Translation and validation of the Depression Outcomes Module (DOM) in Greece

In Greece, as in other countries, major depressive disorder is underdiagnosed. Its severity, implications and outcomes are often not adequately evaluated. The Depression Outcomes Module (DOM) was developed in order to meet the need for a global assessment of this disorder. The objective of the current study was to estimate the psychometric properties of DOM in a Greek population presenting depressive symptoms. The DOM was translated into Greek. Patients were examined twice (baseline and follow-up assessment). The psychometric properties of DOM were calculated. Subjects were 83 psychiatric inpatients and outpatients presenting depressive symptoms. The measures used were DOM, Structured Clinical Interview for DSM III-R (SCID) and Hamilton Rating Scale for Depression (Ham-D). The results were: (a) baseline assessment: test-retest reliability k = 0.90, internal consistency 0.93, sensitivity 97%, specificity 90%; (b) follow up assessment: test-retest reliability k = 0.89, sensitivity 81% and specificity 67%. Recovery from depression detected by DOM at the follow-up was significantly correlated both with pharmacotherapy and with a combination of pharmacotherapy and supportive psychotherapy. It was concluded that the Greek version of DOM is a comprehensive, useful instrument for diagnosing, assessing depression and evaluating its outcomes.     

Chronic depression: Update on classification and treatment

A significant proportion of patients with depressive disorders suffer from chronic conditions. The DSM-IV recognizes several forms of chronic depression. Chronic depressions differ from nonchronic major depressive disorder (MDD) on many clinical, psychosocial, and familial variables. However, less support exists for current distinctions between the various forms of chronic depression. Antidepressant medications and at least some forms of psychotherapy are efficacious in treating chronic depression, and the combination of pharmacotherapy and psychotherapy appears to be superior to either monotherapy alone. Still, chronic depression is often inadequately treated, and many patients fail to respond or continue to experience residual symptoms after treatment. An important direction for future research is to elucidate the multiple pathways to chronic depression and to tailor treatments to specific etiopathogenetic subgroups.     

Tachyphylaxis in unipolar major depressive disorder

BACKGROUND: Major depressive disorder is usually a recurring illness, and maintenance treatment is used to forestall or prevent recurrent episodes of depression. This study describes recurrence of major depression despite maintenance pharmacotherapy, termed tachyphylaxis. METHOD: The study sample consisted of 103 subjects who participated in the NIMH Collaborative Depression Study, a multicenter longitudinal observational study of the mood disorders. Subjects diagnosed with unipolar major depressive disorder according to Research Diagnostic Criteria were enrolled from 1978-1981 and prospectively followed for up to 20 years. As an observational study, treatment was recorded but not controlled by anyone connected with the study. Subjects were selected for the present study if at some point during follow-up they received antidepressant medication for treatment of an episode of major depressive disorder, recovered from this episode, and subsequently received maintenance pharmacotherapy. Some subjects were successfully treated for multiple episodes of major depressive disorder and then received maintenance medication after each of these episodes, resulting in multiple maintenance treatment intervals. Data were collected using the Longitudinal Interval Follow-Up Evaluation, and mixed-effects logistic regression was used to test the association of sociodemographic and clinical variables with tachyphylaxis. RESULTS: For the 103 subjects, there were 171 maintenance treatment intervals in which a subject received maintenance pharmacotherapy after having recovered from an episode of major depressive disorder. The median duration of maintenance treatment was 20 weeks. Tachyphylaxis occurred during 43 (25%) of these 171 maintenance treatment intervals. The subtype of melancholic (endogenous) major depressive disorder significantly elevated the risk of tachyphylaxis during the subsequent maintenance treatment interval. CONCLUSIONS: Despite the use of maintenance pharmacotherapy, major depression recurs in a considerable number of patients. Improved prophylaxis for these patients requires other treatment strategies based upon a greater understanding of recurrence.     

Treatment-resistant depression in late life

Depression is the most prevalent functional psychiatric disorder in late life. It is associated with a high risk of mortality from comorbid medical illness and from suicide. Successful antidepressant treatment is one of the most effective ways to reduce disability, prevent morbidity, and improve quality of life in an older depressed patient. Treatment-resistant depression is a common clinical problem, reported to affect up to one-third of older depressed patients. However, published data on this clinically important topic are sparse. Available data and clinical experience indicate that many depressed patients labeled as "treatment resistant" or even "treatment refractory" are so labeled because of variables involving the diagnostic or treatment process, rather than because they suffer from a depression that is truly unresponsive to treatment. Unidentified comorbid medical or psychiatric conditions and misdiagnosis often contribute to treatment resistance. Atypical depressive symptoms, such as somatic and cognitive symptoms, and comorbid medical conditions that can themselves produce depressive symptoms often make it difficult to accurately assess antidepressant response in this age group. This often leads to inadequate pharmacotherapy, another major factor contributing to apparent treatment resistance. In older patients, as in younger patients, the selection of the right antidepressant, the right dose, and the right treatment duration constitute the treatment variables essential in ensuring optimal therapeutic response. Approach to treatment-resistant depression in the elderly involves reconsideration of the diagnosis and use of alternate therapeutic measures in a systematic way, including switching to another agent, combination therapy, and electroconvulsive therapy.     

Interpersonal psychotherapy and antidepressant medication: evaluation of a sequential treatment strategy in women with recurrent major depression

BACKGROUND: Few data are available to guide treatment selection in major depression. With increasing pressure to maximize the efficiency and minimize the costs of treatment, it is important to have information that could guide treatment selection or point to treatment strategies that have a high probability of success. METHOD: We used a successive cohort approach to compare 2 highly similar groups of women with recurrent unipolar disorder (DSM-III-R or DSM-IV): one in which the combination of interpersonal psychotherapy (IPT) and pharmacotherapy was initiated at the outset of treatment and a second in which IPT alone was provided first and only those who did not remit with IPT alone were offered the combination treatment. RESULTS: In the group in which the combination was initiated at the outset of treatment (N = 180), the remission rate was 66%, comparable to the remission rate observed in most outpatient treatment studies of major depression. In contrast, among the women in the second cohort who were first treated with IPT alone and only those who did not remit were given combination therapy (N = 159), the remission rate was 79%, significantly greater than that observed in the group that received combination treatment from the outset (chi2 = 6.55, p = .02). CONCLUSION: These results suggest that the strategy of offering IPT to women with recurrent unipolar disorder and, in the absence of remission, adding antidepressant pharmacotherapy can be a highly effective treatment, one that may be particularly attractive to women in the childbearing years. Although slower in its onset of action, this sequential strategy is likely to enable the clear majority of such women to achieve a full remission of depressive symptoms.     

Colour associations as predictors of the effectiveness of anti-depressant pharmacotherapy in endogenous depressive patients

The authors examined the number of associations given for the 8 Lüscher colours by 20 endogenous depressive patients (11 unipolar and 9 bipolar II) before anti-depressant pharmacotherapy and on the 7th, 14th and 21st day of treatment. The depressive patients gave significantly fewer total responses before treatment than the 15 healthy control persons. While the number of associations obtained from the control persons was unchanged at the end of the 1st week, the depressive patients responding to the treatment (responders, n = 15) furnished significantly more responses on the 7th day than before treatment, although there had been no change in the intervening period in the severity of their depression measured by Hamilton depression scale; their clinical state showed a gradual improvement only from the end of the 2nd week. The number of associations obtained from non-responder depressive patients (n = 5) increased only slightly (not significantly). Our preliminary findings suggest that this method could be used to follow changes in the state of depressive patients and to predict their response to anti-depressant pharmacotherapy.     

Cognitive therapy for bipolar depression: a pilot study.

OBJECTIVE: While the efficacy of cognitive-behaviour therapy (CBT) for the treatment of acute unipolar major depression is well-documented, there is almost no data evaluating its utility in the treatment of bipolar depression. This pilot study compares the efficacy of CBT combined with mood-stabilizer pharmacotherapy for bipolar depression and CBT alone for unipolar depression. METHOD: A matched-case control design was used to evaluate outcomes following 20 sessions of CBT in 11 depressed bipolar patients and 11 matched recurrent unipolar depressed control subjects. RESULTS: Bipolar depressed patients achieved similar levels of reduction in depressive symptoms following CBT, as did the unipolar depressed group. However, on measures of more pervasive dysfunctional attitudes, bipolar patients did not improve to the same degree. CONCLUSIONS: Preliminary findings suggest that CBT warrants further investigation as an effective psychosocial intervention for depression in bipolar patients already receiving ongoing mood-stabilizing pharmacotherapy.     

Pharmacotherapy in depressed children and adolescents

In children and adolescents, antidepressants are used in the treatment of depressive symptoms and several other psychiatric conditions. In the treatment of mild and moderate depressive symptoms, non-pharmacological approaches such as psychotherapy play a major role, a severe symptomatology may demand a combination with antidepressants. As first-choice medication for the treatment of juvenile depression, the selective serotonin reuptake inhibitor (SSRI) fluoxetine is recommended, due to its efficacy and approval. As second-choice antidepressants the SSRIs sertraline, escitalopram and citalopram might be used. Other antidepressants - such as tricyclic antidepressants, α(2)-adrenoceptor antagonists, selective noradrenalin reuptake inhibitors (SNRI) - may be alternatively used, but not as first- or second-choice medications. In the case of "off-label" use, patients and parents have to be carefully informed prior to the start of medication, after a thorough risk-benefit analysis. In the following overview we address a general framework, therapeutic strategies and the issues of antidepressant pharmacotherapy for the treatment of unipolar depression in childhood and adolescence.     

Pharmacogenetics in modern psychiatry

There is no unique scientific agreement about genetic variations that could beyond any doubt predict phenotype of the response to pharmacotherapy. The knowledge about the predictors for therapy and serious adverse effects could be very useful in clinical practice. It is obvious that the combination of variation in metabolizing enzymes, transporter proteins and drug targets fully explains heterogeneity in response to psychiatric treatment. We assume that genetic polymorphisms of serotoninergic transporter and MDR1 could be important in prediction of therapeutic response in patients with major depression treated with paroxetine. Our results show that SERTPR-LL genotype might predispose significantly better paroxetine treatment response compared to SS genotype in MDD patients and that variants G2677T and C3435T are not associated with therapeutic response to paroxetine in patients with major depressive disorder.     

Differential response to combined treatment in patients with psychotic versus nonpsychotic major depression

Research has demonstrated that depressed patients with psychotic features show poorer outcomes when treated with pharmacotherapy alone compared with those without psychotic features. However, research has not investigated whether this differential response also applies to combined treatment that includes pharmacotherapy and psychotherapy. In the current study, data were pooled from two clinical trials in which patients diagnosed with major depressive disorder with or without psychotic features were treated with combined treatment. Although similar in severity at pretreatment, results indicated that patients with psychotic depression showed a poorer response in terms of depression severity at postoutpatient treatment and at 6-month follow-up compared with those with nonpsychotic depression. Following treatment, patients with psychotic depression were over four times as likely to exhibit high levels of depression and suicidal ideation. Current state-of-the-art combined treatments have poorer efficacy in depressed patients with psychotic symptoms, and adapted treatment approaches are needed.     

Secondary agoraphobia: two case reports

Two patients with agoraphobic symptoms and major depressive disorder exhibited dexamethasone nonsuppression. Antidepressant pharmacotherapy was associated with remission of depressive symptoms and DST normalization. This improvement predated remission of agoraphobic symptoms by 1-2 months. It is suggested that agoraphobia was secondary to the depression in both cases.     

Treatment of recurrent depression

Approximately eight out of ten people experiencing a major depressive episode will have one or more further episodes during their lifetime: a recurrent major depressive disorder. Prolongation or lifelong pharmacotherapy has emerged as the main therapeutic tool for preventing relapse in depression. However, outcome after discontinuation of antidepressants does not seem to be affected by the duration of their administration. Loss of clinical effects, despite adequate compliance, has also emerged as a vexing clinical problem. Use of intermittent pharmacotherapy with follow-up visits is another therapeutic option that would leave patients with periods free of drugs and side effects, in consideration of the fact that a high proportion of patients would discontinue the antidepressant anyway. However, the problems of resistance (the fact that a drug treatment may be associated with a diminished chance of response in those patients who successfully responded to it, but discontinued it) and of discontinuation syndromes are a substantial disadvantage of this therapeutic option. In recent years, several controlled trials have suggested that a sequential use of pharmacotherapy in the treatment of the acute episode and psychotherapy in its residual phase may improve long-term outcome. However, patients should be motivated for psychotherapy and skilled therapists should be available. It is important to discuss with the patient the various therapeutic options and to adapt strategies to the specific needs of patients.     

Treatments for later-life depressive conditions: a meta-analytic comparison of pharmacotherapy and psychotherapy

OBJECTIVE: To improve interventions for depressed older adults, data are needed on the comparative effects of pharmacotherapy versus psychotherapy. Given that most older adults with clinically significant depressive symptoms do not have major depression, data on treatments for minor depression and dysthymia are especially needed. METHOD: Meta-analysis was used to integrate the results of 89 controlled studies of treatments focused on acute major depression (37 studies) and other depressive disorders (52 studies conducted with mixed diagnostic groups, including patients with major depression, minor depression, and dysthymia). A total of 5,328 older adults received pharmacotherapy or psychotherapy in these studies. RESULTS: Clinician-rated depression scores improved, on average, by 0.80 standard deviation (SD) units; self-rated depression scores improved by 0.76 SD units. Clinician-rated depression improved by 0.69 SD units in pharmacotherapeutic studies and by 1.09 SD units in psychotherapeutic studies. Self-rated depression improved by 0.62 SD units and 0.83 SD units, respectively. An interesting finding was the stronger improvements in clinician-rated depression among control subjects participating in medication studies, compared to those in psychotherapeutic studies. CONCLUSIONS: Available treatments for depression work, with effect sizes that are moderate to large. Comparisons of psychotherapy and pharmacotherapy must be interpreted with caution, in part because medication studies are more likely to use a credible active placebo, which may lead to smaller adjusted effect sizes in medication studies. Given that psychotherapy and pharmacotherapy did not show strong differences in effect sizes, treatment choice should be based on other criteria, such as contraindications, treatment access, or patient preferences.     

Management of Major Depression in Adults With Diabetes: Implications of Recent Clinical Trials

Major depressive disorder is present in 15%-20% of patients with diabetes and impairs functioning and quality of life. It has unique importance in diabetes because of its association with poor compliance with diabetes treatment, poor glycemic control, and an increased risk for micro- and macrovascular disease complications. These observations have inspired several recent clinical trials to determine whether these associations may be favorably influenced by depression treatment. The outcome data are scant but promising and suggest that psychotherapy and pharmacotherapy can have important positive effects on both mood and glycemic control. Unfortunately, even after successful treatment, recurrence of depression is the norm. Afflicted subjects are seldom asymptomatic for an entire year at a time. Factors related to the medical illness (eg, presence of diabetes complications, hyperglycemia) are associated with a poorer prognosis for recovery from depression, a finding that suggests that optimal relief of depression in diabetes may require vigorous, simultaneous management of the medical and psychiatric conditions. Whether maintenance antidepressant treatment is useful in preventing depression recurrence and promoting better glycemic control in diabetes is unknown, but this question is the focus of an ongoing clinical trial.     

Examination of the decline in symptoms of anxiety and depression in generalized anxiety disorder: impact of anxiety sensitivity on response to pharmacotherapy

Pharmacotherapy is an effective treatment for generalized anxiety disorder (GAD), but few studies have examined the nature of decline of anxiety and depression during pharmacotherapy for GAD and even fewer studies have examined predictors of symptom decline. This study examined the decline in symptoms of anxiety and depression in patients with GAD during a 6-week open trial of fluoxetine. Growth curve analyses indicated that pharmacotherapy with fluoxetine led to significant declines in symptoms of anxiety and depression over the 6 weeks of treatment. However, the decay slope observed for anxiety symptoms was significantly greater than that for depressive symptoms. Further analyses revealed that the decline in anxiety remained significant after accounting for the changes in symptoms of depression. However, the effect of treatment on depression was no longer significant after controlling for the reduction in anxiety symptoms. Overall anxiety sensitivity (AS) did not moderate the level of reduction in symptoms of anxiety or depression during pharmacotherapy. However, AS specific to physical concerns demonstated a marginal negative association with decline in anxiety and depression. AS specific to social concerns also demonstrated a marginal negative association with decline in anxiety symptoms. These findings suggest that the decline in anxiety symptoms is independent of the decline in symptoms of depression during pharmacotherapy for GAD and specific AS dimensions may predict symptom change in GAD.     

Can enhanced acute-phase treatment of depression improve long-term outcomes? A report of randomized trials in primary care

OBJECTIVE: The authors' goal was to determine whether improved outcomes from enhanced acute-phase (3-month) treatment for depression in primary care persisted. METHOD: They conducted a 19-month follow-up assessment of 156 patients with major depression in the Collaborative Care intervention trials, which had found greater improvements in treatment adherence and depressive symptoms at 4 and 7 months for patients given enhanced acute-phase treatment than for patients given routine treatment in a primary care setting. Sixty-three of the 116 patients who completed the follow-up assessment had received enhanced treatment, and 53 had received routine treatment in primary care. The Inventory for Depressive Symptomatology and the Hopkins Symptom Checklist were used to measure depressive symptoms. Automated pharmacy data and self-reports were used to assess adherence to and adequacy of pharmacotherapy. RESULTS: At 19 months, the patients who had received enhanced acute-phase treatment did not differ from those who had received routine primary care treatment in clinical outcomes or quality of pharmacotherapy. CONCLUSIONS: Even though enhanced acute-phase treatment of depression in primary care resulted in better treatment adherence and better clinical outcomes at 4 and 7 months, these improvements failed to persist over the following year. Continued enhancement of depression treatment may be needed to ensure better long-term results.     

Treatment matching in the posthospital care of depressed patients

OBJECTIVE: This study assessed the efficacy of 1) matching patients to treatments and 2) adding additional family therapy or cognitive therapy in a group of recently discharged patients with major depression. METHOD: Patients with major depression were recruited during a psychiatric hospitalization. After discharge, they were randomly assigned to one of four treatment conditions that were either "matched" or "mismatched" to their pattern of cognitive distortion and family impairment. The four treatment conditions were 1) pharmacotherapy alone; 2) combined pharmacotherapy and cognitive therapy; 3) combined pharmacotherapy and family therapy; and 4) combined pharmacotherapy, cognitive therapy, and family therapy. Randomly assigned treatment continued for 24 weeks on an outpatient basis. RESULTS: Among patients with at least moderate depressive symptoms at hospital discharge, low rates of remission (16%) and improvement (29%) were obtained. Matched treatment led to a significantly greater proportion of patients who improved and greater reductions over time in interviewer-rated depressive symptoms than mismatched treatment. However, matched treatment did not produce greater change in self-reported depression or interviewer-rated suicidal ideation. Treatment that included a family therapy component also led to a greater proportion of patients who improved and to significant reductions in interviewer-rated depression and suicidal ideation than treatment without family therapy. CONCLUSIONS: These results suggest that 1) current treatments are not very efficacious in the aftercare of hospitalized depressed patients, 2) treatment matching moderately improves outcome for patients who are symptomatic at hospital discharge, and 3) inclusion of family therapy improves the outcome of posthospital care for depressed patients.     

Longitudinal Neurocognitive Effects of Combined Electroconvulsive Therapy (ECT) and Pharmacotherapy in Major Depressive Disorder in Older Adults: Phase 2 of the PRIDE Study

ObjectiveThere is limited information regarding neurocognitive outcomes of right unilateral ultrabrief pulse width electroconvulsive therapy (RUL-UB ECT) combined with pharmacotherapy in older adults with major depressive disorder. We report longitudinal neurocognitive outcomes from Phase 2 of the Prolonging Remission in Depressed Elderly (PRIDE) study.MethodAfter achieving remission with RUL-UB ECT and venlafaxine, older adults (≥60 years old) were randomized to receive symptom-titrated, algorithm-based longitudinal ECT (STABLE) plus pharmacotherapy (venlafaxine and lithium) or pharmacotherapy-only. A comprehensive neuropsychological battery was administered at baseline and throughout the 6-month treatment period. Statistical significance was defined as a p-value of less than 0.05 (two-sided test).ResultsWith the exception of processing speed, there was statistically significant improvement across most neurocognitive measures from baseline to 6-month follow-up. There were no significant differences between the two treatment groups at 6 months on measures of psychomotor processing speed, autobiographical memory consistency, short-term and long-term verbal memory, phonemic fluency, inhibition, and complex visual scanning and cognitive flexibility.ConclusionTo our knowledge, this is the first report of neurocognitive outcomes over a 6-month period of an acute course of RUL-UB ECT followed by one of 2 strategies to prolong remission in older adults with major depression. Neurocognitive outcome did not differ between STABLE plus pharmacotherapy versus pharmacotherapy alone over the 6-month continuation treatment phase. These findings support the safety of RUL-UB ECT in combination with pharmacotherapy in the prolonging of remission in late-life depression.     

Prevention of depression-related suicides in primary care

Suicide attempt and completed suicide are rare events in the community, but they are quite common among psychiatric patients who contact their GPs before the suicide event. The current prevalence of unipolar and bipolar major depressive episode in general practice is around ten percent but unfortunately about half of these cases remain unrecognized, untreated or mistreated. Major depressive episode is the most common current psychiatric diagnosis among suicide victims and attempters (56-87%) and successful acute and long-term treatment of depression significantly reduces the risk of suicidal behaviour even in this high-risk population. As over half of all suicide victims contact their GPs within four weeks before their death, primary care doctors play an important role in suicide prediction and prevention. Five large-scale community studies demonstrate that education of GPs and other medical professionals on the diagnosis and appropriate pharmacotherapy of depression, particularly in combination with psycho-social interventions and public education improve the identification and treatment of depression and reduces the rate of completed and attempted suicide in the areas served by trained doctors.     

Depression and epilepsy, pain and psychogenic non-epileptic seizures: clinical and therapeutic perspectives

The clinical manifestations of depression in people with epilepsy (PWE) are pleomorphic, often associated with anxiety symptoms and anxiety disorders. The ongoing debate of whether the clinical presentation of depression in PWE is unique to this neurologic disorder is reviewed. Comorbid depression can impact the recruitment of PWE for pharmacologic trials with antiepileptic drugs (AEDs). Yet, the impact of depression on the response of the seizure disorder to pharmacotherapy with AEDs and its impact on worse adverse events may bias the interpretation of the trial findings, particularly when depressed patients are included in the AED trials. PWE have a greater suicidal risk than the general population. This risk is mediated by multiple factors, and recent data from the FDA have imputed a potential pathogenic role to all AEDs. The recognition of patients at risk is reviewed. Yet, the validity of the FDA data has been questioned, and the status of this controversial question is analyzed. As in the case of epilepsy, depression and pain syndromes have a relatively high comorbidity. The negative impact of depression on pain is reminiscent of that of depression in PWE; furthermore, the high comorbidity may be also associated with the existence of common pathogenic mechanisms. Neurologists and in particular, epileptologists establish the diagnosis of psychogenic non-epileptic seizures (PNES) in whom a comorbid depressive disorder is very often identified. The role of depression in the course of PNES and its treatment are discussed. Scarce data are available on the treatment of depression in PWE. Thus, clinicians have had to adopt data from patients with primary depressive disorders. We outline a consensus strategy on the identification and treatment of depressive disorders in adult and pediatric patients with epilepsy.