'continuation' interventions in this group of patients should be a priority in mental health management.     

Psychosocial functioning during the treatment of major depressive disorder with fluoxetine

BACKGROUND: Major depressive disorder (MDD) is associated with significant disability, having a profound impact on psychosocial functioning. Therefore, studying the impact of treatment on psychosocial functioning in MDD could help further improve the standard of care. METHODS: Two hundred twenty-two MDD outpatients were treated openly with 20 mg fluoxetine for 8 weeks. The self-report version of the Social Adjustment Scale was administered at baseline and during the final visit. We then tested for the relationships between (1) self-report version of the Social Adjustment Scale scores at baseline and clinical response, (2) nonresponse, response and remission status and overall psychosocial adjustment at end point, (3) the number/severity of residual depressive symptoms and overall psychosocial adjustment at end point in responders, and (4) the time to onset of response and overall psychosocial adjustment at end point. RESULTS: An earlier onset of clinical response predicted better overall psychosocial functioning at end point (P = 0.0440). Responders (n = 128) demonstrated better overall psychosocial adjustment at end point than nonresponders (P = 0.0003), while remitters (n = 64) demonstrated better overall psychosocial adjustment at end point than nonremitted responders (P = 0.0031). In fact, a greater number/severity of residual symptoms predicted poorer overall psychosocial adjustment at end point in responders (P = 0.0011). Psychosocial functioning at baseline did not predict response. CONCLUSIONS: While MDD patients appear equally likely to respond to treatment with fluoxetine, regardless of their level of functioning immediately before treatment, the above results stress the importance of achieving early symptom improvement then followed by full remission of depressive symptoms with respect to restoring psychosocial functioning in MDD.     

Folic acid: neurochemistry, metabolism and relationship to depression

The associations of folic acid and its derivatives with depressive disorder are reviewed. Derivatives of folic acid such as biopterins and the synthesis of S-adenosyl methionine (SAM) are known either to be associated with improvement or to have a direct therapeutic effect in depressive disorder. Studies investigating plasma and red cell folic acid levels in depressed patients have used differing assay methodologies which make comparison difficult, although there is substantial evidence of the association between depressive disorder (particularly severe depression) and low folic acid levels. The few studies available suggest folic acid has either antidepressant properties or can act as an augmenting agent for standard antidepressant treatment. A recently discovered genetic variant (5,10 MTHFR) leading to altered folic acid metabolism may explain why some individuals are vulnerable to the effects of folic acid deficiency, despite adequate intake. The links of 5,10 MTHFR to the presence of depressive disorder in the community are being investigated.     

Achieving abstinence by treating depression in the presence of substance-use disorders

BACKGROUND: Antidepressants can have an effect on depressive symptoms in participants with comorbid drug or alcohol dependence and mood disorder, but their effect on drug use is not known. It has been suggested that adding psychosocial intervention to antidepressants would enhance the effect on drug use. METHOD: A meta-analysis was conducted on trials of antidepressants for this comorbidity with and without psychosocial treatment. RESULTS: Studies using cognitive-behavioural therapy (CBT) found no medication effect, whereas with no intervention, medication was superior to placebo, manualised counselling falling in between. CONCLUSION: There is no evidence that antidepressant medication is more efficacious in reducing drug use with conjunctive psychosocial treatment. Antidepressant medication and psychotherapy may both be useful in the treatment of substance-dependent depressed patients, but combining psychotherapy and medication may only be useful in patients failing to respond to one treatment.     

Evidence for the efficacy of duloxetine in treating mild, moderate, and severe depression

Clinicians need to know whether duloxetine is effective in patients across a broad range of depressive symptoms and depression severity. Data were pooled from nine randomized, double-blind, placebo-controlled studies in major depressive disorder (total N=2227) comparing duloxetine (40-120 mg/day) with placebo for 8-9 weeks. Patients were retrospectively stratified by baseline score on the HAMD17 into mild (< or =19; n=682), moderate (n=1099), or severe (> or =25; n=446) groups. Duloxetine produced significantly greater baseline-to-endpoint mean change than placebo in HAMD17 total score, Maier and retardation subscales, and the Clinical Global Impressions-Severity of Illness scale in all three cohorts. Significant improvement was seen in HAMD17 items 1 (depressed mood), 3 (suicide), 7 (work and activities), and 10 (psychic anxiety) regardless of severity. The HAMD17 anxiety subscale and items 13 (somatic symptoms-general) and 15 (hypochondriasis) showed significant improvement only in moderately and severely ill patients. Significant improvement in the HAMD17 Maier subscale was seen in all groups by week 1. In all three groups, placebo was significantly superior to duloxetine at early visits on HAMD17 item 12 (somatic symptoms-GI). Mildly and severely ill patients exhibited significant reduction in visual analog scale overall pain severity at the study endpoint. The studies contained fewer patients with very mild or very severe illness, limiting our ability to draw conclusions in these patient populations. Duloxetine demonstrated superior efficacy in the treatment of major depressive disorder, when compared with placebo, regardless of the baseline severity of depressive symptoms, although effect sizes were largest in the most severely depressed patients.     

Dual Diagnosis: Variations Across Differing Comorbid Diagnoses

ABSTRACT

Objectives: Increasing numbers of research investigations have documented the coexistence of substance use and other psychiatric disorders in a variety of patient populations. The next step in understanding such comorbidity is the exploration of whether the type of psychiatric disorder coexisting with a substance use disorder makes a difference in terms of the sequellae of the disorders for the patient.

Methods: This study explored a variety of psychosocial/demographic and clinical variables for patients with a substance abuse disorder, differentiating five groups based on the type of coexisting psychiatric disorder: schizophrenia, depression, bipolar disorder, adjustment disorder, and personality disorder. Rates and sequellae of comorbidity for the five groups of patients were explored based on a pool of patients hospitalized at the Alaska Psychiatric Institute (API) between 1993 and 2001. The records of 181 patients with coexisting schizophrenia, 251 with depression, 120 with bipolar disorder, 197 with adjustment disorder, and 145 with personality disorder were utilized to explore psychosocial/demo-graphic and clinical differences and commonalities across groups.

Results: Findings revealed significant differences between the five groups on almost all psychosocial/demographic and clinical variables. For example, patients with coexisting schizophrenia evidence more severe pathology and greater use of hospital resources; patients with coexisting personality disorder were more likely to be involved with the legal system; patients with bipolar disorder were most likely to evidence drug involvement at admission; and patients with adjustment disorders evidenced the fewest psychosocial challenges and a less severe course of treatment.

Conclusion: Results confirmed the need to differentiate comorbid patients based on the type of coexisting other psychiatric disorder. Discussion of the implications of these findings for treatment service planning on an individual-patient and systemic-administrative level is presented.     

Higher cerebrospinal fluid homovanillic acid levels in depressed patients with comorbid posttraumatic stress disorder.

Major depression and posttraumatic stress disorder (PTSD) are often comorbid, resulting in more impairment compared than with either diagnosis alone. Both major depression and PTSD are thought to be associated with monoamine transmitter abnormalities. This study compared clinical features and cerebrospinal fluid (CSF) monoamine metabolites in drug-free depressed subjects with a current major depressive episode (MDE) without comorbid PTSD, subjects with a current MDE and comorbid PTSD, and healthy volunteers. Depressed subjects with comorbid PTSD had higher CSF homovanillic acid (HVA) levels compared with depressed subjects without comorbid PTSD or healthy volunteers. Higher HVA was present after adjustment for sex, lifetime aggression severity and depression scores, alcoholism, tobacco smoking, comorbid cluster B personality disorder, reported childhood abuse, and psychosis. We found no group difference in CSF 5-hydroxyindolacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels. Higher dopaminergic activity may contribute to alterations in memory and other cognitive functions, anhedonia, and hypervigilance observed in PTSD.     

Double-blind clinical trial of sertraline treatment for alcohol dependence

Clinical studies that have evaluated serotonergic medications to reduce alcohol consumption have yielded conflicting results. These studies primarily treated patients with alcohol dependence, excluding those with a current depressive disorder, in an effort to differentiate any medication effects directly on drinking from those on mood. Yet despite the exclusion of current depression, a group of alcohol-dependent patients who are not depressed can be highly heterogeneous. For example, this subgroup can include those with a lifetime depressive disorder. If these patients were more sensitive to serotonergic medications than patients without a lifetime depressive disorder, medication effects in a subgroup of patients who were not depressed could be obscured. Thus, the purpose of this study was to examine the efficacy of sertraline for treating alcohol dependence in patient groups that were differentiated by the presence or absence of lifetime depression. This study examined the effectiveness of sertraline (200 mg/day) or placebo for 14 weeks in 100 alcohol-dependent subjects with (N = 53) or without (N = 47) a lifetime diagnosis of comorbid depression. Sertraline treatment seemed to provide an advantage in reducing drinking in alcohol-dependent patients without lifetime depression, illustrated best with a measure of drinking frequency during treatment. However, sertraline was no better than placebo in patients with a diagnosis of lifetime comorbid depression, and current depression did not change the results. Treatment with selective serotonin reuptake inhibitors may be useful in alcohol-dependent patients who are not depressed. Subtyping those with alcohol dependence on the basis of the absence versus the presence of a lifetime depressive disorder may help to resolve conflicting findings in the literature on the treatment of alcohol dependence with serotonergic medications.     

Pharmacotherapy for adolescent alcohol use disorder

Alcohol use disorder (AUD) occurs in few young adolescents, but is as common as in adults by the late teens. To address problems with the current American Psychiatric Association DSM-IV criteria, the anticipated DSM-V will eliminate the distinction between substance abuse and dependence in favour of a single category. For adolescents, pharmacotherapy for AUD may target alcohol withdrawal symptoms, alcohol consumption reinforcement properties, craving or co-morbid mental disorders. While uncommon among adolescents, severe alcohol withdrawal may require the closely monitored application of benzodiazepines. Disulfiram alters alcohol metabolism and has been shown to increase abstinence in adolescents with AUD, but sufficient motivation to maintain abstinence is needed for this approach to be appropriate. Medications to reduce alcohol craving, including naltrexone and acamprosate, may also assist some adolescents in maintaining abstinence. Adolescents with AUD typically also have co-morbid mental disorders and problems with other substances. Co-morbid mental disorders, such as major depressive disorder and attention-deficit hyperactivity disorder, may be addressed by pharmacotherapy. The potential for interactions between prescribed medications and alcohol or illicit substances necessitates patient education and monitoring. While there is a paucity of empirical information on the applicability of these pharmacotherapy approaches in adolescents, cautious application of these medications in selected cases in the context of systematic psychosocial interventions is warranted to promote abstinence and address associated problems.     

A systematic review of psychosocial research on psychosocial interventions for people with co-occurring severe mental and substance use disorders

This report reviews studies of psychosocial interventions for people with co-occurring substance use disorder and severe mental illness. We identified 45 controlled studies (22 experimental and 23 quasi-experimental) of psychosocial dual diagnosis interventions through several search strategies. Three types of interventions (group counseling, contingency management, and residential dual diagnosis treatment) show consistent positive effects on substance use disorder, whereas other interventions have significant impacts on other areas of adjustment (e.g., case management enhances community tenure and legal interventions increase treatment participation). Current studies are limited by heterogeneity of interventions, participants, methods, outcomes, and measures. Treatment of co-occurring severe mental illness and substance use disorder now has a large but heterogeneous evidence base that nevertheless supports several types of interventions. Future research will need to address methodological standardization, longitudinal perspectives, interventions for subgroups and stages, sequenced interventions, and the changing realities of treatment systems.     

Trauma and mental health problems of Sudanese refugees in Uganda

OBJECTIVES: To determine the extent of trauma and mental health problems. DESIGN: Screening surveys. SETTING: Sudanese refugee communities in Northern Ugandan camps. SUBJECTS: 100 adult refugees, 44 ex-soldiers, 60 patients at camp outpatient health facilities, 63 traditional healers' patients and 56 refugee children. MAIN OUTCOME MEASURE: Rate of trauma. RESULTS: The most common trauma events experienced by 100 adults were forced isolation from others (94%), forced separation from family members (91%) and lack of food or water (83%). Thirty-two percent of the adults suffered post traumatic stress disorder (PTSD). Among the 56 children, 12 (20%) suffered from a chronic PTSD. Forty-four ex-soldiers scored a median of 74.6 (Q1 = 62.3; Q3 = 79.1) on the depressive scale of the Hopskins Symptom checklist. Out of 60 outpatients at a dispensary, 12 (20%) had psychological disorder. Out of a total of 63 patients attending traditional and faith healers' facilities, 26% suffered from PTSD and 39% from depressive disorder. CONCLUSION: High rates of trauma and psychosocial problems were found among Sudanese refugees in Uganda.     

A Comparison of Psychosocial and Cognitive Functioning Between Depressed and Non-Depressed Patients with Cannabis Dependence

ABSTRACT

Cannabis use and depressive disorders are thought to impair cognitive performance and psychosocial functioning. Both disorders co-occurring may compound the negative effects of these diagnoses. In this study, the authors used the California Computerized Assessment Package as the cognitive performance measure and the Addiction Severity Index as the psychosocial functioning measure to compare individuals who were cannabis dependent and either depressed or not depressed (N= 108: 54 cannabis dependent only, 54 cannabis dependent and depressed or dysthymic). As predicted, cannabis dependent individuals with comorbid depression showed more psychosocial impairment than individuals with cannabis dependence alone. However, contrary to the authors’ hypothesis, individuals who were cannabis dependent with comorbid depression showed less cognitive impairment in some California Computerized Assessment Package modules than individuals with cannabis dependence alone. Based on the authors’ results, they concluded that the additive effects of cannabis dependency and depression may only be limited to psychosocial domains and may not extend to cognitive functioning.     

Depressive Symptoms and Associated Clinical Characteristics in Outpatients Seeking Community-Based Treatment for Alcohol and Drug Problems

Background: Comorbid psychiatric and substance use disorders are common and associated with poorer treatment engagement, retention, and outcomes. This study examines the presence of depressive symptoms and the demographic and clinical correlates in a diverse sample of substance abuse treatment seekers to better characterize patients with co-occurring depressive symptoms and substance use disorders and understand potential treatment needs. Methods: Baseline data from a randomized clinical effectiveness trial of a computer-assisted, Web-delivered psychosocial intervention were analyzed. Participants (N = 507) were recruited from 10 geographically diverse outpatient drug treatment programs. Assessments included the self-report Patient Health Questionnaire, and measures of coping strategies, social functioning, physical health status, and substance use. Results: One fifth (21%; n = 106) of the sample screened positive for depression; those screening positive for depression were significantly more likely to screen positive for anxiety (66.9%) and posttraumatic stress disorder (PTSD; 42.9%). After controlling for anxiety and PTSD symptoms, presence of depressive symptoms remained significantly associated with fewer coping strategies (P = .001), greater impairment in social adjustment (P < .001), and poorer health status (P < .001), but not to days of drug use in the last 90 days (P = .14). Conclusions: Depression is a clinically significant problem among substance abusers, and, in this study, patients who screened positive for depression were more likely to have co-occurring symptoms of anxiety and PTSD. Additionally, the presence of depressive symptoms was associated with fewer coping strategies and poorer social adjustment. Coping skills are a significant predictor of addiction outcomes, and it may be especially important to screen for and enhance coping among depressed patients. Evidence-based interventions that target coping skills and global functioning among substance abusers with depressive symptoms may be important adjuncts to usual treatment.     

The influence of psychiatric comorbidity on the dexamethasone/CRH test in major depression

BackgroundThe outcome of the dexamethasone/corticotropin-releasing-hormone (DEX/CRH) test in depressed patients is heterogeneous. The present study investigated whether comorbidity of anxiety or somatoform disorders might be an explaining factor for this finding.MethodsThe DEX/CRH test was administered in 36 pure major depressive outpatients, 18 major depressive outpatients with a comorbid anxiety and/or somatoform disorder, and 43 healthy controls. Patients were free of psychotropic medication. Group differences in responsivity to the DEX/CRH test were analysed.ResultsDepressive patients with comorbidity showed a significant lower cortisol response compared to pure depressive patients (p = 0.04) and controls (p = 0.003). Group differences between MDD patients with and without comorbidity in cortisol responses disappeared after adjustment for post-DEX cortisol concentrations (p = 0.34).ConclusionsAn enhanced suppression of cortisol to 1.5 mg DEX is present in a subgroup of depressed patients with psychiatric comorbidity. Distinct hypothalamic-pituitary-adrenal (HPA) axis dysfunctions are revealed when comorbidity is taken into account.     

Duloxetine: pharmacoeconomic implications of an antidepressant that alleviates painful physical symptoms

Major depressive disorder (MDD) is a prevalent, chronic, medical disorder that encompasses a broad constellation of symptoms. The salience of painful physical symptoms in depressive presentations is increasingly appreciated. Duloxetine is a novel, potent, balanced, dual monoamine reuptake-inhibitor antidepressant indicated for the symptomatic relief of MDD. Duloxetine is marketed as an antidepressant that has inherent analgesic properties for depressed patients who present with prominent painful physical symptoms. Taken together, available evidence indicates that duloxetine provides a higher probability of, and shorter time to, remission than some antidepressants (e.g., fluoxetine). Duloxetine also offers symptom relief for painful physical symptoms in depressed patients. Pharmacoeconomic and cost-impact modelling analyses should be reformulated to consider duloxetine's symptom-alleviating effect on the somatic dimension of depressive illness.     

Psychosocial functioning in children of alcoholic fathers, depressed fathers and control fathers

Children of alcoholics are often viewed as having major psychological problems resulting from their interactions within disturbed family structures. Most studies, however, have selected alcoholics from multiproblem families in which it is difficult to disentangle the impact of alcoholism from concomitant psychosocial and psychiatric problems. Further, few studies have used psychometrically sound measures of alcoholism or child functioning. In this investigation, children of alcoholic, depressed and control (social drinkers and not depressed) fathers were assessed by parents on the Child Behavior Checklist and by teachers on the Conner Teacher Rating Scale and the Myklebust Pupil Rating Scale. Although children of alcoholics and of depressives were rated higher on behavior problems by parents than the children of controls, only a minority of these children received scores indicative of severe impairment. The importance of considering the clinical significance of group differences and of examining the joint impact of alcoholism and other psychopathologies is discussed.     

Implications of using different cut-offs on symptom severity scales to define remission from depression.

A fundamental question in the medical management of disease is how well treatment works. Although there are many ways of defining improvement, one endpoint of definite interest is the resolution or remission of the disorder. In short-term antidepressant treatment trials, remission is usually defined according to post-treatment scores on symptom severity measures, such as the Hamilton Rating Scale for Depression (HRSD) or the Montgomery-Asberg Depression Rating Scale (MADRS). However, there is uncertainty as to what cut-offs should be used on these measures to define remission. During the past 2 years, as part of the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, our laboratory has examined the question of how to define remission on the HRSD and MADRS. In the present report from the MIDAS project, we examined the impact of the cut-off score used to define remission on the percentage of depressed outpatients in ongoing treatment who are considered to be in remission. In addition, we examined the association between remission status and psychosocial impairment for different cut-off scores. Three hundred and three depressed psychiatric outpatients were rated on the MADRS, 17-item HRSD, and an index of DSM-IV remission status. Approximately one-third of patients completed a measure of psychosocial impairment. For both the HRSD and the MADRS, we examined four cut-off scores for remission. For each cut-off, we determined the percentage of patients who met the definition of remission, the percentage of patients who continued to meet DSM-IV criteria for major depressive disorder (MDD), and the percentage of patients without any self-reported impairment from depression. For both scales, the range of cut-off scores was associated with more than a two-fold difference in prevalence of remission. Based on higher thresholds to define remission, a small percentage of patients met criteria for MDD, whereas no patients scoring below the low thresholds had MDD. The threshold to define remission was associated with psychosocial impairment: higher cut-off scores were associated with lower rates of no impairment. The cut-offs used to define remission from depression considerably influence the percentage of patients considered to be in remission. Lower cut-off scores than those most commonly used to define remission appear to be more valid.     

Duloxetine: pharmacoeconomic implications of an antidepressant that alleviates painful physical symptoms

Major depressive disorder (MDD) is a prevalent, chronic, medical disorder that encompasses a broad constellation of symptoms. The salience of painful physical symptoms in depressive presentations is increasingly appreciated. Duloxetine is a novel, potent, balanced, dual monoamine reuptake-inhibitor antidepressant indicated for the symptomatic relief of MDD. Duloxetine is marketed as an antidepressant that has inherent analgesic properties for depressed patients who present with prominent painful physical symptoms. Taken together, available evidence indicates that duloxetine provides a higher probability of, and shorter time to, remission than some antidepressants (e.g., fluoxetine). Duloxetine also offers symptom relief for painful physical symptoms in depressed patients. Pharmacoeconomic and cost-impact modelling analyses should be reformulated to consider duloxetine’s sym-ptom-alleviating effect on the somatic dimension of depressive illness.