Open trial of mirtazapine in patients with fibromyalgia

BACKGROUND: Some positive therapeutic effects in fibromyalgia syndrome (FS) were reported with both tricyclic and new antidepressant drugs as well as serotonergic agents (5HT2 and 5HT3 receptor blockers). METHODS: In the present study, a novel antidepressant drug mirtazapine, 15-30 mg/day, has been used in 29 patients with FS in an open trial. RESULTS: Twenty-six patients completed the six-week study. Ten (38%) were considered responders on account of the reduction of > or =40% on pain, fatigue and sleep disturbances and remission of depressive symptoms at the end of study. Eighteen patients had at least moderate depression before mirtazapine treatment and 8 patients presented mild depressive symptoms. Reduction on main symptoms of FS after 6 weeks of mirtazapine treatment significantly correlated with the reduction in depression. However, the percentage of responders and patients with > or = 40% reduction on main symptoms of fibromyalgia was similar in high and low depression groups. CONCLUSIONS: The results obtained suggest that mirtazapine may be promising method of FS treatment. Further double-blind placebo-controlled studies are required to confirm these results.     

Hostility changes following antidepressant treatment: Relationship to stress and negative thinking

It is unclear whether changes in hostility following treatment are primarily related to improvement in depressive symptoms or are also closely associated with reductions in negative thinking or perceived stress. We evaluated 94 outpatients with major depression before and after eight weeks of fluoxetine treatment by administering the Symptom Questionnaire (SQ) Hostility Scale, the Hamilton Rating Scale for Depression (HAM-D), the Cognitions Questionnaire (CQ) and the Perceived Stress Scale (PSS). We observed significant elevations in scores on these questionnaires in depressed patients as compared to normal controls. Following treatment with fluoxetine, there was a statistically significant reduction in scores on all four questionnaires. We observed that changes in SQ Hostility were significantly positively related to changes in both depression severity and perceived stress, with these relationships remaining significant after adjusting for gender and baseline SQ Hostility. The relationship between SQ Hostility changes and reductions in negative thinking became significant only after adjusting for gender and baseline SQ hostility. Our results suggest that the marked decrease in hostility following antidepressant treatment is related to a reduction in depressive symptoms, stress levels and negative thinking.     

Cognitive reactivity to sad mood provocation and the prediction of depressive relapse

CONTEXT: Episode remission in unipolar major depression, while distinguished by minimal symptom burden, can also be a period of marked sensitivity to emotional stress as well as an increased risk of relapse. OBJECTIVE: To examine whether mood-linked changes in dysfunctional thinking predict relapse in recovered patients who were depressed. DESIGN: In phase 1 of this study, patients with major depressive disorder were randomly assigned to receive either antidepressant medication or cognitive behavior therapy. In phase 2, patients who achieved clinical remission underwent sad mood provocation and were then observed with regular clinical assessments for 18 months. SETTING: Outpatient psychiatric clinics at the Centre for Addiction and Mental Health, Toronto, Ontario. PARTICIPANTS: A total of 301 outpatients with major depressive disorder, aged 18 to 65 years, participated in phase 1 of this study and 99 outpatients with major depressive disorder in remission, aged 18 to 65 years, participated in phase 2. MAIN OUTCOME MEASURE: Occurrence of a relapse meeting DSM-IV criteria for a major depressive episode as assessed by the longitudinal interval follow-up evaluation and a Hamilton Depression Rating Scale score of 16 or greater. RESULTS: Patients who recovered through antidepressant medication showed greater cognitive reactivity following the mood provocation than those who received cognitive behavior therapy. Regardless of type of prior treatment, the magnitude of mood-linked cognitive reactivity was a significant predictor of relapse over the subsequent 18 months. Patients whose mood-linked endorsement of dysfunctional attitudes increased by a minimum of 8 points had a significantly shorter time to relapse than those whose scores were not as elevated. CONCLUSIONS: The vulnerability of remitted depressed patients for illness relapse may be related to the (re)activation of depressive thinking styles triggered by temporary dysphoric states. This is the first study to link such differences to prognosis following successful treatment for depression. Further understanding of factors predisposing to relapse/recurrence in recovered patients may help to shorten the potentially lifelong course of depression.     

Cognitive change processes in a group cognitive behavior therapy of depression

The present study attempted to examine the causal relationships among changes in automatic thoughts, dysfunctional attitudes, and depressive symptoms in a 12-week group cognitive behavior therapy (GCBT) program for depression. In all, 35 depressed patients attending the GCBT program were monitored with the Automatic Thoughts Questionnaire, Dysfunctional Attitudes Scale, and Beck Depression Inventory at the pre-treatment, 4th and 8th sessions, and post-treatment. The results were as follows: (1). GCBT reduces negative cognitions; (2). changes in automatic thoughts and dysfunctional attitudes lead to change in depressive symptoms; and (3). automatic thoughts play a mediating role between dysfunctional attitudes and depression. The findings taken as a whole support the Causal Cognition Model of depression.     

Perceived stress and depression in left and right hemisphere post-stroke patients

Although it is well accepted that depression and stress are closely related in the general adult population, this link is less understood in post-stroke patients. Due to the high occurrence of depression in post-stroke patients it is important to look closely at this possible association. The current study explores perceived stress and depression in post-stroke patients. Nineteen left hemisphere (LH) stroke patients and 12 right hemisphere (RH) post-stroke patients were assessed for depression, perceived stress, and neurological functioning with the Stroke Aphasia Depression Questionnaire, the Perceived Stress Scale, and the Scandinavian Stroke Scale once per month for three months. Perceived stress and depressive symptoms were significantly correlated for both stroke groups. Neurological functioning was not correlated with either depressive symptoms or perceived stress in either stroke group. The perception of stress may be a more critical variable in developing post-stroke depression than neurological functioning is in stroke patients. Routine screening of perception of stress may need to occur in post-stroke patients to avoid development of depression.     

The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study

Recent studies suggested a role of brain-derived neurotrophic factor (BDNF) in depression. While BDNF levels are lower in depressed patients, antidepressant treatment increases serum BDNF levels of depressed patients. Our study aims to test the effect of chronic venlafaxine treatment on serum BDNF levels in patients with a major depressive disorder. Ten patients diagnosed as major depressive disorder according to DSM-IV are included in the study. Two of the patients had their first episode and were drug-naive, the other eight patients were drug-free for at least 4 weeks. The severity of depression was assessed with Hamilton Depression Rating Scale (HDRS). The control group consisted of ten age- and sex-matched subjects without any psychiatric disorder. Blood samples were collected at the baseline and after 12 weeks of antidepressant treatment (during remission). At the baseline the mean serum BDNF level was 17.9+/-9.1 ng/ml and the mean HDRS score was 23.2+/-4.6. Serum BDNF levels of the study group were significantly lower than in the control group (31.6+/-8.6 ng/ml). At the end of the study, the mean serum BDNF level was 34.6+/-7.1 ng/ml whereas the mean HDRS score was 8.2+/-3.9. From the baseline to the remission after 12 weeks of treatment, the increase in serum BDNF level and the decrease in HDRS score were statistically significant, respectively. When we compared the serum BDNF level of depressed patients at remission to that of the controls, there was no statistically significant difference. This study shows that venlafaxine treatment of depression improves serum BDNF level which may be considered as a nonspecific peripheral marker of depression.     

Dysfunctional cognitions of depressive inpatients and their relationship with treatment outcome

BackgroundDysfunctional cognitions can contribute to depression and its maintenance. They may be related to a higher relapse rate and a longer duration of the depressive episode. The relevance of dysfunctional cognitions for acute inpatient treatment of unipolar depression is examined in this study and its variability by cognitive behavioural therapy (CBT).Methods222 patients suffering from Major Depressive Disorder (MDD) were evaluated during their inpatient treatment by assessing admission and discharge depression scores and their relationship to dysfunctional cognitions, using the Dysfunctional Attitude Scale (DAS). The relationship between dysfunctional cognitions and treatment outcome was examined. Primary outcome measures were the Hamilton-Rating-Scale (HRSD) and the Beck Depression Inventory (BDI).ResultsHigher age, depression severity at admission, comorbid personality disorders and recurrent depressive disorders are related with higher DAS-scores at admission. DAS-Scores declined during treatment but to a lower extend than depressive symptom scales (effect size d_{DAS-G t1-t2} = .31; d_{HRSD t1-t2} = 2.88; d_{BDI t1-t2} = 1.38). Higher DAS-scores at admission correlated negatively with the improvement of depressive symptoms during treatment (HRSD: r = −.62; p < .01; BDI: r = −.54; p < .01) and remission rates (HRSD: r = −.65; p < .01; BDI: r = −.48; p < .01). CBT did not additionally reduce DAS-scores compared to pharmacotherapy only.ConclusionDysfunctional cognitions are relatively stable compared to other depressive symptoms and are associated with poorer treatment outcome even in combined treatment of antidepressant medication and CBT during inpatient treatment. Changes of dysfunctional cognitions seem to be a long-term treatment goal, especially because of their association with comorbid personality disorders and recurrent depressive disorders.     

Cognitive therapy and pharmacotherapy for depression. Sustained improvement over one year

Seventy patients with nonbipolar affective disorder who completed a 12-week course of either cognitive therapy (CT), pharmacotherapy, CT plus active placebo, or CT plus pharmacotherapy were assessed one month, six months, and one year after termination of active treatment. Of the 44 patients who had originally responded to treatment, 16 relapsed as defined by reentry into treatment or by self-reported depression scores in the moderately depressed range. Twenty-eight patients remained well during the one-year follow-up. Patients with relatively high levels of remaining depressive symptoms on completion of treatment relapsed more often than those who had little or no residual depression. Further, at treatment termination, patients who relapsed had significantly higher scores on a measure of dysfunctional attitudes. Patients who had received CT (with or without tricyclic antidepressants) were less likely to relapse in the one-year follow-up period than patients who received pharmacotherapy.     

Outcomes of depressed patients undergoing inpatient pulmonary rehabilitation.

OBJECTIVE: Approximately 30% of patients with chronic obstructive pulmonary disease (COPD) experience depression. Pulmonary rehabilitation for COPD focuses on physical conditioning, but includes behavioral interventions that may address depressive symptoms. This study tested the hypothesis that brief inpatient pulmonary rehabilitation is followed by improvement in both depressive symptoms and function in patients with COPD with major depression. METHODS: The subjects, who were recruited from the pulmonary rehabilitation unit of the Burke Rehabilitation Hospital in White Plains, NY, who had COPD and major depression were consecutively admitted patients to a pulmonary rehabilitation unit. Symptoms of depression, disability, medical burden, the experience of support, and satisfaction with treatment were systematically ascertained on admission and before discharge. RESULTS: Three hundred sixty-one patients were screened and 63 met criteria for COPD and major depression. Depressive symptoms improved by discharge (z = -6.785, p <0.0001); median length of stay was 16 days. Approximately 51% of subjects met criteria for response (50% or greater reduction in depressive symptoms scores from baseline), and 39% met criteria for remission (final Hamilton Depression scale score equal to or less than 10). History of treatment for depression was associated with limited change in depressive symptoms, whereas social support and satisfaction with treatment were predictors of improvement. All disability domains were lower at discharge compared to baseline (z = -3.928, p <0.0001). Subjects with pronounced disability at baseline had the greatest improvement if their depression improved by discharge. CONCLUSIONS: Acute inpatient rehabilitation is followed by improvement of depressive symptoms and disability in older patients with COPD and major depression. Improvement of depression may be the result of behavioral interventions rather than the use of antidepressant drugs.     

The mediator role of ruminative thinking style in the relationship between dysfunctional attitudes and depression

Background

The main aim of the present study was to examine whether ruminative thinking styles (brooding and reflection) mediate the effects of dysfunctional attitudes on depressive symptoms.

Methods

120 psychotropic drug-naive first episode depression patients recruited from Bulent Ecevit University School of Medicine psychiatry department and Zonguldak State Hospital psychiatry department outpatient clinics were involved in the study. Participants completed the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Beck Depression Inventory (BDI), Dysfunctional Attitude Scale (DAS) and Ruminative Responses Scale (RRS-short version). Regression analyses together with the Sobel tests were performed for testing the mediator hypothesis.

Results

According to the path model, the level of brooding fully mediated the relationship between dysfunctional attitudes and depressive symptomatology but reflection did not play a mediator role in the relationship between dysfunctional attitudes and depressive symptoms.

Conclusions

Assessment of brooding with both mental status examination and specific measurements and focusing on brooding as an intervention strategy would be beneficial components for an effective treatment of depression.     

Depressive and anxiety symptoms, dysfunctional attitudes and social aspects in irritable bowel syndrome and inflammatory bowel disease

OBJECTIVE: Biopsychosocial models for both organic and functional gastrointestinal (GI) disorders have been described in the recent literature. The objective of this study was to give further data to this model by assessing stressful life events, social support, psychopathological symptoms, and dysfunctional attitudes in irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and healthy subjects. METHOD: Age- and gender-matched IBS and IBD patients presenting at a tertiary care gastroenterological center completed self-reported questionnaires on stressful life events, social support, depressive and anxiety symptoms and dysfunctional attitudes. For comparative purposes, data from an age- and gender-matched healthy control group were obtained. RESULTS: No significant differences were found between the groups regarding stressful life events and social support. Both patient groups had higher depressive and anxiety symptoms compared to healthy subjects, and IBS patients had higher depressive scores compared to IBD patients. IBS patients had more dysfunctional attitudes compared to both IBD and healthy subjects, while IBD and healthy subjects did not differ on dysfunctional attitudes. CONCLUSIONS: GI patient status is associated with depressive and anxiety symptoms, in addition IBS patients have more severe depressive symptoms and depressogenic dysfunctional attitudes. The fact that functional GI patients are characterized by more severe psychological, but not social parameters, supports the hypothesis that IBS might be related to the range of depressive disorders.     

How ruminative thinking styles lead to dysfunctional cognitions: evidence from a mediation model

Background and Objectives

Dysfunctional attitudes and a ruminative thinking style are of utmost clinical importance because they are found to be crucially implicated in depression vulnerability. In this study, based on the Diathesis-Stress model (Beck, 1967) and the Differential Activation Hypothesis (Teasdale, 1988), we investigated whether inter-individual differences in a ruminative thinking style would be related to the development of depressive symptoms, leading to the activation of dysfunctional attitudes under stress.

Methods

Seventy-six never depressed undergraduate students completed internet questionnaires measuring rumination, depressive symptoms and dysfunctional attitudes at 4 fixed moments in time (T1, T2, T3, T4): T1 was performed six weeks before their exams (considered as a low stress period); T2, T3 and T4 were performed during three consecutive weeks in their final exams (considered as life stress event).

Results

As expected, results revealed that the relationship between rumination, measured both out of (T1) and in (T2) a stressful period, and dysfunctional attitudes (measured at T4) was mediated by increased depressive symptoms (measured at T3).

Limitations

Because the questionnaire for rumination was developed in the context of understanding responses to depressive symptoms, there might be a construct overlap between the predictor and the mediator of the models that were tested. Moreover, because only healthy undergraduates were included, our results demonstrate a decreased generalizability.

Conclusions

These findings indicate that rumination can be conceived as a stable and underlying mechanism leading to depressed mood and dysfunctional attitudes under stress. Moreover, our findings highlight that clinical interventions should not only target dysfunctional schemas and attitudes, but might also benefit from the use of procedures aimed at changing processes such as a ruminative thinking style.     

Adaptive cognitive emotion regulation moderates the relationship between dysfunctional attitudes and depressive symptoms during a stressful life period: A prospective study

Background and objectivesDysfunctional cognitions are known to emerge in stressful situations and are critical for the onset of depressive symptoms. The goal of this study is to investigate whether adaptive and/or maladaptive emotion regulation strategies moderate the relationship between dysfunctional attitudes and depressive symptoms under stress.MethodsIn a longitudinal study, 92 healthy but unselected undergraduates were followed for three months including a stress period (four weeks of examinations).ResultsOur findings demonstrate that the more adaptive emotion regulation strategies are used in daily life (measured at baseline), the weaker the relationship between dysfunctional attitudes and depressive symptoms during stress. Interestingly, no single strategy demonstrates a unique predictive value, but only the combination of several adaptive strategies moderates the relationship between dysfunctional attitudes and depressive symptoms. Although participants with elevated depressive symptoms use more maladaptive emotion regulation strategies, these latter strategies do not moderate the association between dysfunctional attitudes and depressive symptoms.LimitationsThe use of a sample of undergraduates limits the generalizability and the clinical significance of our results.ConclusionsAltogether, although dysfunctional attitudes are activated and accessible in response to certain life stressors, the strategies that healthy individuals use to adaptively regulate these cognitions seem important in determining the likelihood of depressive symptoms.     

Depressive symptoms and alcohol consumption among nonalcoholic depression patients treated with desipramine.

OBJECTIVE: There are few data addressing the effect of alcohol consumption on response to antidepressants among nonalcoholics with depression. Similarly, the effect of antidepressant treatment on alcohol consumption in this group is not yet understood. This study focuses on changes in depressive symptoms and alcohol consumption in response to treatment with desipramine. METHOD: Twenty-seven nonalcoholic outpatients with major depression (as determined by the Schedule for Affective Disorders and Schizophrenia-Lifetime Version) completed measures of depression (that is, the 17-item Hamilton Depression Rating Scale and the Beck Depression Inventory) and alcohol consumption at intake and after 5 weeks of open treatment with desipramine. Subjects were characterized as minimal or mild-to-moderate drinkers. RESULTS: There was no significant difference between the groups with respect to effectiveness of antidepressant treatment. Analysis for repeated measures demonstrated that alcohol consumption with desipramine was significantly lower after treatment than at intake (F = 4.8, df 23:2, P < 0.01). Further, carbohydrate consumption was also significantly lower after treatment than at intake (F = 4.4, df 23:2, P < 0.05). CONCLUSIONS: Desipramine treatment appeared to result in decreases in alcohol consumption in nonalcoholic patients with depression. Further research is needed to elucidate the effect of alcohol consumption on the course and outcome of major depressive illness among nonalcoholics as well as the effect of antidepressant medication on alcohol consumption in this population.     

Partial remission,residual symptoms,and relapse in depression

Partial remission from depression, with residual symptoms, is an important problem in depression. This paper reviews the frequency and features of this outcome, and its association with relapse. Residual symptoms occur in many depressed patients after acute treatment. They span the typical symptoms of depression, except those characteristic of severe disorders. Other persistent abnormalities include social dysfunction, dysfunctional attitudes, hypothalamic-pituitary-adrenal axis overactivity, shortened REM sleep latency, and mood lowering after tryptophan depletion. Associations of some of these with residual symptoms are not clear. There is growing evidence for similar residual symptoms in bipolar disorder, particularly bipolar depression. The most important consequence of residual symptoms is a much-increased risk of relapse, particularly in the first year. Residual symptoms are a strong indication for vigorous and longer than usual continuation of antidepressant treatment, in order to prevent relapse. There is good evidence for the use of cognitive therapy as an adjunct.     

Obsessive compulsive disorder, depression, and fluoxetine

BACKGROUND: Fluoxetine, a selective serotonin reuptake blocker, is an antidepressant medication that has also been shown in open clinical trials and one controlled trial to be effective in the treatment of obsessive compulsive disorder (OCD). OCD is often complicated by depression, and depressive symptoms may interfere with response to both pharmacologic and behavioral treatments. METHOD: We describe pilot data from 10 outpatients who met DSM-III-R criteria for OCD in whom the possibility of a depressive reaction or lack of antidepressant response occurred during an open trial of fluoxetine. RESULTS: Rapid increase in fluoxetine dose to high doses was associated with depressive symptoms in 6 patients. In 8 patients, improvement in depression was associated with addition of a tricyclic antidepressant to fluoxetine treatment. In 5 patients, both OCD and depressive symptoms improved when the patient was switched to the partially selective serotonin reuptake blocker clomipramine. CONCLUSION: This paper serves to alert clinicians to the possibility of a depressive reaction, or lack of antidepressant response, to fluoxetine in OCD patients. This possibility can only be resolved scientifically by adequately controlled experimental trials. If depression occurs, combined fluoxetine and tricyclic treatment, or a switch to a partially selective serotonin reuptake inhibitor, may be helpful. Special considerations and side effects of combined fluoxetine-tricyclic treatment are described.     

Patients presenting with somatic complaints: epidemiology,psychiatric comorbidity and management

Somatic symptoms are the leading cause of outpatient medical visits and also the predominant reason why patients with common mental disorders such as depression and anxiety initially present in primary care. At least 33% of somatic symptoms are medically unexplained, and these symptoms are chronic or recurrent in 20% to 25% of patients. Unexplained or multiple somatic symptoms are strongly associated with coexisting depressive and anxiety disorders. Other predictors of psychiatric co-morbidity include recent stress, lower self-rated health and higher somatic symptom severity, as well as high healthcare utilization, difficult patient encounters as perceived by the physician, and chronic medical disorders. Antidepressants and cognitive-behavioural therapy are both effective for treatment of somatic symptoms, as well as for functional somatic syndromes such as irritable bowel syndrome, fibromyalgia, pain disorders, and chronic headache. A stepped care approach is described, which consists of three phases that may be useful in the care of patients with somatic symptoms.     

Relapse after cognitive behavior therapy of depression: potential implications for longer courses of treatment.

OBJECTIVE: The authors studied the risk of relapse among depressed patients after cognitive behavior therapy in order to document the need and potential indications for longer-term models of treatment. METHOD: Forty-eight patients with major depression who responded during a 16-week course of cognitive behavior therapy entered a 1-year prospective follow-up study, as did two patients who received 20 weeks of therapy. Standardized, independent clinical assessments were completed 1, 3, 6, 9, and 12 months after treatment. Relapse was defined as, at minimum, a 2-week period in which the subject met the DSM-III-R criteria for major depression and had a Hamilton depression scale score of 15 or more. RESULTS: Sixteen patients (32%) relapsed during the 1-year follow-up. Correlates of relapse included a history of depressive episodes, higher levels of depressive symptoms and dysfunctional attitudes, slower response to therapy, and being unmarried. Patients who fully recovered during therapy (Hamilton depression score of 6 or less for 8 weeks or more) were at significantly lower risk for relapse than those who partially recovered (9% and 52%, respectively). Slower response to therapy, unmarried status, and high residual scores on the Dysfunctional Attitudes Scale were independently and additively related to increased risk of relapse. CONCLUSIONS: These findings provide further evidence of a relation between residual symptoms and relapse after cessation of active treatment. The authors strongly recommend that models of longer-term psychotherapy be developed for depressed patients who do not recover fully during time-limited cognitive behavior therapy.